Andiappan Manoharan

Meta-analysis and meta-regression of hypothalamic-pituitary-adrenal axis activity in functional somatic disorders.

Dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis is the most investigated biological risk marker in functional somatic disorders (FSDs), such as chronic fatigue syndrome (CFS), fibromyalgia (FM), and irritable bowel syndrome (IBS). Our aim was to assess whether there is an association between basal hypocortisolism and FSD and to identify potential moderators of this association. Meta-analysis on 85 studies revealed that although basal cortisol levels were generally lower in FSD subjects compared to controls, this association did not reach statistical significance (SMD -0.07, 95% CI -0.17 to 0.04, p=0.241). However, when the three FSD were assessed separately, statistically significant basal hypocortisolism was observed in CFS subjects compared to controls (SMD -0.14, 95% CI -0.28 to 0.00, p=0.047), but not in FM or IBS. When all potential moderators were entered into a meta-regression analysis, only type of FSD and female gender were significant independent predictors of basal hypocortisolism. In conclusion, we did not find evidence to consider all three main FSD as hypocortisolemic disorders, as significant reduction in basal cortisol compared to healthy controls was only found in CFS and in females with FM, but not in IBS.

Cognitive functioning in patients with affective disorders and schizophrenia: A meta-analysis

There is considerable evidence for cognitive dysfunction in schizophrenia and affective disorders, but the pattern of potential similarities or differences between diagnostic groups remains uncertain. The objective of this study was to conduct a quantitative review of studies on cognitive performance in schizophrenia and affective disorders. Relevant articles were identified through literature search in major databases for the period between January 1980 and December 2005. Meta-analytic treatment of the original studies revealed widespread cognitive deficits in patients with schizophrenia and affective disorders in intellectual ability and speed of information processing, in encoding and retrieval, rule discovery and in response generation and response inhibition. Differences between diagnostic groups were quantitative rather than qualitative.

As good as it gets? A meta-analysis and systematic review of methodological quality of heart rate variability studies in functional somatic disorders

Autonomic nervous system (ANS) dysfunction is a potential mechanism connecting psychosocial stress to functional somatic disorders (FSD), such as chronic fatigue syndrome, fibromyalgia and irritable bowel syndrome. We present the first meta-analysis and systematic review of methodological study quality on the association between cardiac ANS dysfunction, measured as parasympathetic nervous system (PNS) activity using heart rate variability (HRV), and FSD. Literature search revealed 23 available studies including data on 533 FSD patients. Meta-analysis on a subgroup of 14 studies with suitable outcome measures indicated lower PNS activity in FSD patients compared to controls (weighted standardized mean difference (SMD)=-0.32, 95% CI -0.63 to -0.01, p=0.04). The reliability of this summary estimate was, however, significantly limited by unexplained heterogeneity in the effect sizes and potential publication bias (weighted SMD after correction for funnel plot asymmetry=0.01, 95% CI -0.34 to 0.36, p=0.95). The systematic review of overall methodological quality of HRV studies in FSD demonstrates that there is substantial room for improvement, especially in selection of healthy control subjects, blinding of researchers performing HRV measurements, report of adequate HRV outcomes, and assessment of and adjustment for potential confounders. Methodological study quality was, however, not a significant predictor of study findings. We conclude that current available evidence is not adequate to firmly reject or accept a role of ANS dysfunction in FSD. Quality criteria and recommendations to improve future research on HRV in FSD are provided.

