WFSBP guidelines on how to grade treatment evidence for clinical guideline development

Objective and methods: This paper reviews sources of data typically used in guideline development, available grading systems, their pros and cons, and the methods for evaluating risks of bias in publications, and proposes a revised method for grading evidence and recommendations for use in development of clinical treatment guidelines.

Results: The new World Federation of Societies of Biological Psychiatry (WFSBP) grading system allows guideline developers to follow a multi-step approach of defining levels of evidence, applying criteria for grading (define the acceptability) and the grading of recommendations.

Conclusions: Further, these updated WFSBP recommendations for rating evidence and treatment recommendations provide a grading system that takes into account potential biases in sources of evidence in arriving at final ratings that are likely more clinically meaningful and pragmatic and thus should be used for the development of future treatment guidelines.     

Detection of vancomycin variable enterococci (VVE) among clinical isolates of Enterococcus faecium collected across India-first report from the subcontinent

PurposeEmergence of vancomycin variable enterococci (VVE) poses a challenge to empiric vancomycin therapy. Vancomycin-variable enterococci (VVE) are vanA-positive, yet phenotypically vancomycin-susceptible enterococci that can switch to a vancomycin-resistant phenotype when exposed to vancomycin. The aim of the present study was to determine the prevalence of VVE in India.MethodsIsolates of phenotypically vancomycin susceptible Enterococcus faecium from 20 tertiary care hospitals across India were collected and tested for the presence of vanA, vanR, vanS, vanB and vanC genes by conventional PCR using previously published primers. Isolates positive for vanA gene were considered as VVE.ResultsThe prevalence of VVE was 1.5% (5/340). Only one VVE isolate was positive for vanR and vanS, and all the isolates were negative for vanB and vanC.ConclusionsAlthough the prevalence is low, our finding emphasizes the importance of routinely screening for van genes in enterococci that are phenotypically susceptible. Silenced vanA able to escape detection and revert to resistance during vancomycin therapy represents a new challenge in clinical settings.     

Quality of Life Impacts of Bright Light Treatment,Fluoxetine, and the Combination in Patients with Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial

Objective:Bright light therapy is increasingly recommended (alone or in combination with antidepressant medication) to treat symptoms of nonseasonal major depressive disorder (MDD). However, little is known about its impacts on quality of life (QoL), a holistic, patient-valued outcome.Methods:This study utilizes secondary outcome data from an 8-week randomized, controlled, double blind trial comparing light monotherapy (n = 32), fluoxetine monotherapy (n = 30), and the combination of these (n = 27) to placebo (n = 30). QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Treatment-related differences in QoL improvements were assessed using a repeated measures analysis of variance. The influence of potential predictors of QoL (demographic variables and change in depressive symptoms) were investigated via hierarchical linear regression.Results:Q-LES-Q-SF scores significantly improved across all treatment conditions; however, no significant differences were observed between treatment arms. QoL remained poor relative to community norms by the end of the trial period: Across conditions, 70.6% of participants had significantly impaired QoL at the 8-week assessment. Reduction in depressive scores was a significant predictor of improved QoL, with the final model accounting for 54% of variance in QoL change scores.Conclusion:The findings of this study emphasize that improvement in QoL and reduction in depressive symptoms in MDD, while related, cannot be taken to be synonymous. Adjunctive therapies may be required to address unmet QoL needs in patients with MDD receiving antidepressant or light therapies. Further research is required to explore additional predictors of QoL in order to better refine treatments for MDD.     

4-Hydroxynonenal regulates mitochondrial function in human small airway epithelial cells

