An evaluation of computational methods for aggregate data meta-analyses of diagnostic test accuracy studies.

BACKGROUND: A Generalized Linear Mixed Model (GLMM) is recommended to meta-analyze diagnostic test accuracy studies (DTAs) based on aggregate or individual participant data. Since a GLMM does not have a closed-form likelihood function or parameter solutions, computational methods are conventionally used to approximate the likelihoods and obtain parameter estimates. The most commonly used computational methods are the Iteratively Reweighted Least Squares (IRLS), the Laplace approximation (LA), and the Adaptive Gauss-Hermite quadrature (AGHQ). Despite being widely used, it has not been clear how these computational methods compare and perform in the context of an aggregate data meta-analysis (ADMA) of DTAs. METHODS: We compared and evaluated the performance of three commonly used computational methods for GLMM - the IRLS, the LA, and the AGHQ, via a comprehensive simulation study and real-life data examples, in the context of an ADMA of DTAs. By varying several parameters in our simulations, we assessed the performance of the three methods in terms of bias, root mean squared error, confidence interval (CI) width, coverage of the 95% CI, convergence rate, and computational speed. RESULTS: For most of the scenarios, especially when the meta-analytic data were not sparse (i.e., there were no or negligible studies with perfect diagnosis), the three computational methods were comparable for the estimation of sensitivity and specificity. However, the LA had the largest bias and root mean squared error for pooled sensitivity and specificity when the meta-analytic data were sparse. Moreover, the AGHQ took a longer computational time to converge relative to the other two methods, although it had the best convergence rate. CONCLUSIONS: We recommend practitioners and researchers carefully choose an appropriate computational algorithm when fitting a GLMM to an ADMA of DTAs. We do not recommend the LA for sparse meta-analytic data sets. However, either the AGHQ or the IRLS can be used regardless of the characteristics of the meta-analytic data.

Incidence of infection in carpal tunnel surgery with and without the use of local antibiotics.

Objectives: To compare the infection rate in patients who underwent carpal tunnel surgery with and without instilling local antibiotics into the surgical wound. METHODS: The retrospective cohort study was conducted at the Department of Surgery, Unit of Neurosurgery, Government Naseer Ullah Babar Memorial Hospital, Peshawar, Pakistan, and comprised data from July 2019 to July 2021 related to non-diabetic patients without any comorbidity who had undergone fresh carpal tunnel surgery. The cases had been operated by two surgeons having a different approach to preventing infection in carpal tunnel surgery cases. The surgeon in group A did not use any local antibiotics after completing the surgery, while the surgeon in group B instilled local gentamicin in the open wound for 3 minutes after completing the nerve release. All patients were put on oral antibiotics for a period of 5 days after the procedure in both the cohorts, and were assessed fortnightly for any infection and removal of stitches. Demographics of the patients, use of antibiotics and the occurrence of infection were recorded on a proforma. Data was analysed using SPSS 20. RESULTS: Of the 177 patients operated during the period, 13(7.3%) were discarded owing to missing data. Of the 164(92.7%) patients analysed, 138(84.14%) were females and 26(15.85%) were males. The overall mean age was 32.46±8.97 years. The total surgeries conducted were 176; 96(54.54%) in group A and 80(45.45%) in group B. Infections were found in 3(1.7%) patients; all in group A (p=0.160). CONCLUSIONS: Although not statistically significant, instillation of local antibiotics may play a role in preventing surgical site infections in carpal tunnel surgery cases.

Synthesis and biological evaluation of carboxamide and quinoline derivatives as P2X7R antagonists.

