A perspective on the role of uncertainty in sustainability science and engineering.

The Trans-Atlantic Research and Development Interchange on Sustainability Workshop (TARDIS) is a meeting on scientific topics related to sustainability. The 2019 workshop theme was "On the Role of Uncertainty in Managing the Earth for Global Sustainability." This paper presents the perspectives on this topic derived from talks and discussions at the 2019 TARDIS workshop. There are four kinds of uncertainties encountered in sustainability ranging from clear enough futures to true surprises. The current state-of-the-art in assessing and mitigating these uncertainties is discussed.

Leveraging nurse practitioner capacities to achieve global health for all: COVID-19 and beyond.

AIM: To argue that nurse practitioners have been under-utilized generally in the current global health environment, creating barriers to achieving universal health coverage and the Sustainable Development Goals. BACKGROUND: Nurse practitioners are advanced practice nurses possessing expert knowledge and leadership skills that can be optimized to narrow disparities and ensure access to high-quality health care globally. Nurses worldwide have been challenged to meet global public health needs in the context of COVID-19 (SARS-CoV-2 virus), and there are early indications that nurse practitioners are being called upon to the full extent of their capabilities in the current pandemic. SOURCES OF EVIDENCE: PubMed; Google Scholar; the International Council of Nurses; World Health Organization; United Nations; and the experiences of the authors. DISCUSSION: Several international reports, nursing and health organizations have called for continued investment in and development of nursing to improve mechanisms that promote cost-effective and universally accessible care. Expanding nurse practitioner scopes of practice across nations will leverage their clinical capacities, policy and advocacy skills, and talents to lead at all levels. CONCLUSION: Ongoing empirical data and policy change is needed to enable the full scope and strategic utilization of nurse practitioners across healthcare systems and contexts. IMPLICATIONS FOR NURSING PRACTICE, AND NURSING AND HEALTH POLICY: Widespread education regarding nurse practitioner capacities for interdisciplinary partners, policymakers and the public is needed. Policies that safely expand their roles are critical. Role titles and remuneration reflective of their scope and service are required to lead, sustain and grow the workforce internationally.

Platinum-Gemcitabine-Avastin (PGA) for platinum-resistant/refractory ovarian cancer.

OBJECTIVES: Synergism between gemcitabine and platinum is known clinically. Bevacizumab in combination with single-agent chemotherapy has demonstrated significant clinical activity in platinum-resistant recurrent ovarian cancer in AURELIA study. However, the efficacy of platinum-gemcitabine-bevacizumab (PGA) has not been investigated in the platinum-resistant population. MATERIALS AND METHODS: A retrospective chart review was conducted in all patients with platinum-resistant/refractory ovarian cancer treated with triplet combination therapy containing a platinum agent, gemcitabine, and bevacizumab between July 2011 and December 2013. RESULTS: In total, 13 patients met the selection criteria, including ten patients with resistant disease (10/13, 77%) and three patients with refractory disease (3/13, 23%). Most of the patients were heavily pre-treated, having received over three lines of prior chemotherapy regimens on average (range 1-11). All patients had previously received taxane therapy; four patients received gemcitabine, seven patients failed combination regimens including bevacizumab, and three patients progressed on chemotherapy including both gemcitabine and bevacizumab. Ten patients responded biochemically to the therapy (defined by CA-125 declined by at least 50%). Of ten responders, one patient achieved CR for 24 months (8%), six patients achieved PR for 6.8 months (46%), three had stable disease for 6.7 months (23%), and three patients had PD (23%) by RECIST 1.1 criteria. The regimen was well-tolerated. One patient (8%) developed grade 3 neutropenia and neutropenic fever, requiring hospitalization, two patients developed grade 3 thrombocytopenia, two patients (15%) developed thrombosis in internal jugular vein, requiring discontinuation of bevacizumab, one patient (8%) experienced skin ulcer, and two patients developed thrombosis in internal jugular vein, requiring discontinuation of bevacizumab. CONCLUSIONS: Combination of PGA appears to be safe and very active against platinum-resistant/refractory ovarian cancer and merits further evaluation prospectively. A randomized phase II study (NCTO 1936974) is currently under way to confirm this important finding.

