The complex role of Rcor2: Regulates mesenchymal stromal cell differentiation in vitro but is dispensable in vivo.

Recent research has revealed several important pathways of epigenetic regulation leading to transcriptional changes in bone cells. Rest Corepressor 2 (Rcor2) is a coregulator of Lysine-specific histone demethylase 1 (Lsd1), a demethylase linked to osteoblast activity, hematopoietic stem cell differentiation and malignancy of different neoplasms. However, the role of Rcor2 in osteoblast differentiation has not yet been examined in detail. We have previously shown that Rcor2 is highly expressed in mesenchymal stromal cells (MSC) and particularly in the osteoblastic lineage. The role of Rcor2 in osteoblastic differentiation in vitro was further characterized and we demonstrate here that lentiviral silencing of Rcor2 in MC3T3-E1 cells led to a decrease in osteoblast differentiation. This was indicated by decreased alkaline phosphatase and von Kossa stainings as well as by decreased expression of several osteoblast-related marker genes. RNA-sequencing of the Rcor2-downregulated MC3T3-E1 cells showed decreased repression of Rcor2 target genes, as well as significant upregulation of majority of the differentially expressed genes. While the heterozygous, global loss of Rcor2 in vivo did not lead to a detectable bone phenotype, conditional deletion of Rcor2 in limb-bud mesenchymal cells led to a moderate decrease in cortical bone volume. These findings were not accentuated by challenging bone formation by ovariectomy or tibial fracture. Furthermore, a global deletion of Rcor2 led to decreased white adipose tissue in vivo and decreased the capacity of primary cells to differentiate into adipocytes in vitro. The conditional deletion of Rcor2 led to decreased adiposity in fracture callus. Taken together, these results suggest that epigenetic regulation of mesenchymal stromal cell differentiation is mediated by Rcor2, which could thus play an important role in defining the MSC fate.

A 0.05 m Change in Inertial Measurement Unit Placement Alters Time and Frequency Domain Metrics during Running.

Inertial measurement units (IMUs) provide exciting opportunities to collect large volumes of running biomechanics data in the real world. IMU signals may, however, be affected by variation in the initial IMU placement or movement of the IMU during use. To quantify the effect that changing an IMU's location has on running data, a reference IMU was 'correctly' placed on the shank, pelvis, or sacrum of 74 participants. A second IMU was 'misplaced' 0.05 m away, simulating a 'worst-case' misplacement or movement. Participants ran over-ground while data were simultaneously recorded from the reference and misplaced IMUs. Differences were captured as root mean square errors (RMSEs) and differences in the absolute peak magnitudes and timings. RMSEs were ≤1 g and ~1 rad/s for all axes and misplacement conditions while mean differences in the peak magnitude and timing reached up to 2.45 g, 2.48 rad/s, and 9.68 ms (depending on the axis and direction of misplacement). To quantify the downstream effects of these differences, initial and terminal contact times and vertical ground reaction forces were derived from both the reference and misplaced IMU. Mean differences reached up to -10.08 ms for contact times and 95.06 N for forces. Finally, the behavior in the frequency domain revealed high coherence between the reference and misplaced IMUs (particularly at frequencies ≤~10 Hz). All differences tended to be exaggerated when data were analyzed using a wearable coordinate system instead of a segment coordinate system. Overall, these results highlight the potential errors that IMU placement and movement can introduce to running biomechanics data.

Increasing Step Rate Reduces Peak and Cumulative Insole Force in Collegiate Runners.

PURPOSE: The primary goal of this study was to examine changes in peak insole force and cumulative weighted peak force (CWPF)/km with increased step rate in collegiate runners. The secondary goal was to determine whether sacral acceleration correlates with insole force when increasing step rate. METHODS: Twelve collegiate distance runners ran 1000 m outdoors at 3.83 m·s -1 at preferred and 10% increased step rates while insole force and sacral acceleration were recorded. Cumulative weighted peak force/km was calculated from insole force based on cumulative damage models. The effects of step rate on peak insole force and CWPF·km -1 were tested using paired t tests or Wilcoxon tests. Correlation coefficients between peak axial (approximately vertical) sacral acceleration times body mass and peak insole force were calculated on cohort and individual levels. RESULTS: Peak insole force and CWPF·km -1 decreased ( P < 0.001) with increased step rate. Peak axial sacral acceleration did not correlate with peak insole force on the cohort level ( r = 0.35, P = 0.109) but did within individuals (mean, r = 0.69-0.78; P < 0.05). CONCLUSIONS: Increasing step rate may reduce peak vGRF and CWPF·km -1 in collegiate runners. Therefore, clinicians should consider step rate interventions to reduce peak and cumulative vGRF in this population. Individual-specific calibrations may be required to assess changes in peak vGRF in response to increasing step rate using wearable accelerometers.

