Utilizing quantitative dried blood spot analysis to objectively assess adherence to cardiovascular pharmacotherapy among patients at Kenyatta National Hospital, Nairobi, Kenya.

The burden of cardiovascular disease (CVD) is rising in Kenya and non-adherence to cardiovascular pharmacotherapy is a growing global public health issue that leads to treatment failure, an increased risk of cardiac events and poor clinical outcomes. This study assessed adherence to selected cardiovascular therapy medications among CVD patients attending outpatient clinics at Kenyatta National Hospital, Kenya by determining drug concentration(s) in patient dried blood spot (DBS) samples. Patients who had been taking one or more of the five commonly prescribed CVD medications (amlodipine, atenolol, atorvastatin, losartan, and valsartan) for at least six months were enrolled. Each patient completed a short questionnaire about their medication history and then provided a finger-prick blood spot sample from which drug concentrations were determined by liquid chromatography-high resolution mass spectrometry analysis. Two hundred and thirty-nine patients (62.3% female) participated in the study. The median number of medications used by patients was 2 (IQR 75%-25% is 3-1). Less than half (117; 49.0%) of patients were adherent to their prescribed CVD pharmacotherapy. Binary regression analysis revealed a significant correlation between non-adherence and the number of medications in the treatment regimen (Odds Ratio (OR) 1.583; 95%CI: 0.949-2.639; P-value = 0.039) and that gender was not an independent predictor of medication adherence (OR 1.233; 95%CI: 0.730-2.083; P-value = 0.216). Valuable information about adherence to each medication in the patient's treatment regimen was obtained using quantitative DBS analysis showing that adherence to CVD medications was not uniform. DBS sampling, due its minimally invasive nature, convenience and ease of transport is a useful alternative matrix to monitor adherence to pharmacotherapies objectively, when combined with hyphenated mass spectrometry analytical techniques. This information can provide physicians with an evidence-based novel approach towards personalization and optimization of CVD pharmacotherapy and implementing interventions in the Kenyan population, thereby improving clinical outcomes.

Patients Access to Medicines - A Critical Review of the Healthcare System in Kenya.

Access to affordable, safe, effective, and quality-assured medicines by a patient is important for good health outcomes. Unfortunately, there is sparse literature published on the pharmaceutical enablers that may increase the sale of a substandard and falsified (SF) medicine to a patient in Kenya. The review highlights some of the factors that may facilitate the entry of SF medicines into the legitimate pharmaceutical supply chain and discusses their impact on patient access to medicines. Lack of essential medicines in public health facilities is an important factor that may contribute to increased demand for medicine-related out-of-pocket expenses from private health facilities, thus a likelihood for a patient purchasing SF medicine from unlicensed and illegal medicine outlets or unregulated websites. The need to increase medicine availability in the public sector by the Ministry of Health (MOH) is emphasized in addition to the strengthening of public procurement to cushion it from corruption and mismanagement. In addition, the MOH should promote local pharmaceutical manufacturing and implement a medicine pricing containment policy to avoid abuse and prevent overexploitation of patients, increase medicine price transparency, and reduce pharmaceutical supply chain distortion. Recommended regulatory reviews include accreditation of unlicensed illegal medicine outlets to facilitate accountability, regulatory oversight, and active surveillance. The national post-market surveillance regulatory capacity should be strengthened to improve rational medicine use. A 3-year diploma course should be replaced with a shorter 1- or 2-year pharmaceutical support staff training not eligible to superintend a pharmacy. The recommended legislative review includes a mandatory clause to enforce generic prescribing and the implementation of generic substitution by health workers. Unethical manipulative pharmaceutical marketing practices should carry stiffer penalties to deter malpractice. Future research areas include investigation of medicine prescribing and dispensing practices, medicine consumption studies, medicine price differences within different health sub-sectors, and between licensed pharmacies and unlicensed illegal medicine outlets.

Setting research priorities for management and treatment of hyperhidrosis: the results of the James Lind Alliance Priority Setting Partnership.

BACKGROUND: Hyperhidrosis is a common skin condition characterized by excessive sweating, which can negatively impact on quality of life. It is under-researched compared with other conditions of similar prevalence. AIM: To generate a Top 10 list of research priorities for the treatment and management of hyperhidrosis, with equal input from people with hyperhidrosis and healthcare professionals (HCPs). METHODS: A priority setting partnership (PSP) was established and processes from the James Lind Alliance Handbook were followed. An online survey asked participants what questions they would like research to answer. These questions were grouped into 'indicative questions', which were ranked in a second survey of 45 indicative questions. The top 23 questions were then taken to a final workshop event attended by key stakeholders, and ranked to generate the Top 10 list of research priorities. RESULTS: There were 592 questions submitted by 268 respondents for the first survey. For the second survey, 286 participants ranked the indicative questions in order of priority. At the final workshop, the Top 10 list was generated. The top three priorities were: (i) Are there any safe and effective permanent solutions for hyperhidrosis? (ii) What is the most effective and safe oral treatment (drugs taken by mouth) for hyperhidrosis? and (iii) What are the most effective and safe ways to reduce sweating in particular areas of the body? CONCLUSIONS: There are many unanswered research questions that both people with hyperhidrosis and HCPs would like to see answered. The results from this PSP will help to ensure future research funding can be directed to these areas of priority.