P2X7 receptor (P2X7R) has a key role in different pathological conditions, importantly overexpressed and activated in cancers. We explored the structure activity relationship (SAR) of three novel pyrazines, quinoline-carboxamide and oxadiazole series. Their selective inhibitory potency in Ca2+ mobilization assay using h-P2X7R-MCF-7 cells improved with phenyl ring substitutions (-OCF3, -CF3, and -CH3) in carboxamide and oxadiazole derivatives, respectively. However, highly electronegative fluoro, chloro, and iodo substitutions enhanced affinity. 1e, 2f, 2e, 1d, 2 g and 3e were most potent and selective toward h-P2X7R (IC50 values 0.457, 0.566, 0.624, 0.682, 0.813 and 0.890 µM, respectively) and were inactive at h-P2X4R, h-P2X2R, r-P2Y6R, h-P2Y2R, t-P2Y1R expressed in MCF-7 and 1321N1 astrocytoma cells. Cell viability (MTT assay at 100 µM, cell line) for 3e was 62% (HEK-293T), 70% (1321N1 astrocytoma) and 85% (MCF-7). >75% cell viability was noted for 2 g and >80% for 2e and 1d in all non-transfected cell lines. Anti-proliferative effects, compared to control (Bz-ATP), of selective antagonists (10 µM) were 3e (11%) 1d, (19%) 1e, (70%, P = 0.005) and 2f, (24%), indicating involvement of P2X7R. Apoptotic cell death by flow cytometry showed 1e to be most promising, with 35% cell death (PI positive cells), followed by 2e (25%), 2f (20%), and 1d (19%), compared to control. Fluorescence microscopic analysis of apoptotic changes in P2X7R-transfected cell lines was established. 1e and 2f at 1X and 2X IC50 increased cellular shrinkage, nuclear condensation and PI/DAPI fluorescence. In-silico antagonist modeling predicted ligand receptor interactions, and all compounds obeyed Lipinski rules. These results suggest that pyrazine, quinoline-carboxamide and oxadiazole derivatives could be moderately potent P2X7R antagonists for in vivo studies and anti-cancer drug development.

Exploring safety and efficacy of rivaroxaban after living donor liver transplantation: a retrospective study.

PURPOSE: Thromboembolic complications remain a significant concern in postoperative patients, particularly those who have undergone liver transplantation. Warfarin has been the standard oral anticoagulant. Direct oral anticoagulants (DOACs) have several advantages over warfarin, including rapid onset of action and standardized dose guidelines. We aimed to assess the safety of rivaroxaban in living donor liver transplantation (LDLT) recipients. METHODS: This study was a single-center, retrospective descriptive analysis of LDLT recipients who received rivaroxaban between December 2020 and April 2022. A total of 27 recipients received rivaroxaban postoperatively. Liver function tests, immunosuppression levels, serum creatinine, and INR were recorded before the initiation of rivaroxaban and then on post-therapy days 1, 7, 14, 28, 90, and 180. RESULTS: Among the 27 recipients receiving rivaroxaban postoperatively, portal venous thrombosis was the most prevalent indication for anticoagulation (44.4%), followed by Budd-Chiari syndrome (29.6%). Nine patients had a twofold increase in either ALT or AST values, two of whom were treated for biliary strictures and the others for rejection. Eighteen patients were given tacrolimus, and eight were on cyclosporine, with one patient switched from tacrolimus to cyclosporine due to insufficient therapeutic levels. There were no incidents of bleeding or re-thrombosis during the 180-day follow-up period. CONCLUSION: Rivaroxaban may be a safe and effective alternative in LDLT recipients with no significant adverse incidents. Further studies with larger sample sizes are needed to confirm these findings and determine this population's optimal dose and duration of rivaroxaban therapy.

A Novel Intronic Deletion in PDE6B Causes Autosomal Recessive Retinitis Pigmentosa by Interfering with RNA Splicing.

INTRODUCTION: Retinitis pigmentosa (RP) is a rare degenerative retinal disease caused by mutations in approximately seventy genes. Currently, despite the availability of large-scale DNA sequencing technologies, ∼30-40% of patients still cannot be diagnosed at the molecular level. In this study, we investigated a novel intronic deletion of PDE6B, encoding the beta subunit of phosphodiesterase 6 in association with recessive RP. METHODS: Three unrelated consanguineous families were recruited from the northwestern part of Pakistan. Whole exome sequencing was performed for the proband of each family, and the data were analyzed according to an in-house computer pipeline. Relevant DNA variants in all available members of these families were assessed through Sanger sequencing. A minigene-based splicing assay was also performed. RESULTS: The clinical phenotype for all patients was compatible with rod cone degeneration, with the onset during childhood. Whole exome sequencing revealed a homozygous 18 bp intronic deletion (NM_000283.3:c.1921-20_1921-3del) in PDE6B, which co-segregated with disease in 10 affected individuals. In vitro splicing tests showed that this deletion causes aberrant RNA splicing of the gene, leading to the in-frame deletion of 6 codons and, likely, to disease. CONCLUSION: Our findings further expand the mutational spectrum of the PDE6B gene.

