Post‐exposure prophylaxis in resource‐poor settings: review and recommendations for pre‐departure risk assessment and planning for expatriate healthcare workers

It is estimated that more than 3 million healthcare workers worldwide suffer needlestick and splash injuries whilst at work resulting in the potential transmission of blood‐borne pathogens via exposure to bodily fluids. Under‐reporting and the subsequent management of occupational injuries is a problem both in the United Kingdom and abroad. Many expatriate health care workers will work in low resource settings where the risk of transmission is greatest but in contrast to wealthier countries such as the United Kingdom, there is often a lack of effective systems for its safe management. This article provides important information about this risk and how to minimise it. The reasons for an increased risk in transmission, its subsequent management and pre‐departure planning are discussed, together with the evidence for initiation of post‐exposure prophylaxis; current National and International guidelines as well as the urgent need for International standardisation of these is also discussed.     

Nonoccupational HIV post‐exposure prophylaxis: a 10‐year retrospective analysis

Background

We conducted a retrospective analysis of administration of nonoccupational HIV post‐exposure prophylaxis (nPEP) in a single centre where tracing and testing of the source of exposure were carried out systematically over a 10‐year period.

Methods

Files of all nPEP requests between 1998 and 2007 were reviewed. Characteristics of the exposed and source patients, the type of exposure, and clinical and serological outcomes were analysed.

Results

nPEP requests increased by 850% over 10 years. Among 910 events, 58% were heterosexual exposures, 15% homosexual exposures, 6% sexual assaults and 20% nonsexual exposures. In 208 events (23%), the source was reported to be HIV positive. In the remaining cases, active source tracing enabled 298 HIV tests to be performed (42%) and identified 11 HIV infections (3.7%). nPEP was able to be avoided or interrupted in 31% of 910 events when the source tested negative. Of 710 patients who started nPEP, 396 (56%) reported side effects, among whom 39 (5%) had to interrupt treatment. There were two HIV seroconversions, and neither was attributed to nPEP failure.

Conclusions

nPEP requests increased over time. HIV testing of the source person avoided nPEP in 31% of events and was therefore paramount in the management of potential HIV exposures. Furthermore, it allowed active screening of populations potentially at risk for undiagnosed HIV infection, as shown by the increased HIV prevalence in these groups (3.7%) compared with a prevalence of 0.3% in Switzerland as a whole.     

Transmission of hepatitis C virus in HIV‐positive and PrEP‐using MSM in England

We sought to characterize risk factors and patterns of HCV transmission amongst men who have sex with men (MSM). MSM with recently acquired HCV (AHCV) were prospectively recruited ('clinic cohort') between January and September 2017. Clinical data and risk behaviours were identified and blood obtained for HCV whole genome sequencing. Phylogenetic analyses were performed, using sequences from this cohort and two other AHCV cohorts, to identify transmission clusters. Sixteen (40.0%) men in the clinic cohort were HIV‐negative MSM. HIV‐negative MSM were younger than HIV‐positive MSM; most (81.3%) had taken HIV PrEP in the preceding year. Eighteen men (45.0%) reported injection drug use; most (34, 85.0%) reported noninjection drug use in the last year. Most in both groups reported condomless anal sex, fisting and sex in a group environment. Few (7, 17.5%) men thought partners may have had HCV. There were 52 sequences in the HCV genotype 1a phylogeny, 18 from the clinic cohort and 34 from other AHCV cohorts; 47 (90.4%) clustered with ≥1 other sequence. There were 7 clusters of 2‐27 sequences; 6 clusters contained HIV‐negative and HIV‐positive MSM and 1 cluster only HIV‐positive MSM. Four of these clusters were part of larger clusters first described in 2007. PrEP‐using MSM are at risk of HCV, sharing similar risk factors to HIV‐positive MSM. Phylogenetics highlights that PrEP‐using and HIV‐positive MSM are involved in the same HCV transmission networks. Few men demonstrated HCV awareness and risk reduction strategies should be expanded.     

Evaluation of glomerular filtration rate in HIV‐1‐infected patients before and after combined antiretroviral therapy exposure*

Background

The prevalence and factors associated with an increased risk of renal dysfunction in HIV‐infected patients receiving or not receiving antiretroviral therapy (ART) have been poorly evaluated in observational settings.

