Prathap Tharyan

Metastatic spinal cord compression (MSCC), left untreated leads to pain, progressive motor and sensory loss, including possible paraplegia and quadriplegia, bowel and bladder dysfunction, and can have a devastating impact on patients and their families (Loblaw ...

Electroconvulsive therapy (ECT) involves the induction of a seizure (fit) for therapeutic purposes by the administration of a low frequency electrical stimulus shock via electrodes applied to the scalp. At present it is used for those with schizophrenia but its effects are unclear. To determine whether electroconvulsive therapy (ECT) results in clinically meaningful benefit with regard to global improvement, hospitalisation, changes in mental state, behaviour and functioning in those with schizophrenia. Electronic searches of Biological Abstracts (1982-1996), EMBASE (1980-1996), Medline (1966-1996), PsycLIT (1974-1996) and SCISEARCH (1996) were undertaken. The references of all identified studies were investigated. All randomised controlled trials that compared ECT with placebo, 'sham ECT', non-pharmacological interventions and antipsychotics for people with schizophrenia, schizoaffective disorder or chronic mental disorder. The reviewers extracted the data independently and analysed the data on an intention to treat basis. Less people with schizophrenia treated with ECT showed no improvement in general functioning when compared to those given placebo in the short term (OR 0.48 CI 99% 0.26-0.90). This effect, however, does not last. However, ECT is less effective than antipsychotic drug treatment for those with schizophrenia. Limited evidence exists to suggest that combining antipsychotic drugs and ECT increases the rate and extent of clinical improvement, in the short term, in one out of every five to six people. The evidence for the efficacy of ECT in the medium to long term is equivocal. Electroconvulsive therapy is also more effective than the now obsolete insulin coma treatment. There is some evidence to support the use of ECT for those with schizophrenia for short term relief of symptoms. Electroconvulsive therapy may be advocated as an adjunct to antipsychotic medication for those with schizophrenia who show a limited response to medication alone but the evidence for this is not strong. In fact in spite of more than five decades of widespread clinical use, the administration of ECT to those with schizophrenia lacks a strong research base.

The clinical differentiation of epileptic seizures from hysterical pseudo-epileptic seizures is sometimes difficult. The routine inter-ictal electroencephalogram is of limited use in such instances and prolonged electrophysiological monitoring for the detection of ictal changes may not always be feasible, especially in many centres in developing countries. This article focuses on hyperprolactinaemia as a biochemical marker of a recent ictus. It reviews studies that have explored the possibility of utilizing transient post-ictal elevations in serum prolactin as a diagnostic test in aiding the differentiation of epilepsy from hysterical pseudo-epilepticseizures, In the past decade many reports have documented post-ictal elevations in serum prolactin after tonic-clonic and complex partial seizures. Peak prolactin levels were observed 15 to 20 minutes after the ictus and values fell towards baseline within the hour. Evidence from these studies indicates that post-ictal hyperprolactinaemia is caused by involvement of medial temporal structures, especially the amygdala and hippocampus, by ictal discharges and the resultant disruption of tonic dopaminergic inhibition of prolactin release and/or stimulation of serotonin, rather than due to non-specific influences. The factors that affect the specificity, sensitivity and predictive value of post-ictal hyperprolactinaemia as a diagnostic test are discussed and a standard test procedure and definition of test result proposed that would improve its clinical utility. The test is recommended as a simple, relatively inexpensive, highly specific and fairly sensitive aid to diagnosis.

A patient especially in the developing countries has little choice but to assume that doctor knows the best and has the sufficient knowledge of the best available and cost-effective interventions with minimum possible harm. However this belief may be misplaced. There were more than 14000 clinical trials with pain as an outcome published only between 1950 and 1994. This is mind boggling even for a whole time academician not to speak of a busy clinician who is faced with innumerable questions while making clinical decisions. In fact it is not easy to ask the right question as this also requires considerable expertise in itself. The natural tendency at this stage is to trust secondary sources of information and expert opinions mostly expressed in review articles and textbooks. In developing countries practitioners are often at the mercy of information provided by the pharmaceuticals. (excerpt)

The usefulness of post-ictal serum prolactin changes, as an adjunct, in the differentiation of generalized tonic-clonic seizures and complex partial seizures from hysterical pseudoepileptic seizures, was investigated in a double blind study designed to control for variables known to alter prolactin levels. Significant post-ictal hyper-prolactinemia, with a peak at 20 minutes and a fall towards baseline by 1 hour, was found after complex partial seizures, generalized tonic-clonic seizures and after bilateral, unmodified ECT, but not after hysterical pseudoepileptic seizures or in stressed, non-epileptic controls. A proportionate increase in peak prolactin levels of at least thrice baseline values was found to best differentiate genuine seizures from pseudoepileptic seizures. Postictal hyperprolactinemia is a sensitive biochemical marker of a genuine seizure and of potential use in the differentiation of epileptic from hysterical pseudoepileptic seizures.

