What is conventional medicine?

How does it treat:

How is Healthcare:

What is alternative medicine?



A discussion of White Coat Syndrome on another blog.

“The magnitude of white coat effect was 50 +/- 17 (8-84) mm Hg for systolic blood pressure and 18 +/- 11 (-9 +/- 41) mm Hg for diastolic blood pressure. A marked white coat effect (> 40 mm Hg) was observed in 78% of our hypertensive patients. In elderly people (> 60 years), this difference was greater (50 +/- 15 vs 45 +/- 21 mm Hg) though not significantly”

I have a fairly radical view of hypertension, which is that as a risk factor we have been not able to treat it effectively. As a result, patients continue to die while taking expensive medications. I question the viability of blood pressure as a diagnosis in older patients. I base these radical statements in part on the following:   “Lowering blood pressure or treating hypertension with a variety of antihypertensive agents reduced stroke; No effect was seen on vascular or all-cause mortality” (Stroke 2003 Nov;34(11):2741-8)

While lowering blood pressure does decrease other, lesser events, another study from 2016 found: “However, more intensive treatment had no clear effects on heart failure (15% [95% CI -11 to 34]), cardiovascular death (9% [-11 to 26]), total mortality (9% [-3 to 19]), or end-stage kidney disease (10% [-6 to 23])” 

Patients experienced fewer strokes but died at the same rate.

“In spite of its importance in causing cardiovascular disease blood pressure is a poor predictor of cardiovascular events; persons in the top 10% of the distribution of systolic blood pressure experienced only 21% of all ischaemic heart disease events and 28% of all strokes at a given age.. the term hypertension should be avoided because it is not a disease and it implies another category (normotensives) who would not benefit from lowering blood pressure (Health Technol Assess. 2003;7(31):1-94)

These experts recommend hypertension drugs for everyone. “To evaluate the effect of antihypertensive treatment on secondary prevention of CVD events and all-cause mortality among persons without clinically defined hypertension….Among patients with clinical history of CVD but without hypertension, antihypertensive treatment was associated with decreased risk of stroke, CHF, composite CVD events, and all-cause mortality”  So we had better outcomes using blood pressure medications to treat heart disease even if the person didn’t have high blood pressure. Since this is the only study to show a decrease in overall mortality, shouldn’t we change the definition of what we’re doing?

Autism, ADHD And Diet: Old Lecture Notes

Autism, ADHD, and Diet


Chris Maloney, ND

4 Drew Street, Augusta ME 04330

(207) 623-1681

Three things to remember:

1)      You can make a difference

2)      You are the expert

3)      You are the heroes

Diagnosis is not your child:  The genetics of autism and ADHD overlap. [1] Testing fails to show a clear picture of where one diagnosis ends and the other begins.[2] 

Diet probably affects behavior

Watch for diet related behavior changes:  immediate, 2 hours, 12 hours, 48 hours. Gold standard is:  introduction->change, elimination, reintroduction->change

As caregivers, diet is only one issue, but you may observe. 

            Dairy-> sedation OR Dairy->manic

            Wheat-> cascade of allergic responses

What can you do? 

            GABA For AGGRESSION  (typically 500mg twice a day morning and lunch)[3]

            5 HTP for ANXIETY or DEPRESSION  (tapered up from 50mg until symptoms resolve or stomach upset occurs)  [4]

Eleven (65%) of the 17 patients who completed both test days showed a significant global worsening of behavioral symptoms with short-term tryptophan depletion, but none of the 17 patients showed any significant change in clinical status from baseline after sham depletion (P = .001). Tryptophan depletion led to a significant increase in behaviors such as whirling, flapping, pacing, banging and hitting self, rocking, and toe walking (P < .05). In addition, patients were significantly less calm and happy and more anxious. Arch Gen Psychiatry. 1996 Nov;53(11):993-1000.

Homeopathics:  The placebo effect?  I’ll take it.  (No toxicity or drug interactions)

During the screening phase, 84% (70/83) of the children responded to treatment.[5]

Stramonium (all 30c or above) – BITING (vicious)

Pulsatilla –Biting fatigued or crazy.  Normally clingy, very sweet. 

Hyoscyamus-  Need to take clothes off, display oneself. 

Chamomile- child is inconsolable, caregivers feel fed up.

Pulsatilla- child is inconsolable, caregivers just want to hold. 

Calcarea Carbonicum-  child cannot make transitions.  Fine with five minutes warning.

Tarantula- child is manic, dancing. 

Arsenicum Album- child is full of fear, up at night with terrors. 

Dr. Maloney’s Autistic Allergy Quiz

What percent of autistic children have documented allergies?

9 of 96 (9%) children with a diagnosis of autism (cases) and 41 of 449 (9%) children without autism (matched controls) had a history of gastrointestinal disorders

BMJ. 2002 Aug 24;325(7361):419-21

What percent of autistic children have undocumented allergies (estimate)?

Five times as many.  Respiratory, food, and skin allergies were reported by parents more often for children with autism, with food allergies having the strongest relative difference between the groups (odds ratio, 4.5; 95% confidence interval, 3.0-7.0).   Arch Pediatr Adolesc Med. 2006 Aug;160(8):825-30.

The consistency in estimates between the two surveys suggests high reliability for parental report of autism

MMWR Morb Mortal Wkly Rep. 2006 May 5;55(17):481-6.

What can we expect from our doctors in terms of food allergy? 

Diet and child behavior problems: fact or fiction?Cormier E, Elder JH.

Florida State University College of Nursing, Tallahassee, USA.

“Dietary treatment of children with behavioral disorders has had wide public appeal and been a source of controversy since the 1920’s. Yet, to date, there is little empirical evidence supporting the effectiveness of dietary restrictions in treating child psychiatric disorders, in particular, autism” Pediatr Nurs. 2007 Mar-Apr;33(2):138-43.

the fourth outcome, reduction in autistic traits, reported a significant beneficial treatment effect for the combined gluten- and casein- free diet.

Cochrane Database Syst Rev. 2004;(2):CD003498

Elimination diet (double-blinded) produces a 70% reduction in symptoms for ADHD.[6]

What are the most common allergies for autistic children? [7]

ASD children produced more tumor necrosis factor-alpha… irrespective of objective GI symptoms. They also produced more TNF-alpha with gliadin, which was more frequently observed in the group with loose stools

Impaired social interaction, communication and imaginative skills characterize autistic syndromes. In these syndromes urinary peptide abnormalities, derived from gluten, gliadin, and casein, are reported. They reflect processes with opioid effect. The aim of this single blind study was to evaluate effect of gluten and casein-free diet for children with autistic syndromes and urinary peptide abnormalities. A randomly selected diet and control group with 10 children in each group participated. Observations and tests were done before and after a period of 1 year. The development for the group of children on diet was significantly better than for the controls.  Nutr Neurosci. 2002 Sep;5(4):251-61.

My quick answers:

What amount is necessary to cause an allergic reaction?  2mg

What types of allergic reaction are possible? 4 types

How long is it necessary to avoid an allergen before seeing any difference?Four days

How long does a person maintain an allergic response?  Depends on immune system

What is sensitivity?  Behavioral change without allergic responses.

What is intolerance?  Physical changes without allergic responses

What about combinations?  May generate allergic, sensitivity or intolerance responses.

What else should we watch for?


Fifteen (44%) of the psychotic children (autistic and nonautistic) had blood lead levels greater than two standard deviations above the mean for normal controls

Am J Dis Child. 1976 Jan;130(1):47-8

Fifteen autistic children and four typically developing children completed the study. Three autistic subjects excreted one metal in greater quantity during the provoked excretion than baseline. Two of these were very close to the limit of detection. In the third case, the provoked excretion of mercury was between the upper limit of normal and lower limit of the potentially toxic reference range. Fish was removed from this child’s diet for greater than one month, and the provoked excretion test repeated. The repeat excretion of mercury was within the normal range. Clin Toxicol (Phila). 2007 Jun-Aug;45(5):476-81.


autistic children and children with other autistic spectrum disorders had significantly lower plasma concentrations of Mg than normal subjects (p=0.013 and p=0.02, respectively). Biol Trace Elem Res. 2006 Feb;109(2):97-104   

Amino Acids

However, children with autism had more essential amino acid deficiencies consistent with poor protein nutrition than an age/gender matched control group. There was a trend for children with autism who were on restricted diets to have an increased prevalence of essential amino acid deficiencies and lower plasma levels of essential acids including the neurotransmitter precursorstyrosine and tryptophan than both controls and children with autism on unrestricted diets  J Autism Dev Disord. 2003 Aug;33(4):449-54.


Seventy-seven percent had restless sleep at baseline, which improved significantly with iron therapy, suggesting a relationship between sleep disturbance and iron deficiency in children with autism spectrum disorder. Sixty-nine percent of preschoolers and 35% of school-aged children had insufficient dietary iron intake  Pediatr Neurol. 2007 Mar;36(3):152-8

Essential Fatty Acids

We observed an advantage of omega-3 fatty acids compared with placebo for hyperactivity and stereotypy, each with a large effect size. Biol Psychiatry. 2007 Feb 15;61(4):551-3

Cholesterol is essential for neuroactive steroid production, growth of myelin membranes, and normal embryonic and fetal development. It also modulates the oxytocin receptor, ligand activity and G-protein coupling of the serotonin-1A receptor. A deficit of cholesterol may perturb these biological mechanisms and thereby contribute to autism spectrum disorders (ASDs), as observed in Smith-Lemli-Opitz syndrome (SLOS) and some subjects with ASDs in the Autism Genetic Resource Exchange (AGRE). A clinical diagnosis of SLOS can be confirmed by laboratory testing with an elevated plasma 7DHC level relative to the cholesterol level and is treatable by dietary cholesterol supplementation. Individuals with SLOS who have such cholesterol treatment display fewer autistic behaviours, infections, and symptoms of irritability and hyperactivity, with improvements in physical growth, sleep and social interactions. Other behaviours shown to improve with cholesterol supplementation include aggressive behaviours, self-injury, temper outbursts and trichotillomania. Cholesterol ought to be considered as a helpful treatment approach while awaiting an improved understanding of cholesterol metabolism and ASD. There is an increasing recognition that this single-gene disorder of abnormal cholesterol synthesis may be a model for understanding genetic causes of autism and the role of cholesterol in ASD.  Int Rev Psychiatry. 2008 Apr;20(2):165-70.

In double-blind, randomized, controlled trials, DHA and EPA combinations have been shown to benefit attention deficit/hyperactivity disorder (AD/HD), autism, dyspraxia, dyslexia, and aggression.  Altern Med Rev. 2007 Sep;12(3):207-27.

Children aged 8-13 y with impaired visual sustained attention performance received placebo, 250 mg/d EPA + DHA esterified to PL-n-3 (300 mg/d phosphatidylserine), or FO for 3 mo in a randomized double-blind manner. A significant correlation between the alterations in FAs and increased TOVA scores mainly occurred in the PL-n-3 group.  Am J Clin Nutr. 2008 May;87(5):1170-80

Avoid IV treatments without research

There is no evidence that single or multiple dose intravenous secretin is effective and as such it should not currently be recommended or administered as a treatment for autism Cochrane Database Syst Rev. 2005 Jul 20;(3):CD003495

Avoid meds if possible

Some evidence of the benefits of risperidone in irritability, repetition and social withdrawal were apparent. These must however be considered against the adverse effects, the most prominent being weight gain Cochrane Database Syst Rev. 2007 Jan 24;(1):CD005040.


the findings indicate that music therapy may help children with autistic spectrum disorder to improve their communicative skills Cochrane Database Syst Rev. 2006 Apr 19;(2):CD00438

Autism, Aspergers, and ADHD

Are these separate diagnoses?

Structural brain abnormalities in adolescents with autism spectrum disorder and patients with attention deficit/hyperactivity disorder.  With regard to clinical criteria, the clinical groups did not differ with respect to ADHD symptoms; however, only patients with ASD showed deficits in social communication and interaction, according to parental rating. While the shared structural deviations in the medial temporal lobe might be attributed to an unspecific delay in brain development and might be associated with memory deficits, the structural abnormalities in the inferior parietal lobe may correspond to attentional deficits observed in both ASD and ADHD. By contrast, the autism-specific grey matter abnormalities near the right temporo-parietal junction may be associated with impaired ‘theory of mind’ abilities. These findings shed some light on both similarities and differences in the neurocognitive profiles of ADHD and ASD patients.  J Child Psychol Psychiatry. 2007 Dec;48(12):1251-8

Psychological and neurobehavioral comparisons of children with Asperger’s Disorder versus High-Functioning Autism.  There were more similarities than differences between the two clinical samples on the personality scales, although the Asperger’s group scored significantly on the two scales with anxiety components.  J Autism Dev Disord. 2007 May;37(5):847-54

The results showed that the inability to understand sarcastic situation was specific to group with AS, No To Hattatsu. 2006 May;38(3):177-81

Children with Asperger’s syndrome had better social skills and fewer autistic symptoms 2 years after study enrollment than the children with autism. The differences in outcome could not be explained by initial differences in IQ and language abilities. Children with autism who had developed verbal fluency at follow-up were very similar to the children with Asperger’s syndrome at study enrollment. Am J Psychiatry. 2000 Dec;157(12):1980-7

Outcome in high-functioning adults with autism with and without early language delays: implications for the differentiation between autism and Asperger syndrome.