Acceleration-Based Estimation of Vertical Ground Reaction Forces during Running: A Comparison of Methods across Running Speeds, Surfaces, and Foot Strike Patterns.

Twenty-seven methods of estimating vertical ground reaction force first peak, loading rate, second peak, average, and/or time series from a single wearable accelerometer worn on the shank or approximate center of mass during running were compared. Force estimation errors were quantified for 74 participants across different running surfaces, speeds, and foot strike angles and biases, repeatability coefficients, and limits of agreement were modeled with linear mixed effects to quantify the accuracy, reliability, and precision. Several methods accurately and reliably estimated the first peak and loading rate, however, none could do so precisely (the limits of agreement exceeded ±65% of target values). Thus, we do not recommend first peak or loading rate estimation from accelerometers with the methods currently available. In contrast, the second peak, average, and time series could all be estimated accurately, reliably, and precisely with several different methods. Of these, we recommend the 'Pogson' methods due to their accuracy, reliability, and precision as well as their stability across surfaces, speeds, and foot strike angles.

Hoof Expansion, Deformation, and Surface Strains Vary with Horseshoe Nail Positions.

Racehorses are susceptible to underrun heel hoof conformation. Racehorses are often shod with nails placed toward the heel. It is unknown if palmar nails restrict or alter hoof deformation in a manner that could promote the development of underrun heel conformation over time with repeated loading. To determine how the addition of palmar nails affects heel deformation during limb loading, hoof expansion and hoof wall deformations were quantified using rosette strain gauges and kinematic markers during in the vitro limb loading of cadaveric limbs that simulated midstance for walk, trot, and canter loads. Nail treatments used to attach a horseshoe to the hoof included: toe nails (T), toe and quarter nails (TQ), and toe, quarter, and heel nails (TQH). The effects of nail treatment on heel expansion and hoof wall deformations were assessed using repeated measures analysis of variance (p < 0.05). Nails placed palmar to the quarters of the hoof decreased heel expansion (p < 0.001). Heel nails resulted in the largest changes in hoof wall principal strain directions distally. The application of nails palmar to the hoof quarters alters hoof wall deformation during limb loading. The continued loading of the hoof with palmer nails could alter hoof conformation over time.

Unsupervised Gait Event Identification with a Single Wearable Accelerometer and/or Gyroscope: A Comparison of Methods across Running Speeds, Surfaces, and Foot Strike Patterns.

We evaluated 18 methods capable of identifying initial contact (IC) and terminal contact (TC) gait events during human running using data from a single wearable sensor on the shank or sacrum. We adapted or created code to automatically execute each method, then applied it to identify gait events from 74 runners across different foot strike angles, surfaces, and speeds. To quantify error, estimated gait events were compared to ground truth events from a time-synchronized force plate. Based on our findings, to identify gait events with a wearable on the shank, we recommend the Purcell or Fadillioglu method for IC (biases +17.4 and -24.3 ms; LOAs -96.8 to +131.6 and -137.0 to +88.4 ms) and the Purcell method for TC (bias +3.5 ms; LOAs -143.9 to +150.9 ms). To identify gait events with a wearable on the sacrum, we recommend the Auvinet or Reenalda method for IC (biases -30.4 and +29.0 ms; LOAs -149.2 to +88.5 and -83.3 to +141.3 ms) and the Auvinet method for TC (bias -2.8 ms; LOAs -152.7 to +147.2 ms). Finally, to identify the foot in contact with the ground when using a wearable on the sacrum, we recommend the Lee method (81.9% accuracy).

Prophylactic melatonin for delirium in intensive care (Pro-MEDIC): a randomized controlled trial.