Clinical and Radiographic Assessment of the Efficacy of Calcium Silicate Indirect Pulp Capping A Randomized Controlled Clinical Trial

The aims of this study were to assess the effectiveness of calcium silicate cement (Biodentine) versus glass ionomer cement (GIC; control group) as indirect pulp capping materials in patients with reversible pulpitis and to compare the effectiveness of cone beam computed tomography (CBCT) versus periapical (PA) radiographs in detecting PA changes at baseline (T0) and at 12 mo (T12) postoperatively. Seventy-two restorations (36 Biodentine, 36 Fuji IX) were placed randomly in 53 patients. CBCT/PA radiographs were taken at T0 and T12. Two calibrated examiners assessed the presence/absence and increase/decrease in the size of existing PA radiolucencies under standardized conditions. The Kappa coefficient evaluated statistically the effectiveness of CBCT versus PA radiographs in detecting PA changes. Chi-square/Mann-Whitney tests were used to evaluate the association between PA changes in CBCT with various clinical measures. Significance was predetermined at α = 0.05. Clinical success rates for Biodentine and Fuji IX GIC were 83.3%. CBCT was significantly more effective in detecting PA radiolucencies compared with radiographs (P = 0.0069). Of the teeth, 65.4% and 90.4% were deemed healthy using CBCT and PA radiographs, respectively, at T12. Healing/healed rates were 17.3%/0%, while new/progressed radiolucency were 30.8%/9.6% with CBCT/PA radiographs, respectively. Seventy-one percent of healed lesions had received Biodentine; 88% of new/progressed lesions received Fuji IX GIC. Teeth presenting with an initial CBCT PA lesion had a failure rate of 63%, whereas teeth with no initial lesion had a failure rate of 16%. Although no statistically significant difference was detected in the clinical efficacy of Biodentine/Fuji IX when used as indirect pulp capping materials in patients with reversible pulpitis, CBCT showed a significant difference in that most healed CBCT lesions had received Biodentine while most that did not heal received Fuji IX. Longer-term follow-up is needed to establish their effect on the healing dynamics of PA tissues (ClinicalTrials.gov NCT02201641).

Clinical and Radiographic Assessment of the Efficacy of Calcium Silicate Indirect Pulp Capping

The aims of this study were to assess the effectiveness of calcium silicate cement (Biodentine) versus glass ionomer cement (GIC; control group) as indirect pulp capping materials in patients with reversible pulpitis and to compare the effectiveness of cone beam computed tomography (CBCT) versus periapical (PA) radiographs in detecting PA changes at baseline (T0) and at 12 mo (T12) postoperatively. Seventy-two restorations (36 Biodentine, 36 Fuji IX) were placed randomly in 53 patients. CBCT/PA radiographs were taken at T0 and T12. Two calibrated examiners assessed the presence/absence and increase/decrease in the size of existing PA radiolucencies under standardized conditions. The Kappa coefficient evaluated statistically the effectiveness of CBCT versus PA radiographs in detecting PA changes. Chi-square/Mann-Whitney tests were used to evaluate the association between PA changes in CBCT with various clinical measures. Significance was predetermined at α = 0.05. Clinical success rates for Biodentine and Fuji IX GIC were 83.3%. CBCT was significantly more effective in detecting PA radiolucencies compared with radiographs (P = 0.0069). Of the teeth, 65.4% and 90.4% were deemed healthy using CBCT and PA radiographs, respectively, at T12. Healing/healed rates were 17.3%/0%, while new/progressed radiolucency were 30.8%/9.6% with CBCT/PA radiographs, respectively. Seventy-one percent of healed lesions had received Biodentine; 88% of new/progressed lesions received Fuji IX GIC. Teeth presenting with an initial CBCT PA lesion had a failure rate of 63%, whereas teeth with no initial lesion had a failure rate of 16%. Although no statistically significant difference was detected in the clinical efficacy of Biodentine/Fuji IX when used as indirect pulp capping materials in patients with reversible pulpitis, CBCT showed a significant difference in that most healed CBCT lesions had received Biodentine while most that did not heal received Fuji IX. Longer-term follow-up is needed to establish their effect on the healing dynamics of PA tissues (ClinicalTrials.gov NCT02201641).