Scores on tests of language comprehension and expression were also similar, but in both groups language abilities were well below chronological age level. The implications of these results with respect to the differences between Asperger syndrome and high-functioning autism are discussed. The poor performance on language tests also challenges the assumption that early language development in Asperger syndrome is essentially normal.  J Autism Dev Disord. 2003 Feb;33(1):3-13.

Regression analysis revealed that specific language impairment at time 2 (8yrs) more often accounted for the greatest variation in outcome scores in adolescence than the standard diagnosis of AS versus HFA based on history of language delay.

J Autism Dev Disord. 2008 Apr;38(4):616-25.

[1] Significant correlations were found between autistic and ADHD traits in the general population (.54 for parent data, .51 for teacher data). In the bivariate models, all genetic correlations were >.50, indicating a moderate degree of overlap in genetic influences on autistic and ADHD traits…common genetic influences operating across autistic traits and ADHD behaviours throughout normal variation and at the extreme. This is relevant for molecular genetic research, as well as for psychiatrists and psychologists, who may have assumed these two sets of behaviours are independent. J Child Psychol Psychiatry. 2008 May;49(5):535-42

[2] The goal of this study was to evaluate and compare executive functioning (EF) profiles in children with ADHD and in children with ASD with and without comorbid ADHD…Effect sizes showed clear deficits of ADHD children in inhibition and working memory tasks. Participants with ASD were impaired in planning and flexibility abilities…Nevertheless the heterogeneity of these and previous results shows that EF assessment is not useful for differential diagnosis between ADHD and ASD. It might be useful for evaluating strengths and weaknesses in individual children. Child Adolesc Psychiatry Ment Health. 2008 Jan 31;2(1):4

[3] “Multiple lines of evidence, including alterations in levels of GABA and GABA receptors in autistic patients, indicate that the GABAergic system, which is responsible for synaptic inhibition in the adult brain, may be involved in autism.”  Neurogenetics. 2006 Jul;7(3):167-74. Epub 2006 Jun 13  (DUKE)

[4] “The serotonin transporter gene (5-HTT) plays a crucial role in serotonergic neurotransmission and has been found to be associated, with varying degrees of significance, with many diseases, including autism”  Am J Med Genet B Neuropsychiatr Genet. 2008 Feb 19  (HARVARD)

[5] Homeopathy. 2007 Jan;96(1):35-41. Links

Randomised controlled trials of homeopathy in hyperactive children: treatment procedure leads to an unconventional study design. Experience with open-label homeopathic treatment preceding the Swiss ADHD placebo controlled, randomised, double-blind, cross-over trial.Frei H, Everts R, von Ammon K, Kaufmann F, Walther D, Schmitz SF, Collenberg M, Steinlin M, Lim C, Thurneysen A.

Swiss Association of Homeopathic Physicians, Lucerne, Switzerland.

BACKGROUND: Treatment of patients with attention deficit hyperactivity disorder (ADHD) with homeopathy is difficult. The Swiss randomised, placebo controlled, cross-over trial in ADHD patients (Swiss ADHD trial) was designed with an open-label screening phase prior to the randomised controlled phase. During the screening phase, the response of each child to successive homeopathic medications was observed until the optimal medication was identified. Only children who reached a predefined level of improvement participated in the randomised, cross-over phase. Although the randomised phase revealed a significant beneficial effect of homeopathy, the cross-over caused a strong carryover effect diminishing the apparent difference between placebo and verum treatment. METHODS: This retrospective analysis explores the screening phase data with respect to the risk of failure to demonstrate a specific effect of a randomised controlled trial (RCT) with randomisation at the start of the treatment. RESULTS: During the screening phase, 84% (70/83) of the children responded to treatment and reached eligibility for the randomised trial after a median time of 5 months (range 1-18), with a median of 3 different medications (range 1-9). Thirteen children (16%) did not reach eligibility. Five months after treatment start, the difference in Conners Global Index (CGI) rating between responders and non-responders became highly significant (p = 0.0006). Improvement in CGI was much greater following the identification of the optimal medication than in the preceding suboptimal treatment period (p < 0.0001). CONCLUSIONS: Because of the necessity of identifying an optimal medication before response to treatment can be expected, randomisation at the start of treatment in an RCT of homeopathy in ADHD children has a high risk of failure to demonstrate a specific treatment effect, if the observation time is shorter than 12 months.

PMID: 17227746 [PubMed – indexed for MEDLINE]

[6] Eur Child Adolesc Psychiatry. 2008 Apr 21. [Epub ahead of print] Links

A randomised controlled trial into the effects of food on ADHD.Pelsser LM, Frankena K, Toorman J, Savelkoul HF, Pereira RR, Buitelaar JK.

ADHD Research Centre, Liviuslaan 49, 5624 JE, Eindhoven, The Netherlands,

The aim of this study is to assess the efficacy of a restricted elimination diet in reducing symptoms in an unselected group of children with Attention deficit/hyperactivity disorder (ADHD). Dietary studies have already shown evidence of efficacy in selected subgroups. Twenty-seven children (mean age 6.2) who all met the DSM-IV criteria for ADHD, were assigned randomly to either an intervention group (15/27) or a waiting-list control group (12/27). Primary endpoint was the clinical response, i.e. a decrease in the symptom scores by 50% or more, at week 9 based on parent and teacher ratings on the abbreviated ten-item Conners Scale and the ADHD-DSM-IV Rating Scale. The intention-to-treat analysis showed that the number of clinical responders in the intervention group was significantly larger than that in the control group [parent ratings 11/15 (73%) versus 0/12 (0%); teacher ratings, 7/10 (70%) versus 0/7 (0%)]. The Number of ADHD criteria on the ADHD Rating Scale showed an effect size of 2.1 (cohen’s d) and a scale reduction of 69.4%. Comorbid symptoms of oppositional defiant disorder also showed a significantly greater decrease in the intervention group than it did in the control group (cohens’s d 1.1, scale reduction 45.3%). A strictly supervised elimination diet may be a valuable instrument in testing young children with ADHD on whether dietary factors may contribute to the manifestation of the disorder and may have a beneficial effect on the children’s behaviour.

PMID: 18431534 [PubMed – as supplied by publisher]

[7] Peripheral blood mononuclear cells (PBMCs) were obtained from 109 ASD children with or without GI symptoms (GI [+] ASD, N = 75 and GI (-) ASD, N = 34], from children with NFH (N = 15), and control subjects (N = 19). Diarrhea and constipation were the major GI symptoms. We measured production of type 1 T-helper cells (Th1), type 2 T-helper cells (Th2), and regulatory cytokines by PBMCs stimulated with whole cow’s milk protein (CMP), its major components (casein, beta-lactoglobulin, and alpha-lactoalbumin), gliadin, and soy. RESULTS: PBMCs obtained from GI (+) ASD children produced more tumor necrosis factor-alphairrespective of objective GI symptoms. They also produced more TNF-alpha with gliadin, which was more frequently observed in the group with loose stools.  PBMCs obtained from GI (-) ASD children produced more TNF-alpha/IL-12 with CMP than those from control subjects, but not with beta-lactoglobulin, alpha-lactoalbumin, or gliadin. Cytokine production with casein and soy were unremarkable.J Pediatr. 2005 May;146(5):605-10.

Seasonal Affective Disorder

Seasonal Affective Disorder is a subgrouping of major depressive disorder that occurs with seasonal variation.  It is a highly complex, multifactorial illness.

Full MD free SAD article here.

NAMI’s discussion of SAD

Psychoneuroendocrinology. 2010 Dec 8. [Epub ahead of print]

Seasonal differences in the diurnal pattern of cortisol secretion in healthy participants and those with self-assessed seasonal affective disorder.

Thorn L, Evans P, Cannon A, Hucklebridge F, Evans P, Clow A.

Department of Psychology, University of Westminster, 309 Regent Street, London W1B 2UW, UK.


This study compared the daily pattern of free salivary cortisol secretion in winter and in summer between two groups; participants with self-assessed seasonal affective disorder (SAD) and age- and sex-matched healthy controls. Fifty-two participants completed the study with an equal number in each group. The diurnal pattern of cortisol secretion was assessed across two consecutive weekdays in summer, and two in winter, with conditions being counterbalanced. On each study day participants collected multiple saliva samples in the domestic setting to capture the cortisol awakening response (CAR) and declining levels across the day. In addition, perceived stress, anxiety, depression, state stress and state arousal were assessed using validated questionnaires. There was no evidence for any seasonal changes in psychological data or cortisol pattern for the healthy control population. In summer, self-assessed SAD and control participants had similar psychological and cortisol profiles. In winter however, SAD participants reported greater depression, stress and anxiety, and lower levels of arousal. Furthermore, the CAR was significantly attenuated in SAD participants during winter months. There was no difference in cortisol levels during the rest of the day between controls and SAD participants in winter. In line with the above findings and previous research, there was an inverse relationship between the increase in cortisol following awakening and a measure of seasonality in winter. Furthermore in winter, a general dysphoria construct correlated inversely with the CAR, indicating that participants reporting greater depression, stress and anxiety and lower arousal, exhibited lower CARs. In conclusion, during the shortened photoperiod in winter, the cortisol response to awakening is attenuated in participants with self-assessed SAD in comparison to controls. These findings contribute to the understanding of the physiology of SAD.

Copyright © 2010 Elsevier Ltd. All rights reserved

J Psychiatr Pract. 2010 Nov;16(6):387-93.

Light therapy for seasonal affective disorder in a clinical office setting.

Privitera MR, Moynihan J, Tang W, Khan A.University of Rochester Medical Center, Rochester, NY 14642, USA.


OBJECTIVE: To determine predictors of response to light therapy (LT) for seasonal affective disorder, winter version, in a clinical office setting for patients with a spectrum of seasonality defined by the Seasonal Pattern Assessment Questionnaire (SPAQ).

METHOD: A retrospective review was done of charts of 51 patients who had been treated with a 1-week light therapy intervention. Patient self-rated scales applied in a standard manner were used to measure clinical progress. The Beck Depression Inventory (BDI) with added atypical features was used as the primary outcome variable. Sleep patterns were analyzed and the effect of psychotropic medications on outcome was determined. Seven point scales were used to assess expected response and global response. The importance of having LT set up and available in an office setting was evaluated. Retrospective degree of disability was measured based on the SPAQ degree of problem. The severity of the depressive episode was determined based on BDI score at entry.

RESULTS: Seasonality (how a patient’s symptoms vary as a function of the season of the year), degree of disability based on the SPAQ, and severity of depressive episode at entry based on the BDI predicted response to LT. Greater severity at baseline based on BDI score predicted less chance of attaining full remission within 7 days of treatment compared with patients with lower severity scores at entry on the BDI. Sleep patterns relative to a fixed treatment time of 7 AM did not predict LT response. Light therapy was effective on its own, and the results were mixed as to whether adding LT to an existing antidepressant medication produced superior results.

CONCLUSION: Degree of seasonality can be used as a predictor of response to LT and may be clinically useful when suggesting that patients consider a trial of LT.

PMID: 21107143

Aust N Z J Psychiatry. 1997 Apr;31(2):279-84.

Seasonal affective disorder in Australia: is photoperiod critical?

Murray GW, Hay DA.

Department of Psychology, University of Melbourne, Parkville, Victoria, Australia.


OBJECTIVES: Seasonal affective disorder (SAD) is a variant of recurrent depression in which episodes are linked to a particular season, typically winter. SAD is understood as the extreme end of a continuum of seasonality in the general population. Photoperiod (the timing and duration of daylight) has been assumed to be aetiologically critical. The present research used a survey design to investigate the assumed centrality of photoperiod for SAD/seasonality in Australia. Two hypotheses were tested: that self-reported seasonality does not increase further from the equator and that seasonality does not stand alone from non-seasonal neurotic complaints.