PURPOSE: Delirium is common in the critically ill, highly distressing to patients and families and associated with increased morbidity and mortality. Results of studies on preventative use of melatonin in various patient groups have produced mixed results. The aim of this study was to determine whether administration of melatonin decreases the prevalence of delirium in critically ill patients. METHODS: Multicentre, randomized, placebo-controlled, double-blind trial across 12 Australian ICUs recruiting patients from July 2016 to September 2019. Patients of at least 18 years requiring ICU admission with an expected length of stay (LOS) greater than 72 h; enrolled within 48 h of ICU admission. Indistinguishable liquid melatonin (4 mg; n = 419) or placebo (n = 422) was administered enterally at 21:00 h for 14 consecutive nights or until ICU discharge. The primary outcome was the proportion of delirium-free assessments, as a marker of delirium prevalence, within 14 days or before ICU discharge. Delirium was assessed twice daily using the Confusion Assessment Method for ICU (CAM-ICU) score. Secondary outcomes included sleep quality and quantity, hospital and ICU LOS, and hospital and 90-day mortality. RESULTS: A total of 847 patients were randomized into the study with 841 included in data analysis. Baseline characteristics of the participants were similar. There was no significant difference in the average proportion of delirium-free assessments per patient between the melatonin and placebo groups (79.2 vs 80% respectively, p = 0.547). There was no significant difference in any secondary outcomes including ICU LOS (median: 5 vs 5 days, p = 0.135), hospital LOS (median: 14 vs 12 days, p = 0816), mortality at any time point including at 90 days (15.5 vs 15.6% p = 0.948), nor in the quantity or quality of sleep. There were no serious adverse events reported in either group. CONCLUSION: Enteral melatonin initiated within 48 h of ICU admission did not reduce the prevalence of delirium compared to placebo. These findings do not support the routine early use of melatonin in the critically ill.

An observational study of initial HIV RNA decay following initiation of combination antiretroviral treatment during pregnancy.

BACKGROUND: In pregnancy, reduction of HIV plasma viral load (pVL) for the prevention of vertical transmission is time-constrained. The study primary objective is to investigate factors associated with faster initial HIV RNA half-life decay when combination antiretroviral treatment (cART) is initiated in pregnancy. METHODS: This was a multicentre, retrospective, observational study, conducted in south England, United Kingdom, between August 2001 and February 2018. Data were extracted from case notes of eligible women initiating cART during the index pregnancy. Anonymised data were collated and analysed centrally. Regression analyses were conducted to determine factors associated with faster HIV RNA half-life decay in the first 14 days after commencing cART (first-phase), and with achieving an undetectable maternal pVL by 36 weeks' gestation. We then assessed whether HIV- and obstetric- related parameters differed by antiretroviral third agent class and whether the proportions of women with undetectable pVL at 36 weeks' gestation and at delivery differed by antiretroviral third agent class. RESULTS: Baseline pVL was the only independent factor associated with faster first-phase HIV RNA half-life decay on commencing cART. Lower pVL on day 14 after starting cART was associated with an increased likelihood of achieving an undetectable pVL by 36 weeks' gestation. Integrase inhibitor-based cART was associated with a faster first-phase HIV RNA half-life decay on commencing cART. Overall, 73% and 85% of women had an undetectable pVL at 36 weeks' gestation and at delivery respectively, with no significant difference by antiretroviral third agent class. CONCLUSIONS: Only high baseline pVL independently contributed to a faster rate of first-phase viral half-life decay. pVL at 14 days after initiating cART allows early identification of treatment failure. In the first 14 days after initiating cART in pregnancy, integrase inhibitor-based cART reduced maternal pVL faster than protease inhibitor- and non-nucleoside reverse transcriptase-based cART. While our study findings support INSTI use when initiated in pregnancy especially when initiated at later gestations and in those with higher baseline pVL, other non-INSTI based cART with more data on safety in pregnancy also performed well.

Small volume vacuum phlebotomy tubes: a controlled before-and-after study of a patient blood management initiative in an Australian adult intensive care unit.

