Carbon-Supported Nanocomposite Synthesis, Characterization, and Application as an Efficient Adsorbent for Ciprofloxacin and Amoxicillin.

The existence of antibiotics in the environment has recently raised serious concerns about their possible hazards to human health and the water ecosystem. In the current study, an activated carbon-supported nanocomposite, AC-CoFe2O3, was synthesized by a coprecipitation method, characterized, and then applied to adsorb different drugs from water. The synthesized composites were characterized by using energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller plots, and scanning electron microscopy. The adsorption of both Ciprofloxacin (Cipro) and Amoxicillin (Amoxi) antibiotics on the composite followed the pseudo-second-order kinetic model (R2 = 0.9981 and 0.9974 mg g-1 min-1, respectively). Langmuir isotherm was the best-fit model showing 312.17 and 217.76 mg g-1 adsorption capacities for Ciprofloxacin and Amoxicillin, respectively, at 333 K. The negative Gibbs free energy (ΔG°) specified the spontaneity of the method. The positive change in the enthalpy (ΔH) indicated that the adsorption process was assisted by higher temperatures. The different optimized parameters were pH, contact time, adsorbent weight, concentration, and temperature. The maximum adsorption of Cipro was found to be 98.41% at pH 12, while for Amoxi, it was 89.09% at pH 2 at 333 K. The drugs were then successfully determined from natural water samples at optimized conditions using these nanocomposites.

Prevalence and antimicrobial susceptibility of Acinetobacter spp. in a tertiary care hospital in Peshawar: a cross-sectional study.

Acinetobacter spp. have been a primary cause of nosocomial infections worldwide, causing significant morbidity and mortality, especially in Pakistan. The purpose of this study was to investigate the trend of antimicrobial resistance over a 5-year period in a tertiary care hospital in Pakistan. Methods: A retrospective cross-sectional study regarding the occurrence and antimicrobial resistance of Acinetobacter spp. recovered from clinical specimens that were referred to the Pathology Laboratory of Northwest General Hospital, Peshawar. The data from 2014 to 2019 was recorded and analyzed by the laboratory. Sociodemographic characteristics and laboratory record data was analyzed using SPSS, version 25. A chi-square test was applied to see the significance. Results: Of 59 483 clinical samples, Acinetobacter baumannii strains were detected in 114 of them. The majority of the clinical samples were from blood (89.5%) followed by sputum (7.9%), wound swab (1.8%), and bone marrow (0.9%). A. baumannii has been found in 52 men (67.53%) and 28 women (75.67%), with an overall risk of 0.669 times. In 76 men (98.70%), sensitivity for ertapenem (99.1), colistin (96.49), and tigecycline (78.9%) were also observed which indicated the potential viability of these drugs to treat multidrug-resistant (MDR) Acinetobacter infections. The male-to-female risk ratio was 0.98 for colistin and 0.71 for amikacin. Conclusion: Increased frequency of MDR supports the need for continuous surveillance to determine the prevalence and evolution of MDR Acinetobacter spp. in Pakistan. Colistin, tigecyclines, and ertapenem remain the possible line of drugs to treat MDR Acinetobacter.

Synthesis and Characterization of MIPs for Selective Removal of Textile Dye Acid Black-234 from Wastewater Sample.

Herein, a molecularly imprinted polymer (MIP) was prepared using bulk polymerization and applied to wastewater to aid the adsorption of targeted template molecules using ethylene glycol dimethacrylate (EGDMA), methacrylic acid (MAA), acid black-234 (AB-234), 2,2'-azobisisobutyronitrile (AIBN), and methanol as a cross linker, functional monomer, template, initiator, and porogenic solvent, respectively. For a non-molecularly imprinted polymer (NIP), the same procedure was followed but without adding a template. Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), and a surface area analyzer were used to determine the surface functional groups, morphology and specific surface area of the MIP and NIP. At pH 5, the AB-234 adsorption capability of the MIP was higher (94%) than the NIP (31%). The adsorption isotherm data of the MIP correlated very well with the Langmuir adsorption model with Qm 82, 83 and 100 mg/g at 283 K, 298 K, and 313 K, respectively. The adsorption process followed pseudo-second-order kinetics. The imprinted factor (IF) and Kd value of the MIP were 5.13 and 0.53, respectively. Thermodynamic studies show that AB-234 dye adsorption on the MIP and NIP was spontaneous and endothermic. The MIP proved to be the best selective adsorbent for AB-234, even in the presence of dyes with similar and different structures than the NIP.

