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In early October 2014, 7 months after the 2014–2015 Ebola epidemic in West Africa began, a cluster of reported deaths in Koinadugu, a remote district of Sierra Leone, was the first evidence of Ebola virus disease (Ebola) in the district. Prior to this event, geographic isolation was thought to have prevented the introduction of Ebola to this area. We describe our initial investigation of this cluster of deaths and subsequent public health actions after Ebola was confirmed, and present challenges to our investigation and methods of overcoming them. We present a transmission tree and results of whole genome sequencing of selected isolates to identify the source of infection in Koinadugu and demonstrate transmission between its villages. Koinadugu's experience highlights the danger of assuming that remote location and geographic isolation can prevent the spread of Ebola, but also demonstrates how deployment of rapid field response teams can help limit spread once Ebola is detected.
A third of patients diagnosed with major depressive disorder (MDD) experience treatment-resistant depression (TRD). Relatively few pharmacological agents have established efficacy for TRD. Therefore, the evaluation of novel treatments for TRD is a pressing priority. Statins are pleiotropic agents and preclinical studies as well as preliminary clinical trials have suggested that these drugs may have antidepressant properties.
To report on a protocol for a 12-week, randomised, double-blind, placebo-controlled trial of add-on treatment with simvastatin for patients meeting DSM-5 criteria for MDD who have failed to respond to at least two adequate trials with approved antidepressants. The trial has been registered with Clinicaltrials.gov in (ClinicalTrials.gov identifier: NCT03435744).
After screening and randomisation to the two parallel arms of the trial, 75 patients will receive simvastatin and 75 patients will receive placebo as adjuncts to treatment as usual. The primary outcome is change in Montgomery–Åsberg Depression Rating Scale scores from baseline to week 12 and secondary outcomes include changes in scores on the 24-item Hamilton Rating Scale for Depression, the Clinical Global Impression scale, the 7-item Generalized Anxiety Disorder scale and change in body mass index from baseline to week 12. Assessments will take place at screening, baseline, and weeks 2, 4, 8 and 12. Checklists for adverse effects will be undertaken at each visit. Simvastatin (20 mg) will be given once daily. Other secondary outcomes include C-reactive protein and plasma lipids measured at baseline and week 12.
This trial will assess simvastatin's efficacy and tolerability as an add-on treatment option for patients with TRD and provide insights into its putative mechanisms of action.
As the first trial investigating the use of simvastatin as an augmentation strategy in patients with TRD, if the results indicate that adjuvant simvastatin is efficacious in reducing depressive symptoms, it will deliver immediate clinical benefit.
Declaration of interest
I.B.C. and N.H. have given lectures and advice to Eli Lilly, Bristol Myers Squibb, Lundbeck, Astra Zeneca and Janssen pharmaceuticals for which they or their employing institution have been reimbursed. R.R. and M.M.H. have received educational grants and support for academic meetings from Pfizer, Roche, Novartis and Nabiqasim. A.H.Y. has been commissioned to provide lectures and advice to all major pharmaceutical companies with drugs used in affective and related disorders. A.H.Y. has undertaken investigator-initiated studies from Astra Zeneca, Eli Lilly, Lundbeck and Wyeth. None of the companies have a financial interest in this research.
To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications.
Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit.
Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases.
In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive.
We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.
This comprehensive yet practical text reviews the pathology of neoplastic and non-neoplastic conditions of the pleura and peritoneum, with a particular focus on mesothelioma. The anatomy and embryology of serous membranes are discussed, and the causes, epidemiology, and clinical and radiologic features of malignant mesothelioma are reviewed. A comprehensive review of immunostains used for diagnosing serous membrane lesions is given, current treatment options for patients are outlined. The markers of asbestos exposure and their significance are also assessed. The pathology of non-neoplastic conditions of serous membranes, from peritoneal cysts and endometriosis to deciduosis and gliomatosis peritonei are also covered, as are lymphomas and soft tissue tumors in serous membranes. This makes Practical Pathology of Serous Membranes an essential resource for effective diagnosis.
Evidence-based psychosocial treatments for schizophrenia founded on Western belief systems and values may not be efficacious in different cultures without adaptation. This systematic review analyses the nature and outcomes of culturally-adapted psychosocial interventions in schizophrenia, examining how interventions have been adapted, their efficacy and what features drive heterogeneity in outcome.
Articles identified by searching electronic databases from inception to 3 March 2016, reference lists and previous reviews were independently screened by two authors for eligible controlled trials. Data on the nature of adaptations was analysed inductively using thematic analyses. Meta-analyses were conducted using random effects models to calculate effect sizes (Hedges’ g) for symptoms.