METHOD: The sampling frame used was adult females on the Australian Twin Registry roll. A sample of 526 women residing across the latitudes of Australia responded to a survey based around the Seasonal Pattern Assessment Questionnaire (SPAQ). The SPAQ asks respondents to retrospectively report on season-related changes in mood and behaviour. The survey also contained three questionnaire measures of neurotic symptoms of anxiety and depression: the General Health Questionnaire (GHQ), the Community Epidemiological Survey for Depression (CES-D) and the State-Trait Anxiety Inventory-Trait (STAI-T).

RESULTS: Self-reported seasonality did not correlated with latitude (r = 0.01, NS). On the other hand, a substantial relationship was found between seasonality and each of the measures of non-seasonal complaints: GHQ (r = 0.35, p < 0.001); CES-D (r = 0.35, p < 0.001); and STAI-T (r = 0.30, p < 0.001).

CONCLUSIONS: Within the limitations of a design based on retrospective self-report, the findings of the present study suggest that the diathesis for SAD/seasonality may not be photoperiod-specific. At least in Australia, there is provisional support for the proposal that human seasonality may have a broader psychological component. The findings are discussed in terms of established research into normal mood, trait personality and non-seasonal depression.

PMID: 9140637

Ann Clin Psychiatry. 2007 Oct-Dec;19(4):239-46.

Seasonal affective disorder: a clinical update.

Westrin A, Lam RW.

Department of Clinical Sciences, Division of Psychiatry, Lund University Hospital, Lund, Sweden.


BACKGROUND: Seasonal affective disorder (SAD) consists of recurrent major depressive episodes in the fall/winter with remissions in spring/summer.

METHOD: A Medline search was conducted to identify studies relating to clinical management of SAD using the Medical Subject Heading, seasonal affective disorder, and key words, depress* and season*, focusing on studies published in the past 10 years. The Cochrane library of systematic reviews was also searched for relevant studies.

RESULTS: A careful history is important to make the diagnosis and differentiate SAD from other similar conditions such as subsyndromal SAD and atypical depression. Seasonal patterns with winter worsening are also recognized in “nonseasonal” depression as well as many other psychiatric conditions, and comorbidity with SAD is common. The pathophysiology of SAD seems to be heterogeneous as research on circadian, neurotransmitter function and genetic hypotheses have shown discrepant results. A dual vulnerability model with differential loading on separate seasonal and depression factors has been proposed to explain these findings. Recent systematic reviews have shown that light therapy is an efficacious and well-tolerated treatment for SAD. There is also evidence for efficacy of pharmacotherapy to treat and prevent SAD. Clinical studies show equal effectiveness with light and antidepressants, so patient preference should be considered in the selection of initial treatment. Dawn stimulation, negative air ions, exercise and cognitve behaviour therapy are under investigation and may also be helpful treatments for SAD.

CONCLUSIONS: SAD is a common condition with significant psychosocial impairment. Clinicians should be vigilant in recognizing seasonal patterns of depressive episodes because there are effective, evidence-based treatments for SAD.

PMID: 18058281

Soc Psychiatry Psychiatr Epidemiol. 1997 Apr;32(3):149-57.

Seasonal changes in affective state in samples of Asian and white women.

Suhail K, Cochrane R.School of Psychology, University of Birmingham, Edgbaston, UK.


Seasonality of the affective state has been reported to vary in direct proportion to latitude in temperate regions. The frequency of seasonal affective disorder (SAD) and the severity of the symptoms associated with it have been reported to be greater in higher than in lower latitudes. In addition, recent research has suggested a genetic loading for SAD. Most of the research on the seasonality of affect has been done in high latitude areas, seasonal mood cycles have been infrequently investigated in tropical areas, and no study has so far measured and compared seasonal changes in affect and behaviour in indigenous and populations non-indigenous to high latitudes. To rule out the biases associated with retrospective designs, a prospective longitudinal study was designed to investigate seasonal mood variations in indigenous white and non-indigenous Asian populations. Since previous research has indicated the excessive vulnerability of women to winter depression, it was decided to measure seasonality of the affective state only in women. To examine the relative effects of genetic predispositions and physical environment, the Asian group was further divided into “Asian” and “Asian-British”. The former group comprised women who were living in England but who had been born and had spent considerably more time in their country of origin, while the latter group consisted of women who were born in England and who had lived there all their lives. The three groups of 25 women each were matched for age and socio-economic status, and were interviewed every month for 1 year using the Hospital Anxiety and Depression Scale (HAD), a Behavioural Change Inventory (BCI), the Ladder Scale of General Well-being (LSW) and a Monthly Stress Inventory (MSI). One retrospective scale was administered at the end of the study year to compare the extent of seasonal change in affect with that on the HAD-depression subscale. The results showed that seasonal depression peaked in winter in all three groups, with the incidence of winter depression being highest in the Asian group. Seasonal changes on several dimensions of behaviour were in the direction of winter depression for all three groups. States other than depression (anxiety and general well-being) did not show any seasonal variation. Hours of daylight was found to be the best predictor of seasonal variation in mood among environmental and psychosocial variables. There was no evidence to support a genetic hypothesis for SAD.

Am J Geriatr Pharmacother. 2010 Feb;8(1):4-33.

Extraskeletal effects of vitamin D in older adults: cardiovascular disease, mortality, mood, and cognition.

Barnard K, Colón-Emeric C.

Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA.


BACKGROUND: Vitamin D insufficiency is prevalent among older adults and may be associated with higher risk for cardiovascular (CV) disease, mortality, depression, and cognitive deficits.

OBJECTIVE: The aim of this article was to review published observational and experimental studies that explored the association between vitamin D insufficiency and CV disease, mortality, mood, and cognition with an emphasis on older adults.

METHODS: PubMed and Web of Science databases were searched for English-language articles from January 1966 through June 2009 relating to vitamin D, using the following MeSH terms: aged, vitamin D deficiency, physiopathology, drug therapy, cardiovascular diseases, blood pressure, mortality, delirium, dementia, cognitive disorders, depression, depressive disorder, seasonal affective disorder, mental disorders, and vitamin D/therapeutic use. Publications had to include patients > or =65 years of age who had > or =1 recorded measurement of 25-hydroxyvitamin D (25[OH]D) or were receiving vitamin D supplementation. All case-control, cohort, and randomized studies were reviewed.

RESULTS: Forty-two case-control, cohort, and randomized trials were identified and included in the review. Based on these publications, the prevalence of vitamin D insufficiency (25[OH]D concentration <30 ng/mL) in communitydwelling older adults (> or =65 years of age) ranged from 40% to 100%. Epidemiologic data and several small randomized trials found a potential association between vitamin D deficiency (25[OH]D concentration <10 ng/mL) and CV disease, including hypertension and ischemic heart disease. Although subgroup analyses of data from the Women’s Health Initiative Randomized Trial (the largest randomized, placebo-controlled trial of vitamin D plus calcium therapy) did not find reductions in blood pressure, myocardial infarction, or CV disease-related deaths, intervention contamination limited the findingsObservational studies and a meta-analysis of randomized controlled trials found a mortality benefit associated with higher serum 25(OH)D concentrations or vitamin D(2) or D(3) supplementation (mean dose, 528 IU/d). Observational and small randomized trials found a potential benefit of sunlight or vitamin D on symptoms of depression and cognition, but the findings were limited by methodologic problems.

CONCLUSIONS: Vitamin D insufficiency appears to be highly prevalent among older adults. Evidence from epidemiologic studies and small clinical trials suggests an association between 25(OH)D concentrations and systolic blood pressure, risk for CV disease-related deaths, symptoms of depression, cognitive deficits, and mortality. The Women’s Health Initiative Randomized Trial did not find a benefit of vitamin D supplementation on blood pressure, myocardial infarction, or mortality in postmenopausal women.

Copyright 2010 Excerpta Medica Inc. All rights reserved. Published by EM Inc USA.. All rights reserved.

PMID: 20226390

J Nutr Health Aging. 2006 Mar-Apr;10(2):151-3.

Can vitamin D supplementation prevent winter-time blues? A randomised trial among older women.

Dumville JC, Miles JN, Porthouse J, Cockayne S, Saxon L, King C.Area 4, Seebohm Rowntree Building, Dept of Health Sciences, University of York, York YO10 5DD.


BACKGROUND: Seasonal Affective Disorder (SAD) is a sub-type of depression that only occurs during the winter months. A reduction in vitamin D may be linked to SAD. Since vitamin D deficiency has been reported to be common in older people, vitamin D supplementation may be expected to reduce seasonal mood disturbance in this group.

OBJECTIVE: To assess the effect of vitamin D supplementation on the mental health of older women.

SETTING: Primary care in three areas of the UK (Herts, Newcastle, York).

SUBJECTS: Women aged 70 years or more recruited to the trial in the months May-October. Intervention: Eligible women were randomised to receive calcium and vitamin D supplementation or no supplementation.

OUTCOME MEASURE: At baseline and the six monthly assessment the mental component score (MCS), calculated from the SF-12 questionnaire was used to assess participants’ subjective psychological well-being.

RESULTS: A total of 2117 women recruited to the trial had their baseline measures taken between the months of May-October (1205 woman in the control group and 912 women in the intervention group). Of these women, 1621 had a MCS score at baseline and six months. Comparison of the six month mean MCS scores, adjusting for baseline MCS score and age, showed there was no significant difference between the two scores (p = 0.262).

CONCLUSIONS: Supplementing elderly women with 800 IU of vitamin D daily did not lead to an improvement in mental health scores.

PMID: 16554952

J Nutr Health Aging. 1999;3(1):5-7.

Vitamin D vs broad spectrum phototherapy in the treatment of seasonal affective disorder.

Gloth FM 3rd, Alam W, Hollis B.The Department of Medicine, The Union Memorial Hospital, Baltimore, Maryland 21218-2895, USA.


Seasonal Affective Disorder (SAD) is prevalent when vitamin D stores are typically low. Broad-spectrum light therapy includes wavelengths between 280-320 nm which allow the skin to produce vitamin D. This study was designed to test the hypothesis that vitamin D deficiency might play a role in SAD. A prospective, randomized controlled trial was conducted in a group of 15 subjects with SAD. Eight subjects received 100,000 I.U. of vitamin D and seven subjects received phototherapy. At the onset of treatment and after 1 month of therapy subjects were administered the Hamilton Depression scale, the SIGH-SAD, and the SAD-8 depression scale. All subjects also had serum levels of 25-hydroxyvitamin D (25-OH D) measured before and 1 week after intervention therapy. All subjects receiving vitamin D improved in all outcome measures. The phototherapy group showed no significant change in depression scale measures.Vitamin D status improved in both groups (74% vitamin D group, p < 0.005 and 36% phototherapy group, p < 0.01). Improvement in 25-OH D was significantly associated with improvement in depression scale scores (r2=0.26; p=0.05). Vitamin D may be an important treatment for SAD. Further studies will be necessary to confirm these findings.

PMID: 10888476

Med Hypotheses. 1998 Sep;51(3):267-8.

Vitamin D and serotonin in winter.

Partonen T.

Department of Psychiatry, University of Helsinki, Finland.


Calcitriol accumulates in the nuclei of adrenal medullary cells, stimulating the tyrosine hydroxylase gene expression. The transcription of the CREM gene is induced by adrenergic input to the pineal gland at night. Depending on the photoperiod of the prior night length, the CREM gene is either subsensitive or supersensitive to induction. Guided by the memory of past photoperiods, the induced changes in melatonin synthesis may mediate either the inhibitory or stimulatory effects on bodily functions. Calcitriol might inhibit the binding of melatonin to the nuclear retinoid Z receptors, which would result in the increased serotonin levels. Serotonin synthesis is hypothesized to be dependent on the duration of light exposure the previous summer.

PMID: 9792205

J Neurosci. 2010 Nov 3;30(44):14691-4.

Seasonal effects on human striatal presynaptic dopamine synthesis.

Eisenberg DP, Kohn PD, Baller EB, Bronstein JA, Masdeu JC, Berman KF.

Section on Integrative Neuroimaging, Clinical Brain Disorders Branch, Genes Cognition and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA.


