Therapeutic turnaround times for common laboratory tests in a tertiary hospital in Kenya

Access to efficient laboratory services is critical to patient care. Turnaround Time (TAT) is one of the most important measures when judging the efficiency of any laboratory and care system. Few studies on TAT exist for inpatient care settings within low- and middle-income countries (LMICs). Methods We evaluated therapeutic TAT for a tertiary hospital in Western Kenya, using a time-motion study focusing specifically on common hematology and biochemistry orders. The aim was to determine significant bottlenecks in diagnostic testing processes at the institution. Results A total of 356 (155 hematology and 201 biochemistry) laboratory tests were fully tracked from the time of ordering to availability of results to care providers. The total therapeutic TAT for all tests was 21.5 ± 0.249 hours (95% CI). The therapeutic TAT for hematology was 20.3 ± 0.331 hours (95% CI) while that for biochemistry tests was 22.2 ± 0.346 hours (95% CI). Printing, sorting and dispatch of the printed results emerged as the most significant bottlenecks, accounting for up to 8 hours of delay (Hematology—8.3 ± 1.29 hours (95% CI), Biochemistry—8.5 ± 1.18 hours (95% CI)). Time of test orders affected TAT, with orders made early in the morning and those in the afternoon experiencing the most delays in TAT. Conclusion Significant inefficiencies exist at multiple steps in the turnaround times for routine laboratory tests at a large referral hospital within an LMIC setting. Multiple opportunities exist to improve TAT and streamline processes around diagnostic testing in this and other similar settings.publishedVersio

Anthracimycin activity against contemporary methicillin-resistant Staphylococcus aureus.

Anthracimycin is a recently discovered novel marine-derived compound with activity against Bacillus anthracis. We tested anthracimycin against an expanded panel of Staphylococcus aureus strains in vitro and in vivo. All strains of S. aureus tested, including methicillin-susceptible, methicillin-resistant (MRSA) and vancomycin-resistant strains of S. aureus, were susceptible to anthracimycin at MIC values of ⩽0.25 mg l(-1). Although its postantibiotic effects were minimal, anthracimycin exhibited potent and rapid bactericidal activity, with a >4-log kill of USA300 MRSA within 3 h at five times its MIC. At concentrations significantly below the MIC, anthracimycin slowed MRSA growth and potentiated the bactericidal activity of the human cathelicidin, LL-37. The bactericidal activity of anthracimycin was somewhat mitigated in the presence of 20% human serum, and the compound was minimally toxic to human cells, with an IC50 (inhibitory concentration 50)=70 mg l(-1) against human carcinoma cells. At concentrations near the MIC, anthracimycin inhibited S. aureus nucleic acid synthesis as determined by optimized macromolecular synthesis methodology, with inhibition of DNA and RNA synthesis occurring in the absence of DNA intercalation. Anthracimycin at a single dose of 1 or 10 mg kg(-1) was able to protect mice from MRSA-induced mortality in a murine peritonitis model of infection. Anthracimycin provides an interesting new scaffold for future development of a novel MRSA antibiotic

Linear and nonlinear waveguides induced by optical vortex solitons

We study, numerically and analytically, linear and nonlinear waveguides induced by optical vortex solitons in a Kerr medium. Both fundamental and first-order guided modes are analyzed, as well as the cases of effectively defocusing and focusing nonlinearity.Comment: 3 pages, 3 figures, changed conten

Mitigating The Burden Of Diabetes In Sub-Saharan Africa Through An Integrated Diagonal Health Systems Approach

Diabetes is a chronic non-communicable disease (NCD) presenting growing health and economic burdens in sub-Saharan Africa (SSA). Diabetes is unique due to its cross-cutting nature, impacting multiple organ systems and increasing the risk for other communicable and non-communicable diseases. Unfortunately, the quality of care for diabetes in SSA is poor, largely due to a weak disease management framework and fragmented health systems in most sub-Saharan African countries. We argue that by synergizing disease-specific vertical programs with system-specific horizontal programs through an integrated disease-system diagonal approach, we can improve access, quality, and safety of diabetes care programs while also supporting other chronic diseases. We recommend utilizing the six World Health Organization (WHO) health system building blocks – 1) leadership and governance, 2) financing, 3) health workforce, 4) health information systems, 5) supply chains, and 6) service delivery – as a framework to design a diagonal approach with a focus on health system strengthening and integration to implement and scale quality diabetes care. We discuss the successes and challenges of this approach, outline opportunities for future care programming and research, and highlight how this approach can lead to the improvement in the quality of care for diabetes and other chronic diseases across SSA

The relationship between a microfinance-based healthcare delivery platform, health insurance coverage, health screenings, and disease management in rural Western Kenya

