Perspectives on long-acting formulations of pre-exposure prophylaxis (PrEP) among men who have sex with men who are non-adherent to daily oral PrEP in the United States.

INTRODUCTION: Pre-exposure prophylaxis (PrEP) persistence among men who have sex with men (MSM) in real world clinical settings for HIV prevention is suboptimal. New longer-acting formulations of PrEP are becoming available, including injectables, subdermal implants, and other oral medications. These longer-acting formulations have the potential to improve retention among those who have challenges remaining adherent to daily oral PrEP. METHODS: We interviewed 49 MSM who had initiated but discontinued oral PrEP at three diverse clinics across the United States. We examined participants' perspectives about long-acting PrEP formulations and how long-acting options could affect PrEP use using thematic analysis. RESULTS: Participants were not very knowledgeable about long-acting formulations of PrEP but were open to learning about them and considering use. Participants were concerned about safety and efficacy of products given that they were still newer and/or in development. Finally, participants had clear preferences for oral pills, injectables, and then subdermal implants and were most interested in options that reduced the number of visits to the clinic. CONCLUSION: Long-acting formulations of PrEP are acceptable to MSM with suboptimal PrEP persistence and have the potential to improve PrEP persistence. However, many felt they needed more information on safety, efficacy, and use to consider these options. As these long-acting formulations are implemented, public health campaigns and clinical interventions to encourage may maximize uptake particularly among those who are not currently adherent to daily oral PrEP.

Facilitators for retaining men who have sex with men in pre-exposure prophylaxis care in real world clinic settings within the United States.

BACKGROUND: Pre-exposure prophylaxis (PrEP) can significantly reduce HIV acquisition especially among communities with high HIV prevalence, including men who have sex with men (MSM). Much research has been finding suboptimal PrEP persistence; however, few studies examine factors that enhance PrEP persistence in real-world settings. METHODS: We interviewed 33 patients who identified as MSM at three different PrEP clinics in three regions of the U.S. (Northeast, South, Midwest). Participants were eligible if they took PrEP and had been retained in care for a minimum of 6 months. Interviews explored social, structural, clinic-level and behavioral factors that influencing PrEP persistence. RESULTS: Through thematic analysis we identified the following factors as promoting PrEP persistence: (1) navigation to reduce out-of-pocket costs of PrEP (structural), (2) social norms that support PrEP use (social), (3) access to LGBTQ + affirming medical providers (clinical), (4) medication as part of a daily routine (behavioral), and (5) facilitation of sexual health agency (belief). DISCUSSION: In this sample, persistence in PrEP care was associated with structural and social supports as well as a high level of perceived internal control over protecting their health by taking PrEP. Patients might benefit from increased access, LGBTQ + affirming medical providers, and communications that emphasize PrEP can promote sexual health.

An inguinal hernia imposter.

SUMMARY: This is a report of one of the many imposters of an irreducible inguinal hernia, a dermoid cyst. It is a rare entity that should be considered in the differential diagnosis of a groin lump when an atypical clinical presentation or groin examination occurs. Complete excision with histological evaluation remains the mainstay of surgical treatment.

Molecular, Morphological, and Functional Characterization of Corticotropin-Releasing Factor Receptor 1-Expressing Neurons in the Central Nucleus of the Amygdala.

The central nucleus of the amygdala (CeA) is a brain region implicated in anxiety, stress-related disorders and the reinforcing effects of drugs of abuse. Corticotropin-releasing factor (CRF, Crh) acting at cognate type 1 receptors (CRF1, Crhr1) modulates inhibitory and excitatory synaptic transmission in the CeA. Here, we used CRF1:GFP reporter mice to characterize the morphological, neurochemical and electrophysiological properties of CRF1-expressing (CRF1+) and CRF1-non-expressing (CRF1-) neurons in the CeA. We assessed these two neuronal populations for distinctions in the expression of GABAergic subpopulation markers and neuropeptides, dendritic spine density and morphology, and excitatory transmission. We observed that CeA CRF1+ neurons are GABAergic but do not segregate with calbindin (CB), calretinin (CR), parvalbumin (PV), or protein kinase C-δ (PKCδ). Among the neuropeptides analyzed, Penk and Sst had the highest percentage of co-expression with Crhr1 in both the medial and lateral CeA subdivisions. Additionally, CeA CRF1+ neurons had a lower density of dendritic spines, which was offset by a higher proportion of mature spines compared to neighboring CRF1- neurons. Accordingly, there was no difference in basal spontaneous glutamatergic transmission between the two populations. Application of CRF increased overall vesicular glutamate release onto both CRF1+ and CRF1- neurons and does not affect amplitude or kinetics of EPSCs in either population. These novel data highlight important differences in the neurochemical make-up and morphology of CRF1+ compared to CRF1- neurons, which may have important implications for the transduction of CRF signaling in the CeA.