Past studies in rodents have demonstrated circannual variation in central dopaminergic activity as well as a host of compelling interactions between melatonin–a scotoperiod-responsive neurohormone closely tied to seasonal adaptation–and dopamine in the striatum and in midbrain neuronal populations with striatal projections. In humans, seasonal effects have been described for dopaminergic markers in CSF and postmortem brain, and there exists a range of affective, psychotic, and substance abuse disorders that have been associated with both seasonal symptomatic fluctuations and dopamine neurotransmission abnormalities. Together, these data indirectly suggest a potentially crucial link between circannual biorhythms and central dopamine systems. However, seasonal effects on dopamine function in the living, healthy human brain have never been tested. For this study, 86 healthy adults underwent (18)F-DOPA positron emission tomography scanning, each at a different time throughout the year. Striatal regions of interest (ROIs) were evaluated for differences in presynaptic dopamine synthesis, measured by the kinetic rate constant, K(i), between fall-winter and spring-summer scans. Analyses comparing ROI average K(i) values showed significantly greater putamen (18)F-DOPA K(i) in the fall-winter relative to the spring-summer group (p = 0.038). Analyses comparing voxelwise K(i) values confirmed this finding and evidenced intrastriatal localization of seasonal effects to the caudal putamen (p < 0.05, false-discovery rate corrected), a region that receives dopaminergic input predominantly from the substantia nigra. These data are the first to directly demonstrate a seasonal effect on striatal presynaptic dopamine synthesis and merit future research aimed at elucidating underlying mechanisms and implications for neuropsychiatric disease and new treatment approaches.

PMID: 21048126

Neurosci Biobehav Rev. 2011 Jan;35(3):669-79. Epub 2010 Aug 26.

Potential animal models of seasonal affective disorder.

Workman JL, Nelson RJ.

Department of Psychology, The Ohio State University, Columbus, OH 43201, USA.


Seasonal affective disorder (SAD) is characterized by depressive episodes during winter that are alleviated during summer and by morning bright light treatment. Currently, there is no animal model of SAD. However, it may be possible to use rodents that respond to day length (photoperiod) to understand how photoperiod can shape the brain and behavior in humans. As nights lengthen in the autumn, the duration of the nightly elevation of melatonin increase; seasonally breeding animals use this information to orchestrate seasonal changes in physiology and behavior. SAD may originate from the extended duration of nightly melatonin secretion during fall and winter. These similarities between humans and rodents in melatonin secretion allows for comparisons with rodents that express more depressive-like responses when exposed to short day lengths. For instance, Siberian hamsters, fat sand rats, Nile grass rats, and Wistar rats display a depressive-like phenotype when exposed to short days. Current research in depression and animal models of depression suggests that hippocampal plasticity may underlie the symptoms of depression and depressive-like behaviors, respectively. It is also possible that day length induces structural changes in human brains. Many seasonally breeding rodents undergo changes in whole brain and hippocampal volume in short days. Based on strict validity criteria, there is no animal model of SAD, but rodents that respond to reduced day lengths may be useful to approximate the neurobiological phenomena that occur in people with SAD, leading to greater understanding of the etiology of the disorder as well as novel therapeutic interventions.

Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID: 20800614

Chronobiol Int. 2010 Aug;27(7):1438-53.

Increased sensitivity to light-induced melatonin suppression in premenstrual dysphoric disorder.

Parry BL, Meliska CJ, Sorenson DL, Lopez A, Martínez LF, Hauger RL, Elliott JA.

Department of Psychiatry, University of California, San Diego, La Jolla, California 92093-0804, USA. bparry@ucsd.eduAbstract

Increased sensitivity to light-induced melatonin suppression characterizes some, but not all, patients with bipolar illness or seasonal affective disorder. The aim of this study was to test the hypothesis that patients with premenstrual dysphoric disorder (PMDD), categorized as a depressive disorder in Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), have altered sensitivity to 200 lux light during mid-follicular (MF) and late-luteal (LL) menstrual cycle phases compared with normal control (NC) women. As an extension of a pilot study in which the authors administered 500 lux to 8 PMDD and 5 NC subjects, in the present study the authors administered 200 lux to 10 PMDD and 13 NC subjects during MF and LL menstrual cycle phases. Subjects were admitted to the General Clinical Research Center (GCRC) in dim light (<50 lux) to dark (during sleep) conditions at 16:00 h where nurses inserted an intravenous catheter at 17:00 h and collected plasma samples for melatonin at 30-min intervals from 18:00 to 10:00 h, including between 00:00 and 01:00 h for baseline values, between 01:30 and 03:00 h during the 200 lux light exposure administered from 01:00 to 03:00 h, and at 03:30 and 04:00 h after the light exposure. Median % melatonin suppression was significantly greater in PMDD (30.8%) versus NC (-0.2%) women (p = .040), and was significantly greater in PMDD in the MF (30.8%) than in the LL (-0.15%) phase (p = .047). Additionally, in the LL (but not the MF) phase, % suppression after 200 lux light was significantly positively correlated with serum estradiol level (p = .007) in PMDD patients, but not in NC subjects (p > .05).

PMID: 20795885

Psychiatry Res. 2008 Oct 30;161(1):76-86. Epub 2008 Sep 11.

Late, but not early, wake therapy reduces morning plasma melatonin: relationship to mood in Premenstrual Dysphoric Disorder.

Parry BL, Meliska CJ, Martínez LF, López AM, Sorenson DL, Hauger RL, Elliott JA.

Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093-0804, United States.


Wake therapy improves mood in Premenstrual Dysphoric Disorder (PMDD), a depressive disorder in DSM-IV. We tested the hypothesis that the therapeutic effect of wake therapy in PMDD is mediated by altering sleep phase with melatonin secretion. We measured plasma melatonin every 30 min (18:00-09:00 h) in 19 PMDD and 18 normal control (NC) women during mid-follicular (MF) and late luteal (LL) menstrual cycle phases, and during LL interventions with early wake therapy (EWT) (sleep 03:00-07:00 h)(control condition) vs. late wake therapy (LWT) (sleep 21:00-01:00 h)(active condition). Melatonin offset was delayed and duration was longer in the symptomatic LL vs. asymptomatic MF phase in both NC and PMDD subjects. LWT, but not EWT, advanced offset and shortened duration vs. the LL baseline, although they improved mood equally. Later baseline LL morning melatonin offset was associated with more depressed mood in PMDD patients, and longer melatonin duration in the MF phase predicted greater mood improvement following LWT. That LWT, but not EWT, advanced melatonin offset and shortened duration while they were equally effective in improving mood suggests that decreasing morning melatonin secretion is not necessary for the therapeutic effects of wake therapy in PMDD.

PMID: 18789826

Biol Psychiatry. 2000 Nov 1;48(9):920-31.

Cortisol circadian rhythms during the menstrual cycle and with sleep deprivation in premenstrual dysphoric disorder and normal control subjects.

Parry BL, Javeed S, Laughlin GA, Hauger R, Clopton P.

Department of Psychiatry, University of California, San Diego, California 92093-0804, USA.


BACKGROUND: In this study we extended previous work by examining whether disturbances in the circadian rhythms of cortisol during the menstrual cycle distinguish patients with premenstrual dysphoric disorder (PMDD) from normal control (NC) subjects. In addition, we tested the differential response to the effects of early and late partial sleep deprivation on cortisol rhythms.

METHODS: In 15 PMDD and 15 NC subjects we measured cortisol levels every 30 min from 6:00 PM to 9:00 AM during midfollicular (MF) and late luteal (LL) menstrual cycle phases and also during a randomized crossover trial of early (sleep 3:00 AM-7:00 AM) versus late (sleep 9:00 PM-1:00 AM) partial sleep deprivation administered in two subsequent and separate luteal phases.

RESULTS: In follicular versus luteal menstrual cycle phases we observed altered timing but not quantitative measures of cortisol secretion in PMDD subjects, compared with NC subjects: in the LL versus MF phase the cortisol acrophase was a mean of 1 hour earlier in NC subjects, but not in PMDD subjects. The effect of sleep deprivation on cortisol timing measures also differed for PMDD versus NC subjects: during late partial sleep deprivation (when subjects’ sleep was earlier), the cortisol acrophase was almost 2 hours earlier in PMDD subjects.

CONCLUSIONS: Timing rather than quantitative measures of cortisol secretion differentiated PMDD subjects from NC subjects both during the menstrual cycle and in response to early versus late sleep deprivation interventions.

PMID: 11074230

J Biol Rhythms. 1997 Feb;12(1):34-46.

Temperature circadian rhythms during the menstrual cycle and sleep deprivation in premenstrual dysphoric disorder and normal comparison subjects.

Parry BL, LeVeau B, Mostofi N, Naham HC, Loving R, Clopton P, Gillin JC.

Department of Psychiatry, University of California, San Diego, La Jolla 92093, USA.


The aim of this study was to test the hypothesis that the circadian rhythm of core body temperature is altered in premenstrual dysphoric disorder (PMDD) subjects compared to that in normal comparison (NC) subjects and that it is normalized in PMDD subjects after treatment with early night partial sleep deprivation (ESD) or late night partial sleep deprivation (LSD). A total of 23 subjects meeting DSM-IV criteria for PMDD and 18 NC subjects had 24-h core body temperature recordings taken during the following conditions: (1) baseline midfollicular (preovulatory) and (2) late luteal (postovulatory) menstrual cycle phases and after a randomized crossover trial in subsequent luteal phases of (3) ESD, in which subjects slept from 03:00 to 07:00 h, followed by (4) a night of recovery sleep (ESD-R: sleep 22:30 to 06:30 h), and (5) LSD, in which subjects slept from 21:00 to 01:00 h, also followed by (6) a night of recovery sleep (LSD-R: sleep 22:30 to 06:30 h). Temperature amplitudes were significantly decreased in the luteal phase compared to those in the follicular menstrual cycle phase and increased after nights of recovery sleep. Compared to the baseline late luteal phase, during LSD, temperature amplitude increased in PMDD subjects but decreased in NC subjects. During ESD, the temperature acrophase was delayed in PMDD subjects but was advanced in NC subjects; during LSD, the temperature acrophase was advanced in PMDD subjects but was delayed in NC subjects compared to the late luteal baseline. Nocturnal temperature and temperature maxima and mesors tended to be higher in PMDD subjects than in NC subjects; when not reduced during sleep deprivation interventions, these were not associated with therapeutic effects. Alterations in both phase and amplitude of temperature circadian rhythms characterize PMDD subjects as contrasted with NC subjects in response to sleep deprivation. The changes in phase reflected more shifts in temperature acrophase in response to shifts in sleep in PMDD subjects. This realignment of the timing of sleep and temperature in addition to the enhancement of blunted amplitude rhythms during recovery nights of sleep may provide corrective mechanisms that contribute to the therapeutic effects of sleep deprivation.

PMID: 9104689

Aust Fam Physician. 2010 May;39(5):307-10.

Circadian rhythms and depression.

Boyce P, Barriball E.

Discipline of Psychiatry, University of Sydney and Department of Psychiatry, Westmead Hospital, Sydney, New South Wales, Australia.


BACKGROUND: Depression is a common disorder in primary care. Disruptions to the circadian rhythms associated with depression have received little attention yet offer new and exciting approaches to treatment.

OBJECTIVE: This article discusses circadian rhythms and the disruption to them associated with depression, and reviews nonpharmaceutical and pharmaceutical interventions to shift circadian rhythms.

DISCUSSION: Features of depression suggestive of a disturbance to circadian rhythms include early morning waking, diurnal mood changes, changes in sleep architecture, changes in timing of the temperature nadir, and peak cortisol levels. Interpersonal social rhythm therapy involves learning to manage interpersonal relationships more effectively and stabilisation of social cues, such as including sleep and wake times, meal times, and timing of social contact. Bright light therapy is used to treat seasonal affective disorders. Agomelatine is an antidepressant that works in a novel way by targeting melatonergic receptors.

PMID: 20485718

Psychiatry Res. 2010 Feb 28;175(3):217-20. Epub 2009 Dec 31.

Climatic relationships with specific clinical subtypes of depression.

Radua J, Pertusa A, Cardoner N.

Department of Psychiatry, Bellvitge University Hospital, University of Barcelona, Barcelona, Spain.


Studies on the relationship between climate and unipolar depression rates have yielded mixed results, which could be attributed to the inclusion of heterogeneous clinical samples and the use of admission rather than onset dates. This study aimed to overcome these methodological issues. During an 8-year timeframe, onset rates of unipolar depressive episodes requiring hospitalization from individuals living up to 15 km from a selected meteorological station were stratified by clinical subtypes and modeled as Autoregressive Integrated Moving Average (ARIMA) functions of orthogonal climatic factors obtained by Principal Components Analysis (PCA). For comparison purposes, onset rates stratified by demographic factors and by diagnosis of Seasonal Affective Disorder (SAD) and admission rates were also modeled. The main findings were a negative 1-month delayed relationship between onset rates of episodes with melancholic features and a climatic factor mainly composed of ambient temperature/sunlight, and a negative 1-month delayed relationship between onset rates of episodes with psychotic features and a climatic factor mainly composed of barometric pressure. Results of this study support a climatic-rather than seasonal-influence in specific subtypes of depression. If replicated, they may have nosological and therapeutic implications.

2008 Elsevier Ireland Ltd. All rights reserved.

PMID: 20045197

Aviat Space Environ Med. 2008 Jul;79(7):695-9.