Real-world effectiveness of peginterferon α-2b plus ribavirin in a Canadian cohort of treatment-naïve chronic hepatitis C patients with genotypes 2 or 3: results of the PoWer and RediPEN studies.

The purpose of this investigation was to assess the real-life effectiveness of pegylated interferon (peg-IFN) α-2b with ribavirin (RBV) in a cohort of treatment-naïve patients with chronic genotypes 2 (G2) or 3 (G3) hepatitis C virus (HCV) infection. A post-hoc pooled analysis of two Canadian multicenter, observational studies, RediPEN and PoWer, was carried out. A total of 1242 G2- or G3-infected patients were included. The primary outcome was sustained virologic response (SVR). Secondary endpoints included early virologic response (EVR), end-of-treatment (EOT) response, and relapse. Multivariate logistic regression was used to identify independent predictors of treatment response. SVR in G2 and G3 was 74.4 % and 63.6 %, respectively. Relapse occurred in 12.7 % and 19.1 % of G2- and G3-infected patients achieving EOT response, respectively. Overall, G3 was found to independently predict reduced SVR [odds ratio (OR) = 0.20; p = 0.007] and increased relapse (OR = 6.84; p = 0.022). Among G3-infected patients, increasing fibrosis score was the most important factor predicting reduced SVR [F2 vs. F0/F1 (OR = 0.41; p = 0.009); F3 vs. F0/F1 (OR = 0.72; p = 0.338); F4 vs. F0/F1 (OR = 0.27; p = 0.001)]. Male gender (OR = 13.16; p = 0.020) and higher fibrosis score [F2 vs. F0/F1 (OR = 9.72; p = 0.016); F3/F4 vs. F0/F1 (OR = 4.23; p = 0.113)] were associated with increased relapse in G3 patients. These results support the real-life effectiveness of peg-IFN α-2b plus ribavirin in HCV G2- and G3-infected patients. Overall, genotype was identified as the most significant predictor of treatment outcome. Fibrosis score and gender were key outcome predictors in the G3-infected population. In clinical settings, peg-INF/RBV offers an alternative for patients without access to all oral direct-acting antivirals.

Fracture rate associated with quality metric-based anti-osteoporosis treatment in glucocorticoid-induced osteoporosis.

UNLABELLED: Anti-osteoporosis medication (AOM) use in patients exposed to glucocorticoids is thought to reduce fractures. We found post-menopausal women using glucocorticoids for at least 90 days who also used an AOM within 90 days had 48 % fewer fractures by 1 year and 32 % fewer fractures by 3 years compared to non-AOM users. INTRODUCTION: The purpose of this study is to explore the effectiveness of adherence to quality measures by estimating the effect of anti-osteoporosis medication (AOM) initiation within 90 days after chronic (≥90 days) glucocorticoid (GC) therapy on osteoporotic fracture. METHODS: A new-user cohort was assembled using the MarketScan databases between 2000 and 2012. Included patients were female, age ≥50 at GC initiation, had a first GC fill daily dose ≥10 mg and persisted for at least 90 days. During a 365-day baseline period, patients were excluded for prior GC or AOM (bisphosphonate, denosumab, teriparatide) use, fracture, or cancer diagnosis. Initiators of an AOM in the 14 days pre- or 90 days post-GC fill were characterized as AOM users; those without, AOM non-users. Follow-up began 91 days after GC fill with patients followed until fracture, loss of continuous enrollment, initiation of AOM by AOM non-users, or end of study period. A propensity score was estimated for AOM receipt using all measured covariates and converted to a stabilized inverse probability of treatment weights (IPTW). Weighted hazard ratios (HR) and associated 95% confidence intervals (95% CI) were estimated using weighted Cox proportional hazard models. RESULTS: Of the 7885 women eligible for the study, 12.1% were AOM users. AOM use was associated with lower fracture incidence: weighted HR of 0.52 (95% CI 0.29, 0.94) at 1 year and weighted HR of 0.68 (95% CI 0.47, 0.99) at 3 years. CONCLUSIONS: AOM initiation within 90 days of chronic GC use was associated with a fracture reduction of 48% at 1 year and 32% at 3 years.

Exploring HIV disease indicators at MDR-TB treatment initiation in South Africa.