Enhancing Localization Efficiency and Accuracy in Wireless Sensor Networks.

Accuracy is the vital indicator in location estimation used in many scenarios, such as warehousing, tracking, monitoring, security surveillance, etc., in a wireless sensor network (WSN). The conventional range-free DV-Hop algorithm uses hop distance to estimate sensor node positions but has limitations in terms of accuracy. To address the issues of low accuracy and high energy consumption of DV-Hop-based localization in static WSNs, this paper proposes an enhanced DV-Hop algorithm for efficient and accurate localization with reduced energy consumption. The proposed method consists of three steps: first, the single-hop distance is corrected using the RSSI value for a specific radius; second, the average hop distance between unknown nodes and anchors is modified based on the difference between actual and estimated distances; and finally, the least-squares approach is used to estimate the location of each unknown node. The proposed algorithm, named Hop-correction and energy-efficient DV-Hop (HCEDV-Hop), is executed and evaluated in MATLAB to compare its performance with benchmark schemes. The results show that HCEDV-Hop improves localization accuracy by an average of 81.36%, 77.99%, 39.72%, and 9.96% compared to basic DV-Hop, WCL, improved DV-maxHop, and improved DV-Hop, respectively. In terms of message communication, the proposed algorithm reduces energy usage by 28% compared to DV-Hop and 17% compared to WCL.

Differential Regulation of Innate Lymphoid Cells in Human and Murine Oral Squamous Cell Carcinoma.

Oral squamous cell carcinomas (OSCC) remain a major healthcare burden in Asian countries. In Pakistan alone, it is the most common cancer in males and second only to breast cancer in females. Alarmingly, treatment options for OSCC remain limited. With this context, investigations made to explore the inflammatory milieu of OSCC become highly relevant, with the hope of practicing immunotherapeutic approaches to address this highly prevalent tumor. We investigated the newly identified innate lymphoid cells (ILCs) and associated cytokines in well-defined human oral squamous cell carcinoma (OSCC) as well as in a 7,12-dimethylbenz[a]anthracene (DMBA)-induced murine model of OSCC using flow cytometry and quantitative real-time polymerase chain reaction (qPCR). We further went on to explore molecular circuitry involved in OSCC by developing a murine model of OSCC and using an α-Thy1 antibody to inhibit ILCs. Amongst the ILCs that we found in human OSCC, ILC3 (23%) was the most abundant, followed by ILC2 (17%) and ILC1 (1%). Mice were divided into four groups: DMBA (n = 33), DMBA+antibody (Ab) (n = 30), acetone (n = 5), and control (n = 5). In murine OSCC tissues, ILC1 and ILC3 were down-infiltrated, while ILC2 remained unchanged compared to controls. Interestingly, compared to the controls (DMBA group), mice treated with the α-Thy1 antibody showed fewer numbers of large tumors, and a larger percentage of these mice were tumor-free at this study's end point. We present novel data on the differential expansion/downsizing of ILCs in OSCC, which provides a pivotal basis to dive deeper into molecular circuitry and the OSCC tumor niche to devise novel diagnostic, therapeutic, and prognostic strategies to prevent/treat oral cancers.

The Role of the Shortened Proximal Phalanx in the Setting of Brachymetatarsia.

Brachymetatarsia is a condition in which a metatarsal bone does not grow out to full length. This is caused by premature physeal closure. The proximal phalanx associated with the shortened metatarsal helps achieve the natural parabola of the foot. A hypoplastic proximal phalanx is a common finding in patients with brachymetatarsia. The goal of this study was to determine the length of the proximal phalanx in the setting of brachymetatarsia, and how much the shortening is attributed to the clinically smaller toe. We performed a retrospective study to evaluate the length of the proximal phalanx in the shortened ray. After the metatarsal was brought out to the desired length of correction, the proximal phalanx was measured on radiographs. Ninety-seven feet with congenital brachymetatarsia were reviewed in a cohort of 66 patients who underwent surgical correction between January 2005 and February 2020 at a single institution. The group was comprised of 61 females and 5 males, with a mean age of 27.5 years. The average length of the proximal phalanx associated with the affected metatarsal was noted to be 18.9 ± 3.83 mm for males and 15.6 ± 4.02 mm for females. Our results indicate the shortened proximal phalanx is 5 mm shorter when compared to normal population and is a contributing factor to the shortened clinical appearance of the digit in brachymetatarsia. Treating surgeons should be aware of this to better educate patients on the influence of the digit on the overall shortening seen in cases of brachymetatarsia.