Role of TLR4 in the Modulation of Central Amygdala GABA Transmission by CRF Following Restraint Stress.

AIMS: Stress induces neuroimmune responses via Toll-like receptor 4 (TLR4) activation. Here, we investigated the role of TLR4 in the effects of the stress peptide corticotropin-releasing factor (CRF) on GABAergic transmission in the central nucleus of the amygdala (CeA) following restraint stress. METHODS: Tlr4 knock out (KO) and wild-type rats were exposed to no stress (naïve), a single restraint stress (1 h) or repeated restraint stress (1 h per day for 3 consecutive days). After 1 h recovery from the final stress session, whole-cell patch-clamp electrophysiology was used to investigate the effects of CRF (200 nM) on CeA GABAA-mediated spontaneous inhibitory postsynaptic currents (sIPSCs). RESULTS: TLR4 does not regulate baseline GABAergic transmission in the CeA of naive and stress-treated animals. However, CRF significantly increased the mean sIPSC frequencies (indicating enhanced GABA release) across all genotypes and stress treatments, except for the Tlr4 KO rats that experienced repeated restraint stress. CONCLUSIONS: Overall, our results suggest a limited role for TLR4 in CRF's modulation of CeA GABAergic synapses in naïve and single stress rats, though TLR4-deficient rats that experienced repeated psychological stress exhibit a blunted CRF cellular response. SHORT SUMMARY: TLR4 has a limited role in CRF's activation of the CeA under basal conditions, but interacts with the CRF system to regulate GABAergic synapse function in animals that experience repeated psychological stress.

Pre-pregnancy counseling for women with heart disease: A prospective study.

BACKGROUND: Women with cardiac disease and their infants are at a greater risk of mortality and morbidity during pregnancy. Expert groups recommend preconception counseling (PCC) for all women with cardiac disease so they are made aware of these risks. We have run a specialist maternal cardiac clinic since 1996. The aim of this study was to evaluate the experience of women who have received PCC within an established multidisciplinary tertiary clinic and to establish their views regarding the counseling they received. METHODS: Single centre prospective study using a patient questionnaire was given to women attending a specialist cardiac preconception counseling clinic from November 2015 to August 2016, with analysis of descriptive data and free text comments from the questionnaire responders. RESULTS: 40/65 returned patient questionnaires. Prior to the consultation fewer than half felt well informed regarding how their heart disease could impact upon pregnancy but a similar proportion felt nonetheless that they would be able to have a healthy pregnancy. Women reported two main areas of concerns, their own health (whether they would survive a pregnancy) and the health of their child. 15% of women reported that these concerns had prevented them from pursuing a pregnancy. Women reported high satisfaction rates with the clinic. CONCLUSIONS: There is an increasing demand for PCC services for women with cardiac disease; our study is the first attempt to determine both the acceptability and the impact of PCC from the patient perspective. Patients reported a high level of satisfaction with the service provided.

2nd BASHH Oxford Diagnostics Course, November 2015.

The second British Association for Sexual Health and HIV Oxford Diagnostics Course of 2015 focussed on recent challenges and emerging concepts within diagnostics and service design. In response to increasing sexually transmitted infection rates and subsequent demand on UK sexual health services, multiple approaches to improving patient flow and reducing waiting times were presented. The value of novel remote sexually transmitted infection testing was explored, with a description of the patient journey, emerging demographics and rates of testing uptake for the UK's leading National Health Service provider. A cost-benefit evaluation was made for the use of nucleic acid amplification tests versus traditional microscopy and culture for detecting Trichomonas vaginalis, with practical consideration of application to higher risk groups. Two speakers stressed the importance of vigilance against growing antimicrobial resistance. The significance of testing for genotypic markers for antimicrobial resistance, and the emergence of point-of-care tests for resistance were also presented. The meeting closed with a first-hand account of tendering, and practical advice on rebuilding professional relationships and services after a competitive process.

Management of acute complex traumatic wound with a dermal regeneration template: Case report.