BACKGROUND: Understanding relationships between HIV and multidrug-resistant TB (MDR-TB) is crucial for ensuring successful MDR-TB outcomes.METHODS: We used a cross-sectional analysis to evaluate sociodemographic and clinical characteristics as correlates of antiretroviral therapy (ART) use, having an HIV viral load (VL) result, and HIV viral suppression in a cross-sectional sample of people with HIV (PWH) and MDR-TB enrolled in a cluster-randomized trial of nurse case management to improve MDR-TB outcomes.RESULTS: Among 1,479 PWH, the mean age was 37.1 years; 809 (54.7%) were male, and 881 (59.6%) were taking ART. Housing location, employment status, and CD4 count differed significantly between those taking vs. those not taking ART. Among the 881 taking ART, 681 (77.3%) had available HIV VL results. Housing location, CD4 count, and prior history of TB differed significantly between those with and without a VL result. Among the 681 with a VL result, 418 (61.4%) were virally suppressed. Age, education level, CD4 count, TB history, housing location, and ART type differed significantly between those with and without viral suppression.CONCLUSION: PWH presenting for MDR-TB treatment with a history of TB, taking a protease inhibitor, or living in a township may risk poor MDR-TB outcomes.

Age estimation and validation for South Pacific albacore Thunnus alalunga.

Validated estimates of age are presented for albacore Thunnus alalunga, sampled from a large part of the south-western Pacific Ocean, based on counts of annual opaque growth zones from transverse sections of otoliths. Counts of daily increments were used to estimate the location of the first opaque growth zone, which was completed before the first assumed birthday. The periodicity of opaque zones was estimated by marginal increment analysis and an oxytetracycline mark-recapture experiment. Both validation methods indicated that opaque zones formed over the austral summer and were completed by autumn to winter (April to August). The direct comparison of age estimates obtained from otoliths and dorsal-fin spines of the same fish indicated bias, which was assumed to be due to poor increment clarity and resorption of early growth zones in spines, resulting in imprecise age estimates. As such, age estimates from otoliths are considered to be more accurate than those from spines for T. alalunga. This is consistent with results for a growing number of tropical and temperate tuna Thunnini species. It is recommend that validated counts of annual growth zones from sectioned otoliths is used as the preferred method for estimating age-based parameters for assessment and management advice for these important stocks.

Macrolide antibiotics inhibit mucus secretion and calcium entry in Swine airway submucosal mucous gland cells.

Macrolide antibiotics such as erythromycin (EM) and azithromycin (AZM) are beneficial in the treatment of mucus hypersecretion in inflammatory pulmonary diseases. Several indirect and direct mechanisms of action have been proposed. This study investigates the direct effect of macrolides on secretory function of isolated submucosal mucous gland cells (SMGCs). We hypothesize that macrolides inhibit the calcium influx necessary for evoked mucus secretion. To test this, we quantified mucin protein release using enzyme-linked immunosorbent assay, calcium-activated K(+) (K(Ca)), and calcium-activated Cl(-) (Cl(Ca)) currents. We measured nonselective cation current (NSCC) using whole-cell patch-clamp techniques; intracellular calcium concentration ([Ca(2+)](i)) was measured using fura-2 Ca(2+) imaging. We found that both EM and AZM are agonists at muscarinic receptors. EM (10 µM) evoked a small but significant increase in mucin release but inhibited the mucin release induced by subsequent acetylcholine (ACh) treatment. Both EM and AZM (10 µM) evoked K(Ca) and Cl(Ca) whole-cell currents, which were blocked by atropine. EM and AZM also accelerated the decay of inositol trisphosphate-induced K(Ca) and Cl(Ca) currents without changing the peak current amplitudes. Likewise, internal application of AZM (10 µM) enhanced the decay rate of ACh-induced K(Ca) and Cl(Ca) currents. EM (1-10 µM) and AZM (0.1-10 µM) slowly (over 25-30 min) inhibited thapsigargin (TG)-induced Ca(2+) entry when applied during the plateau phase of Ca(2+) entry but blunted TG-induced Ca(2+) entry by 70% after a 5-min pretreatment before initiating calcium entry. EM blocked TG-induced NSCC. We conclude that macrolide antibiotics are partial agonists at muscarinic receptors but inhibit stimulated mucus release by inhibiting calcium entry in SMGCs.