Methods

Patients in the ICONA Foundation cohort with at least two creatinine values available while still ART‐naïve were enrolled in the study. A logistic regression analysis was performed to identify predictors of an estimated glomerular filtration rate (eGFR)<90 mL/min/1.73 m² at baseline. The incidence and predictors of a >20% reduction in eGFR from pre‐combination ART (cART) levels (or a decrease from ≥90 to <90 mL/min/1.73 m²) were evaluated by Poisson regression.

Results

A total of 1505 patients were included in the study; 363 (24%) had eGFR<90 mL/min/1.73 m² at baseline. Older patients [odds ratio (OR) 1.58 per 10 years older; P<0.00001], female patients (OR 2.41 vs. male patients; P<0.00001), those who had diabetes and/or hypertension (OR 2.36 vs. neither; P<0.03) and patients with higher baseline CD4 count (OR 1.06 per 100 cells/μL higher; P<0.03) showed a greater risk of eGFR<90 mL/min/1.73 m². Ninety‐six patients experienced an eGFR decrease of >20% from pre‐cART levels (6.8 per 100 person‐years). Older age [relative risk (RR) 1.41 per 10 years older; P=0.005], female gender (RR 2.25 vs. male; P=0.003) and current exposure to didanosine (ddI), tenofovir and protease inhibitors were the major determinants.

Conclusions

We observed a relatively high rate of mild renal dysfunction in the absence of ART. In addition to traditional risk factors such as older age and diabetes/hypertension, female gender and current use of ddI, tenofovir and protease inhibitors were associated with a greater risk of decreased renal function as measured by eGFR.     

Laboratory‐based interventions targeting food craving: A systematic review and meta‐analysis

This systematic review and meta‐analysis aimed to quantify the effects of laboratory‐based interventions targeting specific mechanisms of food craving, to identify moderators of effects, and to qualitatively summarize findings. The study was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Sixty‐nine studies were included in the quantitative synthesis, and separate meta‐analyses were conducted for the outcomes self‐reported craving and objective food intake. Results show small to medium positive effects across specific craving interventions on both outcomes. Effect sizes were partly moderated by intervention type. The most effective intervention regarding food intake was in sensu cue exposure. For subjective craving, the most robust evidence was found for beneficial effects of cognitive regulation strategies (ie, reappraisal, suppression, and distraction). Results further indicate that training inhibitory control through behavioral inhibition might be more effective than approach‐avoidance training when considering its effect on subjective craving and food intake. People with external eating habits, overeating, or loss‐of‐control eating might benefit from these types of specific craving interventions. Future research should focus on long‐term effects, transferability, and effectiveness in clinical samples.     

Pre‐attentive exposure to the thin female beauty ideal does not affect women's mood,self‐esteem and eating behaviour

Exposure to the thin beauty ideal has been found to decrease women's mood and self‐esteem as well as to increase self‐reported eating pathology. In the present study, it was tested whether the changes in mood, self‐esteem and eating behaviour could be activated outside of conscious attention by ultrashort exposure to either slides of thin media models, obese models or neutral slides. The subliminal exposure did not affect women's mood and self‐esteem in the expected way and the eating behaviour of restrained and unrestrained subjects was unaffected by the manipulation. It is concluded that pre‐attentive exposure to the thin beauty ideal had no devastating effect on the well‐being of women. Note that data from supraliminal studies may be seriously confounded by demand characteristics like answering in a socially desirable way. Copyright © 2001 John Wiley & Sons, Ltd and Eating Disorders Association.     

The environmental neurotoxin β‐N‐methylamino‐L‐alanine inhibits melatonin synthesis in primary pinealocytes and a rat model