The Prevalence of Bunions in the Setting of Brachymetatarsia.

Brachymetatarsia is caused by premature closure of the physis and is characterized by a short metatarsal. Additional foot conditions may exist in patients presenting with brachymetatarsia, such as hallux valgus (HV). A retrospective study was performed to evaluate the prevalence of HV and brachymetatarsia in the ipsilateral foot. Ninety-seven feet with congenital brachymetatarsia were reviewed in a multi-study cohort of 66 patients who underwent surgical correction between January 2005 and August 2020 at a single institution. The group was comprised of 61 females and 5 males, with a mean age of 27 years. HV deformities were verified with standardized anteroposterior radiographs. HV was present in 29 of 97 feet for a prevalence of 30% in the feet with brachymetatarsia. Our results demonstrate a 30% prevalence of HV associated with brachymetatarsia. This information is helpful for foot and ankle surgeons managing brachymetatarsia to determine appropriate conservative or surgical management of this condition.

Beliefs about causes of psychotic disorders and subsequent help-seeking behaviour in caregivers presenting at the Department of Psychiatry, Civil Hospital, Karachi.

OBJECTIVE: To assess the beliefs about causes of psychotic disorders and subsequent help-seeking behaviour in caregivers. Methods: The descriptive cross-sectional study was conducted at the Department of Psychiatry, Civil Hospital, Karachi, from September 2020 to February 2021, and comprised caregivers of patients with psychotic disorders. Data was collected using a questionnaire that was filled up by caregivers mentioning their beliefs about the cause of the disorder and subsequent help-seeking behaviour. Data was analysed using SPSS 22. RESULTS: Of the 162 participants, 69(42.6%) were male and 93(52.4%) were female. The overall mean age was 39.9+12.9 years. The majority 157(96.9%) subjects were Muslims. In terms of beliefs, anxious personality 62(38.3%), evil eye 62(38.3%) and God's will 56(34.6%) were the major choices picked. With respect to help-seeking behaviour, the choices most picked were taking the patient to a psychiatrist 129(79.6%), praying 108(66.6%) and taking the patient to a family physician 103(63.6%). CONCLUSIONS: There was found to be sufficient awareness among the caregivers, but help-seeking behaviour needed to improve considerably.

Synthesis, X-ray diffraction analysis, quantum chemical studies and α-amylase inhibition of probenecid derived S-alkylphthalimide-oxadiazole-benzenesulfonamide hybrids.

Sulphonamide and 1,3,4-oxadiazole moieties are present as integral structural parts of many drugs and pharmaceuticals. Taking into account the significance of these moieties, we herein present the synthesis, single-crystal X-ray analysis, DFT studies, and α-amylase inhibition of probenecid derived two S-alkylphthalimide-oxadiazole-benzenesulfonamide hybrids. The synthesis has been accomplished in high yields. The final structures of both hybrids have been established completely with the help of different spectro-analytical techniques, including NMR, FTIR, HR-MS, and single-crystal X-ray diffraction analyses. In an effort to confirm the experimental findings, versatile quantum mechanical calculations and Hirshfeld Surface analysis have been performed. α-Amylase inhibition assay has been executed to investigate the enzyme inhibitory potential of both hybrids. The low IC50 value (76.92 ± 0.19 µg/mL) of hybrid 2 shows the good α-amylase inhibition potential of the respective compound. Ultimately, the binding affinities and features of the two hybrids are elucidated utilising a molecular docking technique against the α-amylase enzyme.

Usefulness of Vaccine Adverse Event Reporting System for Machine-Learning Based Vaccine Research: A Case Study for COVID-19 Vaccines.