BACKGROUND: Patients admitted to intensive care units (ICUs) undergo multiple blood tests. Small volume vacuum phlebotomy tubes (SVTs) provide an important blood conservation measure. SVTs reduce summative blood loss and may reduce odds of transfusion. We aimed to determine whether low volume blood sampling using SVTs for routine diagnostic purposes translates to decreased fall in haemoglobin concentration, and examine downstream effects on anaemia and need for transfusion during ICU admission. STUDY DESIGN AND METHODS: A single-centre, controlled before-and-after study, evaluating a unit-wide changeover from conventional volume vacuum phlebotomy tubes (CVTs) to SVTs on April 2015. All ICU patients admitted for > 48 hours during the 12 months before and after the intervention were included in multivariate and univariate analysis. Groups were stratified into short admissions (2-7 days) and long admissions (> 7 days). RESULTS: A total of 318 patients were analysed. For short admissions, SVTs decreased fall in haemoglobin concentration (unstandardized coefficient, -6.7; P = 0.001) and episodes of severe anaemia (odds ratio, 0.37, P = 0.02). There were no changes to haemoglobin concentration in long admissions. No effects on need for transfusion were observed (short admissions, P = 0.05; long admissions, P = 0.11). SVTs reduced daily sampling volumes by 50% with no increase in laboratory error (short admissions, P = 0.61; long admissions, P = 0.98). A moderate correlation existed between blood draws and fall in haemoglobin concentration (short admissions, r = 0.5; long admissions, r = 0.32). CONCLUSION: SVTs reduce sampling volume without increasing laboratory error. Follow-on effects include reduced fall in haemoglobin concentration and severe anaemia. These correlations are absent in long admissions.

Hepcidin predicts response to IV iron therapy in patients admitted to the intensive care unit: a nested cohort study.

BACKGROUND: Both anaemia and red blood cell (RBC) transfusion are common and associated with adverse outcomes in patients admitted to the intensive care unit (ICU). The aim of this study was to determine whether serum hepcidin concentration, measured early after ICU admission in patients with anaemia, could identify a group in whom intravenous (IV) iron therapy decreased the subsequent RBC transfusion requirement. METHODS: We conducted a prospective observational study nested within a multicenter randomized controlled trial (RCT) of IV iron versus placebo. The study was conducted in the ICUs of four tertiary hospitals in Perth, Western Australia. Critically ill patients with haemoglobin (Hb) of < 100 g/L and within 48 h of admission to the ICU were eligible for participation after enrolment in the IRONMAN RCT. The response to IV iron therapy compared with placebo was assessed according to tertile of hepcidin concentration. RESULTS: Hepcidin concentration was measured within 48 h of ICU admission in 133 patients. For patients in the lower two tertiles of hepcidin concentration (< 53.0 µg), IV iron therapy compared with placebo was associated with a significant decrease in RBC transfusion requirement [risk ratio 0.48 (95% CI 0.26-0.85), p = 0.013]. CONCLUSIONS: In critically ill patients with anaemia admitted to an ICU, baseline hepcidin concentration predicts RBC transfusion requirement and is able to identify a group of patients in whom IV iron compared with placebo is associated with a significant decrease in RBC transfusion requirement. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry: ANZCTRN12612001249 Registered 26/11/2012.

Accelerometer-based prediction of running injury in National Collegiate Athletic Association track athletes.

Running-related injuries (RRI) may result from accumulated microtrauma caused by combinations of high load magnitudes (vertical ground reaction forces; vGRFs) and numbers (strides). Yet relationships between vGRF and RRI remain unclear - potentially because previous research has largely been constrained to collecting vGRFs in laboratory settings and ignoring relationships between RRI and stride number. In this preliminary proof-of-concept study, we addressed these constraints: Over a 60-day period, each time collegiate athletes (n = 9) ran they wore a hip-mounted activity monitor that collected accelerations throughout the entire run. Accelerations were used to estimate peak vGRF, number of strides, and weighted cumulative loading (sum of peak vGRFs weighted to the 9th power) across the entirety of each run. Runners also reported their post-training pain/fatigue and any RRI that prevented training. Across 419 runs and >2.1 million strides, injured (n = 3) and uninjured (n = 6) participants did not report significantly different pain/fatigue (p = 0.56) or mean number of strides per run (p = 0.91). Injured participants did, however, have significantly greater peak vGRFs (p = 0.01) and weighted cumulative loading per run (p < 0.01). Results from this small but extensively studied sample of elite runners demonstrate that loading profiles (load magnitude-number combinations) quantified with activity monitors can provide valuable information that may prove essential for: (1) testing hypotheses regarding overuse injury mechanisms, (2) developing injury-prediction models, and (3) designing and adjusting athlete- and loading-specific training programs and feedback.

Effect of immediate initiation of antiretroviral treatment on the risk of acquired HIV drug resistance.