Testicular choriocarcinoma with small bowel metastasis and active gastrointestinal bleeding.

Testicular choriocarcinomas make up less than 1% of all germ-cell tumors and are highly malignant, attributable to hematogenous spread. While the most common sites of metastasis are the lungs and liver, metastatic spread to the gastrointestinal tract is rare wherein patients may present with GI distress or even an upper GI bleed. In this report, we present a case of known testicular choriocarcinoma in a 40-year-old male who presented to the emergency room with severe anemia and a suspected upper GI bleed.

Color doppler ultrasound for diagnosis of testicular carcinoma: A comparison with gold standard histopathology.

Introduction: Testicular carcinoma is the most common cancer among males aged 15-34 years. The known risk factors for testicular cancer include undescended testis (cryptorchidism), testicular dysfunction, perinatal factors and prior history of cancer in one testis. We aimed to determine the diagnostic accuracy of color doppler ultrasound in diagnosis of testicular carcinoma using histopathology as GOLD STANDARD. Method: ology: A cross sectional study was conducted from July 2015 to Feb 2016 at the Department of Radiology, Jinnah Post Graduate Medical Center, Karachi. 311 subjects were selected through inpatient/outpatient or emergency department. Patients were evaluated for testicular carcinoma by color doppler ultrasound on Toshiba nemio. Finding of color doppler ultrasound was compared with histopathology. True positive, true negative, false positive, false negative as per operational definition was determined. Results: Mean age of the patients of the study was 41.76 ± 8.11 (30-50) and mean and SD of Duration of symptoms was 5.5 ± 3.5 (4-15) months. Of 175(56.27%) subjects diagnosed as testicular carcinoma on CDUS, only 160(48.55%) were subsequently found to have testicular carcinoma. sensitivity of CDUS in diagnosing scrotal diseases was 88.8% while specificity was 78.1%. Conclusion: We conclude that CDUS is an excellent, safe, and reliable method for evaluating patients with testicular carcinoma. It helps to improve patient's management, especially by preventing unnecessary surgical exploration. It is also convenient and easy to perform. But it has its own limitations, and requires adequate expertise and experience. Its results are also equipment dependent.

Inpatient assessment of the neurological outcome of acute stroke patients based on the National Institute of Health Stroke Scale (NIHSS).

Objective: Identify the association between stroke severity and the neurological outcome of an acute stroke using the National Institutes of Health stroke scale (NIHSS). Study design: A descriptive cross-sectional study.Place and duration of study: Northwest hospital Hayatabad Peshawar. Methodology: A cross-sectional descriptive study was done in the general plus stroke unit of the northwest hospital in Peshawar, KPK during Jan 2022 to July 2022.400 admitted patients diagnosed with acute stroke in the past three months were included for NIHSS assessment and were classified as mild, moderate, or severe stroke. After entering all of the data from the collection into SPSS version 16, the information was transferred to an Excel spreadsheet. To further assess the results, the researcher and statistician evaluated all of the cases, radiological findings, and laboratory test data. Results: In this cross-sectional descriptive study, 400 individuals ranging from 30 to 90 years of age were divided into two groups: males and females. The survey was conducted by 49% of men and 51% of women. The stroke severity was assessed to be mild in 22% of cases, moderate in 49%, and severe in 29% of patients. As evaluated by the NIHSS, Patients with acute ischemic stroke were divided into four groups depending on their neurological outcomes: those who improved were 160 (40%), those who remained stable were 124 (31%), and those who deteriorated were 52 (13%), and those who died were 64 (16%). Patients with greater triglyceride levels were 88, while those with lower levels were 312. Acute stroke was also detected in 34% of patients with a covid history, 28% of patients who were covid positive, and 38% of patients who were covid free in this investigation. Conclusion: According to our findings, the NIHSS is a reliable scale for evaluating patients' neurological outcomes and determining the association between acute stroke severity and cognitive functioning (NIHSS).

Estimating Radiation Shielding of Fired Clay Bricks Using ANN and GEP Approaches.

