Integrated safety studies of the urate reabsorption inhibitor lesinurad in treatment of gout.

ObjectiveLesinurad (LESU) is a selective urate reabsorption inhibitor approved at 200 mg daily for use with a xanthine oxidase inhibitor (XOI) to treat hyperuricaemia in gout patients failing to achieve target serum urate on XOI. The aim of the study was to investigate the long-term safety of LESU + XOI therapy.MethodsSafety data were pooled from three 12-month phase III (core) trials evaluating LESU 200 and 400 mg/day combined with an XOI (LESU200+XOI and LESU400+XOI), and two 12-month extension studies using descriptive statistics. To adjust for treatment duration, treatment-emergent adverse events (TEAEs) were expressed as exposure-adjusted incidence rates (patients with events per 100 person-years).ResultsIn the core studies, exposure-adjusted incidence rates for total and total renal-related TEAEs were comparable for XOI alone and LESU200+XOI but higher with LESU400+XOI. Exposure-adjusted incidence rates for serum creatinine (sCr) elevations ⩾1.5×baseline were 2.9, 7.3 and 18.7, respectively. Resolution (sCr ⩽1.2×baseline) occurred in 75-90% of all events, with 66-75% occurring without any study medication interruption. Major adverse cardiovascular events were 3, 4 and 9 with XOI, LESU200+XOI and LESU400+XOI, respectively. Longer exposure in core+extension studies did not increase rates for any safety signals.ConclusionAt the approved dose of 200 mg once-daily combined with an XOI, LESU did not increase renal, cardiovascular or other adverse events compared with XOI alone, except for sCr elevations. With extended exposure in the core+extension studies, the safety profile was consistent with that observed in the core studies, and no new safety concerns were identified

Empirical Study of Carbon Dioxide Released to the Atmosphere during Commercial Red Grape Fermentation

Carbon dioxide (CO2) is a pollutant (greenhouse gas) that is emitted during winemaking but not currently regulated by the Environmental Protection Agency. While winery CO2 emissions have been modeled, they have never been measured continuously or confirmed during a commercial fermentation. As international interest increases in greenhouse gases, it is important to know the amount of CO2 release and the determining factors; yeast strain, temperature, and dissolved CO2 are potentially important parameters. The study was designed to quantify emissions and test a theoretical model for atmospheric release of CO2 during alcoholic fermentation in a commercial winery. Gas release was channeled through a manifold system with an in-line mass flow meter calibrated for CO2, providing real-time and integrated measurement of atmospheric emission. Intermittent use of a hot-wire anemometer was used as a check on the mass-flow measurements. Initial results indicate that integrated mass of CO2 release is dependent on total Brix decrease and not duration of fermentation, consistent with the Williams and Boulton model. However, the time course of release and the shape of the release curves differed substantially among ferments and were primarily dependent on the length of active fermentation

Sex differences in the temperature dependence of kidney stone presentations: a population-based aggregated case-crossover study.

Previous studies assumed a uniform relationship between heat and kidney stone presentations. Determining whether sex and other characteristics modify the temperature dependence of kidney stone presentations has implications for explaining differences in nephrolithiasis prevalence and improving projections of the effect of climate change on nephrolithiasis. We performed an aggregated case-crossover study among 132,597 children and adults who presented with nephrolithiasis to 68 emergency departments throughout South Carolina from 1997 to 2015. We used quasi-Poisson regression with distributed lag non-linear models to estimate sex differences in the cumulative exposure and lagged response between maximum daily wet-bulb temperatures and emergent kidney stone presentations, aggregated at the ZIP-code level. We also explored interactions by age, race, payer, and climate. Compared to 10 °C, daily wet-bulb temperatures at the 99th percentile were associated with a greater increased relative risk (RR) of kidney stone presentations over 10 days for males (RR 1.73; 95% CI 1.56, 1.91) than for females (RR 1.15; 95% CI 1.01, 1.32; interaction P < 0.001). The shape of the lagged response was similar for males and females, with the greatest risk estimated for the 2 days following high temperatures. There were weak differences by age, race, and climatic zone, and no differences by payer status. The estimated risk of presenting emergently with kidney stones within 10 days of high daily wet-bulb temperatures was substantially greater among men than women, and similar between patients with public and private insurance. These findings suggest that the higher risk among males may be due to sexually dimorphic physiologic responses rather than greater exposure to ambient temperatures