Prolonged exposure to oxidative stress causes Acute Lung Injury (ALI) and significantly impairs pulmonary function. Previously we have demonstrated that mitochondrial dysfunction is a key pathological factor in hyperoxic ALI. While it is known that hyperoxia induces the production of stable, but toxic 4-hydroxynonenal (4-HNE) molecule, it is unknown how the reactive aldehyde disrupts mitochondrial function. Our previous in vivo study indicated that exposure to hyperoxia significantly increases 4-HNE-Protein adducts, as well as levels of MDA in total lung homogenates. Based on the in vivo studies, we explored the effects of 4-HNE in human small airway epithelial cells (SAECs). Human SAECs treated with 25 μM of 4-HNE showed a significant decrease in cellular viability and increased caspase-3 activity. Moreover, 4-HNE treated SAECs showed impaired mitochondrial function and energy production indicated by reduced ATP levels, mitochondrial membrane potential, and aconitase activity. This was followed by a significant decrease in mitochondrial oxygen consumption and depletion of the reserve capacity. The direct effect of 4-HNE on the mitochondrial respiratory chain was confirmed using Rotenone. Furthermore, SAECs treated with 25 μM 4-HNE showed a time-dependent depletion of total Thioredoxin (Trx) proteins and Trx activity. Taken together, our results indicate that 4-HNE induces cellular and mitochondrial dysfunction in human SAECs, leading to an impaired endogenous antioxidant response.     

Unusual Complication of Toxic Megacolon in Typhoid Colitis

Colitis is a rare manifestation of enteric fever in children. Toxic megacolon complicating typhoid colitis is even rarer and requires early recognition and aggressive management due to the high mortality associated with this condition. The authors report a rare case of Toxic megacolon secondary to typhoid colitis in a seven-year-old girl.     

CDC Kerala 15: Developmental Evaluation Clinic (2–10 y) – Developmental Diagnosis and Use of Home Intervention Package

Objective

To describe the last 5 years' experience of Child Development Centre (CDC), Kerala Developmental Evaluation Clinic II for children between 2 and 10 y, referred for suspicion of developmental lag in the preschool years and scholastic difficulty in the primary classes with specific focus on developmental profile and the experience of the home based intervention package taught to the mothers.

Methods

A team of evaluators including developmental therapist, preschool teacher with special training in clinical child development, speech therapist, special educator, clinical psychologist and developmental pediatrician assessed all the children referred to CDC Kerala. Denver Developmental Screening Test (DDST-II), Vineland Social Maturity Scale (VSMS) and Intelligent Quotient (IQ) tests were administered to all children below 6 y and those above 6 with apparent developmental delay.

Results

Speech/delay (35.9 %), behavior problem (15.4 %), global delay/ intellectual disability (15.4 %), learning problem (10.9 %), pervasive developmental disorders (7.7 %), seizure disorder (1.7 %), hearing impairment (0.7 %), and visual impairment (0.7 %) were the clinical diagnosis by a developmental pediatrician. Each child with developmental problem was offered a home based intervention package consisting of developmental therapy and special education items, appropriate to the clinical diagnosis of the individual child and the same was taught to the mother.

Conclusions

The experience of conducting the developmental evaluation clinic for children between 2 and 10 y has shown that a team consisting of developmental therapist, speech therapist, preschool teacher, special educator, clinical child psychologist and developmental pediatrician, using appropriate test results of the child could make a clinical diagnosis good enough for providing early intervention therapy using a home based intervention package.

     

Normal serum bone markers in bisphosphonate-induced osteonecrosis of the jaws

We obtained serum bone markers and other relevant endocrine assays on 5 patients with osteonecrosis of the jaw (ONJ). The assays were C-telopeptide, N-telopeptide, bone-specific alkaline phosphatase, osteocalcin, intact parathyroid hormone, T3, T4, TSH, and Vitamin D 25 hydroxy. Diagnostic criteria for ONJ were those formulated by the American Association of Oral and Maxillofacial Surgeons. Four of our patients were women. Two had metastatic breast cancer and had been treated with zoledronic acid; one had also received pamidronate. Two others had osteoporosis and had been treated with daily alendronate. One man had metastatic prostate cancer treated with zoledronic acid. All patients had been withdrawn from bisphosphonate for at least 6 months. None were taking or had taken corticosteroids. None of the lesions had shown any significant healing and all were still causing the patients considerable distress. Yet the bone markers were within the normal range as measured in our laboratory, except for intact parathyroid hormone, which was slightly elevated in one case of metastatic breast cancer (177 pg/mL). Because the jaws have a greater blood supply than other bones, and a high bone turnover rate, bisphosphonates are highly concentrated in the jaws. This anatomic concentration of bisphosphonates might cause bisphosphonate-osteonecrosis to be manifested exclusively in the jaws and is consistent with our finding of normal serum bone markers in ONJ patients.