Shades of Grey: Ethical Dilemmas

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Lost to follow-up - contributing factors and challenges in South African patients on antiretroviral therapy

Background. Patients who do not return for follow-up at clinics providing comprehensive HIV/AIDS care require special attention. This is particularly true where resources are limited and clinic loads are high. Themba Lethu Clinic at Helen Joseph Hospital in Johannesburg is a facility supported by PEPFAR funding through Right to Care (Grant CA-574-A-00-02-00018); more than 800 HIV/AIDS patients are seen there each week. Data on a sample of patients who failed to return for follow-up were analysed to identify the causes and to plan strategies to overcome the problem. Methods. A group of 182 patients who missed follow-up appointments at the clinic were identified. Their files were examined to identify possible contributing factors. The patients were then contacted telephonically and asked their reasons for non-attendance. Results. Results show that the leading cause of failure to follow up was financial (34% of patients). Patients cited transport costs and having to pay to open a file at each visit as the biggest monetary obstacles to obtaining treatment. Fifty-five per cent of patients lost to follow-up showed an improvement in CD4 count on treatment. Death accounted for 27% of the patients lost to follow-up and the mean (± standard deviation (SD)) duration of treatment in this group was only 8 (± 6) weeks. Of the patients in this group who had been seen at 4 months, 60% had failed to respond to treatment. The mean duration of ARV treatment before being lost to follow-up was 21 (± 28) weeks. The mean CD4+ count was 92 (± 74.5) cells/μl and the mean number of visits was 3.33 (± 2.17). Seventy-four per cent of the patients were on regimen 1A, and only 1 cited side-effects of medication as a reason for not returning. Conclusions. This study highlighted financial difficulty as the major obstacle to obtaining treatment. There is evidence in support of providing ARV treatment free of charge to HIVpositive patients who qualify, as occurs in other provinces in South Africa. It is also suggested that providing ARV therapy at more local clinics in the community would make treatment more accessible. Provision of several months\' supply of medicines per visit would help to reduce transport costs and minimise patient expenditure. These interventions may reduce the incidence of patients lost to follow-up in this community. South African Medical Journal Vol. 97 (9) 2007: pp. 853-85

The SKA Particle Array Prototype: The First Particle Detector at the Murchison Radio-astronomy Observatory

We report on the design, deployment, and first results from a scintillation detector deployed at the Murchison Radio-astronomy Observatory (MRO). The detector is a prototype for a larger array -- the Square Kilometre Array Particle Array (SKAPA) -- planned to allow the radio-detection of cosmic rays with the Murchison Widefield Array and the low-frequency component of the Square Kilometre Array. The prototype design has been driven by stringent limits on radio emissions at the MRO, and to ensure survivability in a desert environment. Using data taken from Nov.\ 2018 to Feb.\ 2019, we characterize the detector response while accounting for the effects of temperature fluctuations, and calibrate the sensitivity of the prototype detector to through-going muons. This verifies the feasibility of cosmic ray detection at the MRO. We then estimate the required parameters of a planned array of eight such detectors to be used to trigger radio observations by the Murchison Widefield Array.Comment: 17 pages, 14 figures, 3 table

Highly flexible silica/chitosan hybrid scaffolds with oriented pores for tissue regeneration

Inorganic/organic sol–gel hybrids have nanoscale co-networks of organic and inorganic components that give them the unique potential of tailored mechanical properties and controlled biodegradation in tissue engineering applications. Here, silica/chitosan hybrid scaffolds with oriented structures were fabricated through the sol–gel method with a unidirectional freeze casting process. 3-Glycidoxypropyl trimethoxysilane (GPTMS) was used to obtain covalent inorganic/organic coupling. Process variables were investigated such as cooling rate, GPTMS and inorganic content, which can be used to tailor the mechanical properties and hybrid chemical coupling. Structural characterization and dissolution tests confirmed the covalent cross-linking of the chitosan and the silica network in hybrids. The scaffolds had a directional lamellar structure along the freezing direction and a cellular morphology perpendicular to the freezing direction. Compression testing showed that the scaffolds with 60 wt% organic were flexible and elastomeric perpendicular to the freezing direction whilst behaving in an elastic-brittle fashion parallel to the freezing direction. The compressive strengths are about one order of magnitude higher in the latter direction reaching values of the order of 160 kPa. This behaviour provides potential for clinicians to be able to squeeze the materials to fit tissue defect sites while providing some mechanical support from the other direction

Selective priming of rate and duration of the respiratory burst of neutrophils by 1, 2-diacyl and 1-O-alkyl-2-acyl diglycerides. Possible relation to effects on protein kinase C.