Asthma management programs in managed care organizations

The aim of this work was to investigate how managed care organizations (MCOs) currently approach asthma treatment and management and to determine factors affecting asthma outcomes. A Web-based survey was administered to a national sample of 351 medical directors of MCOs to investigate the asthma management program components in their organizations as well as gaps and barriers in the management of patients with asthma. All 134 (38.2%) responding medical directors reported that their organizations monitor asthma patients. Plans use a variety of asthma management activities, including general member education (90%), member education by mail (87%), self-management education (85%), and provider education (82%). Educational resources (89%) and telephone advice nurse (77%) were the most common self-management strategies offered. Among factors impeding the provision of effective asthma care, noncompliance with asthma treatment, the inappropriate use of medications, and the need for multiple medications were cited by virtually all respondents. Health plans rely on an array of strategies to manage asthma patients. Education encouraging patient self-management is a key component of asthma management programs. However, a considerable number of treatment approach barriers are impeding the achievement of proper asthma care. Without innovative approaches to care, it appears that current MCOs’ asthma management efforts may not result in substantial improvements in asthma outcomes

Microbiology of Urinary Tract Infections in Gaborone, Botswana

Objective The microbiology and epidemiology of UTI pathogens are largely unknown in Botswana, a high prevalence HIV setting. Using laboratory data from the largest referral hospital and a private hospital, we describe the major pathogens causing UTI and their antimicrobial resistance patterns. Methods This retrospective study examined antimicrobial susceptibility data for urine samples collected at Princess Marina Hospital (PMH), Bokamoso Private Hospital (BPH), or one of their affiliated outpatient clinics. A urine sample was included in our dataset if it demonstrated pure growth of a single organism and accompanying antimicrobial susceptibility and subject demographic data were available. Results A total of 744 samples were included. Greater than 10% resistance was observed for amoxicillin, co-trimoxazole, amoxicillin-clavulanate, and ciprofloxacin. Resistance of E. coli isolates to ampicillin and co-trimoxazole was greater than 60% in all settings. HIV status did not significantly impact the microbiology of UTIs, but did impact antimicrobial resistance to co-trimoxazole. Conclusions Data suggests that antimicrobial resistance has already emerged to most oral antibiotics, making empiric management of outpatient UTIs challenging. Ampicillin, co-trimoxazole, and ciprofloxacin should not be used as empiric treatment for UTI in this context. Nitrofurantoin could be used for simple cystitis; aminoglycosides for uncomplicated UTI in inpatients

“Like works of our hands are giving testimony!” A qualitative study on kangaroo mother care and health worker empowerment in southern Malawi

The purpose of this paper is to explore health worker perspectives of empowerment associated with kangaroo mother care in southern Malawi. We conducted a secondary analysis of 27 in-depth interviews collected between May-Aug 2019 at a large Malawian tertiary hospital and three rural referral hospitals. Data was analyzed using a thematic approach with NVivo 12 software (QSR International, Melbourne, Australia). Health workers reported positive perceptions of kangaroo mother care because it helped save the lives of preterm and low birthweight infants who previously did not frequently survive. This gave them hope due to increased capacity to care for low birthweight infants and subsequently increased job satisfaction. Experiences of success supported workplace morale and strengthened commitment to their clinical roles. This study suggests that kangaroo mother care may support health worker empowerment and resilience in their work. &nbsp; Cet article-ci se prend pour son objectif d'explorer les perspectives de l'autonomie associée avec les soins maternels kangourous implémentés aux cliniques médicales dans le sud du Malawi. Les perspectives de l'autonomie dont on parle ici appartiennent aux travailleurs de la santé. Nous avons effectué une analyse secondaire de vingt-sept entrevues collectionnées entre les mois mai et août en 2019 au Malawi à une hôpital de soins tertiaires et aux trois hôpitaux d'aiguillage ruraux. Les données ont été analysées en utilisant l'approche thématique avec le logiciel NVivo 12 (QSR International, Melbourne, Australia). Les travailleurs de la santé ont communiqué les perceptions positives des soins maternels kangourous parce que ceux-ci les ont aidé à sauver les vies des nourrissons prématurés et de faible poids de naissance qui autrefois souvent n'avaient pas survécu. Ceci leur a donné de l'espoir parce que leur capacité de prendre soin des nourrissons de faible poids de naissance est accrue et ensuite leur satisfaction au travail a augmenté aussi. Ces expériences de succès ont soutenu leur morale au travail et ont renforcé leur engagement envers leur rôles cliniques. Cette étude-ci suggère que les soins maternels kangourou peuvent promouvoir l'autonomie des travailleurs de la santé et leur résilience dans leur travail. &nbsp