BACKGROUND: Acute complex traumatic wounds of the lower limbs are usually managed by a combination of multiple debridements, dressing changes, and specialized surgical procedures which may include tissue transfers for the reconstruction of the soft tissue injury. The recovery is lengthy, and the outcome dependent on the initial injury, the surgical procedures undertaken and rehabilitation programs with a multidisciplinary team. METHOD: A nine-year-old male patient presented to Kimberly Hospital with an extensive soft tissue injury of the leg associated with a tibia fracture caused by a high velocity pedestrian vehicle accident. RESULTS: A combination of proper wound care, "homemade" negative pressure wound therapy dressings, reduction of fracture and use of a dermal regeneration template over the fracture site, followed by skin grafting was used to manage the wound. CONCLUSION: The final functional and cosmetic results obtained with the case suggest that the dermal regeneration template may provide a potential alternative for coverage of complex wounds, which might include an open fracture, without the need for complex tissue transfer interventions.

A Case of Adenovirus Viremia in a Pediatric Liver Transplant Recipient With Neutropenia and Lymphopenia: Who and When Should We Treat?

Human adenovirus (HAdV) is one of the most feared infections among immunocompromised patients. In particular, in liver transplant patients, HAdV has been implicated in acute liver failure with resultant mortality. The development of current molecular techniques and surveillance testing protocols have provided tools for early detection of HAdV infection, prior to or at the early onset of HAdV disease. Although reduction in immune suppression is the mainstay of therapy, many researchers have also advocated for early administration of antiviral therapy. In multiple reports, cidofovir treatment has been associated with declines in HAdV viral loads or clinical improvement in solid organ and bone marrow transplant recipients. However, there have also been case reports that raise questions about the effectiveness of antiviral therapy in controlling systemic HAdV disease. We report a case of a 26-month-old male recipient of a liver transplantation for hepatoblastoma who developed adenoviremia with an associated hepatitis and gastroenteritis. He recovered with reduced immune suppression but without antiviral therapy, thus avoiding potential toxicities associated with cidofovir therapy. This case a contrast to previous reports, and it highlights the ambiguity regarding which patients should receive HAdV-specific antiviral therapy. Additional knowledge regarding specific pediatric host factors and HAdV factors that predict poor outcomes are needed. Such information would allow clinicians to better stratify patients by risk at the time of adenoviremia detection so that low-risk patients are not unnecessarily exposed to medications with potential toxicities.

Gene expression profiling to predict the risk of locoregional recurrence in breast cancer: a pooled analysis.

The 70-gene signature (MammaPrint) has been developed to predict the risk of distant metastases in breast cancer and select those patients who may benefit from adjuvant treatment. Given the strong association between locoregional and distant recurrence, we hypothesize that the 70-gene signature will also be able to predict the risk of locoregional recurrence (LRR). 1,053 breast cancer patients primarily treated with breast-conserving treatment or mastectomy at the Netherlands Cancer Institute between 1984 and 2006 were included. Adjuvant treatment consisted of radiotherapy, chemotherapy, and/or endocrine therapy as indicated by guidelines used at the time. All patients were included in various 70-gene signature validation studies. After a median follow-up of 8.96 years with 87 LRRs, patients with a high-risk 70-gene signature (n = 492) had an LRR risk of 12.6% (95% CI 9.7-15.8) at 10 years, compared to 6.1% (95% CI 4.1-8.5) for low-risk patients (n = 561; P < 0.001). Adjusting the 70-gene signature in a competing risk model for the clinicopathological factors such as age, tumour size, grade, hormone receptor status, LVI, axillary lymph node involvement, surgical treatment, endocrine treatment, and chemotherapy resulted in a multivariable HR of 1.73 (95% CI 1.02-2.93; P = 0.042). Adding the signature to the model based on clinicopathological factors improved the discrimination, albeit non-significantly [C-index through 10 years changed from 0.731 (95% CI 0.682-0.782) to 0.741 (95% CI 0.693-0.790)]. Calibration of the prognostic models was excellent. The 70-gene signature is an independent prognostic factor for LRR. A significantly lower local recurrence risk was seen in patients with a low-risk 70-gene signature compared to those with high-risk 70-gene signature.

Treatment of the edentulous atrophic maxilla using zygomatic implants: evaluation of survival rates over 5-10 years.

The aim of this retrospective observational cohort study was to analyse and report the 5-10-year survival rates of endosseous zygomatic implants used in the rehabilitation of the atrophic maxilla. Forty-three consecutive zygomatic implant placements in 25 patients were evaluated over a 5-10-year period. All zygomatic implant surgery was carried out under general anaesthesia. Nobel Biocare zygomatic machined-surface implants were used, and placement was undertaken using the modified sinus slot method. The main outcome measures and determinants for success were survival of the restored implants and the proportion of originally planned prostheses delivered to patients. Of the 25 patients treated, 12 were male and 13 were female; 19 were non-smokers, and the mean age at time of surgery was 64 years. Patients were treatment-planned for implant-retained bridgework, a removable prosthesis retained by fixed cast gold or milled titanium beams, or magnet-retained removable prostheses. A combination of zygomatic and conventional implants was used in all but one patient. In this study it was shown that the overall success rate for zygomatic implants was 86%, with six of the implants either failing to integrate or requiring removal due to persistent infection associated with the maxillary sinus. All patients received their planned prosthesis, although in six cases the method of retention required modification. This study illustrates that zygomatic implants are a successful and important treatment option when trying to restore the atrophic maxilla, with the potential to avoid additional augmentation/grafting procedures and resulting in a high long-term success rate.