BACKGROUND: Structural barriers often prevent rural Kenyans from receiving healthcare and diagnostic testing. The Bridging Income Generation through grouP Integrated Care (BIGPIC) Family intervention facilitates microfinance groups, provides health screenings and treatment, and delivers education about health insurance coverage to address some of these barriers. This study evaluated the association between participation in BIGPIC microfinance groups and health screening/disease management outcomes. METHODS: From November 2018 to March 2019, we interviewed a sample of 300 members of two rural communities in Western Kenya, 100 of whom were BIGPIC microfinance members. We queried participants about their experiences with health screening and disease management for HIV, diabetes, hypertension, tuberculosis, and cervical cancer. We used log-binomial regression models to estimate the association between microfinance membership and each health outcome, adjusting for key covariates. RESULTS: Microfinance members were more likely to be screened for most of the health conditions we queried, including those provided by BIGPIC [e.g. diabetes: aPR (95% CI): 3.46 (2.60, 4.60)] and those not provided [e.g. cervical cancer: aPR (95% CI): 2.43 (1.21, 4.86)]. Microfinance membership was not significantly associated with health insurance uptake and disease management outcomes. CONCLUSIONS: In rural Kenya, a microfinance program integrated with healthcare delivery may be effective at increasing health screening. Interventions designed to thoughtfully and sustainably address structural barriers to healthcare will be critical to improving the health of those living in low-resource settings

Targeted Therapies Compared to Dacarbazine for Treatment of BRAF V600E Metastatic Melanoma: A Cost-Effectiveness Analysis

. Purpose. Two BRAF V600E targeted therapies, dabrafenib and vemurafenib, have received US approval for treatment of metastatic melanoma in BRAF V600E patients, a mutation that affects ∼50% of patients. We evaluated the cost-effectiveness of BRAF inhibitors and traditional chemotherapy for treatment of metastatic melanoma. Methods. A Markov model was developed using a societal perspective. Transition probabilities were derived from two Phase III registration trials comparing each BRAF inhibitor against dacarbazine. Costs were obtained from literature, national databases, and Medicare fee schedules. Utilities were obtained from published literature. Deterministic and probabilistic sensitivity analyses were run to test the impact of uncertainties. Results. The incremental cost-effectiveness ratio of dabrafenib was $149,035/QALY compared to dacarbazine. Vemurafenib was dominated by dabrafenib. Probabilistic sensitivity analysis showed that, at a willingness-to-pay (WTP) threshold of ≤$100,000/QALY, dacarbazine was the optimal treatment in ∼85% of simulations. At a WTP threshold of ≥$150,000/QALY, dabrafenib was the optimal treatment. Conclusion. Compared with dacarbazine, dabrafenib and vemurafenib were not cost-effective at a willingness-to-pay threshold of$100,000/QALY. Dabrafenib is more efficient compared to vemurafenib. With few treatment options, dabrafenib is an option for qualifying patients if the overall cost of dabrafenib is reduced to $30,000-$31,000 or a WTP threshold of ≥$150,000/QALY is considered. More comparative data is needed

Supply-chain strategies for essential medicines in rural western Kenya during COVID-19

Problem: The coronavirus disease 2019 (COVID-19) pandemic has disrupted health systems worldwide and threatened the supply of essential medicines. Especially affected are vulnerable patients in low- and middle-income countries who can only afford access to public health systems. Approach: Soon after physical distancing and curfew orders began on 15 March 2020 in Kenya, we rapidly implemented three supply-chain strategies to ensure a continuous supply of essential medicines while minimizing patients' COVID-19 exposure risks. We redistributed central stocks of medicines to peripheral health facilities to ensure local availability for several months. We equipped smaller, remote health facilities with medicine tackle boxes. We also made deliveries of medicines to patients with difficulty reaching facilities. Local setting: Τo implement these strategies we leveraged our 30-year partnership with local health authorities in rural western Kenya and the existing revolving fund pharmacy scheme serving 85 peripheral health centres. Relevant changes: In April 2020, stocks of essential chronic and non-chronic disease medicines redistributed to peripheral health facilities increased to 835 140 units, as compared with 316 330 units in April 2019. We provided medicine tackle boxes to an additional 46 health facilities. Our team successfully delivered medications to 264 out of 311 patients (84.9%) with noncommunicable diseases whom we were able to reach. Lessons learnt: Our revolving fund pharmacy model has ensured that patients' access to essential medicines has not been interrupted during the pandemic. Success was built on a community approach to extend pharmaceutical services, adapting our current supply-chain infrastructure and working quickly in partnership with local health authorities