This study aimed to determine how radiation attenuation would change when the thickness, density, and compressive strength of clay bricks, modified with partial replacement of clay by fly ash, iron slag, and wood ash. To conduct this investigation, four distinct types of bricks-normal, fly ash-, iron slag-, and wood ash-incorporated bricks were prepared by replacing clay content with their variable percentages. Additionally, models for predicting the radiation-shielding ability of bricks were created using gene expression programming (GEP) and artificial neural networks (ANN). The addition of iron slag improved the density and compressive strength of bricks, thus increasing shielding capability against gamma radiation. In contrast, fly ash and wood ash decreased the density and compressive strength of burnt clay bricks, leading to low radiation shielding capability. Concerning the performance of the Artificial Intelligence models, the root mean square error (RMSE) was determined as 0.1166 and 0.1876 nC for the training and validation data of ANN, respectively. The training set values for the GEP model manifested an RMSE equal to 0.2949 nC, whereas the validation data produced RMSE = 0.3507 nC. According to the statistical analysis, the generated models showed strong concordance between experimental and projected findings. The ANN model, in contrast, outperformed the GEP model in terms of accuracy, producing the lowest values of RMSE. Moreover, the variables contributing towards shielding characteristics of bricks were studied using parametric and sensitivity analyses, which showed that the thickness and density of bricks are the most influential parameters. In addition, the mathematical equation generated from the GEP model denotes its significance such that it can be used to estimate the radiation shielding of burnt clay bricks in the future with ease.

Oculomotor nerve palsy in neurofibromatosis type 2.

Neurofibromatosis (NF) type 2 is a rare neurological, autosomal dominant and genetic disorder. It is caused by a mutation in the tumor suppressor gene, called NF2 gene. The disorder results in several benign tumors of the nervous system. These typically include vestibular schwannomas, meningiomas, and ependymomas. Multiple cranial nerve abnormalities affect the brain, spinal cord, nerves, and skin and cause significant morbidity in patients. We describe a 20-year-old patient, with a family history of brain tumors, with symptoms of left sided third nerve palsy. Magnetic Resonance Imaging (MRI) of the brain and orbits revealed a small sized cavernous sinus meningioma and bilateral vestibular schwannomas. As per the differential diagnosis and optimal resolution brain imaging, NF2 was diagnosed. The patient was referred for specific treatment to the neuro-oncology unit. The case is distinct as the patient presented with a parasellar meningioma leading to third nerve palsy besides bilateral vestibular schwannomas. Manchester criteria and high contrast MR imaging proved more beneficial in our patient for the diagnosis of a wider clinical spectrum of NF2.

Computational AI Models for Investigating the Radiation Shielding Potential of High-Density Concrete.

Concrete is an economical and efficient material for attenuating radiation. The potential of concrete in attenuating radiation is attributed to its density, which in turn depends on the mix design of concrete. This paper presents the findings of a study conducted to evaluate the radiation attenuation with varying water-cement ratio (w/c), thickness, density, and compressive strength of concrete. Three different types of concrete, i.e., normal concrete, barite, and magnetite containing concrete, were prepared to investigate this study. The radiation attenuation was calculated by studying the dose absorbed by the concrete and the linear attenuation coefficient. Additionally, artificial neural network (ANN) and gene expression programming (GEP) models were developed for predicting the radiation shielding capacity of concrete. A correlation coefficient (R), mean absolute error (MAE), and root mean square error (RMSE) were calculated as 0.999, 1.474 mGy, 2.154 mGy and 0.994, 5.07 mGy, 5.772 mGy for the training and validation sets of the ANN model, respectively. Similarly, for the GEP model, these values were recorded as 0.981, 13.17 mGy, and 20.20 mGy for the training set, whereas the validation data yielded R = 0.985, MAE = 12.2 mGy, and RMSE = 14.96 mGy. The statistical evaluation reflects that the developed models manifested close agreement between experimental and predicted results. In comparison, the ANN model surpassed the accuracy of the GEP models, yielding the highest R and the lowest MAE and RMSE. The parametric and sensitivity analysis revealed the thickness and density of concrete as the most influential parameters in contributing towards radiation shielding. The mathematical equation derived from the GEP models signifies its importance such that the equation can be easily used for future prediction of radiation shielding of high-density concrete.