Seasonal levels of melatonin, thyroid hormones, mood, and cognition near the Arctic Circle.

Pääkkönen T, Leppäluoto J, Mäkinen TM, Rintamäki H, Ruokonen A, Hassi J, Palinkas LA.

Department of Biomedicine/Physiology, University of Oulu, Oulu, Finland. tiina.paakkonen@oulu.fiAbstract

INTRODUCTION: The associations between melatonin and thyroid hormones and changes in mood and cognitive performance caused by exposure to cold and darkness were examined in 12 circumpolar residents during winter and summer.

METHODS: Each participant was exposed to three different experimental conditions in random order: 1) 22 degrees C and bright light; 2) 10 degrees C and bright light; and 3) 10 degrees C and dim light. The duration of each exposure was 24 h. RESULTs: Increased serum melatonin and thyrotropin were associated with decreased rectal temperature (r = -0.446 – -0.580) and increased mean skin temperature (r = 0.204-0.519). Higher serum melatonin was associated with increased vigor (r = 0.330) and decreased accuracy on simple cognitive tasks (r = -0.332 – -0.430). Increased serum free triiodothyronine (fT3) was associated with decreased negative mood scores (r = -0.365 – -0.483), decreased response time (RT) on the simple reaction time (SRT) task (r = -0.606), and decreased accuracy on the addition/subtraction task (r = -0.372). Higher serum free thyroxine was associated with decreased fatigue and anger (r = -0.409 – -0.522). Increased serum thyrotropin was associated with decreased accuracy and RT on the SRT task and decreased RT on the grammatical reasoning task (r = -0.315 – -0.415).

CONCLUSIONS: Associations between serum melatonin and thyroid hormones with mood were consistent with the psychological changes associated with the polar triiodothyronine syndrome. Also, serum melatonin and thyrotropin were associated with impaired and fT3 with improved cognitive performance, supporting the decrements in cognitive performance associated with the polar triiodothyronine syndrome.

PMID: 18619130

A critical review of 27 herbal medicines and formulas in treating a broad range of psychiatric disorders (in addition to anxiety and depression), including obsessive-compulsive, seasonal affective, bipolar depressive, psychotic, phobic and somatoform disorders. Ovid Medline, Pubmed and the Cochrane Library were searched for pharmacological and clinical evidence of herbal medicines with psychotropic activity. A forward search of later citations was also conducted. Whilst substantial high-quality evidence exists for the use of kava and St John’s wort in the treatment of anxiety and depression respectively, urgently require more research are Rhodiola rosea (roseroot) and Crocus sativus (saffron) for depression; Passiflora incarnata (passionflower), Scutellaria lateriflora (scullcap) and Zizyphus jujuba (sour date) for anxiety disorders; and Piper methysticum (kava) for phobic, panic and obsessive-compulsive disorders.

 The maintenance of light therapy-induced remission from depression in patients with seasonal mood cycles seems to depend on the functional integrity of the brain serotonin system. 

The decline in melatonin levels correlated with the decline in specific SAD symptoms of hyperphagia and carbohydrate craving.

 Low melatonin levels were seen in bulimia or neuralgia and in women with fibromyalgia; replacement reduced pain, sleeping disorders, and depression in fibromyalgia and bulimia. Melatonin profiles are a diagnostic tool to distinguish between several forms of depression, like major depression, winter depression (SAD), unipolar depression, delayed sleep phase syndrome (DSPS). In patients with a major depression success with antidepressants correlated with an increase in their melatonin profiles but only patients suffering from DSPS can be successfully treated with melatonin. In perimenopausal women melatonin administration did produce a change in LH, FSH and thyroid hormones. 

 A review of the literature showed that melatonin has an inhibiting effect on insulin sensitivity. 

Back Pain: Herniated Disc Treatment

Zhonghua Yi Xue Za Zhi. 2011 Jan 4;91(1):23-7.


[Quantitative evaluation for diagnostic efficacy of computed tomography and magnetic resonance imaging in patients with lumbar disc herniation].


 [Article in Chinese]


Yu XW, Niu G, Yang J, Ni L, Zhang WS, Guo YM.





PET-CT Department, First Hospital of Medical College of Xi’an Jiaotong University, Xi’an 710061, China.







To evaluate the diagnostic performances of CT and MRI in patients with lumbar intervertebral disc herniation through the Meta analytical method.




The relevant English and Chinese articles published between 1980 and 2010 were searched in PubMed, Medline, Ovid database, Cochrane library and Chinese Periodical Web. According to the criteria for diagnostic researches published by Cochrane Method Group on Screening and Diagnostic Tests, each article was critically appraised and screened with regards to the absolute numbers of true-positive, false-negative, true-negative and false-positive. Statistical analysis was performed by the Meta-Disc version 1.4, SPSS 13.0 and Comprehensive Meta-analysis version II. Heterogeneity was tested and publication bias analyzed. And the pooled weighted sensitivity and specificity and the corresponding 95%CI were calculated. The summary receiver operating characteristic (SROC) curve was performed and the area under the curve (AUC) calculated to summarize and evaluate the diagnostic efficiency of CT and MRI in lumbar intervertebral disc herniation. Finally a sensitivity analysis was performed.




According to the criteria of internalization, 9 articles were included. Among them, the themes were CT (n = 3), MRI (n = 3) and CT & MRI (n = 3). Eight was prospectively studied and one retrospectively. At the diagnosis of lumbar intervertebral disc herniation, the pooled weighted sensibility and specificity and 95% confidence interval and area under SROC curve for CT to the lumbar intervertebral disc herniation was 0.73 (0.68 – 0.77), 0.78 (0.72 – 0.82) and 83.5% respectively. The MRI was 0.88 (0.83 – 0.91), 0.79 (0.71 – 0.87) and 88.8% respectively. There was statistically significant difference in the pooled weighted sensibility (P < 0.05); No statistically significant difference was found in the pooled weighted specificity (P > 0.05); And there was statistically significant difference in the AUC curve (P < 0.05).




After a meta-analysis of the diagnostic value of CT and MRI for the lumbar intervertebral disc herniation, MRI is more accurate than CT in the diagnosis of lumbar intervertebral disc herniation.



PMID: 21418957






Cochrane Database Syst Rev. 2010 Feb 17;(2):CD007431.


Physical examination for lumbar radiculopathy due to disc herniation in patients with low-back pain.


van der Windt DA, Simons E, Riphagen II, Ammendolia C, Verhagen AP, Laslett M, Devillé W, Deyo RA, Bouter LM, de Vet HC, Aertgeerts B.





Department of Primary Care & Health Sciences, Keele University, Keele, Staffordshire, UK, ST5 5BG.







Low-back pain with leg pain (sciatica) may be caused by a herniated intervertebral disc exerting pressure on the nerve root. Most patients will respond to conservative treatment, but in carefully selected patients, surgical discectomy may provide faster relief of symptoms. Primary care clinicians use patient history and physical examination to evaluate the likelihood of disc herniation and select patients for further imaging and possible surgery.




(1) To assess the performance of tests performed during physical examination (alone or in combination) to identify radiculopathy due to lower lumbar disc herniation in patients with low-back pain and sciatica;(2) To assess the influence of sources of heterogeneity on diagnostic performance.




We searched electronic databases for primary studies: PubMed (includes MEDLINE), EMBASE, and CINAHL, and (systematic) reviews: PubMed and Medion (all from earliest until 30 April 2008), and checked references of retrieved articles.




We considered studies if they compared the results of tests performed during physical examination on patients with back pain with those of diagnostic imaging (MRI, CT, myelography) or findings at surgery.




Two review authors assessed the quality of each publication with the QUADAS tool, and extracted details on patient and study design characteristics, index tests and reference standard, and the diagnostic two-by-two table. We presented information on sensitivities and specificities with 95% confidence intervals (95% CI) for all aspects of physical examination. Pooled estimates of sensitivity and specificity were computed for subsets of studies showing sufficient clinical and statistical homogeneity.




We included 16 cohort studies (median N = 126, range 71 to 2504) and three case control studies (38 to100 cases). Only one study was carried out in a primary care population. When used in isolation, diagnostic performance of most physical tests (scoliosis, paresis or muscle weakness, muscle wasting, impaired reflexes, sensory deficits) was poor. Some tests (forward flexion, hyper-extension test, and slump test) performed slightly better, but the number of studies was small. In the one primary care study, most tests showed higher specificity and lower sensitivity compared to other settings.Most studies assessed the Straight Leg Raising (SLR) test. In surgical populations, characterized by a high prevalence of disc herniation (58% to 98%), the SLR showed high sensitivity (pooled estimate 0.92, 95% CI: 0.87 to 0.95) with widely varying specificity (0.10 to 1.00, pooled estimate 0.28, 95% CI: 0.18 to 0.40). Results of studies using imaging showed more heterogeneity and poorer sensitivity. The crossed SLR showed high specificity (pooled estimate 0.90, 95% CI: 0.85 to 0.94) with consistently low sensitivity (pooled estimate 0.28, 95% CI: 0.22 to 0.35).Combining positive test results increased the specificity of physical tests, but few studies presented data on test combinations.




When used in isolation, current evidence indicates poor diagnostic performance of most physical tests used to identify lumbar disc herniation. However, most findings arise from surgical populations and may not apply to primary care or non-selected populations. Better performance may be obtained when tests are combined.



Comment in

Evid Based Med. 2010 Jun;15(3):82-3.



PMID: 20166095

Praxis (Bern 1994). 2011 Nov 30;100(24):1475-85.


[The lumbar disc herniation – management, clinical aspects and current recommendations].


 [Article in German]


Stienen MN, Cadosch D, Hildebrandt G, Gautschi OP.





Klinik für Neurochirurgie, Kantonsspital St. Gallen.





Lumbar disc herniation has a high prevalence and strong social-medical impact. Patients suffer from lower back pain that radiates from the spine. Loss of sensation or paresis adds to the clinical picture. The diagnosis should be confirmed by imaging in patients considered for surgery. High remission rates initially warrant conservative treatment (adequate analgesia and physiotherapy) in many patients. If this treatment does not lead to significant alleviation within 5-8 weeks, surgery should be performed to reduce the risk of chronic nerve affection. Posterior interlaminar fenestration is the intervention primarily conducted for this diagnosis. A relapse in the same region occurs in up to 10% of patients after months through years, which sometimes necessitates a reoperation if symptoms are pertinent.



PMID: 22124958

Spine (Phila Pa 1976). 2012 Jan 15;37(2):E109-18.


Evaluation of treatment effectiveness for the herniated cervical disc: a systematic review.


Gebremariam L, Koes BW, Peul WC, Huisstede BM.





Erasmus Medical Center, Department of General Practice, Rotterdam, The Netherlands.







Systematic review.




To assess the effectiveness of interventions for treating cervical disc herniation.




Cervical disc herniation is 1 of the 23 specific disorders included in the CANS (Complaints of the Arm, Neck, and/or Shoulder) model. Treatment options range from conservative to surgical, but evidence for the effectiveness of these interventions is not yet well documented.




The Cochrane Library, MEDLINE, EMBASE, PEDro, and CINAHL were searched for relevant systematic reviews and randomized clinical trials (RCTs) up to February 2009. Two reviewers independently selected relevant studies, assessed the methodological quality, and extracted data.




Pooling of the data was not possible; thus, a best-evidence synthesis was used to summarize the results. Of the 11 RCTs included, 1 compared conservative with surgical intervention, and 10 compared various surgical interventions. No evidence was found for the effectiveness of conservative treatment (nonsteroidal anti-inflammatory drugs, cortisonics, and physical therapy) compared with percutaneous nucleoplasty. Moderate evidence was found for the effectiveness of anterior cervical discectomy with fusion (ACDF) using a titanium cage compared with ACDF using polymethyl methacrylate, and for BRYAN cervical disc (Medtronic Sofamor Danek, Memphis, TN) prostheses compared with ACDF using allograft bone and plating. No outcomes regarding adjacent-level disease were reported. There is conflicting evidence for the effectiveness of ACD compared with ACDF. Only limited or no evidence was found for the other surgical interventions.




No evidence for effectiveness of conservative treatment compared with surgery was found. Although there is moderate evidence for the effectiveness of some surgical interventions, no unequivocal evidence for the superiority of 1 particular surgical treatment was found. Worldwide, most patients receive supplementary implants; however, cervical discectomy without graft may be preferred because of similar outcomes, lower costs, and possibly a lower risk of adjacent-level disease. More high-quality RCTs using validated outcome measures (including adjacent level disease) are needed.



PMID: 21587105

Pain Physician. 2012 Mar;15(2):E115-29.