The environmental neurotoxin β‐N‐methylamino‐L‐alanine (BMAA) is a glutamate receptor agonist that can induce oxidative stress and has been implicated as a possible risk factor for neurodegenerative disease. Detection of BMAA in mussels, crustaceans, and fish illustrates that the sources of human exposure to this toxin are more abundant than previously anticipated. The aim of this study was to determine uptake of BMAA in the pineal gland and subsequent effects on melatonin production in primary pinealocyte cultures and a rat model. Autoradiographic imaging of 10‐day‐old male rats revealed a high and selective uptake in the pineal gland at 30 minutes to 24 hours after ¹⁴C‐L‐BMAA administration (0.68 mg/kg). Primary pinealocyte cultures exposed to 0.05‐3 mmol/L BMAA showed a 57%‐93% decrease in melatonin synthesis in vitro. Both the metabotropic glutamate receptor 3 (mGluR3) antagonist Ly341495 and the protein kinase C (PKC) activator phorbol‐12‐myristate‐13‐acetate prevented the decrease in melatonin secretion, suggesting that BMAA inhibits melatonin synthesis by mGluR3 activation and PKC inhibition. Serum analysis revealed a 45% decrease in melatonin concentration in neonatal rats assessed 2 weeks after BMAA administration (460 mg/kg) and confirmed an inhibition of melatonin synthesis in vivo. Given that melatonin is a most important neuroprotective molecule in the brain, the etiology of BMAA‐induced neurodegeneration may include mechanisms beyond direct excitotoxicity and oxidative stress.     

Peak provoked craving: an alternative to smoking cue‐reactivity

Smoking cue‐exposure research has provided a powerful tool for examining cravings in the laboratory. A key attraction of this method is that tightly controlled experimental procedures can model craving experiences that are presumed to relate to addiction. Despite its appeal, key assumptions underlying the clinical relevance of smoking cue‐reactivity studies have been questioned recently. For both conceptual and methodological reasons it may be difficult to tease apart cue‐based and abstinence‐based cravings. Moreover, conventional cue‐reactivity procedures typically generate levels of craving with only minimal clinical relevance. We argue here that sometimes it is unfeasible—and in some instances conceptually misguided—to disentangle abstinence‐based and cued components of cigarette cravings. In light of the challenges associated with cue‐reactivity research, we offer an alternative approach to smoking cue‐exposure experimental research focusing on peak provoked craving (PPC) states. The PPC approach uses nicotine‐deprived smokers and focuses on urges during smoking cue‐exposure without subtracting out urge ratings during control cue or baseline assessments. This design relies on two factors found in many cue‐exposure studies—nicotine deprivation and exposure to explicit smoking cues—which, when combined, can create powerful craving states. The PPC approach retains key aspects of the cue‐exposure method, and in many circumstances may be a viable design for studies examining robust laboratory‐induced cravings.     

Use of a dose‐dependent follow‐up protocol and mechanisms to reduce patients and staff radiation exposure in congenital and structural interventions

Background: Increasingly complex structural/congenital cardiac interventions require efforts at reducing patient/staff radiation exposure. Standard follow‐up protocols are often inadequate in detecting all patients that may have sustained radiation burns. Methods: Single‐center retrospective chart review divided into four intervals. Phase 1 (07/07–06/08, 413 procedures (proc)): follow‐up based on fluoroscopy time only; frame rate for digital acquisition (DA) 30 fps, and fluoroscopy (FL) 30 fps. Dose‐based follow‐up was used for phase 2–4. Phase 2 (07/08–08/09, 458 proc): DA: 30 fps, FL: 15 fps. Phase 3 (09/09–06/10, 350 proc): DA: 15–30 fps, FL: 15 fps, use of added radiation protection drape. Phase 4 (07/10–10/10, 89 proc): DA: 15–30 fps, FL: 15 fps, superior noise reduction filter (SNRF) with high‐quality fluoro‐record capabilities. Results: There was a significant reduction in the median cumulative air kerma between the four study periods (710 mGy vs. 566 mGy vs. 498 mGy vs. 241 mGy, P < 0.001), even though the overall fluoroscopy times remained very similar (25 min vs. 26 min vs. 26 min vs. 23 min, P = 0.957). There was a trend towards lower physician radiation exposure over the four study periods (137 mrem vs. 126 mrem vs. 108 mrem vs. 59 mrem, P = 0.15). Fifteen patients with radiation burns were identified during the study period. When changing to a dose‐based follow‐up protocol (phase 1 vs. phase 2), there was a significant increase in the incidence of detected radiation burns (0.5% vs. 2%, P = 0.04). Conclusions: Dose‐based follow‐up protocols are superior in detecting radiation burns when compared to fluoroscopy time‐based protocols. Frame rate reduction of fluoroscopy and cine acquisition and use of modified imaging equipment can achieve a significant reduction to patient/staff exposure. © 2011 Wiley‐Liss, Inc.