Although tubal sterilization procedures are considered to be permanent, requests for reversal of the procedure (re-canalisation) are not infrequent. The reversal procedure can be done either by an open laparotomy or by minimally invasive surgery (laparoscopic or robotic approach). To compare the relative effectiveness and safety of reversal of tubal sterilization by open laparotomy, laparoscopy and robotically assisted endoscopy. On 23 October 2012 we searched the Cochrane Menstrual Disorders and Subfertility Review Group Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 10, 2012); MEDLINE; EMBASE; LILACS; clinical trials registries; regional databases; conference proceedings; and references for relevant published, unpublished and ongoing trials. Randomised trials comparing the different methods of surgical reversal of tubal sterilisation. No trials that met the selection criteria were identified. No data for evaluation were obtained Currently there is no evidence from randomised controlled trials to recommend or refute the use of a minimally invasive surgical approach (laparoscopic or robotic) or open surgery for reversal of tubal sterilization. There is a need for well conducted and reported randomised clinical trials to generate reliable evidence to inform clinical practice.

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) account for one-quarter of cases of acute respiratory failure in intensive care units (ICUs). A third to half of patients will die in the ICU, in hospital or during follow-up. Mechanical ventilation of people with ALI/ARDS allows time for the lungs to heal, but ventilation is invasive and can result in lung injury. It is uncertain whether ventilator-related injury would be reduced if pressure delivered by the ventilator with each breath is controlled, or whether the volume of air delivered by each breath is limited. To compare pressure-controlled ventilation (PCV) versus volume-controlled ventilation (VCV) in adults with ALI/ARDS to determine whether PCV reduces in-hospital mortality and morbidity in intubated and ventilated adults. In October 2014, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Isssue 9), MEDLINE (1950 to 1 October 2014), EMBASE (1980 to 1 October 2014), the Latin American Caribbean Health Sciences Literature (LILACS) (1994 to 1 October 2014) and Science Citation Index-Expanded (SCI-EXPANDED) at the Institute for Scientific Information (ISI) Web of Science (1990 to 1 October 2014), as well as regional databases, clinical trials registries, conference proceedings and reference lists. Randomized controlled trials (RCTs) and quasi-RCTs (irrespective of language or publication status) of adults with a diagnosis of acute respiratory failure or acute on chronic respiratory failure and fulfilling the criteria for ALI/ARDS as defined by the American-European Consensus Conference who were admitted to an ICU for invasive mechanical ventilation, comparing pressure-controlled or pressure-controlled inverse-ratio ventilation, or an equivalent pressure-controlled mode (PCV), versus volume-controlled ventilation, or an equivalent volume-controlled mode (VCV). Two review authors independently screened and selected trials, assessed risk of bias and extracted data. We sought clarification from trial authors when needed. We pooled risk ratios (RRs) for dichotomous data and mean differences (MDs) for continuous data with their 95% confidence intervals (CIs) using a random-effects model. We assessed overall evidence quality using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. We included three RCTs that randomly assigned a total of 1089 participants recruited from 43 ICUs in Australia, Canada, Saudi Arabia, Spain and the USA. Risk of bias of the included studies was low. Only data for mortality and barotrauma could be combined in the meta-analysis. We downgraded the quality of evidence for the three mortality outcomes on the basis of serious imprecision around the effect estimates. For mortality in hospital, the RR with PCV compared with VCV was 0.83 (95% CI 0.67 to 1.02; three trials, 1089 participants; moderate-quality evidence), and for mortality in the ICU, the RR with PCV compared with VCV was 0.84 (95% CI 0.71 to 0.99; two trials, 1062 participants; moderate-quality evidence). One study provided no evidence of clear benefit with the ventilatory mode for mortality at 28 days (RR 0.88, 95% CI 0.73 to 1.06; 983 participants; moderate-quality evidence). The difference in effect on barotrauma between PCV and VCV was uncertain as the result of imprecision and different co-interventions used in the studies (RR 1.24, 95% CI 0.87 to 1.77; two trials, 1062 participants; low-quality evidence). Data from one trial with 983 participants for the mean duration of ventilation, and from another trial with 78 participants for the mean number of extrapulmonary organ failures that developed with PCV or VCV, were skewed. None of the trials reported on infection during ventilation or quality of life after discharge. Currently available data from RCTs are insufficient to confirm or refute whether pressure-controlled or volume-controlled ventilation offers any advantage for people with acute respiratory failure due to acute lung injury or acute respiratory distress syndrome. More studies including a larger number of people given PCV and VCV may provide reliable evidence on which more firm conclusions can be based.