Usefulness of Vaccine-Adverse Event-Reporting System (VAERS) data and protocols required for statistical analyses were pinpointed with a set of recommendations for the application of machine learning modeling or exploratory analyses on VAERS data with a case study of COVID-19 vaccines (Pfizer-BioNTech, Moderna, Janssen). A total of 262,454 duplicate reports (29%) from 905,976 reports were identified, which were merged into a total of 643,522 distinct reports. A customized online survey was also conducted providing 211 reports. A total of 20 highest reported adverse events were first identified. Differences in results after applying various machine learning algorithms (association rule mining, self-organizing maps, hierarchical clustering, bipartite graphs) on VAERS data were noticed. Moderna reports showed injection-site-related AEs of higher frequencies by 15.2%, consistent with the online survey (12% higher reporting rate for pain in the muscle for Moderna compared to Pfizer-BioNTech). AEs {headache, pyrexia, fatigue, chills, pain, dizziness} constituted >50% of the total reports. Chest pain in male children reports was 295% higher than in female children reports. Penicillin and sulfa were of the highest frequencies (22%, and 19%, respectively). Analysis of uncleaned VAERS data demonstrated major differences from the above (7% variations). Spelling/grammatical mistakes in allergies were discovered (e.g., ~14% reports with incorrect spellings for penicillin).

The Development and Evaluation of a Patient Educational Resource for Cancer-Related Cognitive Dysfunction.

Cancer patients and survivors frequently experience cognitive deficits, including problems with attention and memory. These symptoms, referred to as cancer-related cognitive dysfunction (CRCD), are associated with distress. Learning about CRCD and self-management strategies may improve functioning and quality of life in cancer survivors. This study describes the development and evaluation of a CRCD resource for cancer patients. An educational booklet was developed in accordance with multiple evidence-based guidelines for cancer patient education. Cancer patients on chemotherapy (N = 113; 34% men; median age 55, range 19-85) reviewed the booklet and self-reported CRCD knowledge before and after reading the booklet. They also gave ratings on general impressions of the booklet. Seventy-five percent of participants reported that the resource increased their self-reported CRCD knowledge. A Wilcoxon signed-rank test demonstrated that exposure to the booklet elicited a statistically significant change in self-reported knowledge (Z = - 7.13, p < 0.001). A repeated-measures ANCOVA determined that the means of self-reported CRCD knowledge were significantly different between pre- and post-exposure (F(1, 92) = 7.96, p = 0.006, η2 = 0.08). Exploratory analyses revealed that self-reported CRCD knowledge increased across all educational attainment levels from pre- to post-exposure. Ninety-one percent of participants reported that all patients undergoing cancer treatment would find this booklet helpful. Cancer patients at risk for cognitive challenges gained self-reported CRCD knowledge from the booklet, and they think this knowledge would be helpful to others. A resource that makes CRCD understandable and manageable can bridge the gap in self-rated knowledge across education levels.

Knowledge and perception regarding prostate cancer among men in Karachi, Pakistan.

OBJECTIVE: To assess the perception and attitude towards prostate cancer and its screening practices in Pakistan. METHODS: The cross-sectional study was conducted at Ruth Pfau Civil Hospital, Karachi June to October 2019, and comprised male subjects aged >40 years with no prior diagnosis of prostate cancer who were enrolled from the community. Data was collected using a structured questionnaire which was available in English and Urdu languages. Data was analysed using SPSS 23. RESULTS: Of the 383 subjects, 144(37.6%) were aged 40-49 years, 302(78.9%) were married, 120(31.3%) had received education up to the secondary level, and 204(53.3%) earned. CONCLUSIONS: The level of knowledge regarding prostate cancer and its screening practices was poor, and the attitude towards its screening was negative.

A survey of violence and vulgarity in children television programmes: A content analysis, and assessment of perceptions of parents and children (ViCTiM study).

OBJECTIVE: To quantify the depiction of violence and vulgarity in television programmes for children, and to assess the perception and practices of parents and children about television programmes meant for children. METHODS: We conducted this mixed-methods cross-sectional study in Karachi, Pakistan in the months of August-September 2018, after approval from the ethics review board of Dow University of Health Sciences, Karachi. First, a content analysis of over 102 hours of various television programmes meant for children was performed in the light of the guidelines set out by the World Health Organisation, the United States Federal Communication Commission and the Pakistan Electronic Media Regulatory Authority. Seven trained researchers sampled the children prime time throughout a week, including the weekends, using a structured tally sheet. Subsequently, interviews were conducted with dyad of parent-children from the employees' list of a public-sector university. A questionnaire was also administered to assess the practices and perceptions of the parents-children dyad about the programmes. Data was analysed using SPSS 24. RESULTS: Of the 173 subjects, 84(48.6%) were parents and 89(51.4%) were children. The mean age of the children was 9.8±3.7 years. Content analysis comprised 6130 minutes, of which 5442(88.8%) had depictions of violence and vulgarity. Depiction of violence and vulgarity was prevalent on television channels that were watched the most, but there was no significant difference in this regard (p=0.238). Of the parents, 68(81%) expressed concern over the effect of screen time and content on the mental health of their children. CONCLUSIONS: Television programmes meant for children were found to be inappropriate with seriously high proportion of violence and vulgarity in their contents.