New Delhi Metallo-β-Lactamase in Klebsiella pneumoniae and Escherichia coli, Canada

Multidrug-resistant Klebsiella pneumoniae and Escherichia coli isolates harboring New Delhi metallo-β-lactamase (NDM-1) were isolated from a patient who had returned to Canada from India. The NDM-1 gene was found on closely related incompatibility group A/C type plasmids. The occurrence of NDM-1 in North America is a major public health concern

Ge quantum dot arrays grown by ultrahigh vacuum molecular beam epitaxy on the Si(001) surface: nucleation, morphology and CMOS compatibility

Issues of morphology, nucleation and growth of Ge cluster arrays deposited by ultrahigh vacuum molecular beam epitaxy on the Si(001) surface are considered. Difference in nucleation of quantum dots during Ge deposition at low (<600 deg C) and high (>600 deg. C) temperatures is studied by high resolution scanning tunneling microscopy. The atomic models of growth of both species of Ge huts---pyramids and wedges---are proposed. The growth cycle of Ge QD arrays at low temperatures is explored. A problem of lowering of the array formation temperature is discussed with the focus on CMOS compatibility of the entire process; a special attention is paid upon approaches to reduction of treatment temperature during the Si(001) surface pre-growth cleaning, which is at once a key and the highest-temperature phase of the Ge/Si(001) quantum dot dense array formation process. The temperature of the Si clean surface preparation, the final high-temperature step of which is, as a rule, carried out directly in the MBE chamber just before the structure deposition, determines the compatibility of formation process of Ge-QD-array based devices with the CMOS manufacturing cycle. Silicon surface hydrogenation at the final stage of its wet chemical etching during the preliminary cleaning is proposed as a possible way of efficient reduction of the Si wafer pre-growth annealing temperature.Comment: 30 pages, 11 figure

Renal Replacement Therapy and Incremental Hemodialysis for Veterans with Advanced Chronic Kidney Disease.

Each year approximately 13,000 Veterans transition to maintenance dialysis, mostly in the traditional form of thrice-weekly hemodialysis from the start. Among &gt;6000 dialysis units nationwide, there are currently approximately 70 Veterans Affairs (VA) dialysis centers. Given this number of VA dialysis centers and their limited capacity, only 10% of all incident dialysis Veterans initiate treatment in a VA center. Evidence suggests that, among Veterans, the receipt of care within the VA system is associated with favorable outcomes, potentially because of the enhanced access to healthcare resources. Data from the United States Renal Data System Special Study Center "Transition-of-Care-in-CKD" suggest that Veterans who receive dialysis in a VA unit exhibit greater survival compared with the non-VA centers. Substantial financial expenditures arise from the high volume of outsourced care and higher dialysis reimbursement paid by the VA than by Medicare to outsourced providers. Given the exceedingly high mortality and abrupt decline in residual kidney function (RKF) in the first dialysis year, it is possible that incremental transition to dialysis through an initial twice-weekly hemodialysis regimen might preserve RKF, prolong vascular access longevity, improve patients' quality of life, and be a more patient-centered approach, more consistent with "personalized" dialysis. Broad implementation of incremental dialysis might also result in more Veterans receiving care within a VA dialysis unit. Controlled trials are needed to examine the safety and efficacy of incremental hemodialysis in Veterans and other populations; the administrative and health care as well as provider structure within the VA system would facilitate the performance of such trials