Forty-six studies with 7828 participants were included, seven adapted for minority populations. Cultural adaptations were grouped into nine themes: language, concepts and illness models, family, communication, content, cultural norms and practices, context and delivery, therapeutic alliance, and treatment goals. Meta-analyses showed significant post-treatment effects in favour of adapted interventions for total symptom severity (n = 2345, g: −0.23, 95% confidence interval (CI) −0.36 to −0.09), positive (n = 1152, g: −0.56, 95% CI −0.86 to −0.26), negative (n = 855, g: −0.39, 95% CI −0.63 to −0.15), and general (n = 525, g: −0.75, CI −1.21 to −0.29) symptoms.
The adaptation process can be described within a framework that serves as a benchmark for development or assessment of future adaptations. Culturally adapted interventions were more efficacious than usual treatment in proportion to the degree of adaptation. There is insufficient evidence to show that adapted interventions are better than non-adapted interventions. Features of context, intervention and design influenced efficacy. Investigating whether adaptation improves efficacy, most importantly amongst ethnic minorities, requires better designed trials with comparisons against unadapted interventions.
To evaluate the incidence of surgical-site infections (SSIs) in a cohort of liver transplant recipients and to assess risk factors predisposing patients to these infections.
Prospective observational cohort study.
Single transplant center in Canada.
Patients who underwent liver transplantation between February 2011 and August 2014.
Multivariate logistic regression was used to identify independent risk factors for SSIs in liver transplant patients.
We enrolled 250 liver transplant recipients. The recipients’ median age at the time of transplantation was 56 years (range, 19–70 years), and 166 patients (66.4%) were male. Moreover, 47 SSIs were documented in 43 patients (17.2%). Organ-space, superficial, and deep SSIs were noted in 29, 7, and 3 patients, respectively. In addition, 2 patients developed superficial and organ-space SSIs, and another 2 patients were found to have deep as well as organ-space infections. In total, we identified 33 organ-space SSIs (70.2%), 9 superficial SSIs (19.1%), and 5 deep SSIs (10.6%). Factors predictive of SSIs by multivariate analysis were duct-to-duct anastomosis (odds ratio [OR], 3.88; 95% CI, 1.85–8.13; P<.001) and dialysis (OR, 3.57; 95% CI, 1.02–12.50; P=.046). Of the 66 organisms isolated in both deep and organ-space SSIs, 55 (83%) were resistant to cefazolin.
Organ-space SSIs are a common complication after liver transplantation. Duct-to-duct anastomosis and dialysis were independent risk factors associated with SSIs. Appropriate perioperative prophylaxis targeting patients with duct-to-duct anastomosis and dialysis while simultaneously providing optimum coverage for the potential pathogens causing SSIs is warranted.
Soybean is a leading oilseed crop in India, which contains about 40% of protein and 20% of oil. Core collection will accelerate the management and utilization of soybean genetic resources in breeding programmes. In the present study, eight agromorphological traits of 3443 soybean germplasm were analysed for the development of core collection using the principal component score (PCS) strategy and the power core method. The PCS strategy yielded core collection (CC1) of 576 accessions, which accounted for 16.72% of the entire collection (EC). The analysis based on the power core programme resulted in CC2 of 402 accessions, which accounted for 11.67% of the EC. Statistical analysis showed similar trends for the mean and range estimated in both core collections and EC. In addition, the variance, standard deviation and coefficient of variance were in general higher in core collections than in the EC. The correlations observed in the EC in general were preserved in core collections. A total of 311 and 137 unique accessions were found in CC1 and CC2 in addition to 265 accessions that were found to be common in both core collections. These 265 common accessions were the most diverse core sets, which accounted for 7.64% of the EC. We proposed to constitute an integrated core collection (ICC) by integrating both common and unique accessions. The ICC comprised 713 accessions, which accounted for about 20.62% of the EC. Statistical analysis indicated that the ICC captured maximum variation than CC1 and CC2. Therefore, the ICC can be extensively evaluated for a large number of economically important traits for the identification of desirable genotypes and for the development of mini core collection in soybean.
Drinking raw date palm sap is the primary route of Nipah virus (NiV) transmission from bats to people in Bangladesh; subsequent person-to-person transmission is common. During December 2010 to March 2011, we investigated NiV epidemiology by interviewing cases using structured questionnaires, in-depth interviews, and group discussions to collect clinical and exposure histories. We conducted a case-control study to identify risk factors for transmission. We identified 43 cases; 23 were laboratory-confirmed and 20 probable. Thirty-eight (88%) cases died. Drinking raw date palm sap and contact with an infected person were major risk factors; one healthcare worker was infected and for another case transmission apparently occurred through contact with a corpse. In absence of these risk factors, apparent routes of transmission included drinking fermented date palm sap. For the first time, a case was detected in eastern Bangladesh. Identification of new epidemiological characteristics emphasizes the importance of continued NiV surveillance and case investigation.