Background: There are multiple economic, psychological, and physical consequences of high job stress, low job satisfaction and burnout in faculty of a teaching hospital in South India. Data from developing countries on these domains are sparse. Materials and Methods: In a cross-sectional study we assessed the prevalence and sources of perceived job stress, job satisfaction and burnout in faculty, as well as ways of coping with stress among consenting faculty of a large, private, charitable, teaching hospital in India using standardized, self-rated questionnaires. Results: A total of 304 respondents, 156 (51.3%) were Assistant Professors; 71 (23.4%) were Associate Professors, and 77 (25.3%) were Professors. The majority (175; 58%) were male, younger than 45 years (235; 76%) and from clinical departments (248; 81.5%) A third (96; 31%) reported high overall levels of perceived job stress. In multivariate analyses, age less than 45 years, designation as Assistant or Associate Professor, and working in a clinical department were associated with perceived high job stress; reporting high perceived job satisfaction was protective. Nearly two-thirds (217; 71.4%) of faculty reported high levels of job satisfaction. In multivariate analysis, age less than 45 years and reporting high job stress were associated with low perceived job satisfaction. Causes of stress and satisfaction differed by age, gender and designation. On the Maslach Burnout Inventory (MBI), 88 (29%) had high scores on the emotional exhaustion subscale, 63 (20.8%) had high scores on the depersonalization subscale, and 90 (29.7%) had low scores on the personal achievement subscales. High job stress and low job satisfaction were significantly associated with burnout on the three domains. Conclusions: High job stress and low job satisfaction were inversely related in this survey of medical faculty and were significantly associated with levels of burnout. The sources of job stress and job satisfaction identified provide insights that could inform formal institutional mechanisms to prevent burnout in doctors.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:To evaluate the efficacy and safety of shortened treatment regimens, versus the standard six‐month treatment regimen, in individuals with drug‐sensitive pulmonary tuberculosis.

Background: Metastatic epidural spinal cord compression (MESCC) is often treated with radiotherapy and corticosteroids. Recent reports suggest benefit from decompressive surgery. Objectives: To determine effectiveness and adverse effects of radiotherapy, surgery and corticosteroids in MESCC. Search strategy: CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS and CANCERLIT were searched; last search ran July 2008 Selection criteria: We selected randomized controlled trials (RCTs) of radiotherapy, surgery and corticosteroids in adults with MESCC. Data collection and analysis: Three review authors independently assessed quality of included studies and extracted data. We calculated risk ratios (RR) and numbers needed to treat to benefit (NNT) with 95% confidence intervals (CI) and assessed heterogeneity. Main results: We identified six trials (n = 544). One trial (n = 276) compared radiotherapy 30 Gray in eight fractions with 16 Gray in two fractions and showed no difference. Overall ambulatory rates were 71% versus 68%, (RR 1.02, CI 0.90 to 1.15); 91% versus 89% of ambulant patients maintained ambulation (RR 1.02, CI 0.93 to 1.12); 28% versus 29% of non-ambulant patients regained ambulation (RR 0.98, CI 0.51 to 1.88). In one trial (n = 101) decompressive surgery had significantly better outcomes than radiotherapy in selected patients. Overall ambulatory rates were 84% versus 57% (RR 0.67, CI 0.53 to 0.86, NNT 3.70 CI 2.38 to 7.69); 94% versus 74% maintained ambulation (RR 0.79, CI 0.64 to 0.98, NNT 5.00 CI 2.78 to 33.33); 63% versus 19% regained ambulation (RR 0.30, CI 0.10 to 0.89; NNT 2.27 CI 1.35 to 7.69). Median survival was 126 days versus 100 days. Laminectomy offered no advantage (n = 29, 1 trial). Three trials provided insufficient evidence about the role of corticosteroids (n = 105, Overall ambulation RR 0.91, CI 0.68 to 1.23). Serious adverse effects were significantly higher in high dose corticosteroid arms (n = 77, two RCTs, RR 0.12, CI 0.02 to 0.97). Authors' conclusions: Patients with stable spines retaining the ability to walk may be treated with radiotherapy. One trial indicates that short course radiotherapy suffices in patients with unfavourable histologies or predicted survival of less than six months. There is some evidence of benefit from decompressive surgery in ambulant patients with poor prognostic factors for radiotherapy; and in non-ambulant patients with a single area of compression, paraplegia < 48 hours, non-radiosensitive tumours and a predicted survival of more than three months. High dose corticosteroids carry a significant risk of serious adverse effects.