HBV S antigen evolution in the backdrop of HDV infection affects epitope processing and presentation.

INTRODUCTION: HBV can evolve under selection pressure exerted by drugs and/or host immunity, resulting in accumulation of escape mutations that can affect the drug or the immune activity. Hepatitis delta virus (HDV) coinfection is also known to exert selection pressure on HBV, which leads to selective amplification of certain mutations, especially in genes that are required for HDV pathogenesis, such as HBsAg. However, little is known about the function of these mutations on HBV or HDV life cycle. The purpose of this study is to determine mutations selectively amplified in the backdrop of HDV, and how these mutations affect processing of CD4- and CD8-T cell epitopes. METHODS: HBsAg was successfully amplified from 49/50 HBV mono- and 36/50 coinfected samples. The sequences were used to identify mutations specific to each study group, followed by an in silico analysis to determine the effect of these mutations on (1) proteasomal degradation, (2) MHC-I and MHC-II biding, and (3) processing of T-cell epitopes. RESULTS: HBV-HDV coinfected sequences exhibited certain unique mutations in HBsAg genes. Some of these mutations affected the generation of proteasomal sites, binding of HBsAg epitopes to MHC-I and -II ligands, and subsequent generation of T- cell epitopes. CONCLUSION: These observations suggest that HBV selectively amplifies certain mutations in the backdrop of HDV coinfection. Selective amplification of these mutations at certain strategic locations might not only enable HBV to counteract the inhibitory effects of HDV on HBV replication but also facilitate its survival by escaping the immune response.

Bi-Directional Mutual Energy Trade between Smart Grid and Energy Districts Using Renewable Energy Credits.

A central authority, in a conventional centralized energy trading market, superintends energy and financial transactions. The central authority manages and controls transparent energy trading between producer and consumer, imposes a penalty in case of contract violation, and disburses numerous rewards. However, the management and control through the third party pose a significant threat to the security and privacy of consumers'/producers' (participants) profiles. The energy transactions between participants involving central authority utilize users' time, money, and impose a computational burden over the central controlling authority. The Blockchain-based decentralized energy transaction concept, bypassing the central authority, is proposed in Smart Grid (SG) by researchers. Blockchain technology braces the concept of Peer-to-Peer (P2P) energy transactions. This work encompasses the SolarCoin-based digital currency blockchain model for SG incorporating RE. Energy transactions from Prosumer (P) to Prosumer, Energy District to Energy District, and Energy District to SG are thoroughly investigated and analyzed in this work. A robust demand-side optimized model is proposed using Genetic Algorithm (GA) and Particle Swarm Optimization (PSO) to maximize Prosumer Energy Surplus (PES), Grid revenue (GR), percentage energy transactions accomplished, and decreased Prosumer Energy Cost (PEC). Real-time averaged energy data of Australia are employed, and a piece-wise energy price mechanism is implemented in this work. The graphical analysis and tabular statistics manifest the efficacy of the proposed model.

Need for Standardization of Measurement of Time to Reorientation as a Predictor of Cognitive Adverse Effects of Electroconvulsive Therapy.