Enhancement of Confinement in Scaled RC Columns using Steel Fibers Extracted from Scrap Tyres.

Steel fibers are widely extracted from scrap tyres, causing environmental concerns. This paper presents the use of steel fibers in variable proportions extracted from scrap tyres. The enhancement of the confinement was envisaged through the addition of steel fibers obtained from scrap tyres. The study included an experimental program for the development of constitutive material models for ordinary Portland cement (OPC) concrete and concrete with added steel fibers. A mix design was carried out for OPC, targeting a compressive strength of 3000 psi. Steel fibers were added to OPC in ratios of 1.0% to 3.0%, with an increment of 0.5%. Concrete columns, with cross-sectional dimensions of 6 × 6 inches and a length of 30 inches, were cast with both OPC and fiber-reinforced concrete. The column confinement was evaluated with a different spacing of ties (3- and 4-inch center-to-center). Compression tests on the concrete columns indicate that the addition of steel fibers to a concrete matrix results in an appreciable increase in strength and ductility. Overall, increasing the percentage of steel fibers increased the compression strength and the ductility of concrete. The maximum strain in the concrete containing 2.5% steel fibers increased by 285% as compared to the concrete containing 1% of steel fibers. An optimum percentage of 2.5% steel fibers added to the concrete resulted in a 39% increase in compressive strength, accompanied by a significant improvement in ductility. The optimum content of steel fibers, when used in confined columns, showed that confined compression strength increased with the addition of steel fibers. However, it is recommended that additional columns on the basis of the optimum steel fiber content shall be tested to evaluate their effectiveness in reducing the stirrup spacing.

Identification of the economics, composition, and supplementation of maggot meal in broiler production.

The primary goal of this study was to conduct a preliminary assessment of maggot meal protein supplements in broiler production. Maggot meal comprises 55 percent crude protein (CP), 27.65% ether extract, 8.33% Ash, 3.37 crude fiber (CF), 2.14 NFE, 94.7 percent Dry Matter, 5702 kcal/kg gross energy, and 3955 kcal/kg metabolizing energy, according to proximate analysis. Maggot meal supplementation affected broiler meat feed intake, body weight gain, FCR, dressing %, mortality, antibody titer against ND, and organoleptic features. The cost-effectiveness of maggot supplementation was also evaluated. Birds were put into four experimental groups after a week of adaptation:Control group (M0), the first experimental group (M1), the second experimental group (M2), and the third experimental group (M3), which received supplements of 0, 2, 3, and 4 g/kg, respectively. A plane ratio was given to the control group as well. The overall feed intake findings were inversely proportional to the supplementation rate. Thus, the highly supplemented group (M3) showed the lowest feed intake than the control group (M0). Bodyweight gain was directly proportional to the supplementation rate, as evident by a considerable increase in the highly supplemented group (M3) compared to the control group.

Prognostic accuracy of time to sputum culture conversion in predicting cure in extensively drug-resistant tuberculosis patients: a multicentre retrospective observational study.