Risk factors for poor engagement in drug-resistant TB care in South Africa: a systematic review.

BACKGROUND: Metrics of poor patient engagement, including missed appointments, treatment interruption, sub-optimal medication adherence, and loss to follow-up, have been linked to poor clinical multidrug-resistant TB (MDR-TB) outcomes. Understanding the risk factors for poor patient engagement is necessary to improve outcomes and control TB. This review synthesizes the risk factors for poor patient engagement in MDR-TB treatment across South Africa. DESIGN: A systematic review of five databases (PubMed, Embase, CINAHL, Cochrane, and Web of Science) was conducted, covering articles published between 2010 and 2020. Articles were included if they provided information about risk factors associated with poor engagement among adults (⩾15 years) in treatment for MDR-TB in South Africa. Reviews, editorials, abstracts, and case studies were excluded. RESULTS: Six studies met the inclusion criteria. Male sex and younger age were the most consistently identified risk factors for poor engagement; however, there was a lack of consistency in the choice of covariates, measurement of the variables, analytic methods, and significant factors associated with poor engagement between studies. Alcohol use, substance use, living with HIV, pulmonary TB site, and ethnicity were all identified as risk factors in at least one included study, while formal housing and steady employment were found to be protective. CONCLUSION: The available literature offers little cohesive data to address poor patient engagement in this population. Further research needs to focus on identifying and addressing risk factors for poor patient engagement. This is particularly salient within the context of newer all-oral and short-course MDR-TB treatment regimens.

CONTEXTE: Les indicateurs d'une faible coopération des patients, tels que les rendez-vous manqués, les arrêts de traitement, une observance thérapeutique sous-optimale et une perte de vue du patient, ont été associés à de mauvais résultats cliniques dans le cadre de la TB multirésistante (MDR-TB). Il convient de comprendre les facteurs de risque d'une faible coopération des patients pour améliorer les résultats et contrôler la TB. Cette revue synthétise les facteurs de risque d'une faible coopération des patients dans le cadre du traitement de la MDR-TB en Afrique du Sud. MÉTHODE: Une revue systématique de cinq bases de données (PubMed, Embase, CINAHL, Cochrane et Web of Science) a été réalisée, englobant les articles publiés entre 2010 et 2020. Les articles ont été inclus s'ils apportaient des informations sur les facteurs de risque associés à la faible coopération des patients adultes (⩾15 ans) sous traitement pour MDR-TB en Afrique du Sud. Les revues, les éditoriaux, les résumés et les études de cas ont été exclus. RÉSULTATS: Six études satisfaisaient les critères d'inclusion. Les facteurs de risque d'une faible coopération les plus fréquents étaient le genre masculin et le jeune âge. Cependant, un manque de cohérence a été observé entre les études dans le choix des covariables, la mesure des variables, les méthodes analytiques et les facteurs significatifs associés à une faible coopération. La consommation d'alcool et de drogues, la séropositivité au VIH, une TB pulmonaire et l'origine ethnique ont tous été identifiés comme facteurs de risque dans au moins une étude incluse, alors que des facteurs tels que « logement formel ¼ et « emploi stable ¼ étaient des facteurs protecteurs. CONCLUSION: La littérature disponible offre peu de données cohérentes permettant d'examiner la faible coopération des patients dans cette population. Les recherches à venir doivent identifier et analyser les facteurs de risque de la faible coopération des patients. Ceci est particulièrement important au vu des nouveaux schémas thérapeutiques courts et entièrement par voie orale de la MDR-TB.

Determining the prevalence of tuberculosis in emergency departments in the Eastern Cape region of South Africa and the utility of the World Health Organization tuberculosis screening tool.