Both 1,2-diacyl- and 1-O-alkyl-2-acyl-sn-glycerols are released during stimulation of human polymorphonuclear leukocytes (PMNL). 1,2-Diacylglycerols have received intense interest as intracellular "second messengers" due to their ability to activate protein kinase C (Ca2+ phospholipid-dependent enzyme). However, little is known about bioactivities of the alkylacylglycerols. This study compared the ability of 1,2-diacyl- and 1-O-alkyl-2-acylglycerols to modulate the respiratory burst of stimulated PMNL, a response which depends on the activation of an NADPH oxidase to generate bactericidal species of reduced oxygen. Direct stimulation by N-formyl-Met-Leu-Phe caused an abrupt release of H2O2 which ceased within 2.5 min. Preincubation with diacylglycerols (1-oleoyl-2-acetylglycerol,5-30 microM, and 1,2-dioctanoylglycerol,2-5 microM) caused a decrease in lag time, 3-fold increase in initial rate of H2O2 release, and marked prolongation of the response to N-formyl-Met-Leu-Phe (features characteristic of a priming effect). Preincubation with alkylacylglycerols (1-O-delta 9-octadecenyl-2-acetylglycerol, 5-30 microM, and 1-O-octyl-2-octanoylglycerol, 20-50 microM) primed initiation (shortened lag time and increased velocity) but, in contrast to diacylglycerols, did not alter duration of H2O2 release. While low concentrations of diacylglycerols (5-30 microM) primed PMNL, higher concentrations (greater than or equal to 70 microM) stimulated the cells directly. In contrast, higher (70-100 microM) concentrations of alkylacylglycerols did not prime the responses but, in fact, inhibited priming (especially of duration) induced by diacylglycerol. The high concentrations of alkylacylglycerol also inhibited direct stimulation induced by high concentrations of diacylglycerol. Direct stimulation by high concentrations of diacylglycerol probably involves activation of protein kinase C, whereas alkylacylglycerol was found to inhibit activation of protein kinase C by diacylglycerol in vitro. Thus, diacylglycerols are complete priming agonists, altering both rate and duration of the response. In contrast, alkylacylglycerols may have biphasic, concentration-related effects in modulation of functions of PMNL. At low concentrations, they may facilitate initiation of functional events; however, as their concentration increases, they may serve to terminate responses. The distinct priming effects of these diglycerides also reveal that priming can involve at least two distinct events: 1) initiation and 2) prolongation.(ABSTRACT TRUNCATED AT 400 WORDS

Reducing falls after hospital discharge: Protocol for a randomised controlled trial evaluating an individualised multi-modal falls education program for older adults

Introduction: Older adults frequently fall after discharge from hospital. Older people may have low self-perceived risk of falls and poor knowledge about falls prevention. The primary aim of the study is to evaluate the effect of providing tailored falls prevention education in addition to usual care on falls rates in older people after discharge from hospital compared to providing a social intervention in addition to usual care. Methods and analyses: The ‘Back to My Best’ study is a multisite, single blind, parallel-group randomised controlled trial with blinded outcome assessment and intention-to-treat analysis, adhering to CONSORT guidelines. Patients (n=390) (aged 60 years or older; score more than 7/10 on the Abbreviated Mental Test Score; discharged to community settings) from aged care rehabilitation wards in three hospitals will be recruited and randomly assigned to one of two groups. Participants allocated to the control group shall receive usual care plus a social visit. Participants allocated to the experimental group shall receive usual care and a falls prevention programme incorporating a video, workbook and individualised follow-up from an expert health professional to foster capability and motivation to engage in falls prevention strategies. The primary outcome is falls rates in the first 6 months after discharge, analysed using negative binomial regression with adjustment for participant\u27s length of observation in the study. Secondary outcomes are injurious falls rates, the proportion of people who become fallers, functional status and health-related quality of life. Healthcare resource use will be captured from four sources for 6 months after discharge. The study is powered to detect a 30% relative reduction in the rate of falls (negative binomial incidence ratio 0.70) for a control rate of 0.80 falls per person over 6 months. Ethics and dissemination: Results will be presented in peer-reviewed journals and at conferences worldwide. This study is approved by hospital and university Human Research Ethics Committees