Risk factors for multidrug-resistant tuberculosis in urban Pakistan: A multicenter case-control study

Objective: To evaluate risk factors for multidrug-resistant tuberculosis (MDR-TB) in an urban setting of Pakistan.DESIGN AND Methods: In this multicenter case-control study, patients aged 15years old or older with sputum culture and sensitivity (C/S) diagnosed with pulmonary MDR-TB were defined as cases, whereas patients aged 15years old or older with sputum C/S diagnosed and susceptible to pulmonary TB were regarded as controls. Fifty cases and 75 controls were enrolled from three tertiary-care hospitals in Karachi.Results: Multivariable logistic regression models showed that cases were more likely to have had a TB patient in the house prior to the diagnosis of MDR-TB (adjusted odds ratio [ORadj]=3.1, 95% confidence interval [CI]: 1.2, 8.3) or had a history of prior TB treatment (ORadj=4.2, 95% CI: 1.1, 15.4). Furthermore, cases compared with controls tended to be male (ORadj=3.6, 95% CI: 1.4, 9.7), 15-25years of age (ORadj=3.7, 95% CI: 1.2, 11.3), of Sindhi ethnicity (adjusted OR=9.1, 95% CI: 1.9, 43.4) or with low educational attainment (ORadj OR=5.5, 95% CI: 1.7-17.6, for no formal schooling; ORadj=3.8, 95% CI: 1.1-14.1, 1 for 1-5 school years).CONCLUSIONS: A TB patient in the house or a history of prior TB treatment was strongly associated with MDR-TB in this study. Furthermore, younger age, male gender, Sindhi ethnicity and poor educational attainment entailed a high risk for MDR-TB. Targeted educational intervention for patients and their contacts may minimize the noncompliance with prescribed TB treatment and lessen MDR-TB magnitude in settings like Karachi

Water Arsenic Exposure and Children’s Intellectual Function in Araihazar, Bangladesh

Exposure to arsenic has long been known to have neurologic consequences in adults, but to date there are no well-controlled studies in children. We report results of a cross-sectional investigation of intellectual function in 201 children 10 years of age whose parents participate in our ongoing prospective cohort study examining health effects of As exposure in 12,000 residents of Araihazar, Bangladesh. Water As and manganese concentrations of tube wells at each child’s home were obtained by surveying all wells in the study region. Children and mothers came to our field clinic, where children received a medical examination in which weight, height, and head circumference were measured. Children’s intellectual function on tests drawn from the Wechsler Intelligence Scale for Children, version III, was assessed by summing weighted items across domains to create Verbal, Performance, and Full-Scale raw scores. Children provided urine specimens for measuring urinary As and creatinine and were asked to provide blood samples for measuring blood lead and hemoglobin concentrations. Exposure to As from drinking water was associated with reduced intellectual function after adjustment for sociodemographic covariates and water Mn. Water As was associated with reduced intellectual function, in a dose–response manner, such that children with water As levels > 50 μg/L achieved significantly lower Performance and Full-Scale scores than did children with water As levels < 5.5 μg/L. The association was generally stronger for well-water As than for urinary As

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p&lt;0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p&lt;0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Recent insights on nanomedicine for augmented infection control

Sima Singh,1,* Afzal Hussain,1,* Faiyaz Shakeel,2,* Mohamed Jawed Ahsan,3 Sultan Alshehri,2 Thomas J Webster,4,* Uma Ranjan Lal5 1Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Ranchi 835215, Jharkhand, India; 2Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia; 3Department of Pharmaceutical Chemistry, Maharishi Arvind College of Pharmacy, Jaipur, Rajasthan, 302023, India; 4Department of Chemical Engineering, Northeastern University, Boston, MA 02115, USA; 5School of Pharmaceutical Sciences, Shoolini University, Solan 173229, Himacahal Pradesh, India *These authors contributed equally to this work Abstract: Antimicrobial agents have been widely investigated for protecting against microbial infections in modern health. Drug-related limitations, poor bioavailability, toxicity to mammalian cells, and frequent bacteria drug resistance are major challenges faced when exploited in nanomedicine forms. Specific attention has been paid to control nanomaterial-based infection against numerous challenging pathogens in addition to improved drug delivery, targeting, and pharmacokinetic (PK) profiles, and thus, efficient antimicrobials have been fabricated using diverse components (metals, metal oxides, synthetic and semisynthetic polymers, natural or biodegradable polymers, etc). The present review covers several nanocarriers delivered through various routes of administration, highlighting major findings to control microbial infection as compared to using the free drug. Results over the past decade support the consistent development of various nanomedicines capable of improving biological significance and therapeutic benefits against an array of microbial strains. Depending on the intended application of nanomedicine, infection control will be challenged by various factors such as weighing the risk&ndash;benefits in healthcare settings, nanomaterial-induced (eco)toxicological hazards, frequent development of antibiotic resistance, scarcity of in vivo toxicity data, and a poor understanding of microbial interactions with nanomedicine at the molecular level. This review summarizes well-established informative data for nanomaterials used for infection control and safety concerns of nanomedicines to healthcare sectors followed by the significance of a unique &ldquo;safe-by-design&rdquo; approach. Keywords: recent nanomedicines, infection control, antimicrobial agents, drug delivery, biosafet

Effect of methanol extract of Dicranopteris linearis against carbon tetrachloride- induced acute liver injury in rats

Background: Dicranopteris linearis (family Gleicheniaceae) has been reported to possess anti-inflammatory and antioxidant activities but no attempt has been made to study its hepatoprotective potential. The aim of the present study was to determine the hepatoprotective effect of methanol extracts of D. linearis (MEDL) against carbon tetrachloride (CCl4)-induced acute liver injury in rats. Methods: 6 groups (n = 6) of rats received oral test solutions: 10% dimethyl sulfoxide (DMSO), 200 mg/kg silymarin, or MEDL (50, 250, and 500 mg/kg), once daily for 7 consecutive days, followed by hepatotoxicity induction with CCl4. Blood and liver were collected for biochemical and microscopic analysis. The extract was also subjected to antioxidant studies (e.g. 2, 2-diphenyl-1-picrylhydrazyl (DPPH)- and superoxide anion-radical scavenging assays, oxygen radical absorbance capacity (ORAC) test and total phenolic content (TPC) determination), phytochemical screening and HPLC analysis. Results: Pretreatment with MEDL and silymarin significantly (P < 0.05) reduced the serum levels of AST, ALT and ALP, which were increased significantly (P < 0.05) in DMSO-pretreated group following treatment with CCl4. Histological analysis of liver tissues in groups pretreated with MEDL and silymarin showed mild necrosis and inflammation of the hepatocytes compared to the DMSO-pretreated group (negative control group). The MEDL showed higher DPPH- and superoxide anion-radical scavenging activity as well as high TPC and ORAC values indicating high antioxidant activity. Conclusions: MEDL exerts hepatoprotective activity that could be partly contributed by its antioxidant activity and high phenolic content, and hence demands further investigation