BACKGROUND: South Africa (SA) faces a significant tuberculosis (TB) burden complicated by high rates of HIV-TB co-infection. In SA, emergency departments (EDs) play an important role in screening for TB. OBJECTIVES: To determine the prevalence of TB in the ED and the effectiveness of the World Health Organization (WHO) TB screening tool. METHODS: This was a cross-sectional observational study, conducted in the ED at Livingstone Hospital, Port Elizabeth, from 4 June to 15 July 2018. All patients aged >18 years and able to consent were administered the WHO TB screening questions and underwent a point-of-care HIV test and demographic data collection. Patients were followed up for 1 year and tracked in the National Health Laboratory Service database to determine TB status using laboratory testing. RESULTS: Over the study period, 790 patients were enrolled. Overall, 121 patients (15.3%) were TB-positive, with 46 (38.0%) diagnosed after presenting to the ED and 75 (62.0%) with a previous TB history determined by self-report or confirmed laboratory testing. A greater proportion of the TB-positive patients were HIV-positive (49.6%) compared with the TB-negative population (24.8%). TB-positive individuals were more likely to present to the ED with a chief complaint of shortness of breath (SoB) (18.2%) compared with the TB-negative population (10.5%). Overall, the WHO TB screening tool had poor sensitivity (46.5%) and specificity (62.5%) for identifying TB-positive patients in the ED. A multiple logistic regression analysis, controlled for age and sex, showed HIV status (odds ratio (OR) 2.81; p<0.001) and SoB (OR 2.19; p<0.05) to be significant predictors of TB positivity. Adding positive HIV status and a presenting complaint of SoB increased sensitivity to 78.3%. CONCLUSIONS: EDs in SA face a high burden of TB. While WHO screening guidelines identify some of these patients, including routine HIV testing in the ED could significantly affect the number of TB diagnoses made.

Deduced amino acid sequences of class 1 protein (PorA) from three strains of Neisseria meningitidis. Synthetic peptides define the epitopes responsible for serosubtype specificity.

The previously determined nucleotide sequence of the porA gene, encoding the class 1 outer membrane protein of meningococcal strain MC50, has been used to clone and sequence the porA gene from two further strains with differing serosubtype specificities. Comparison of the predicted amino acid sequences of the three class 1 proteins revealed considerable structural homology with major variation confined to two discrete regions (VR1 and VR2). The high degree of structural homology between the sequences gave predicted secondary structures that were almost identical, with the variable domains located in hydrophilic regions that are likely to be surface located and hence accessible to antibody binding. The predicted amino acid sequences have been used to define the epitopes recognized by mAbs with serosubtype specificity. A series of overlapping decapeptides spanning each of the class 1 protein sequences have been synthesized on solid-phase supports and probed with mAbs. Antibodies with P1.16 and P1.15 subtype specificity reacted with sequences in the VR2 domain, while antibodies with P1.7 subtype specificity reacted with sequences in the VR1 domain. Further peptides have been constructed to define the minimum epitopes recognized by each antibody. Thus we have been able to define linear peptides on each class 1 protein molecule that are responsible for subtype specificity and that represent targets for a protective immune response.

Risk of hearing loss among multidrug-resistant tuberculosis patients according to cumulative aminoglycoside dose.

SETTING: The ototoxic effects of aminoglycosides (AGs) lead to permanent hearing loss, which is one of the devastating consequences of multidrug-resistant tuberculosis (MDR-TB) treatment. As AG ototoxicity is dose-dependent, the impact of a surrogate measure of AG exposure on AG-induced hearing loss warrants close attention for settings with limited therapeutic drug monitoring.OBJECTIVE: To explore the prognostic impact of cumulative AG dose on AG ototoxicity in patients following initiation of AG-containing treatment for MDR-TB.DESIGN: This prospective cohort study was nested within an ongoing cluster-randomized trial of nurse case management intervention across 10 MDR-TB hospitals in South Africa.RESULTS: The adjusted hazard of AG regimen modification due to ototoxicity in the high-dose group (≥75 mg/kg/week) was 1.33 times higher than in the low-dose group (<75 mg/kg/week, 95%CI 1.09-1.64). The adjusted hazard of developing audiometric hearing loss was 1.34 times higher than in the low-dose group (95%CI 1.01-1.77). Pre-existing hearing loss (adjusted hazard ratio [aHR] 1.71, 95%CI 1.29-2.26) and age (aHR 1.16 per 10 years of age, 95%CI 1.01-1.33) were also associated with an increased risk of hearing loss.CONCLUSION: MDR-TB patients with high AG dose, advanced age and pre-existing hearing loss have a significantly higher risk of AG-induced hearing loss. Those at high risk may be candidates for more frequent monitoring or AG-sparing regimens.

The effects of hedgehog ligand neutralising antibody 5E1 in a mouse model of endometriosis.