ABSTRACT: Testing for time to reorientation (TRO) after electroconvulsive therapy (ECT) has been one of the most predictive measures for cognitive adverse effects of ECT. However, measuring TRO varies between clinical trials, and there is no standardized approach on its measurement between studies. The objective of this report is to systematically review the literature on the different ways of measuring TRO. This would be a first step to establish a consensus on a standard method for TRO. We performed a systematic literature review from 1968 to October 2019 for clinical trials with a sample size of more than 50 and published in English that describe measures of TRO. We searched both PubMed and Web of Science databases. The literature search generated 12 clinical trials, which met the inclusion criteria. Studies measured TRO using 3-, 5-, or 10-item questionnaires. Most studies measured full orientation as answering 4/5 questions. Other studies smaller than 50 required 14/14 items to be answered correctly. There was wide variation between studies on how often and when orientation questions were initiated. These factors have obvious implications to the results and interpretation of the ECT literature.There was no clear consensus on measuring TRO in a uniform fashion. Research and clinical care would benefit from a standardized approach to measuring TRO. Measuring TRO using a 4/5 method seems the most common and quickest way, whereas using a 14/14 method seems to be the most rigorous and sensitive to change in trials.

Sub-genomic analysis of Chikungunya virus E2 mutations in Pakistani isolates potentially modulating B-cell & T-Cell immune response.

BACKGROUND & OBJECTIVES: The Chikungunya virus (CHIKV) transmitted to the humans through Aedes species of the mosquitoes. In December 2016, a severe outbreak reported from Pakistan. However, there is no vaccine or anti-viral treatment currently available so host immune response against CHIKV gained significant interest. Therefore, this study was conducted to identify the mutations in CHIKV E2 region of currently circulating Pakistani strains & determine their potential immunogenicity in Pakistani population. METHODS: It was a cross sectional study in which a total of 60 CHIKV PCR positive samples were collected from Molecular Department of Pathology, Dow University of Health Sciences (DUHS), Karachi during November 2017 to February 2018. CHIKV E2 gene was amplified by PCR & sequenced. Sequences were analyzed by using bioinformatic tools followed by epitope prediction in E2 sequences by In-silico immunoinformatic approach. RESULTS: Several single nucleotide variations (SNVs) were identified in Pakistani isolates with six novel mutations in E2 sequences. Immunoinformatic analyses showed more proteasomal sites, CTL & B-Cell epitopes in Pakistani strains with respect to S27 prototype with 69.4% population coverage against these epitopes in Pakistan. The study also identified key mutations responsible for generation of unique epitopes and HLA restriction in Pakistani isolates. The strain specific mutations revealed the current outbreak was caused by ESCA.IOL lineage of CHIKV. CONCLUSION: The evolution of E2 protein in Pakistani strains has increased its immunogenicity in comparison to ancestral s27 strain. The identification of most immunogenic and conserved epitopes with high population coverage has high potential to be used in vaccine development against these local strains.

Cost-effectiveness of Direct Antiviral Agents for Hepatitis C Virus Infection and a Combined Intervention of Syringe Access and Medication-assisted Therapy for Opioid Use Disorders in an Injection Drug Use Population.

BACKGROUND: There are too many plausible permutations and scale-up scenarios of combination hepatitis C virus (HCV) interventions for exhaustive testing in experimental trials. Therefore, we used a computer simulation to project the health and economic impacts of alternative combination intervention scenarios for people who inject drugs (PWID), focusing on direct antiviral agents (DAA) and medication-assisted treatment combined with syringe access programs (MAT+). METHODS: We performed an allocative efficiency study, using a mathematical model to simulate the progression of HCV in PWID and its related consequences. We combined 2 previously validated simulations to estimate the cost-effectiveness of intervention strategies that included a range of coverage levels. Analyses were performed from a health-sector and societal perspective, with a 15-year time horizon and a discount rate of 3%. RESULTS: From a health-sector perspective (excluding criminal justice system-related costs), 4 potential strategies fell on the cost-efficiency frontier. At 20% coverage, DAAs had an incremental cost-effectiveness ratio (ICER) of $27 251/quality-adjusted life-year (QALY). Combinations of DAA at 20% with MAT+ at 20%, 40%, and 80% coverage had ICERs of $165 985/QALY, $325 860/QALY, and $399 189/QALY, respectively. When analyzed from a societal perspective (including criminal justice system-related costs), DAA at 20% with MAT+ at 80% was the most effective intervention and was cost saving. While DAA at 20% with MAT+ at 80% was more expensive (eg, less cost saving) than MAT+ at 80% alone without DAA, it offered a favorable value compared to MAT+ at 80% alone ($23 932/QALY). CONCLUSIONS: When considering health-sector costs alone, DAA alone was the most cost-effective intervention. However, with criminal justice system-related costs, DAA and MAT+ implemented together became the most cost-effective intervention.