OBJECTIVE: We estimated and compared the risk of clinically identified acquired drug resistance under immediate initiation [the currently recommended antiretroviral therapy (ART) initiation strategy], initiation with CD4 cell count less than 500 cells/µl and initiation with CD4 cell count less than 350 cells/µl. DESIGN: Cohort study based on routinely collected data from the HIV-CAUSAL collaboration. METHODS: For each individual, baseline was the earliest time when all eligibility criteria (ART-naive, AIDS free, and others) were met after 1999. Acquired drug resistance was defined using the Stanford classification as resistance to any antiretroviral drug that was clinically identified at least 6 months after ART initiation. We used the parametric g-formula to adjust for time-varying (CD4 cell count, HIV RNA, AIDS, ART regimen, and drug resistance testing) and baseline (calendar period, mode of acquisition, sex, age, geographical origin, ethnicity and cohort) characteristics. RESULTS: In 50 981 eligible individuals, 10% had CD4 cell count more than 500 cells/µl at baseline, and 63% initiated ART during follow-up. Of 2672 tests for acquired drug resistance, 794 found resistance. The estimated 7-year risk (95% confidence interval) of acquired drug resistance was 3.2% (2.8,3.5) for immediate initiation, 3.1% (2.7,3.3) for initiation with CD4 cell count less than 500 cells/µl, and 2.8% (2.5,3.0) for initiation with CD4 cell count less than 350 cells/µl. In analyses restricted to individuals with baseline in 2005-2015, the corresponding estimates were 1.9% (1.8, 2.5), 1.9% (1.7, 2.4), and 1.8% (1.7, 2.2). CONCLUSION: Our findings suggest that the risk of acquired drug resistance is very low, especially in recent calendar periods, and that immediate ART initiation only slightly increases the risk. It is unlikely that drug resistance will jeopardize the proven benefits of immediate ART initiation.

Randomized controlled trial of the tolerability and completion of maraviroc compared with Kaletra® in combination with Truvada® for HIV post-exposure prophylaxis (MiPEP Trial).

Objectives: Post-exposure prophylaxis (PEP) for HIV is often poorly tolerated and not completed. Alternative PEP regimens may improve adherence and completion, aiding HIV prevention. We conducted a randomized controlled trial of a maraviroc-based PEP regimen compared with a standard-of-care regimen using ritonavir-boosted lopinavir. Methods: Patients meeting criteria for PEP were randomized to tenofovir disoproxil/emtricitabine (200/245 mg) once daily plus ritonavir-boosted lopinavir (Kaletra ® 400/100 mg) or maraviroc 300 mg twice daily. The composite primary endpoint was completion of 28 days of the allocated PEP regimen without grade 3 or 4 clinical or laboratory adverse events (AEs) related to the PEP medication. Results: Two hundred and thirteen individuals were randomized (107 to maraviroc; 106 to Kaletra ® arm). Follow-up rates were high in both groups. There was no difference in the primary endpoint; 70 (71%) in the maraviroc and 64 (65%) in the Kaletra ® arm ( P = 0.36) completed PEP without grade 3 or 4 AEs. Discontinuation of PEP was the same (18%) in both groups. There were no grade 3 or 4 clinical AEs in either arm, but more grade 1 or 2 clinical AEs in the Kaletra ® arm (91% versus 70%; P < 0.001). Antidiarrhoeal medication use was higher in the Kaletra ® arm (67% versus 25%; P < 0.001). There were no HIV seroconversions in the study period. Conclusions: The completion rate in the absence of grade 3 or 4 AEs was similar with both regimens. Maraviroc-based PEP was better tolerated, supporting its use as an option for non-occupational PEP.

Incidence and cost of stress ulcer prophylaxis after discharge from the intensive care unit: a retrospective study.

OBJECTIVE: To describe current patterns in initiation and cessation of proton pump inhibitors (PPIs) for stress ulcer prophylaxis (SUP) in intensive care units, and to assess the costs associated with inappropriate (non-evidence-based) SUP. DESIGN, SETTING AND PARTICIPANTS: Retrospective observational study in five ICUs in Western Australia. We assessed the medical records of consecutive patients admitted to the ICUs between September 2013 and January 2015. Patients aged < 18 years were excluded. RESULTS: We included 531 patients in the study. Of the 184 patients in whom PPIs were initiated for SUP in the ICU, 90 (48.9%) were still taking the therapy at the time of discharge from hospital. A documented indication for ongoing therapy was present in only nine patients (10%). We assumed a 10-year life expectancy after ICU discharge and that most patients continued taking a PPI, and calculated an additional cost of $180.20 per patient admitted to the ICU. This was based only on unnecessary PPI costs (ignoring costs of managing additional adverse events). The direct cumulative annual cost to the WA health system of PPIs continued unnecessarily for patients at discharge from hospital is estimated to be $250 800 for each year they continue to receive them. CONCLUSION: A substantial proportion of patients prescribed SUP in the ICU continue receiving this therapy at hospital discharge despite no clear indication. In addition to potential adverse clinical effects, this is associated with major direct and indirect cost implications.