OBJECTIVE: Endometriosis is a common and painful condition characterised by the formation of endometrial lesions within the peritoneal cavity. Previous studies have suggested a role for hedgehog signalling in the pathogenesis of endometriosis. We investigated the role of hedgehog signalling in the establishment of endometriosis lesions using 5E1, a hedgehog ligand neutralising antibody, and a mouse model of endometriosis. To mimic the initiation of endometriosis by retrograde menstruation, which is believed to occur in humans, donor mice underwent an artificial menstruation protocol. Fragments of menstrual endometrium were injected into the peritoneal cavity of estrogen primed recipients. Recipients received twice weekly injections of 5E1 or an isotype matched control antibody for three weeks. Lesions were collected and analysed for markers of epithelium, proliferation and apoptosis by immunofluorescence microscopy. RESULTS: Treatment with 5E1 reduced the number of lesions found on the mesentery. No significant changes were found in the size of lesions, abundance of endometrial epithelial cells, proliferation or apoptosis.

Neural organization predicts stimulus specificity for a retained associative behavioral change.

Paired, but not random, presentations of light and rotation produced long-term changes in Hermissenda's response to light. The nature of this change depended on the orientation of the animals with respect to the center of rotation and was predicted by known organizational features of Hermissenda's nervous system. When rotation that excited caudal hair cells was paired with light, a significant increase in response latency to test lights resulted. Rotation exciting cephalic hair cells when paired with light decreased the response latencies compared with latencies produced by random presentation of light and rotation.

Fluoride directly stimulates proliferation and alkaline phosphatase activity of bone-forming cells.

Fluoride is one of the most potent but least well understood stimulators of bone formation in vivo. Bone formation was shown to arise from direct effects on bone cells. Treatment with sodium fluoride increased proliferation and alkaline phosphatase activity of bone cells in vitro and increased bone formation in embryonic calvaria at concentrations that stimulate bone formation in vivo.

Membrane changes in a single photoreceptor cause associative learning in Hermissenda.

Single type B photoreceptors in intact, restrained Hermissenda were impaled with a microelectrode and exposed to either paired or unpaired presentations of light and depolarizing current to simulate natural stimulus effects during conditioning with light and rotation. Paired, but not unpaired, stimulus presentations produced cumulative depolarization and increased input resistance in type B cells. These membrane changes are similar to those observed after pairings of light and rotation are administered to either intact animals or isolated nervous systems or when light is paired with electrical stimulation of the vestibular system in isolated nervous systems. One and two days after treatment, pairing- and light-specific suppression of phototactic behavior was observed in recovered animals. These findings indicate that the membrane changes of type B cells produced by pairing light with current injections cause acquisition of the learned behavior.

Cardiovascular risk prevalence in South Africans with drug-resistant tuberculosis: a cross-sectional study.

In South Africa, the risk factors for cardiovascular disease (CVD) are increasing, thereby impacting patients with drug-resistant tuberculosis (DR-TB). To determine the prevalence of traditional CVD risk factors (diabetes mellitus [DM], smoking, hypertension, increased body mass index [BMI]) and a total risk score for CVD among patients with DR-TB. This cross-sectional study was nested within an ongoing cluster-randomized trial in 10 DR-TB hospitals in South Africa. The data for the present study were collected between November 2014 and July 2016. Of 900 participants aged 18 years, 75.1% were co-infected with the human immunodeficiency virus (HIV), and 52.3% had one or more CVD risk factors. The prevalence of CVD risk factors was hypertension (16.7%), increased BMI (16.6%), DM (5.2%), and smoking (31.4%). Among patients with DM or hypertension, 58.8-95.5% had additional comorbid CVD risk factors. Of 398 participants eligible for the CVD risk score (age 35 years), 23.4% had a moderate or high CVD risk score. Patients with multiple diseases, including DR-TB and HIV, with traditional CVD risk factors, may have higher risks for negative outcomes during treatment for DR-TB. TB providers should identify people at risk to initiate primary and secondary prevention to improve outcomes. .

Evaluation of miLINC to shorten time to treatment for rifampicin-resistant Mycobacterium tuberculosis.