Strong Lensing Analysis of A1689 from Deep Advanced Camera Images

We analyse deep multi-colour Advanced Camera images of the largest known gravitational lens, A1689. Radial and tangential arcs delineate the critical curves in unprecedented detail and many small counter-images are found near the center of mass. We construct a flexible light deflection field to predict the appearance and positions of counter-images. The model is refined as new counter-images are identified and incorporated to improve the model, yielding a total of 106 images of 30 multiply lensed background galaxies, spanning a wide redshift range, 1.0$<$z$<$5.5. The resulting mass map is more circular in projection than the clumpy distribution of cluster galaxies and the light is more concentrated than the mass within $r<50kpc/h$. The projected mass profile flattens steadily towards the center with a shallow mean slope of $d\log\Sigma/d\log r \simeq -0.55\pm0.1$, over the observed range, r$<250kpc/h$, matching well an NFW profile, but with a relatively high concentration, $C_{vir}=8.2^{+2.1}_{-1.8}$. A softened isothermal profile ($r_{core}=20\pm2$\arcs) is not conclusively excluded, illustrating that lensing constrains only projected quantities. Regarding cosmology, we clearly detect the purely geometric increase of bend-angles with redshift. The dependence on the cosmological parameters is weak due to the proximity of A1689, $z=0.18$, constraining the locus, $\Omega_M+\Omega_{\Lambda} \leq 1.2$. This consistency with standard cosmology provides independent support for our model, because the redshift information is not required to derive an accurate mass map. Similarly, the relative fluxes of the multiple images are reproduced well by our best fitting lens model.Comment: Accepted by ApJ. For high quality figures see http://wise-obs.tau.ac.il/~kerens/A168

Hematopoietic IKBKE limits the chronicity of inflammasome priming and metaflammation

Obesity increases the risk of developing life-threatening metabolic diseases including cardiovascular disease, fatty liver disease, diabetes, and cancer. Efforts to curb the global obesity epidemic and its impact have proven unsuccessful in part by a limited understanding of these chronic progressive diseases. It is clear that low-grade chronic inflammation, or metaflammation, underlies the pathogenesis of obesity-associated type 2 diabetes and atherosclerosis. However, the mechanisms that maintain chronicity and prevent inflammatory resolution are poorly understood. Here, we show that inhibitor of κB kinase epsilon (IKBKE) is a novel regulator that limits chronic inflammation during metabolic disease and atherosclerosis. The pathogenic relevance of IKBKE was indicated by the colocalization with macrophages in human and murine tissues and in atherosclerotic plaques. Genetic ablation of IKBKE resulted in enhanced and prolonged priming of the NLRP3 inflammasome in cultured macrophages, in hypertrophic adipose tissue, and in livers of hypercholesterolemic mice. This altered profile associated with enhanced acute phase response, deregulated cholesterol metabolism, and steatoheptatitis. Restoring IKBKE only in hematopoietic cells was sufficient to reverse elevated inflammasome priming and these metabolic features. In advanced atherosclerotic plaques, loss of IKBKE and hematopoietic cell restoration altered plaque composition. These studies reveal a new role for hematopoietic IKBKE: to limit inflammasome priming and metaflammation

Microfinance, retention in care, and mortality among patients enrolled in HIV 2 Care in East Africa

Objective: To measure associations between participation in community-based microfinance groups, retention in HIV care, and death among people with HIV (PWH) in low-resource settings. Design and methods: We prospectively analyzed data from 3609 patients enrolled in an HIV care program in western Kenya. HIV patients who were eligible and chose to participate in a Group Integrated Savings for Health Empowerment (GISHE) microfinance group were matched 1 : 2 on age, sex, year of enrollment in HIV care, and location of initial HIV clinic visit to patients not participating in GISHE. Follow-up data were abstracted from medical records from January 2018 through February 2020. Logistic regression analysis examined associations between GISHE participation and two outcomes: retention in HIV care (i.e. >1 HIV care visit attended within 6 months prior to the end of follow-up) and death. Socioeconomic factors associated with HIV outcomes were included in adjusted models. Results: The study population was majority women (78.3%) with a median age of 37.4 years. Microfinance group participants were more likely to be retained in care relative to HIV patients not participating in a microfinance group [adjusted odds ratio (aOR) = 1.31, 95% confidence interval (CI) 1.01–1.71; P = 0.046]. Participation in group microfinance was associated with a reduced odds of death during the follow-up period (aOR = 0.57, 95% CI 0.28–1.09; P = 0.105). Conclusion: Participation in group-based microfinance appears to be associated with better HIV treatment outcomes. A randomized trial is needed to assess whether microfinance groups can improve clinical and socioeconomic outcomes among PWH in similar settings