The evidence base for many aspects of the management of foot ulcers in people with diabetes is weak, and good-quality research, especially relating to studies of direct relevance to routine clinical ...care, is needed. In this paper, we summarise the core details required in the planning and reporting of intervention studies in the prevention and management of diabetic foot ulcers, including studies that focus on off-loading, stimulation of wound healing, peripheral artery disease, and infection. We highlight aspects of trial design, conduct, and reporting that should be taken into account to minimise bias and improve quality. We also provide a 21-point checklist for researchers and for readers who assess the quality of published work.
A 68-year-old woman with a history of diabetes mellitus type 2, depression, and migraines presented with painless, acute, consecutive vision loss affecting the right eye for 1 week and the left eye ...for 2 weeks. Neuro-ophthalmic examination was notable for visual acuities of finger-counting peripherally, a central scotoma, anterior uveitis, vitritis, and placoid macular pigmentary changes in each eye (OU). Proprioception was diminished in the bilateral lower extremities. Optical coherence tomography (OCT) revealed hyper-reflectivity and attenuation of the outer retina OU with normal inner retinal architecture and reflectivity. Fluorescein angiography (FA) demonstrated normal filling of the central retinal arteries with patchy choroidal perfusion in the right eye and targetoid punctate foci of leakage in the macula OU. Before the recognition of intraocular inflammation and findings on OCT and FA, the patient was treated for presumed central retinal artery occlusion at an outside hospital. Additional diagnostic testing at our institution revealed an alternate diagnosis. This case highlights a rare presentation of a well-known disease entity and underscores the importance of avoiding diagnostic anchoring in clinical practice.
•We assessed a newly developed tool for child burn prevention in Mongolia.•Mixed research methods were used for the assessment.•Families with children reported that the tool reduces child burn ...risks.•The tool was well accepted, hence context-appropriate.
Child burn injuries in Mongolia are often caused by electric cooking appliances used on the floor or low table in traditional tent-like dwellings (called a ger) which have no separate kitchen. To prevent these injuries, we developed a context-specific kitchen rack to make electric appliances inaccessible to children, and the rack was provided to 50 families with children aged 0–3 years living in gers for a pilot test. In the present study, we investigated their opinions about the rack after they used it for about 10 months through semi-structured interviews, their willingness-to-pay (WTP) for the rack using a contingent valuation method, and their preference for potential modifications of the rack using best–worst scaling. The estimated median WTP was about USD 40 (which was higher than USD 37 at the baseline when they started to use the rack). The highest priority of modifications of the rack was to enclose the lower section of the rack with doors (which was originally open without doors to reduce the production cost). A few families did not use the rack in winter because they used heating stoves instead of electric appliances for cooking, but we found a unanimous view that the rack reduces burn injuries to children, which may be reflected in their increased WTP for the rack. These findings would guide us to make our burn prevention efforts more relevant to real-life situations and socially acceptable in Mongolia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The design of HIV prevention trials in the context of effective HIV preventive methods is a challenge. Alternate designs, including using non-randomised 'observational control arms' have been ...proposed. We used HIV simulated vaccine efficacy trials (SiVETs) to show pitfalls that may arise from using such observational controls and suggest how to conduct the analysis in the face of the pitfalls. Two SiVETs were nested within previously established observational cohorts of fisherfolk (FF) and female sex workers (FSW) in Uganda. SiVET participants received a licensed Hepatitis B vaccine in a schedule (0, 1 and 6 months) similar to that for a possible HIV vaccine efficacy trial. All participants received HIV counselling and testing every quarter for one year to assess HIV incidence rate ratio (IRR) between SiVET and non-SiVET (observational data). Propensity scores, conditional on baseline characteristics were calculated for SiVET participation and matched between SiVET and non-SiVET in the period before and during the SiVET study. We compared IRR before and after propensity score matching (PSM). In total, 3989 participants were enrolled into observational cohorts prior to SiVET, (1575 FF prior to Jul 2012 and 2414 FSW prior to Aug 2014). SiVET enrolled 572 participants (Jul 2012 to Apr 2014 in FF and Aug 2014 to Apr 2017 in FSW), with 953 non-SiVET participants observed in the SiVET concurrent period and 2928 from the pre-SiVET period (before Jul 2012 in FF or before Apr 2014 in FSW). Imbalances in baseline characteristics were observed between SiVET and non-SiVET participants in both periods before PSM. Similarly, HIV incidence was lower in SiVET than non-SiVET; SiVET-concurrent period, IRR = 0.59, 95% CI 0.31-0.68, p = 0.033 and pre-SiVET period, IRR = 0.77, 95% CI 0.43-1.29, p = 0.161. After PSM, participants baseline characteristics were comparable and there were minimal differences in HIV incidence between SiVET and non-SiVET participants. The process of screening for eligibility for efficacy trial selects participants with baseline characteristics different from the source population, confounding any observed differences in HIV incidence. Propensity score matching can be a useful tool to adjust the imbalance in the measured participants' baseline characteristics creating a counterfactual group to estimate the effect of interventions on HIV incidence.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
•Many child burns are caused by electric appliances in Mongolian traditional dwelling.•We developed a context appropriate kitchen rack for child burn prevention.•The use of the rack resulted in safer ...and less stressful cooking environment.•The median willingness-to-pay for the rack was about 15–20% of the monthly income.