Ozone Therapy as a Treatment for Low Back Pain Secondary to Herniated Disc: A Systematic Review and Meta-analysis of Randomized Controlled Trials.


De Oliveira Magalhaes FN, Dotta L, Sasse A, Teixera MJ, Fonoff ET.





Hospital das Clnicas University of Sao Paulo Medical School, Sao Paulo, Brazil.







Low back pain (LBP) is one of the most common and important health problems affecting the population worldwide and remains mostly unsolved. Ozone therapy has emerged as an additional treatment method. Questions persist concerning its clinical efficacy.




The purpose of our study was to evaluate the therapeutic results of percutaneous injection of ozone for low back pain secondary to disc herniation.




A systematic review and meta-analysis of randomized controlled trials.




A comprehensive literature search was conducted using all electronic databases from 1966 through September 2011. The quality of individual articles was assessed based on the modified Cochrane review criteria for randomized trials and criteria from the Agency for Healthcare Research and Quality. OUTCOME PARAMETERS: The outcome measure was short-term pain relief of at least 6 months or long-term pain relief of more than 6 months.




Eight observational studies were included in the systematic review and 4 randomized trials in the meta-analysis. The indicated level of evidence for long-term pain relief was II-3 for ozone therapy applied intradiscally and II-1 for ozone therapy applied paravertebrally. The grading of recommendation was 1C for intradiscal ozone therapy and 1B for paravertebral ozone therapy.




The main limitations of this review are the lack of precise diagnosis and the frequent use of mixed therapeutic agents. The meta-analysis included mainly active-control trials. No placebo-controlled trial was found.




Ozone therapy appears to yield positive results and low morbidity rates when applied percutaneously for the treatment of chronic low back pain.



PMID: 22430658

Zhongguo Gu Shang. 2010 Sep;23(9):696-700.


[Systematic review of clinical randomized controlled trials on manipulative treatment of lumbar disc herniation].


 [Article in Chinese]


Li L, Zhan HS, Zhang MC, Chen B, Yuan WA, Shi YY.





Department of Orthopaedics, Shuguang Hospital Affiliated to Shanghai University of TCM, Shanghai 200021, China.







To evaluate the efficacy and safety of the manipulative treatment on lumbar disc herniation and analyze the current status of clinical studies.




The PubMed, OVID, Cochrane Library, CBM – disc database, CNKI database and VIP Database were retrieved, and 832 literatures on manipulative treatment for lumbar disc herniation were collected, in which 8 articles met the inclusion criteria. Cochrane systematic review was used to evaluate the quality; and RevMan 4.2 was used for Meta Analysis of Literatures.




There were total 911 patients in the 8 articles. The summary OR for the combined cure rate of the 8 articles was 3.65, and the 95% CI was [2.15, 6.20]. The summary OR for the combined efficiency was 3.56, and the 95% CI was [2.35, 5.38]. The cure rate and effective rate of the patients in manipulative group were superior to those of patients treated with other methods such as drugs, traction, acupuncture, microwave thermotherapy (all the methods were called as “other therapies”).




This study shows that manipulative treatment on lumbar disc herniation is safe, effective, and both cure rate and the effective rate is better than other therapies. But the number of documents is limited and the quality is not very high, and the conclusion is still uncertain, high-quality evidence is needed to be further validated.



PMID: 20964003

Eur Spine J. 2011 Apr;20(4):513-22. Epub 2010 Oct 15.


Surgery versus conservative management of sciatica due to a lumbar herniated disc: a systematic review.


Jacobs WC, van Tulder M, Arts M, Rubinstein SM, van Middelkoop M, Ostelo R, Verhagen A, Koes B, Peul WC.





Department of Neurosurgery, Leiden University Medical Center, Albinusdreef 2, PO Box 9600, 2300 RC Leiden, The Netherlands.





The effectiveness of surgery in patients with sciatica due to lumbar disc herniations is not without dispute. The goal of this study was to assess the effects of surgery versus conservative therapy (including epidural injections) for patients with sciatica due to lumbar disc herniation. A comprehensive search was conducted in MEDLINE, EMBASE, CINAHL, CENTRAL, and PEDro up to October 2009. Randomised controlled trials of adults with lumbar radicular pain, which evaluated at least one clinically relevant outcome measure (pain, functional status, perceived recovery, lost days of work) were included. Two authors assessed risk of bias according to Cochrane criteria and extracted the data. In total, five studies were identified, two of which with a low risk of bias. One study compared early surgery with prolonged conservative care followed by surgery if needed; three studies compared surgery with usual conservative care, and one study compared surgery with epidural injections. Data were not pooled because of clinical heterogeneity and poor reporting of data. One large low-risk-of-bias trial demonstrated that early surgery in patients with 6-12 weeks of radicular pain leads to faster pain relief when compared with prolonged conservative treatment, but there were no differences after 1 and 2 years. Another large low-risk-of-bias trial between surgery and usual conservative care found no statistically significant differences on any of the primary outcome measures after 1 and 2 years. Future studies should evaluate who benefits more from surgery and who from conservative care.



PMID: 20949289

Back Pain: Surgery Vs. Non-Surgical Options

Summary:  Just went through the literature again looking for back pain and long term outcomes for surgery vs. nonsurgical treatment.  Can we just say that the studies will never be done?  Just finding long term follow up on patients after back surgery means I need to look outside the U.S. The short answer is that around 15% of patients will need another back surgery in ten years (based on one small study).  But patients with larger areas of involvement are more than five times more likely to need another surgery.  Personally, I’ve never seen a back where the whole back wasn’t involved to some extent.  It may not show up on the scans, but when one area is in crisis, the rest of the back accommodates the wounded part. 

Spine J. 2008 Mar-Apr;8(2):397-403. Epub 2007 Jan 30.

Spontaneous resorption of intradural lumbar disc fragments.

Borota L, Jonasson P, Agolli A.

Department of Radiology, Section of Neuroradiology, University Hospital of Northern Sweden, 90185, Umeå, Sweden.


BACKGROUND CONTEXT: Intradural disc herniation is relatively rare complication of the spinal degenerative process that occurs most frequently in the lumbar part of the spine. Both myelographic and magnetic resonance features of this entity have been described, and the mechanism of intradural herniation has already been proposed and generally accepted. In this article, we present a case of spontaneous resorption of an intradural, fragmented intervertebral disc. Spontaneous resorption of intradural disc fragments has not been previously reported.

PURPOSE: To discuss a possible mechanism of spontaneous resorption of the subdural disc fragments.

STUDY DESIGN: Case report and literature review.

METHODS: Radiological follow-up of a 46-year-old man with the intradural herniation of disc fragments.

CONCLUSION: The reaction generated by the meninges might lead to the complete resorption of intrathecally localized disc fragments.

PMID: 18299107

Neurosurg Rev. 2004 Apr;27(2):75-80; discussion 81-2. Epub 2003 Oct 15.

Intradural lumbar disc herniations: the role of MRI in preoperative diagnosis and review of the literature.

D’Andrea G, Trillò G, Roperto R, Celli P, Orlando ER, Ferrante L.

Department of Neurological Sciences, “La Sapienza” University, Rome, Italy.


The goal of this article is to report our experience on intradural lumbar disc herniation, consider the causes of this pathology, and analyze it from clinical, diagnostic, and therapeutic perspectives with a particular emphasis on the role of MRI in preoperative diagnosis. We analyzed nine patients treated surgically for intradural lumbar disc hernia. All of them underwent surgery, and hemilaminectomy was performed. In six cases, the diagnosis of intradural herniation was definitive and, in the three remaining, it was confirmed at surgery. In five cases, CT (with no contrast medium) of the lumbar area revealed disc herniation, but none could it confirm its intradural location. Myelography was performed in two cases but also could not prove intradural extrusion. Magnetic resonance imaging study was used in four cases. In five, the postoperative outcome has been excellent. Patients 6 and 9 recovered anal function postoperatively; patient 6 suffered from occasional and mild micturition urgency. The three patients previously operated (1, 2, 7) showed good outcome. Presently, we believe that radiologic diagnosis of intradural herniation is possible in carefully selected patients, thanks to MRI with gadolinium.

PMID: 14564663

Pain Physician. 2009 May-Jun;12(3):561-72.

A systematic review of mechanical lumbar disc decompression with nucleoplasty.

Manchikanti L, Derby R, Benyamin RM, Helm S, Hirsch JA.

Pain Management Center of Paducah, Paducah, KY, USA.


BACKGROUND: Lumbar disc prolapse, protrusion, or extrusion account for less than 5% of all low back problems, but are the most common causes of nerve root pain and surgical interventions. The primary rationale for any form of surgery for disc prolapse is to relieve nerve root irritation or compression due to herniated disc material. The primary modality of treatment continues to be either open or microdiscectomy, but several alternative techniques including nucleoplasty, automated percutaneous discectomy, and laser discectomy have been described. There is a paucity of evidence for all decompression techniques, specifically alternative techniques including nucleoplasty.

STUDY DESIGN: A systematic review of the literature.

OBJECTIVE: To determine the effectiveness of mechanical lumbar disc decompression with nucleoplasty.

METHODS: A comprehensive evaluation of the literature relating to mechanical lumbar disc decompression with nucleoplasty was performed. The literature was evaluated according to Cochrane review criteria for randomized controlled trials (RCTs), and Agency for Healthcare Research and Quality (AHRQ) criteria was utilized for observational studies. The level of evidence was classified as Level I, II, or III with 3 subcategories in Level II based on the quality of evidence developed by the United States Preventive Services Task Force (USPSTF). A literature search was conducted using only English language literature through PubMed, EMBASE, the Cochrane library, systematic reviews, and cross-references from reviews and systematic reviews.

OUTCOME MEASURES: Pain relief was the primary outcome measure. Other outcome measures were functional improvement, improvement of psychological status, opioid intake, and return to work. Short-term effectiveness was defined as one year or less, whereas, long-term effectiveness was defined as greater than one year.

RESULTS: Based on USPSTF criteria the level of evidence for nucleoplasty is Level II-3 in managing predominantly lower extremity pain due to contained disc herniation.

LIMITATIONS: Paucity of literature, both observational and randomized.

CONCLUSION: This systematic review illustrates Level II-3 evidence for mechanical lumbar percutaneous disc decompression with nucleoplasty in treatment of leg pain. However, there is no evidence available in managing axial low back pain.

PMID: 19461823

Pain Physician. 2009 Mar-Apr;12(2):361-78.

Systematic review of percutaneous adhesiolysis and management of chronic low back pain in post lumbar surgery syndrome.

Epter RS, Helm S 2nd, Hayek SM, Benyamin RM, Smith HS, Abdi S.

Augusta Pain Center, Augusta, GA 30917-1839, USA.


BACKGROUND: Post lumbar surgery syndrome or failed back surgery syndrome with persistent pain continues to increase over the years. The speculated causes of post lumbar laminectomy syndrome include acquired stenosis, epidural fibrosis, arachnoiditis, radiculopathy, and recurrent disc herniation. Epidural fibrosis may account for as much as 20% to 36% of all cases of failed back surgery syndrome. Percutaneous epidural adhesiolysis has been employed in interventional pain management in the treatment of chronic, refractory low back and lower extremity pain after back surgery.

STUDY DESIGN: A systematic review of randomized trials and observational studies.

OBJECTIVE: To evaluate the effectiveness of percutaneous adhesiolysis in managing chronic low back and lower extremity pain due to post lumbar surgery syndrome.


METHODS: A comprehensive literature search was conducted utilizing electronic databases, as well as systematic reviews and cross references from 1966 through December 2008. The quality of individual articles used in this analysis was assessed by modified Cochrane review criteria for randomized trials and the Agency for Healthcare Research and Quality (AHRQ) criteria for assessment of observational studies. Clinical relevance was evaluated using 5 questions according to the criteria recommended by the Cochrane Review Back Group. Analysis was conducted using 5 levels of evidence, ranging from Level I to III, with 3 subcategories in Level II. OUTCOME PARAMETERS: The primary outcome measure was pain relief (short-term relief of at least 6 months and long-term relief of more than 6 months). Secondary outcome measures were improvement in functional status, psychological status, return to work, and change in opioid intake.

RESULTS: Of the 13 studies considered for inclusion, 3 randomized trials and 4 observational studies met the inclusion criteria for methodologic quality assessment and evidence synthesis based on methodologic quality scores of 50 or more. Evidence of percutaneous adhesiolysis in the management of chronic low back pain in post-lumbar surgery syndrome is Level I to Level II-1, with evidence derived from 3 randomized trials.

LIMITATIONS: There is a paucity of efficacy and pragmatic trials. No trials have been published after 2006.