Electroconvulsive therapy (ECT) involves the induction of a seizure (fit) for therapeutic purposes by the administration of a variable frequency electrical stimulus shock via electrodes applied to the scalp. The effects of its use in people with schizophrenia are unclear. To determine whether electroconvulsive therapy (ECT) results in clinically meaningful benefit with regard to global improvement, hospitalisation, changes in mental state, behaviour and functioning for people with schizophrenia, and whether variations in the practical administration of ECT influences outcome. Electronic searches of Biological Abstracts (1982-1996), EMBASE (1980-1996), MEDLINE (1966-2001), PsycLIT (1974-1996),SCISEARCH (1996) and the Cochrane Schizophrenia Group&amp;amp;amp;amp;amp;#39;s Register (July 2001) were undertaken. The references of all identified studies were also inspected and authors contacted. All randomised controlled clinical trials that compared ECT with placebo, &amp;amp;amp;amp;amp;#39;sham ECT&amp;amp;amp;amp;amp;#39;, non-pharmacological interventions and antipsychotics, and different schedules and methods of administration of ECT for people with schizophrenia, schizoaffective disorder or chronic mental disorder. Studies were reliably selected, quality rated and data extracted. For dichotomous data, relative risks (RR) were estimated, with the 95% confidence intervals (CI). Where possible, the number needed to treat statistic (NNT) was calculated. Analysis was by intention-to-treat. Normal continuous data was summated using the weighted mean difference (WMD). Scale data was presented for only those tools that had attained pre-specified levels of quality. Tests of heterogeneity and for publication bias were undertaken. This review includes 24 trials with 46 reports. When ECT is compared with placebo or sham ECT, fewer people remain unimproved in the real ECT group (n=400, RR fixed &amp;amp;amp;amp;amp;#39;not globally improved in the short term&amp;amp;amp;amp;amp;#39; 0.77 CI 0.6 to 0.9, chi-square 13.46 df=8 p=0.1). Removal of the one study with clearly heterogeneous results causes a change in the findings (n=380, 8 RCTs, RR fixed 0.83 CI 0.7 to 1.01), as does removal of a clinically heterogeneous trial (n=370, 8 RCTs, RR fixed 0.74 CI 0.6 to 0.9, chi-square 10.97 df=7 p=0.14). There was a suggestion that ECT resulted in less relapses than sham ECT (n=47, 2 RCTs, RR fixed 0.26 CI 0.03 to 2.2), and a greater likelihood of being discharged from hospital (n=98, 1 RCT, RR fixed 0.59, CI 0.34 to 1.01). There is no evidence that this early advantage for ECT is maintained over the medium to long term. People treated with ECT did not drop out of treatment earlier than those treated with sham ECT (n=495, 14 RCTs, RR fixed 0.71 CI 0.33 to 1.52). Very limited data indicated that visual memory might decline after ECT compared with sham ECT (n=24, 1 RCT, WMD -14.0 CI -23 to -5); the results of verbal memory tests were equivocal. When ECT is directly compared with antipsychotic drug treatment (total n=419, 8 RCTs), results favour the medication group (n=175, 3 RCTs, RR fixed &amp;amp;amp;amp;amp;#39;not improved at the end of ECT course&amp;amp;amp;amp;amp;#39; 2.18 CI 1.3 to 3.6). One small study suggested more memory impairment after a course of ECT combined with antipsychotics than with antipsychotics alone (n=20, MD serial numbers and picture recall -4.90 CI -0. 8 to -9), though this proved transient. When continuation ECT was added to antipsychotic drugs, the combination was superior to the use of antipsychotics alone (n=30, WMD Global Assessment of Functioning 19.1 CI 9.7 to 28.5), or CECT alone (n=30, WMD -20.3 CI -11.5 to -29.1). Unilateral and bilateral ECT were equally effective in terms of global improvement (n=78, 2 RCTs, RR fixed &amp;amp;amp;amp;amp;#39;not improved at end of course of ECT&amp;amp;amp;amp;amp;#39; 0.79 CI 0.5 to 1.4). One trial showed a significant advantage for 20 treatments over 12 treatments for numbers globally improved at the end of the ECT course (n=43, RR fixed 2.53 CI 1.1 to 5.7). There is no evidence to clearly refute the use of ECT for people with schizophrenia. There is some limited evidence to support its use, particularly combined with antipsychotic drugs for those with schizophrenia who show limited response to medication alone. The research base for the use of ECT in people with schizophrenia is growing but, even after more than five decades of clinical use, is still inadequate.