BACKGROUND: There was a lack of information about prognostic accuracy of time to sputum culture conversion (SCC) in forecasting cure among extensively drug-resistant tuberculosis (XDR-TB) patients. Therefore, this study evaluated the prognostic accuracy of SCC at various time points in forecasting cure among XDR-TB patients. METHODS: This retrospective observational study included 355 eligible pulmonary XDR-TB patients treated at 27 centers in Pakistan between 01-05-2010 and 30-06-2017. The baseline and follow-up information of patients from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. Time to SCC was analyzed by Kaplan-Meier method, and differences between groups were compared through log-rank test. Predictors of time to SCC and cure were respectively evaluated by multivariate Cox proportional hazards and binary logistic regression analyses. A p-value < 0.05 was considered statistically significant. RESULTS: A total of 226 (63.6%) and 146 (41.1%) patients respectively achieved SCC and cure. Median time to SCC was significantly shorter in patients who achieved cure, 3 months (95% confidence interval [CI]: 2.47-3.53), than those who did not (median: 10 months, 95% CI: 5.24-14.76) (p-value < 0.001, Log-rank test). Patient's age > 40 years (hazards ratio [HR] = 0.632, p-value = 0.004), baseline sputum grading of scanty, + 1 (HR = 0.511, p-value = 0.002), + 2, + 3 (HR = 0.523, p-value = 0.001) and use of high dose isoniazid (HR = 0.463, p-value = 0.004) were significantly associated with early SCC. Only SCC at 6 month of treatment had statistically significant association with cure (odds ratio = 15.603, p-value < 0.001). In predicting cure, the sensitivities of SCC at 2, 4 and 6 months were respectively 41.8% (95%CI: 33.7-50.2), 69.9% (95%CI: 61.7-77.2) and 84.9% (95%CI: 78.1-90.3), specificities were respectively, 82.8% (95%CI: 76.9-87.6), 74.6% (95%CI: 68.2-80.4) and 69.4% (95%CI: 62.6-75.5) and prognostic accuracies were respectively 65.9% (95%CI: 60.7-70.8), 72.7% (95%CI: 67.7-77.2) and 75.8% (95%CI: 71.0-80.1). CONCLUSION: In forecasting cure, SCC at month 6 of treatment performed better than SCC at 2 and 4 months. However, it would be too long for clinicians to wait for 6 months to decide about the regimen efficacy. Therefore, with somewhat comparable prognostic accuracy to that SCC at 6 month, using SCC at 4 month of treatment as a prognostic marker in predicting cure among XDR-TB patients can decrease the clinicians waiting time to decide about the regimen efficacy.

Risk Assessment and Prophylaxis of Venous Thromboembolism in Patients of Medical Ward of Northwest General Hospital and Research Center, Peshawar, Pakistan: A Quality Improvement Project.

Background Venous thromboembolism (VTE) is a condition that occurs when a blood clot forms in veins. Hospitalization increases the risk of VTE so timely risk assessment and adequate prophylaxis for VTE should be done to prevent this potentially fatal complication. Local problem Data from developing countries regarding VTE prophylaxis is scarce. VTE is a neglected area of research in Pakistan. So this closed-loop clinical audit was conducted to evaluate the VTE risk assessment and prophylaxis practices and to analyze the importance of educational intervention in improving the standard of care. Patients and methods We adopted the National Institute for Health and Care Excellence (NICE) guidelines for VTE prophylaxis as an audit standard. We collected data on a specially designed proforma by prospectively reviewing the hospital notes of patients in the Medical Ward of Northwest General Hospital and Research Center, Peshawar, Pakistan. Phase A included 60 patients and after educational intervention, Phase B was conducted with 90 patients. Intervention The results of Phase A were presented in the Clinicopathological Conference (CPC) meetings of the hospital. Healthcare workers were educated regarding the risks of VTE and the importance of timely prophylaxis. Posters were also displayed in the ward for highlighting the importance of VTE prophylaxis. Results In Phase A, only 5% of patients were risk assessed for VTE and of those eligible for prophylaxis only 22.2% received the prescription. Phase B showed a significant adherence to standard practices. In Phase B, 100% of patients were risk assessed for VTE and 75% received the prophylaxis. Conclusion There was poor compliance with standard VTE risk assessment and prophylaxis prescribing practices. However, a simple and effective educational intervention markedly improved patient care in terms of VTE strengthening the impact of clinical audits in the improvement of care.

High rate of successful treatment outcomes among childhood rifampicin/multidrug-resistant tuberculosis in Pakistan: a multicentre retrospective observational analysis.