The majority of pediatric burns in Mongolia occur within the home, particularly in the spaces dedicated to cooking. This makes home environment modification a priority for injury prevention. Many of these injuries are caused by electric appliances used in traditional tent-like dwellings (called a ger). In the present study, we designed and provided a context appropriate kitchen rack to 50 households with children aged 0–3 years living in gers and investigated parental views on the acceptability of the rack and willingness-to-pay (WTP) through face-to-face structured individual and group interviews and the contingent valuation method. We used the DCchoice package of R to estimate the median WTP and its 95% confidence interval by the household income, previous experience of childhood burn injury, and the number of children in the household. There was a total of 89 children aged <5 years in the 50 households, with a total of 59 burn experiences since birth including 29 treated at inpatient facilities. The median WTP was MNT 106,000 (about USD 37). The WTP appeared to be higher for the households with a higher income, more severe child burn experiences, and a greater number of children in the household. In the group interviews conducted after 4–6 weeks of routine use, the participants indicated that the use of the rack had resulted in a less stressful cooking environment, and the kitchen rack was described as a positive contribution to the reduction of risk to their young children. Whilst there were some suggestions for minor modifications, the rack was well accepted as a means of child burn prevention by the parents of infants and toddlers in Mongolia.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To describe immunologic, virologic, and clinical HIV disease progression by HIV-1 subtype among Africans with well documented estimated dates of HIV infection (EDIs).
Prospective cohort.
Adults and ...youth with documented HIV-1 infection in the past 12 months were recruited from seroincidence cohorts in East and Southern Africa and followed at 3-6 month intervals. Blood for lymphocyte subset and viral load determination was collected at each visit. Pol was sequenced from the first positive specimen to ascertain subtype. Preantiretroviral therapy disease progression was measured by three time-to-event endpoints: CD4 cell count 350 cells/μl or less, viral load measurement at least 1 × 10 copies/ml, and clinical AIDS.
From 2006 to 2011, 615 participants were enrolled at nine research centers in Kenya, Rwanda, South Africa, Uganda, and Zambia; 579 (94.1%) had viral subtyping completed. Predominant subtypes were C (256, 44.2%), A (209, 36.1%), and D (84, 14.5%). After adjustment for age, sex, and human leukocyte antigen alleles in Cox regression analyses, subtype C-infected participants progressed faster than subtype A to all three endpoints CD4 hazard ratio 1.60, 95% (confidence interval) CI 1.16, 2.20; viral load hazard ratio 1.59, 95% CI 1.12, 2.25; and AIDS hazard ratio 1.60, 95% CI 1.11, 2.31). Subtype D-infected participants reached high viral load more rapidly (hazard ratio 1.61, 95% CI 1.01, 2.57) and progressed nearly twice as fast to AIDS compared to subtype A (hazard ratio 1.93, 95% CI 1.21, 3.09).
Subtype-specific differences in HIV disease progression suggest that the local subtype distribution be considered when planning HIV programs and designing and defining clinical endpoints for HIV prevention trials.
ObjectivesAs part of an ongoing, long-term project to co-create burn prevention strategies in Nepal, we collected baseline data to share and discuss with the local community, use as a basis for a ...co-created prevention strategy and then monitor changes over time. This paper reports on the method and outcomes of the baseline survey and demonstrates how the data are presented back to the community.DesignA community-based survey.SettingCommunity based in three rural municipalities in Nepal.Participants1305 households were approached: the head of 1279 households participated, giving a response rate of 98%. In 90.3% of cases, the head of the household was male.ResultsWe found that 2.7% (CI 1.8 to 3.7) of 1279 households, from three representative municipalities, reported at least one serious burn in the previous 12 months: a serious burn was defined as one requiring medical attention and/or inability to work or do normal activities for 24 hours. While only 4 paediatric and 10 adult cases in the previous 12 months reached hospital care, the impact on the lives of those involved was profound. Only one patient was referred on from primary to secondary/tertiary care; the average length of hospital stay for those presenting directly to secondary/tertiary care was 21 days. A range of first-aid behaviours were used, many of which are appropriate for the local context while a few may be potentially harmful (eg, the use of dung).ConclusionThe participatory approach used in this study ensured a high response rate. We have demonstrated that infographics can link the pathway for each of the cases observed from initial incident to final location of care.
•New HIV infections continue to occur amidst available HIV prevention interventions.•Poor adherence is indicated, therefore an affordable HIV vaccine is urgently needed.•HIV vaccine efficacy trials ...need accurate estimate of incidence in the control arm.•Designs using comparison to ‘observational data as control arms’ are contemplated.•We show some of the pitfalls that may arise with comparison to observational control.
Fisherfolks (FF) and female sex workers (FSW) in Uganda could be suitable key populations for HIV vaccine efficacy trials because of the high HIV incidence and good retention in observational cohorts. However, the observed HIV incidence may differ in participants who enroll into a trial. We used simulated vaccine efficacy trials (SiVET) nested within observational cohorts in these populations to evaluate this difference.