The physical characteristics of resin composite-calcium silicate interface as part of a layered/laminate adhesive restoration

OBJECTIVES To compare in-vitro micro-shear bond strengths (μSBS) of resin composite to calcium silicate cement (Biodentine™) vs. glass ionomer cement vs. resin modified glass ionomer cement (RM-GIC) using an adhesive in self-etch (SE)/total etch (TE) mode after aging three substrates and bond and characterizing their failure modes. METHODS Resin composite was SE/TE bonded to 920 standardized disks of Biodentine™, GIC & RM-GIC. Dividing samples into two groups, the first underwent early (t=0min, 5min, 20min, 24h) or delayed (t=2wk, 1 month, 3 months, 6 months) substrate aging before bonding and μSBS (t=24h) testing. In the second, adhesive was applied after either early (t=5min) or delayed (t=2wk) substrate aging and then tested after bond aging (t=2wk, 1 month, 3 months, 6 months). The failure modes were identified using stereomicroscope. SEM images of selected samples were analyzed. RESULTS No significant differences were observed between (SE)/(TE) bonding modes (P=0.42). With substrate aging, a significant reduction in μSBS occurred between early and delayed time intervals for Biodentine™ (P=0.001), but none for the GIC/RM-GIC (P=0.465, P=0.512 respectively). With bond aging, there was no significant difference between time intervals for all groups, except at 6 months for the GIC (P<0.05). Modes of failure were primarily cohesive within all the substrates (68.82%) followed by adhesive failure at the resin-substrate interface (21.71%). SIGNIFICANCE Biodentine™ is a weak restorative material in its early setting phase. Placing the overlying resin composite as part of the laminate/layered definitive restoration is best delayed for >2wk to allow sufficient intrinsic maturation to withstand contraction forces from the resin composite. A total-etch or self-etch adhesive may be used.

More than the sum of its parts: meta-analysis and its potential to discover sources of heterogeneity in psychosomatic medicine.

Meta-analyses may contribute to more reliable knowledge about the existence of certain relations in the area of psychosomatic research. Surprisingly, the increasing popularity of meta-analysis is not reflected in the number of meta-analyses of observational studies published in Psychosomatic Medicine. This may be due to the specific difficulties that apply to meta-analyses of observational research. The aim of this paper is to provide a nontechnical overview of the principles of meta-analysis applied to observational research. We will highlight general principles of meta-analysis and discuss the major threats to its validity, with an emphasis on its specific merits and pitfalls for psychosomatic research, using several examples. We conclude that meta-analysis is a relatively simple technique, leaving little reason for not routinely applying it when performing a systematic review. An adequately conducted meta-analysis may not only provide a summary estimate of a certain association, but it has additional value in discovering relevant confounders, mediators, and moderators, as well as identifying areas of research that require more attention. BMI = body mass index; IL = interleukin; IPD = individual patient data; OR = odds ratio; PTSD = posttraumatic stress disorder; SEM = standard error of the mean; SMD = standardized mean difference.

The development and evaluation of a large-scale self-referral CBT-I intervention for men who have insomnia: an exploratory study.

BACKGROUND Whilst effective psychological treatments such as CBT-I have been developed for insomnia, few services provide CBT-I and awareness of CBT-I is low among referrers. In addition, men tend to seek help less frequently for their insomnia than women. This paper describes the development and evaluation of psycho-educational CBT-I workshops, each for up to 25 people, and designed to be acceptable to men. METHOD The CBT-I programme was based on Morin and Espie (2003), and adapted into a self-referral one-day workshop format designed specifically to improve access. Workshops were held on Saturdays in leisure centres. A one group pretest-posttest design was used and assessments were collected before and 6 weeks after each workshop. Over a 6-month period, 74 men self-referred, and attended the Introductory Talks preceding the workshops. Of these, 49.3% had never sought help from their GP, 66.2% suffered from clinical insomnia (ISI) and 61.6% were experiencing elevated depression symptoms (BDI over 10). RESULTS At follow-up, the workshops were found to be effective in reducing insomnia and depression. Satisfaction ratings with the workshops were very high. CONCLUSIONS Given these promising results, further work is now proposed for a larger controlled study with a longer-term follow-up.