BACKGROUND: There was a complete lack of information about the treatment outcomes of rifampicin/multidrug resistant (RR/MDR) childhood TB patients (age ≤ 14 years) from Pakistan, an MDR-TB 5th high burden country. Therefore, this study evaluated the socio-demographic characteristics, drug resistance pattern, treatment outcomes and factors associated with unsuccessful outcomes among childhood RR/MDR-TB patients in Pakistan. METHODS: This was a multicentre retrospective record review of all microbiologically confirmed childhood RR/MDR-TB patients (age ≤ 14 years) enrolled for treatment at seven units of programmatic management of drug-resistant TB (PMDT) in Pakistan. The baseline and follow-up information of enrolled participants from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. World Health Organization (WHO) defined criterion was used for deciding treatment outcomes. The outcomes of "cured" and "treatment completed" were collectively grouped as successful, whereas "death", "treatment failure" and "lost to follow-up" were grouped together as unsuccessful outcomes. Multivariable binary logistic regression analysis was used to find factors associated with unsuccessful outcomes. A p-value < 0.05 reflected statistically significant findings. RESULTS: A total of 213 children RR/MDR-TB (84 RR and 129 MDR-TB) were included in the study. Majority of them were females (74%), belonged to the age group 10-14 years (82.2%) and suffered from pulmonary TB (85.9%). A notable proportion (37.1%) of patients had no history of previous TB treatment. Patients were resistant to a median of two drugs (interquartile range: 1-4) and 23% were resistant to any second line anti-TB drug. A total of 174 (81.7%) patients achieved successful treatment outcomes with 144 (67.6%) patients being cured and 30 (14.1%) declared treatment completed. Among the 39 (18.3%) patients with unsuccessful outcomes, 35 (16.4%) died and 4 (1.9%) experienced treatment failure. In multivariable analysis, the use of ethambutol had statistically significant negative association with unsuccessful outcomes (odds ratio = 0.36, p-value = 0.02). CONCLUSIONS: In this study, the WHO target of successful treatment outcomes (≥ 75%) among childhood RR/MDR-TB patients was achieved. The notable proportion of patients with no history of previous TB treatment (37.1%) and the disproportionately high number of female patients (74%) respectively stress for infection control measures and provision of early and high quality care for female drug susceptible TB patients.

Treatment Outcomes of Extensively Drug-Resistant Tuberculosis in Pakistan: A Countrywide Retrospective Record Review.

Background: The current study is conducted with the aim to the fill the gap of information regarding treatment outcomes and variables associated with unsuccessful outcome among XDR-TB patients from Pakistan. Methods: A total of 404 culture confirmed XDR-TB patients who received treatment between 1st May 2010 and June 30, 2017 at 27 treatment centers all over Pakistan were retrospectively followed until their treatment outcomes were reported. A p-value <0.05 reflected a statistical significant association. Results: The patients had a mean age 32.9 ± 14.1 years. The overall treatment success rate was 40.6% (95% confidence interval [CI]:35.80-45.60%). A total of 155 (38.4%) patients were declared cured, 9 (2.2%) completed treatment, 149 (36.9%) died, 60 (14.9%) failed treatment and 31 (7.7%) were lost to follow up (LTFU). The results of the multivariate binary logistic regression analysis revealed that the patients' age of >60 years (OR = 4.69, 95%CI:1.57-15.57) and receiving high dose isoniazid (OR = 2.36, 95%CI:1.14-4.85) had statistically significant positive association with death, whereas baseline body weight >40 kg (OR = 0.43, 95%CI:0.25-0.73) and sputum culture conversion in the initial two months of treatment (OR = 0.33, 95%CI:0.19-0.58) had statistically significant negative association with death. Moreover, male gender had statistically significant positive association (OR = 1.92, 95%CI:1.04-3.54) with LTFU. Conclusion: The treatment success rate (40.6%) of XDR-TB patients in Pakistan was poor. Providing special attention and enhanced clinical management to patients with identified risk factors for death and LTFU in the current cohort may improve the treatment outcomes.

Treatment Outcomes of Childhood Tuberculosis in Three Districts of Balochistan, Pakistan: Findings from a Retrospective Cohort Study.

BACKGROUND: This study aimed to evaluate treatment outcomes and factors associated unsuccessful outcomes among pediatric tuberculosis (TB) patients (age ≤14 years). METHODS: This was a retrospective cohort study conducted at three districts (Quetta, Zhob and Killa Abdullah) of Balochistan, Pakistan. All childhood TB patients enrolled for treatment at Bolan Medical Complex Hospital (BMCH) Quetta and District Headquarter Hospitals of Zhob and Killa Abdullah from 1 January 2016 to 31 December 2018 were included in the study and followed until their treatment outcomes were reported. Data were collected through a purpose developed standardized data collection form and analyzed by using SPSS 20. A p-value <0.05 was considered statistically significant. RESULTS: Out of 5152 TB patients enrolled at the study sites, 2184 (42.4%) were children. Among them, 1941 childhood TB patients had complete medical record were included in the study. Majority of the study participants were <5 years old (66.6%) and had pulmonary TB (PTB; 65%). A total of 45 (2.3%) patients were cured, 1680 (86.6%) completed treatment, 195 (10%) lost to follow-up, 15 (0.8%) died, 5 (0.3%) failed treatment and 1 (0.1%) was not evaluated for outcomes. In multivariate binary logistic regression analysis, treatment at BMCH Quetta (OR = 25.671, p-value < 0.001), rural residence (OR = 3.126, p-value < 0.001) and extra-PTB (OR = 1.619, p-value = 0.004) emerged as risk factors for unsuccessful outcomes. CONCLUSION: The study sites collectively reached the World Health Organization's target of treatment success (>85%). Lost to follow-up was the major reason for unsuccessful outcomes. Special attention to patients with identified risk factors for unsuccessful outcomes may improve outcomes further.