Corrigendum to Jin et al. Do Undergraduate Students Change Their Attitudes to People with Obesity After Following a Healthy Lifestyle Challenge? Current Developments in Nutrition, 2020;4 (Supp_2):nzaa059_029.

[This corrects the article DOI: 10.1093/cdn/nzaa059_029.].

Remote effects of acute kidney injury in a porcine model.

Acute kidney injury (AKI) is a common and serious condition with no specific treatment. An episode of AKI may affect organs distant from the kidney, further increasing the morbidity associated with AKI. The mechanism of organ cross talk after AKI is unclear. The renal and immune systems of pigs and humans are alike. Using a preclinical animal (porcine) model, we tested the hypothesis that early effects of AKI on distant organs is by immune cell infiltration, leading to inflammatory cytokine production, extravasation, and edema. In 29 pigs exposed to either sham surgery or renal ischemia-reperfusion (control, n = 12; AKI, n = 17), we assessed remote organ (liver, lung, brain) effects in the short (from 2- to 48-h reperfusion) and longer term (5 wk later) using immunofluorescence (for leukocyte infiltration, apoptosis), a cytokine array, tissue elemental analysis (e.g., electrolytes), blood hematology and chemistry (e.g., liver enzymes), and PCR (for inflammatory markers). AKI elicited significant, short-term (∼24 h) increments in enzymes indicative of acute liver damage (e.g. , AST: ALT ratio; P = 0.02) and influenced tissue biochemistry in some remote organs (e.g., lung tissue [Ca(2+)] increased; P = 0.04). These effects largely resolved after 48 h, and no further histopathology, edema, apoptosis, or immune cell infiltration was noted in the liver, lung, or hippocampus in the short and longer term. AKI has subtle biochemical effects on remote organs in the short term, including a transient increment in markers of acute liver damage. These effects resolved by 48 h, and no further remote organ histopathology, apoptosis, edema, or immune cell infiltration was noted.

Maternal protein-energy malnutrition during early pregnancy in sheep impacts the fetal ornithine cycle to reduce fetal kidney microvascular development.

This paper identifies a common nutritional pathway relating maternal through to fetal protein-energy malnutrition (PEM) and compromised fetal kidney development. Thirty-one twin-bearing sheep were fed either a control (n=15) or low-protein diet (n=16, 17 vs. 8.7 g crude protein/MJ metabolizable energy) from d 0 to 65 gestation (term, ∼ 145 d). Effects on the maternal and fetal nutritional environment were characterized by sampling blood and amniotic fluid. Kidney development was characterized by histology, immunohistochemistry, vascular corrosion casts, and molecular biology. PEM had little measureable effect on maternal and fetal macronutrient balance (glucose, total protein, total amino acids, and lactate were unaffected) or on fetal growth. PEM decreased maternal and fetal urea concentration, which blunted fetal ornithine availability and affected fetal hepatic polyamine production. For the first time in a large animal model, we associated these nutritional effects with reduced micro- but not macrovascular development in the fetal kidney. Maternal PEM specifically impacts the fetal ornithine cycle, affecting cellular polyamine metabolism and microvascular development of the fetal kidney, effects that likely underpin programming of kidney development and function by a maternal low protein diet.

Remote conditioning or erythropoietin before surgery primes kidneys to clear ischemia-reperfusion-damaged cells: a renoprotective mechanism?

Acute kidney injury is common, serious with no specific treatment. Ischemia-reperfusion is a common cause of acute kidney injury (AKI). Clinical trials suggest that preoperative erythropoietin (EPO) or remote ischemic preconditioning may have a renoprotective effect. Using a porcine model of warm ischemia-reperfusion-induced AKI (40-min bilateral cross-clamping of renal arteries, 48-h reperfusion), we examined the renoprotective efficacy of EPO (1,000 iu/kg iv.) or remote ischemic preconditioning (3 cycles, 5-min inflation/deflation to 200 mmHg of a hindlimb sphygmomanometer cuff). Ischemia-reperfusion induced significant kidney injury at 24 and 48 h (χ(2), 1 degree of freedom, >10 for 6/7 histopathological features). At 2 h, a panel of biomarkers including plasma creatinine, neutrophil gelatinase-associated lipocalin, and IL-1ß, and urinary albumin:creatinine could be used to predict histopathological injury. Ischemia-reperfusion increased cell proliferation and apoptosis in the renal cortex but, for pretreated groups, the apoptotic cells were predominantly intratubular rather than interstitial. At 48-h reperfusion, plasma IL-1ß and the number of subcapsular cells in G2-M arrest were reduced after preoperative EPO, but not after remote ischemic preconditioning. These data suggest an intrarenal mechanism acting within cortical cells that may underpin a renoprotective function for preoperative EPO and, to a limited extent, remote ischemic preconditioning. Despite equivocal longer-term outcomes in clinical studies investigating EPO as a renoprotective agent in AKI, optimal clinical dosing and administration have not been established. Our data suggest further clinical studies on the potential renoprotective effect of EPO and remote ischemic preconditioning are justified.