CONCLUSION: The indicated level of evidence for percutaneous adhesiolysis is Level I or II-1 based on the US Preventative Services Task Force (USPSTF) criteria.

PMID: 19305485

Pain Physician. 2009 Jul-Aug;12(4):E123-98.

Comprehensive review of therapeutic interventions in managing chronic spinal pain.

Manchikanti L, Boswell MV, Datta S, Fellows B, Abdi S, Singh V, Benyamin RM, Falco FJ, Helm S, Hayek SM, Smith HS; ASIPP.

Pain ManagementCenter of Paducah, Paducah, KY, USA.


BACKGROUND: Available evidence documents a wide degree of variance in the definition and practice of interventional pain management.

OBJECTIVE: To provide evidence-based clinical practice guidelines for interventional techniques in the treatment of chronic spinal pain.

DESIGN: Best evidence synthesis.

METHODS: Strength of evidence was assessed by the U.S. Preventive Services Task Force (USPSTF) criteria utilizing 5 levels of evidence ranging from Level I to III with 3 subcategories in Level II.

OUTCOMES: Short-term pain relief was defined as relief lasting 6 months or less and long-term relief as longer than 6 months, except < or = one year and > one year for intradiscal therapies, mechanical disc decompression, spinal cord stimulation, and intrathecal infusion systems.

RESULTS: The indicated evidence for therapeutic interventions is Level I for caudal epidural steroid injections in managing disc herniation or radiculitis, and discogenic pain without disc herniation or radiculitis. The evidence is Level I to II-1 for percutaneous adhesiolysis in management of pain secondary to post-lumbar surgery syndrome. The evidence is Level II-1 or II-2 for therapeutic cervical, thoracic, and lumbar facet joint nerve blocks; for caudal epidural injections in managing pain of post-lumbar surgery syndrome, and lumbar spinal stenosis, for cervical interlaminar epidural injections in managing cervical pain (Level II-1); for lumbar transforaminal epidural injections; and spinal cord stimulation for post-lumbar surgery syndrome.

LIMITATIONS: The limitations of this guideline preparation included a paucity of literature, lack of updates, and lack of conflicts in preparation of systematic reviews and guidelines by various organizations.

CONCLUSION: The indicated evidence for therapeutic interventions is variable from Level I to III. This comprehensive review includes the evaluation of evidence for therapeutic procedures in managing chronic spinal pain and recommendations. However, this review and recommendations do not constitute inflexible treatment recommendations or “standard of care.”

PMID: 19668281

Rev Chir Orthop Reparatrice Appar Mot. 2008 Sep;94(5):464-71. Epub 2008 May 2.

[Long-term survival analysis after surgical management for degenerative lumbar stenosis]

[Article in French]

Lenoir T, Dauzac C, Rillardon L, Guigui P.

Service de Chirurgie Orthopédique, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy Cedex, France.


PURPOSE OF THE STUDY: The short- and mid-term symptom-relief of surgical treatment for lumbar stenosis is generally acknowledged, but the probability of a long-term reoperation remains to be studied. The purpose of this work was to determine the long-term risk of reoperation after surgical treatment of degenerative lumbar stenosis and to search for factors influencing this probability.

MATERIAL AND METHODS: All patients who underwent from 1989 to 1992 surgical treatment for degenerative lumbar spine stenosis were included in this work. At last follow-up, we noted functional outcome using a specific self-administered questionnaire, patient satisfaction, lumbalgia and radiculalgia using a visual analog scale, SF36 quality-of-life, reoperation or not with time since first operation if performed and the reasons and modalities of the reoperation. The probability of reoperation was determined with the acturarial method. A Cox model was used to search for factors linked with the probability of reoperation; variables studied were: age, comorbid factors, extent of the release, posterolateral arthrodesis or not, extent of the potential fusion, use or not of instrumentation for arthrodesis.

RESULTS AND DISCUSSION: The study included 262 patients. At last follow-up, 61 patients had died a mean 3.7+/-3 years after the operation; only one of these patients had a second operation 22 months after the first. Forty-four patients were lost to follow-up at mean 6.6+/-3 years. Among these 44 patients, four had a second operation during their initial follow-up at mean 47 months. One hundred fifty-seven patients were retained for this analysis at mean 15+/-1 years follow-up. Among these 157 patients, 29 had a second operation a mean 75 months after the first. There were four reasons for reoperating: insufficient release, destabilization within or above the zone of release, development or renewed zone of stenosis, development or renewed discal herniation. The risk of a second operation was 7.4% [95% CI 4.8-11.6], 15.4% [95% CI 10.7-21.1] and 16.5% [95% CI 11.7-219] at five, 10 and 15 years respectively after the first operation. Among the risk factors studied, only one had a significant impact on reoperation: extent of the zone of release (p=0.003). Compared with a release limited to one level, the risk of reoperation after release of three levels or more was five times greater [95% CI 1.8-12.7].

PMID: 18774021

Back Pain

Summary: A number of treatments may be effective for low back pain with apparent disagreement between studies due to grouping all lower back pain into the same category. Degenerative disc pain should be separated from sciatica and chronic muscle spasm in future studies. Individualized treatment plans beginning with less intrusive mobilization before manipulation would greatly increase chiropractic outcomes. Long term studies incorporating patient self-treatment with passive (neutral pelvis) as well as active (hydrotherapy, lifestyle) interventions are still lacking.

Eur Spine J 2003 Apr;12(2):149-65

Low back pain: what is the long-term course? A review of studies of general patient populations.

Hestbaek L, Leboeuf-Yde C, Manniche C.

The Backcenter, Ringe Hospital, Odense University Hospital, 5950 Ringe, Denmark,

It is often claimed that up to 90% of low back pain (LBP) episodes resolve spontaneously within 1 month. However, the literature in this area is confusing due to considerable variations regarding the exact definitions of LBP as well as recovery. Therefore, the claim – attractive as it might be to some – may not reflect reality. In order to investigate the long-term course of incident and prevalent cases of LBP, a systematic and critical literature review was undertaken. A comprehensive search of the topic was carried out utilizing both Medline and EMBASE databases. The Cochrane Library and the Danish Article Base were also screened. Journal articles following the course of LBP without any known intervention were included, regardless of study type. However, the population had to be representative of the general patient population and a follow-up of at least 12 months was a requirement. Data were extracted independently by two reviewers using a standard check list. The included articles were also independently assessed for quality by the same two reviewers before they were studied in relation to the course of LBP using various definitions of recovery. Thirty-six articles were included. The results of the review showed that the reported proportion of patients who still experienced pain after 12 months was 62% on average (range 42-75%), the percentage of patients sick-listed 6 months after inclusion into the study was 16% (range 3-40%), the percentage who experienced relapses of pain was 60% (range 44-78%), and the percentage who had relapses of work absence was 33% (range 26-37%). The mean reported prevalence of LBP in cases with previous episodes was 56% (range 14-93%), which compared with 22% (range 7-39%) for those without a prior history of LBP. The risk of LBP was consistently about twice as high for those with a history of LBP. The results of the review show that, despite the methodological variations and the lack of comparable definitions, the overall picture is that LBP does not resolve itself when ignored. Future research should include subgroup analyses and strive for a consensus regarding the precise definitions of LBP.

PMID: 12709853 [PubMed – in process]

Spine 2002 Sep 1;27(17):1896-910

Massage for low-back pain: a systematic review within the framework of the Cochrane Collaboration Back Review Group.

Furlan AD, Brosseau L, Imamura M, Irvin E.

Institute for Work & Health, Toronto, Canada.

BACKGROUND: Low back pain (LBP) is one of the most common and costly musculoskeletal problems in modern society. Proponents of massage therapy claim it can minimize pain and disability and speed return-to-normal function. OBJECTIVES: To assess the effects of massage therapy for nonspecific LBP. SEARCH STRATEGY: We searched MEDLINE, Embase, Cochrane Controlled Trials Register, HealthSTAR, CINAHL, and dissertation abstracts through May 2001 with no language restrictions. References in the included studies and in reviews of the literature were screened. Contact with content experts and massage associations was also made. SELECTION CRITERIA: The studies had to be randomized or quasirandomized trials investigating the use of any type of massage (using the hands or a mechanical device) as a treatment for nonspecific LBP. DATA COLLECTION AND ANALYSIS: Two reviewers blinded to authors, journals, and institutions selected the studies, assessed the methodologic quality using the criteria recommended by the Cochrane Collaboration Back Review Group, and extracted the data using standardized forms. The studies were analyzed in a qualitative way because of heterogeneity of population, massage technique, comparison groups, timing, and type of outcome measured. RESULTS: Nine publications reporting on eight randomized trials were included. Three had low and five had high methodologic quality scores. One study was published in German, and the rest, in English. Massage was compared with an inert treatment (sham laser) in one study that showed that massage was superior, especially if given in combination with exercises and education. In the other seven studies, massage was compared with different active treatments. They showed that massage was inferior to manipulation and transcutaneous electrical nerve stimulation; massage was equal to corsets and exercises; and massage was superior to relaxation therapy, acupuncture, and self-care education. The beneficial effects of massage in patients with chronic LBP lasted at least 1 year after the end of the treatment. One study comparing two different techniques of massage concluded in favor of acupuncture massage over classic (Swedish) massage. CONCLUSIONS: Massage might be beneficial for patients with subacute and chronic nonspecific LBP, especially when combined with exercises and education. The evidence suggests that acupuncture massage is more effective than classic massage, but this needs confirmation. More studies are needed to confirm these conclusions, to assess the effect of massage on return-to-work, and to measure longer term effects to determine cost-effectiveness of massage as an intervention for LBP.

Publication Types:


Review Literature
PMID: 12221356 [PubMed – indexed for MEDLINE]

Spine 2002 Oct 15;27(20):2193-204

A randomized trial of medical care with and without physical therapy and chiropractic care with and without physical modalities for patients with low back pain: 6-month follow-up outcomes from the UCLA low back pain study.

Hurwitz EL, Morgenstern H, Harber P, Kominski GF, Belin TR, Yu F, Adams AH; University of California-Los Angeles.

Department of Epidemiology, University of California-Los Angeles School of Public Health, Los Angeles, California 90095-1772, USA.

STUDY DESIGN: A randomized clinical trial. OBJECTIVES: To compare the effectiveness of medical and chiropractic care for low back pain patients in managed care; to assess the effectiveness of physical therapy among medical patients; and to assess the effectiveness of physical modalities among chiropractic patients. SUMMARY OF BACKGROUND DATA: Despite the burden that low back pain places on patients, providers, and society, the relative effectiveness of common treatment strategies offered in managed care is unknown. METHODS: Low back pain patients presenting to a large managed care facility from October 30, 1995, through November 9, 1998, were randomly assigned in a balanced design to medical care with and without physical therapy and to chiropractic care with and without physical modalities. The primary outcome variables are average and most severe low back pain intensity in the past week, assessed with 0 to 10 numerical rating scales, and low back-related disability, assessed with the 24-item Roland-Morris Disability Questionnaire. RESULTS: Of 1,469 eligible patients, 681 were enrolled; 95.7% were followed through 6 months. The mean changes in low back pain intensity and disability of participants in the medical and chiropractic care-only groups were similar at each follow-up assessment (adjusted mean differences at 6 months for most severe pain, 0.27, 95% confidence interval, -0.32-0.86; average pain, 0.22, -0.25-0.69; and disability, 0.75, -0.29-1.79). Physical therapy yielded somewhat better 6-month disability outcomes than did medical care alone (1.26, 0.20-2.32). CONCLUSIONS: After 6 months of follow-up, chiropractic care and medical care for low back pain were comparable in their effectiveness. Physical therapy may be marginally more effective than medical care alone for reducing disability in some patients, but the possible benefit is small.

Publication Types:

Clinical Trial

Randomized Controlled Trial
PMID: 12394892 [PubMed – indexed for MEDLINE]

J Manipulative Physiol Ther 2002 Jan;25(1):10-20

Erratum in:

J Manipulative Physiol Ther 2002 Mar-Apr;25(3):183. Kominsky Gerald F [corrected to Kominski Gerald F]
Comment in:

J Manipulative Physiol Ther. 2002 Oct;25(8):538-9; discussion 539-40.

Second Prize: The effectiveness of physical modalities among patients with low back pain randomized to chiropractic care: findings from the UCLA low back pain study.

Hurwitz EL, Morgenstern H, Harber P, Kominski GF, Belin TR, Yu F, Adams AH, Kominsky GF.

UCLA School of Public Health, Department of Epidemiology, Los Angeles, Calif. 90095-1772, USA.