An Engineered Microvirin Variant with Identical Structural Domains Potently Inhibits Human Immunodeficiency Virus and Hepatitis C Virus Cellular Entry.

Microvirin (MVN) is one of the human immunodeficiency virus (HIV-1) entry inhibitor lectins, which consists of two structural domains sharing 35% sequence identity and contrary to many other antiviral lectins, it exists as a monomer. In this study, we engineered an MVN variant, LUMS1, consisting of two domains with 100% sequence identity, thereby reducing the chemical heterogeneity, which is a major factor in eliciting immunogenicity. We determined carbohydrate binding of LUMS1 through NMR chemical shift perturbation and tested its anti-HIV activity in single-round infectivity assay and its anti-hepatitis C virus (HCV) activity in three different assays including HCVcc, HCVpp, and replicon assays. We further investigated the effect of LUMS1 on the activation of T helper (Th) and B cells through flow cytometry. LUMS1 showed binding to (1-2)mannobiose, the minimum glycan epitope of MVN, potently inhibited HIV-1 and HCV with EC50 of 37.2 and 45.3 nM, respectively, and showed negligible cytotoxicity with CC50 > 10 µM against PBMCs, Huh-7.5 and HepG2 cells, and 4.9 µM against TZM-bl cells. LUMS1 did not activate Th cells, and its stimulatory effect on B cells was markedly less as compared to MVN. Together, with these effects, LUMS1 represents a potential candidate for the development of antiviral therapies.

Evaluation of treatment outcomes and factors associated with unsuccessful outcomes in multidrug resistant tuberculosis patients in Baluchistan province of Pakistan.

BACKGROUND: Evaluating treatment outcomes of a cohort of patients is an effective way for analyzing the effectiveness of a program. Information regarding drug resistance pattern, detailed management, treatment outcomes and factors associated with unsuccessful outcomes in multidrug resistant (MDR-TB) patients is missing from Baluchistan province of Pakistan. METHODS: This study was carried out at Programmatic Management of Drug Resistant TB unit at Fatimah Jinnah General and Chest Hospital Quetta. All eligible 186 MDR-TB patients enrolled at the study site from January 1, 2012 to April 30, 2016 were retrospectively followed until the treatment outcomes were reported. Data was abstracted through a standardized data collection form and analysed by SPSS 20. Multivariate binary logistic regression (MVBLR) analysis was used to evaluate factors associated with i) death and treatment failure and ii) lost to follow up. A p-value of <0.05 was considered statistically significant. RESULTS: The study participants were resistant to a median of four drugs (range 2-8) with majority being resistant to any second-line anti-TB drug (SLD) (55.5%). Among SLD, resistance was highest for ofloxacin (52.2%). The study site had an overall treatment success rate of 71.6%. A total of 129 (69.4%) patients were cured, four (2.2%) completed treatment, 37 died (19.9%), 14 (7.5%) were lost to follow up and two (1.1%) were declared treatment failures. In MVBLR analysis, patients' age of >40 years (OR = 4.249, p-value = 0.001) had statistically significant positive and baseline body weight of >40 kg (OR = 0.256, p-value = 0.002) had statistically significant negative association with death and treatment failure. No factor had statistical significant association with lost to follow up. CONCLUSION: Overall treatment success rate was promising but did not achieve the target success rate (>75%) set by World Health Organization. It can be further improved by paying special attention and providing enhanced management to the patients with risk factors for unsuccessful outcomes.