SiVETs were nested in two observational cohorts (Jul 2012–Apr 2014 in FF and Aug 2014–Apr 2017 in FSW). From Jan 2012 all observational cohort participants (aged 18–49 years) presenting for quarterly visits were screened for enrolment into SiVETs, until 572 were enrolled. Those not enrolled (screened-out or not screened) in SiVET continued participation in the observational cohorts. In addition to procedures in the observational cohorts (HIV testing & risk assessment), SiVET participants were given a licensed Hepatitis B vaccine mimicking a schedule of a possible HIV vaccine, and followed-up for 12 months.
In total, 3989 participants were enrolled into observational cohorts (1575 FF prior to Jul 2012 and 2414 FSW prior to Aug 2014). Of these 3622 (90.8%) returned at least once, 672 (44.1%) were screened and 572 enrolled in the SiVETs. HIV incidence pre SIVETs was 4.5/100 person years-at-risk (pyar), 95%CI (3.8–5.5). HIV incidence in SiVET was 3.5/100 pyar, (2.2–5.6) and higher in those not enrolled in the SiVET, 5.9/100 pyar, (4.3–8.1). This difference was greatest among FF. In the 12 months post-SIVET period (FF, May 2014–Apr 2015 and FSW, May 2017–Apr 2018), the HIV incidence was 3.7/100 pyar, (2.5–5.8).
HIV incidence was lower in SiVET participants compared to non-SiVET. This difference was different for the two populations. Researchers designing HIV efficacy trials using observational cohort data need to consider the potential for lower than expected HIV incidence following screening and enrolment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Outcomes in observational studies may not best estimate those expected in the HIV vaccine efficacy trials. We compared retention in Simulated HIV Vaccine Efficacy Trials (SiVETs) and observational ...cohorts drawn from two key populations in Uganda.
Two SiVETs were nested within two observational cohorts, one in Fisherfolk (FF) and another one in Female Sex Workers (FSW). Adult participants in each observational cohort were screened for enrolment into SiVETs. Those screened-out or not screened continued participation in the observational (non-SiVET) cohorts. SiVET participants were administered a licensed hepatitis B vaccine in a schedule that mimicked an actual HIV vaccine efficacy trial. Both cohorts were followed for 12 months and retention was assessed through dropout, defined as lost to follow up, being uncontactable, refusal to continue or missing the last study clinic visit. Dropout rates were compared using Poisson models giving rate ratios and 95% confidence intervals (95%CI).
Out of 1525 participants (565 FF and 960 FSW), 572 (38%) were enrolled into SiVETs (282-FF and 290-FSW), and 953 (62%) remained in the non-SiVET cohorts. Overall, 326 (101 SiVET, 225 non-SiVET) dropped out in 1260 Person Years of Observation (PYO), a dropout rate of 25.9 /100 PYO (95%CI: 23.2-28.8); fewer dropped out in the SiVET cohorts (18.4, 95% CI: 15.1-22.4) than in the non-SiVET cohorts (31.6, 95% CI: 27.8-36.1), rate ratio (RR) =0.58, 95% CI: 0.46-0.73. In all cohorts, the dropout was more marked in FSW than in FF population. Duration lived in community was associated with dropout in both SiVETs and religion in both non-SiVET cohorts.
The rate of dropout was lower in SiVET compared to non-SiVET cohort. Though the difference in dropout between SiVET and non-SiVET was generally similar, the actual dropout rates were higher in the FSW population. Conduct of SiVETs in these key populations could mean that designing HIV Vaccine Efficacy Trials will benefit from lower dropout rate shown in SiVET than non-SiVET observational cohort.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intramuscular electroporation (IM/EP) is a vaccine delivery technique that improves the immunogenicity of DNA vaccines. We evaluated the acceptability and tolerability of electroporation among ...healthy African study participants.
Forty-five participants were administered a DNA vaccine (HIV-MAG) or placebo by electroporation at three visits occurring at four week-intervals. At the end of each visit, participants were asked to rate pain at four times: (1) when the device was placed on the skin and vaccine injected, before the electrical stimulation, (2) at the time of electrical stimulation and muscle contraction, and (3) at 10 minutes and (4) 30 minutes after the procedure was completed. For analyses, pain level was dichotomized as either "acceptable" (none/slight/uncomfortable) or "too much" (Intense, severe, and very severe) and examined over time using repeated measures models. Optional brief comments made by participants were summarized anecdotally.
All 45 participants completed all three vaccination visits; none withdrew from the study due to the electroporation procedure. Most (76%) reported pain levels as acceptable at every time point across all vaccination visits. The majority of "unacceptable" pain was reported at the time of electrical stimulation. The majority of the participants (97%) commented that they preferred electroporation to standard injection.
Repeated intramuscular electroporation for vaccine delivery was found to be acceptable and feasible among healthy African HIV vaccine trial participants. The majority of participants reported an acceptable pain level at all vaccination time points. Further investigation may be warranted into the value of EP to improve immunization outcomes. ClinicalTrials.gov NCT01496989.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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