... References. 1 Reynolds F. The Cochrane Library now available across India. Cochrane News 2007; 39: 2. PubMed. 2 Shojania KG, Sampson M, Ansari MT, Ji J, Doucette S, Moher D. How quickly do systematic reviews go out of date? A survival analysis. ...

BACKGROUND The Revised National Tuberculosis Control Program (RNTCP) envisages shifting from thrice-weekly to a daily anti-tuberculosis treatment (ATT) regimen. The potential merits and demerits of both regimens continue to be debated. METHODS This retrospective study compared treatment outcomes in 191 HIV-negative, newly diagnosed, sputum-positive adults with pulmonary tuberculosis from Vellore district of Tamil Nadu who were treated at a private medical college during 2009 to 2012 with intermittent Directly Observed Treatment Short Course (intermittent DOTS cohort, n=132) or who opted for daily Self-Administered Treatment (daily SAT cohort, n=59). Treatment outcomes obtained from medical records were supplemented by interviews with consenting, traceable patients. RESULTS The rates for the RNTCP-recommended sputum smear examinations were suboptimal (42% for daily SAT and 72% for intermittent DOTS). However, treatment success with daily SAT and intermittent DOTS (76.2% vs. 70.4%); default (11.9% vs. 18.2%); death (6.8% vs. 5.3%); treatment failure (5.1% vs. 4.6%); and relapse (0% vs. 1.5%) did not significantly differ. CONCLUSIONS While evaluable treatment outcomes were not significantly different with daily SAT and intermittent DOTS, rates for timely smear examinations and for treatment success were lower, and for default higher, in both cohorts than comparable RNTCP data from Vellore district. Further strengthening of RNTCP facilities within private medical colleges and regular, real-time audits of performance and outcomes are needed if daily ATT regimen under the RNTCP is to succeed.

ObjectiveTo summarise latent tuberculosis infection (LTBI) management strategies among household contacts of bacteriologically confirmed pulmonary tuberculosis (TB) patients in high‐TB burden countries.MethodsPubMed/MEDLINE (NCBI) and Scopus were searched (January 2006 to December 2021) for studies reporting primary data on LTBI management. Study selection, data management and data synthesis were protocol‐driven (PROSPERO‐CRD42021208715). Primary outcomes were the proportions of LTBI, initiating and completing tuberculosis preventive treatment (TPT). Reported factors influencing the LTBI care cascade were qualitatively synthesised.ResultsFrom 3694 unique records retrieved, 58 studies from 23 countries were included. Most identified contacts were screened (median 99%, interquartile range [IQR] 82%–100%; 46 studies). Random‐effects meta‐analysis yielded pooled proportions for: LTBI 41% (95% confidence interval [CI] 33%–49%; 21,566 tested contacts); TPT initiation 91% (95% CI 79%–97%; 129,573 eligible contacts, 34 studies); TPT completion 65% (95% CI 54%–74%; 108,679 TPT‐initiated contacts, 28 studies). Heterogeneity was significant (I 2 ≥ 95%–100%) and could not be explained in subgroup analyses. Median proportions (IQR) were: LTBI 44% (28%–59%); TPT initiation 86% (60%–100%); TPT completion 68% (44%–82%). Nine broad themes related to diagnostic testing, health system structure and functions, risk perception, documentation and adherence were considered likely to influence the LTBI care cascade.ConclusionThe proportions of household contacts screened, detected with LTBI and initiated on TPT, though variable was high, but the proportions completing TPT were lower indicating current strategies used for LTBI management in high TB burden countries are not sufficient.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:To assess the efficacy, safety and vaccination coverage of combined DPT‐HBV vaccine in comparison to separate DPT and HBV vaccines administered to children up to two years of age.To summarise current evidence on the (incremental) resource use, costs and cost‐effectiveness associated with combined DPT‐HBV vaccine in comparison to separate DPT and HBV vaccines administered to children up to two years of age.