Validity of Time to Sputum Culture Conversion to Predict Cure in Patients with Multidrug-Resistant Tuberculosis: A Retrospective Single-Center Study.

To evaluate the predictive value of time to sputum culture conversion (SCC) in predicting cure and factors associated with time to SCC and cure in multidrug-resistant tuberculosis (MDR-TB) patients, a retrospective study was conducted at programmatic management unit of drug resistant tuberculosis (TB), Peshawar. A total of 428 pulmonary MDR-TB patients enrolled at the study site from January 1, 2012 to August 31, 2014 were followed until treatment outcome was recorded. Survival analysis using Cox proportional hazards model and multivariate binary logistic regression were, respectively, used to identify factors associated with time to SCC and cure. A P value < 0.05 was considered statistically significant. Overall, 90.9% patients achieved SCC, and 76.9% were cured. Previous use of second-line drugs (SLDs) (hazard ratio [HR] = 0.637; 95% confidence interval [CI] = 0.429-0.947), ofloxacin resistance (HR = 0.656; 95% CI = 0.522-0.825) and lung cavitation (HR = 0.744; 95% CI = 0.595-0.931) were significantly associated with time to SCC. In predicting cure, sensitivities of SCC at 2, 4, and 6 months were 64.1% (95% CI = 58.69-69.32), 93.0% (95% CI = 89.69-95.52), and 97.6% (95% CI = 95.27-98.94), respectively, whereas specificities were 67.7% (95% CI = 57.53-76.73), 51.5% (95% CI = 41.25-61.68), and 44.4% (95% CI = 34.45-54.78), respectively. Furthermore, patients' age of 41-60 (odds ratio [OR] = 0.202; 95% CI = 0.067-0.605) and > 60 years (OR = 0.051; 95% CI = 0.011-0.224), body weight > 40 kg (OR = 2.950; 95% CI = 1.462-5.952), previous SLD use (OR = 0.277; 95% CI = 0.097-0.789), lung cavitation (OR = 0.196; 95% CI = 0.103-0.371) and ofloxacin resistance (OR = 0.386; 95% CI = 0.198-0.749) were significantly associated with cure. Association of SCC with cure was substantially stronger at 6 months (OR = 32.10; 95% CI = 14.34-71.85) than at 4 months (OR = 14.13; 95% CI = 7.92-25.21). However in predicting treatment outcomes, the combined sensitivity and specificity of SCC at 4 months was comparable to SCC at 6 months. Patients with risk factors for delayed SCC were also at high risk of unsuccessful outcomes.

Resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients

Abstract Background Fluoroquinolones are the backbone of multidrug resistant tuberculosis treatment regimens. Despite the high burden of multidrug resistant tuberculosis in the country, little is known about drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance among multidrug resistant tuberculosis patients from Pakistan. Objective To evaluate drug resistance patterns, prevalence, and predictors of fluoroquinolones resistance in multidrug resistant tuberculosis patients. Methods This was a cross-sectional study conducted at a programmatic management unit of drug resistant tuberculosis, Lady Reading Hospital Peshawar, Pakistan. Two hundred and forty-three newly diagnosed multidrug resistant tuberculosis patients consecutively enrolled for treatment at study site from January 1, 2012 to July 28, 2013 were included in the study. A standardized data collection form was used to collect patients’ socio-demographic, microbiological, and clinical data. SPSS 16 was used for data analysis. Results High degree of drug resistance (median 5 drugs, range 2–8) was observed. High proportion of patients was resistant to all five first-line anti-tuberculosis drugs (62.6%), and more than half were resistant to second line drugs (55.1%). The majority of the patients were ofloxacin resistant (52.7%). Upon multivariate analysis previous tuberculosis treatment at private (OR = 1.953, p = 0.034) and public private mix (OR = 2.824, p = 0.046) sectors were predictors of ofloxacin resistance. Conclusion The high degree of drug resistance observed, particularly to fluoroquinolones, is alarming. We recommend the adoption of more restrictive policies to control non-prescription sale of fluoroquinolones, its rational use by physicians, and training doctors in both private and public–private mix sectors to prevent further increase in fluoroquinolones resistant Mycobacterium tuberculosis strains.