BACKGROUND: Although chiropractors often use physical modalities with spinal manipulation, evidence that modalities yield additional benefits over spinal manipulation alone is lacking. OBJECTIVE: The purpose of the study was to estimate the net effect of physical modalities on low back pain (LBP) outcomes among chiropractic patients in a managed-care setting. METHODS: Fifty percent of the 681 patients participating in a clinical trial of LBP treatment strategies were randomized to chiropractic care with physical modalities (n = 172) or without physical modalities (n = 169). Subjects were followed for 6 months with assessments at 2, 4, and 6 weeks and at 6 months. The primary outcome variables were average and most severe LBP intensity in the past week, assessed with numerical rating scales (0-10), and low back-related disability, assessed with the 24-item Roland-Morris Disability Questionnaire. RESULTS: Almost 60% of the subjects had baseline LBP episodes of more than 3 months’ duration. The 6-month follow-up was 96%. The adjusted mean differences between groups in improvements in average and most severe pain and disability were clinically insignificant at all follow-up assessments. Clinically relevant improvements in average pain and disability were more likely in the modalities group at 2 and 6 weeks, but this apparent advantage disappeared at 6 months. Perceived treatment effectiveness was greater in the modalities group. CONCLUSIONS: Physical modalities used by chiropractors in this managed-care organization did not appear to be effective in the treatment of patients with LBP, although a small short-term benefit for some patients cannot be ruled out.

Publication Types:

Clinical Trial

Randomized Controlled Trial
PMID: 11898014 [PubMed – indexed for MEDLINE]

Am J Public Health 2002 Oct;92(10):1628-33

Comparing the satisfaction of low back pain patients randomized to receive medical or chiropractic care: results from the UCLA low-back pain study.

Hertzman-Miller RP, Morgenstern H, Hurwitz EL, Yu F, Adams AH, Harber P, Kominski GF.

Department of Epidemiology, UCLA School of Public Health, University of California-Los Angeles, Los Angeles, CA, USA.

OBJECTIVES: This study examined the difference in satisfaction between patients assigned to chiropractic vs medical care for treatment of low back pain in a managed care organization. METHODS: Satisfaction scores (on a 10-50 scale) after 4 weeks of follow-up were compared among 672 patients randomized to receive medical or chiropractic care. RESULTS: The mean satisfaction score for chiropractic patients was greater than the score for medical patients (crude difference = 5.5; 95% confidence interval = 4.5, 6.5). Self-care advice and explanation of treatment predicted satisfaction and reduced the estimated difference between chiropractic and medical patients’ satisfaction. CONCLUSIONS: Communication of advice and information to patients with low back pain increases their satisfaction with providers and accounts for much of the difference between chiropractic and medical patients’ satisfaction.

Publication Types:

Clinical Trial

Randomized Controlled Trial
PMID: 12356612 [PubMed – indexed for MEDLINE]

Spine 2002 May 1;27(9):984-93; discussion 994


Low back pain recollection versus concurrent accounts: outcomes analysis.

Dawson EG, Kanim LE, Sra P, Dorey FJ, Goldstein TB, Delamarter RB, Sandhu HS.

UCLA Comprehensive Spine Center and Department of Orthopaedic Surgery, UCLA School of Medicine, Los Angeles, California 90404, USA.

STUDY DESIGN: Patients with low back pain were asked to recall the pain and impaired functioning that they reported 5-10 years previously as part of the National Low Back Pain prospective follow-up study. In 1998, patients completed an additional follow-up. OBJECTIVES: To compare outcomes using patient-recalled data and prospectively collected data from patients with low back pain and to identify simple, symptom-specific questions that yield reliable responses over an extended period of time. SUMMARY OF BACKGROUND DATA: Outcome assessment based on patient recall may be influenced by a patient’s age, gender, reporting tendency, and current health status. The impact of data collected retrospectively on outcome analyses in spinal patients has not been addressed. METHODS: Patients enrolled in the National Low Back Pain study from 1986 to 1991 completed a self-administered questionnaire at their initial visit. A sample was interviewed by telephone in 1996 and asked to recall pain characteristics and impaired functioning reported at initial examination. A 10-year follow-up (1998) on current health status was conducted by mail. The 1998 follow-up response was separately compared with recalled and initial responses, such that two patient outcome status values were calculated for each question. Agreement was evaluated using Cohen’s kappa. RESULTS: The follow-up evaluation was completed by 144 patients, with a mean interval of 9.4 years. The overall simple kappa was 0.37, indicating “fair” agreement between outcomes based on initial and recalled accounts of pain. Questions on location of pain had kappa values of 0.12-0.58, radicular symptoms 0.28-0.48, and severity of pain 0.11-0.30. CONCLUSIONS: “Fair” to “moderate” agreement was found between outcomes determined by recalled versus initial reports. Accuracy was greatest for queries on frequency, location of pain, and activities affecting pain. Discrepancies were noted for queries on severity of pain, with error bias toward less pain when using the recalled data. Careful selection of questions may yield more accurate outcome measures.

PMID: 11979175 [PubMed – indexed for MEDLINE]

Clin Rehabil 2002 Dec;16(8):811-20

Systematic review of conservative interventions for subacute low back pain.

Pengel HM, Maher CG, Refshauge KM.

School of Physiotherapy, University of Sydney, Sydney, NSW, Australia.

OBJECTIVE: To evaluate the effect of conservative interventions on clinically relevant outcome measures for patients with subacute low back pain. This is particularly important because effective treatment for subacute low back pain will prevent the transition to chronic low back pain, a condition that is largely responsible for the high health care costs of low back pain. DESIGN: Systematic review of randomized controlled trials. MAIN OUTCOME MEASURES: Methodological quality of each trial was assessed. Effect sizes and 95% confidence intervals were calculated for pain and disability and risk ratios for return to work. RESULTS: Thirteen trials were located, evaluating the following interventions: manipulation, back school, exercise, advice, transcutaneous electrical nerve stimulation (TENS), hydrotherapy, massage, corset, cognitive behavioural treatment and co-ordination of primary health care. Most studies were of low quality and did not show a statistically significant effect of intervention. For the strict duration of low back pain (six weeks to three months), no evidence of high internal validity was found but when other methodological criteria were considered, evidence was found for the efficacy of advice. Furthermore, there is evidence that when a broader view is taken of the duration of subacute low back pain (seven days to six months), other treatments (e.g. manipulation, exercise, TENS) may be effective. CONCLUSIONS: Our review identified a major gap in the evidence for interventions that are currently recommended in clinical practice guidelines for the treatment of subacute low back pain. Lack of a uniform definition of subacute low back pain further limited current evidence.

Publication Types:


Review, Tutorial
PMID: 12501942 [PubMed – indexed for MEDLINE]

Z Orthop Ihre Grenzgeb 2002 Sep-Oct;140(5):503-8

[The Efficacy of homeopathy in the treatment of chronic low back pain compared to standardized physiotherapy]

[Article in German]

Gmunder R, Kissling R.

Abteilung fur Physikalische Medizin und Rheumatologie, Orthopadische Universitatsklinik Balgrist, Zurich, Switzerland.

AIM: The aim of this pilot project was to evaluate the efficacy of treatment of chronic low back pain during two months either by homeopathy or by standardised physiotherapy. METHOD: 43 patients suffering from chronic low back pain were included in this controlled, randomised prospective study. They were divided in two treatment groups: homeopathy and standardised physiotherapy. Based on the initial and final clinical investigations, the Oswestry questionnaire and the visual analogue scale, that were assessed at the beginning, at the end and 18.5 months after therapy, the results were statistically evaluated. A further questionnaire documented the acceptance of treatment. RESULTS: A comparison of the groups from the beginning to the end of treatment reveals a significant decrease of the Oswestry score in patients treated by homeopathy. This tendency could not be confirmed 18.5 months later.Homeopathy was well accepted by most of the patients. CONCLUSIONS: Based on these results, nothing can be said against attempting treatment of chronic low back pain by means of homeopathy. Further research is recommended to confirm the results of our investigation, using a larger number of patients, a third treatment group, homeopathy double blinded.

Publication Types:

Clinical Trial

Randomized Controlled Trial
PMID: 12226773 [PubMed – indexed for MEDLINE]

Measles In the 21st Century: Is It Vaccine Refusal That Causes Outbreaks?

Whenever there are cases of measles, or any childhood illness that has a vaccine, the immediate blame falls on parents who refuse to vaccinate their children.  (Pittsburgh editorial)

In the U.S. the rate of refusal of vaccines by parents is less than 2%. (CDC 2010) Given that outbreaks often include both vaccinated and unvaccinated individuals, it is clear that the transmission of measles can take place between vaccinated individuals.

While it is enticing to simply blame outbreaks of measles on unvaccinated individuals, the reality is that the vaccine itself is not fool proof, and may provide varying immunity based even on the timing of the vaccination. “Vaccine efficacy rose from 85% in children vaccinated at 12 months of age to > or = 94% in those vaccinated at 15 months and older.” (study here)

Rather than focusing on the tiny percentage of parents refusing vaccination, public health dollars and attention should be focused on the evolving threat of measles in a vaccinated world. Studies from France found that health care workers who had been vaccinated still contracted measles, and likely passed on the virus to their charges (below). Even after mandatory universal vaccination, Singapore still sees a few cases of measles.  They also see a large number of false positive diagnoses, where the majority of cases diagnosed as measles are not that virus at all.

Measles represents the most highly effective vaccine within its MMR combination.  The mumps component has at best 88% efficacy (below), making the primary problem with its transmission the strength of the vaccine rather than the resistance of parents. 

Ann Dermatol Venereol. 2011 Feb;138(2):107-10. Epub 2011 Feb 1.

[Measles in adults: an emerging disease not sparing medical staff].

Monsel G, Rapp C, Duong TA, Farhi D, Bouaziz JD, Meyssonnier V, Mirkamali A, Jaureguiberry S, Caumes E.

“We retrospectively studied all the consecutive cases of measles seen in adults between the 1/1/2007 and the 30/4/2009 in four Parisian hospitals.Twenty-one patients were included. Six patients (29%) were health care workers (HCW) including five (83%) who were vaccinated.”


Euro Surveill. 2010 Sep 9;15(36). pii: 19656.

Spotlight on measles 2010: update on the ongoing measles outbreak in France, 2008-2010.

Parent du Châtelet I, Antona D, Freymuth F, Muscat M, Halftermeyer-Zhou F, Maine C, Floret D, Lévy-Bruhl D.

“Since early 2008, France has been experiencing a measles outbreak with almost 5,000 notified cases as of 30 June 2010, including three measles-related deaths. The proportion of cases 20 years or older reached 38% during the first half of 2010. This situation is the consequence of insufficient vaccine coverage (90% at age 24 months in 2007) that led to the accumulation of susceptibles over the last years.”


Southeast Asian J Trop Med Public Health. 2006 Jan;37(1):96-101.

A 24-year review on the epidemiology and control of measles in Singapore, 1981-2004.

Ong G, Hoon HB, Ong A, Chua LT, Kai CS, Tai GK.

 “Vaccine efficacy of the trivalent MMR vaccine based on institutional outbreak investigations was consistently above 92%. We also found that the overall seroprevalence of the population to measles has decreased from approximately 91.5% in 1989/1990 to 1993 to 77.9% in 1998 (mainly in children < 4 years old) and that only 7% of clinically notified cases of measles were serologically confirmed to be positive for measles.”” 


Singapore Med J. 2007 Jul;48(7):656-61.

Outbreak of measles in primary school students with high first dose MMR vaccination coverage.

Ong G, Rasidah N, Wan S, Cutter J.

“Indigenous cases of measles continue to occur in Singapore despite the implementation of a two-dose mumps, measles and rubella (MMR) vaccination policy in 1998…  The attack rate was 1.2 percent in the vaccinated group and 53.8 percent in the unvaccinated group.”


Bull Acad Natl Med. 2010 Apr-May;194(4-5):719-32; discussion 732.

[Consequences of opposition to vaccination in France and Europe. How to maintain effective vaccine coverage in 2010?].

[Article in French]

Bégué P.


 “Low vaccine coverage can lead to the persistence of preventable diseases and, in some cases, to a dangerous shift in the age of pathogen encounter towards adulthood. This is the case of measles in Europe, where some countries, including France, have not reached the effective vaccine coverage rate of 95%.” 


CMAJ. 2011 May 16. [Epub ahead of print]

An assessment of mumps vaccine effectiveness by dose during an outbreak in Canada.

“Vaccine effectiveness of one dose of the MMR vaccine ranged from 49.2% to 81.6%, whereas vaccine effectiveness of two doses ranged from 66.3% to 88.0%. If we assume vaccine effectiveness of 85% for two doses of the vaccine, vaccine coverage of 88.2% and 98.0% would be needed to interrupt community transmission of mumps”