This study investigated improvements in quality of life associated with eight weeks of montelukast and/or intranasal steroid treatment for moderate to severe allergic rhinitis.
A single-centre, prospective, randomised, double-blind, placebo-controlled study was carried out. Assessments were made using the Rhinoconjunctivitis Quality of Life Questionnaire and symptom scales.
A total of 128 patients (aged 13–51 years) were randomly assigned to one of two groups. In the montelukast group, patients were treated with montelukast tablets and fluticasone propionate nasal spray (n = 64). In the placebo group, treatment comprised a placebo and fluticasone propionate. The results showed significant improvements in symptom scores and quality of life scores for both groups after one month and two months of treatment, compared with baseline values; these improvements were significantly greater for the montelukast group compared with the placebo group. The mean number of loratadine tablets taken by each patient during the study period was only 0.73 for the montelukast group compared with 9 for the placebo group.
The combination of montelukast tablets and fluticasone propionate nasal spray improved symptom control and overall quality of life for moderate to severe allergic rhinitis patients.
Cognitive remediation (CR) preceding cognitive–behavioural therapy for psychosis (CBTp) was trialled within routine clinical services, with the hypothesis that following first-episode non-affective psychosis CR would enhance CBTp efficacy by improving neuropsychological performance.
A total of 61 patients with DSM-IV non-affective psychoses waiting for routine CBTp were randomized to computerized CR over 12 weeks, supported by a trained support worker, or time-matched social contact (SC). Primary outcome was the blind-rated Psychotic Symptoms Rating Scale (PSYRATS). Secondary outcomes included measures of CBTp progress, cognition, symptoms, insight and self-esteem: all at baseline, after CR (12 weeks) and after CBTp (42 weeks). PSYRATS and global neuropsychological efficacy were tested using mixed-effects models with a group × time interaction term. Measures of CBTp progress and some neuropsychological measures were modelled by regression.
There was no significant difference between the CR and SC groups in PSYRATS (group × time coefficient 0.3, 95% confidence interval −0.4 to 1.1, p = 0.39). However, after CR CBTp was shorter [median 7 sessions, interquartile range (IQR) 2–12 after CR; median 13, IQR 4–18 after SC; model p = 0.011] and linked to better insight (p = 0.02). Global cognition did not improve significantly more after CR (p = 0.20) but executive function did (Wisconsin Card Sort, p = 0.012).
CBTp courses preceded by CR were far shorter but achieved the same outcome as CBTp preceded by an active control, consistent with neuropsychological improvement enhancing CBTp. CR was delivered by staff with minimal training, offering the potential to reduce the costs of CBTp considerably.
The phase transformations occurring on quenching and subsequent aging of a Cu-Al-Ni β phase alloy have been studied using transmission electron microscopy, x-ray diffraction and optical microscopy. Quenching produces an ordered solid solution, β1, based on the DO3 structure of Cu3A1. X-ray and electron diffraction show satellite diffraction peaks. On aging, these satellite peaks disappear and the parent phase undergoes a martensitic transformation. It is suggested that the parent phase undergoes a process of phase separation through the mechanism of spinodal decomposition before the martensitic transformation occurs. The martensitic transformation shows isothermal kinetics for which a transformation diagram is presented. Prolonged aging results in the formation of equilibrium phases.
Introduction: Major depressive disorder (MDD) is thought to negatively impact cognitive function; however, the relationship has not been well explored.
Objective: This study examined the association between depression severity and global cognitive function and memory in subjects with severe, treatment-resistant MDD.
Methods: We enrolled 66 subjects with Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosed unipolar MDD in a multicenter trial to assess the efficacy and neurocognitive effects of electroconvulsive therapy (ECT). We measured depression severity with the 24 item Hamilton Rating Scale for Depression (HRSD24). Neuropsychologic measures included the Mini Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), and the Complex Figure Test (CFT). Correlational and regression analyses were conducted to explore associations between depression severity and cognitive function.
Results: The mean age of the subjects was 53.6 years (SD=15.8), 65% were female, and mean HRSD24 was 33.9 (SD=6.7). Mean demographic-corrected T-scores for each neurocognitive measure were in the average to borderline range, and HRSD24 values were unrelated to performance on the MMSE, RAVLT immediate and delayed recall, and CFT immediate and delayed recall.
Conclusion: In this sample of severely depressed subjects referred for ECT, depression severity was unrelated to global cognitive function or memory. Future research should examine the interactions between other depressive characteristics and neurocognitive function.