Anti-N-methyl-D-aspartate receptor encephalitis with an imaging-invisible ovarian teratoma: a case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis is a recently discovered disease entity of paraneoplastic limbic encephalitis. It largely affects young women and is often associated with an ovarian teratoma. It is a serious yet treatable condition if diagnosed early. Its remedy involves immunotherapy and surgical removal of the teratoma of the ovaries. This case of anti-N-methyl-D-aspartate receptor encephalitis involves an early surgical intervention with bilateral oophorectomy, despite negative imaging evidence of a teratoma. CASE PRESENTATION: A 25-year-old white woman with anti-N-methyl-D-aspartate receptor encephalitis presented with behavioral changes and seizures that were confirmed to be secondary to anti-N-methyl-D-aspartate receptor encephalitis. She required an admission to our intensive care unit for ventilator support and received a number of immunological therapies. Multiple imaging investigations showed no evidence of an ovarian teratoma; she had a bilateral oophorectomy 29 days after admission. Ovarian histology confirmed the presence of a teratoma with neuronal cells. A few days after the operation she began to show signs of improvement and, apart from mild short-term memory loss, she returned to normal function. CONCLUSIONS: Our patient is an example of teratoma-associated anti-N-methyl-D-aspartate receptor encephalitis, in which the teratoma was identified only microscopically. Her case highlights that even with negative imaging evidence of a teratoma, ovarian pathology should still be considered and explored.

Intravenous iron or placebo for anaemia in intensive care: the IRONMAN multicentre randomized blinded trial : A randomized trial of IV iron in critical illness.

PURPOSE: Both anaemia and allogenic red blood cell transfusion are common and potentially harmful in patients admitted to the intensive care unit. Whilst intravenous iron may decrease anaemia and RBC transfusion requirement, the safety and efficacy of administering iron intravenously to critically ill patients is uncertain. METHODS: The multicentre, randomized, placebo-controlled, blinded Intravenous Iron or Placebo for Anaemia in Intensive Care (IRONMAN) study was designed to test the hypothesis that, in anaemic critically ill patients admitted to the intensive care unit, early administration of intravenous iron, compared with placebo, reduces allogeneic red blood cell transfusion during hospital stay and increases the haemoglobin level at the time of hospital discharge. RESULTS: Of 140 patients enrolled, 70 were assigned to intravenous iron and 70 to placebo. The iron group received 97 red blood cell units versus 136 red blood cell units in the placebo group, yielding an incidence rate ratio of 0.71 [95 % confidence interval (0.43-1.18), P = 0.19]. Overall, median haemoglobin at hospital discharge was significantly higher in the intravenous iron group than in the placebo group [107 (interquartile ratio IQR 97-115) vs. 100 g/L (IQR 89-111), P = 0.02]. There was no significant difference between the groups in any safety outcome. CONCLUSIONS: In patients admitted to the intensive care unit who were anaemic, intravenous iron, compared with placebo, did not result in a significant lowering of red blood cell transfusion requirement during hospital stay. Patients who received intravenous iron had a significantly higher haemoglobin concentration at hospital discharge. The trial was registered at http://www.anzctr.org.au as # ACTRN12612001249842.

UK guideline for the use of HIV Post-Exposure Prophylaxis Following Sexual Exposure, 2015.

We present the updated British Association for Sexual Health and HIV guidelines for HIV post-exposure prophylaxis following sexual exposure (PEPSE). This document includes a review of the current data to support the use of PEPSE, considers how to calculate the risks of infection after a potential exposure, and provides recommendations on when PEPSE should and should not be considered. We also review which medications to use for PEPSE, provide a checklist for initial assessment, and make recommendations for monitoring individuals receiving PEPSE. Special scenarios, cost-effectiveness of PEPSE, and issues relating to service provision are also discussed. Throughout the document, the place of PEPSE within the broader context of other HIV prevention strategies is considered.