BACKGROUND: Achieving the 90-90-90 targets for tuberculosis (TB) will require interventions that enhance diagnosis, linkage, treatment and adherence to care. As a first step in the process, our team designed a suite of smartphone applications known as miLINC to improve time from diagnosis to treatment initiation in drug-resistant TB patients.SETTING: Three clinical locations in a large, peri-urban district in KwaZulu-Natal, South Africa.OBJECTIVE: To assess the acceptability, feasibility and impact of the miLINC mobile health applications as a solution to reducing the time from presentation to treatment initiation of rifampicin-resistant (RR) TB patients.METHODS: We used a prospective, observational quality improvement evaluation of miLINC's impact among newly diagnosed patients with RR-TB.RESULTS: A convenience sample comprising details of 6341 patients with presumptive TB were entered into miLINC. Of the 631 TB-positive sputum specimens, 41 (6.5%) were found to be RR-TB. The mean time from clinical presentation to RR-TB treatment initiation was 3 days, 21 h, 17 min.CONCLUSION: This is the first study to suggest that the time from presentation to diagnosis and to treatment initiation for patients with RR-TB can be significantly improved using an integrated approach combining technology with appropriate human resources.

Effect of the women's health initiative on prescription anti-osteoporosis medication utilization.

UNLABELLED: Publication of the Women's Health Initiative (WHI) resulted in a 39% reduction in hormone therapy utilization and a 29% increase in the use of new anti-osteoporosis medications. Overall, the prevalence of prescription anti-osteoporosis medication use declined following the WHI. This has important implications for osteoporosis prevention and treatment. INTRODUCTION: Women who discontinued hormone therapy (HT) following the Women's Health Initiative (WHI) may have been more likely to initiate treatment with newer anti-osteoporosis medications (AOM). The objective of this study was to examine the influence of the WHI on AOM utilization among a nationally representative sample of older adult women in the U.S. METHODS: We used the Medical Expenditure Panel Survey (MEPS) to examine AOM utilization among women aged 50 years and older. National estimates of AOM utilization were predicted from a sample of 2089 women interviewed five times between 2002 and 2003. AOM utilization was dichotomized for HT and newer AOM. Generalized estimating equations were used to predict odds ratios (OR) for AOM utilization controlling for potential predisposing, enabling, and need confounders. RESULTS: Prior to the WHI, there were 8.7 and 3.6 million U.S. women using HT and newer AOM, respectively. One year following publication of the WHI, 5.3 million HT users persisted [OR 0.638 (95% CI: 0.617, 0.756)] while 4.7 million women used newer AOM [1.337 (95% CI: 1.120, 1.597)]. CONCLUSIONS: Although reductions in HT utilization were accompanied by increased utilization of newer AOM, treatment prevalence for osteoporosis remains sub-optimal.

Increased risk of aminoglycoside-induced hearing loss in MDR-TB patients with HIV coinfection.

SETTING: A high proportion of individuals with multidrug-resistant tuberculosis (MDR-TB) develop permanent hearing loss due to ototoxicity caused by injectable aminoglycosides (AGs). The prevalence of AG-induced hearing loss is greatest in tuberculosis (TB) and human immunodeficiency virus (HIV) endemic countries in sub-Saharan Africa. However, whether HIV coinfection is associated with a higher incidence of AG-induced hearing loss during MDR-TB treatment is controversial. OBJECTIVE: To evaluate the impact of HIV coinfection on AG-induced hearing loss among individuals with MDR-TB in sub-Saharan Africa. DESIGN: This was a meta-analysis of articles published in PubMed, Embase, Scopus, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Cochrane Review, and reference lists using search terms 'hearing loss', 'aminoglycoside', and 'sub-Saharan Africa'. RESULTS: Eight studies conducted in South Africa, Botswana and Namibia and published between 2012 and 2016 were included. As the included studies were homogeneous (χ2 = 8.84, df = 7), a fixed-effects model was used. Individuals with MDR-TB and HIV coinfection had a 22% higher risk of developing AG-induced hearing loss than non-HIV-infected individuals (pooled relative risk 1.22, 95%CI 1.10-1.36) during MDR-TB treatment. CONCLUSION: This finding is critical for TB programs with regard to the expansion of injectable-sparing regimens. Our findings lend credibility to using injectable-sparing regimens and more frequent hearing monitoring, particularly in resource-limited settings for HIV-coinfected individuals.