Applied peritoneal anatomy.

The peritoneal cavity is a complex anatomical structure with multiple attachments and connections. These are better understood with reference to the embryological development of this region. Armed with this knowledge, the diagnosis and assessment of a wide range of common intra-abdominal diseases becomes straightforward. This article will review and simplify the terminology, complex embryological development, and anatomy of the peritoneum, peritoneal attachments, and the reflections forming the peritoneal boundaries. Normal anatomy will be described using schematic diagrams with corresponding computed tomography (CT) and magnetic resonance imaging (MRI) images, including CT peritoneograms. The relevance of intra- and extra-peritoneal anatomy to common pathological processes will be demonstrated.

Effects of radiotherapy to the jaws. I: The scale of the problem.

Cancer care has become one of the main targets of the National Health Service in England and with cancer patients surviving longer, it is likely that head and neck cancer patients will make up a large proportion of patients seen within secondary care settings in the future. The management of these patients can be very difficult for a number of reasons. Part one of this paper attempts to highlight the major oral health problems encountered by these patients during and after their cancer treatment and supported by the current literature. Part two of this series will address the dental management of head and neck oncology patients undergoing radiotherapy with particular attention of possible improvement to current management strategies for these patients.

Effects of radiotherapy to the jaws. 2: Potential solutions.

Dental maintenance and rehabilitation of head and neck cancer care is becoming more important as the outcome of cancer treatment improves. The management of these patients can be very difficult for a number of reasons as discussed in part one of this two-part series. This second part attempts to suggest possible solutions for the management of the major oral health problems encountered by these patients during and after their cancer treatment.

Management and outcome of pregnancies with parvovirus B19 infection over seven years in a tertiary fetal medicine unit.

OBJECTIVES: To determine rates of fetal anaemia and pregnancy outcome in susceptible pregnant women infected with human parvovirus B19 infection in a tertiary fetal medicine department over a 7-year period. Additional features enabling identification of fetuses that progress to severe anaemia were also investigated. METHODS: Forty-seven susceptible, pregnant women with confirmed parvovirus infection referred to a regional fetal medicine unit, over a 7-year period (1999-2006), were identified. Where possible maternal serum AFP measurements were obtained from second-trimester serum screening and the presence or absence of echogenic bowel noted. RESULTS: Of the 47 cases, one was excluded. Of the remaining 46 cases, 34 (74%) showed no signs of fetal anaemia and delivered at term. The remaining 12 (26%) showed signs of fetal anaemia. Eight of the 12 developed hydrops and underwent fetal blood sampling and transfusion (median pretransfusion Hb 3.6 g/dl). Seven of the 8 transfused fetuses were thrombocytopenic with a platelet count <150 x 10(9)/l, with 2 fetuses having platelet counts <50 x 10(9)/l. The median gestation age at transfusion was 22 weeks (range 18-27 weeks). The median number of weeks between seroconversion and transfusion was 6 (range 3-12). The signs of anaemia resolved after one transfusion in 5 of the 8 transfused fetuses and they subsequently delivered at term. There were 2 fetal deaths during or shortly after transfusion and one neonatal death following delivery at 28 weeks gestation due to severe pre-eclampsia, 5 days after successful transfusion. CONCLUSIONS: Following parvovirus seroconversion, the incidence of significant fetal anaemia requiring transfusion was 17%. Seroconversion after 21 weeks did not result in severe fetal anaemia. Significant anaemia requiring intervention did not occur 12 weeks after maternal seroconversion. We did not demonstrate a correlation with either maternal serum AFP or the presence of fetal echogenic bowel and the development of severe fetal anaemia. Because of the association between fetal anaemia and severe thrombocytopenia, it may be prudent to have compatible platelets available at the time of fetal blood sampling.

B-type natriuretic peptide and the prediction of outcome in patients admitted to intensive care.

B-type natriuretic peptide is known to predict outcome in congestive cardiac failure and myocardial infarction. We aimed to determine whether measurement of B-type natriuretic peptide would predict hospital mortality in patients admitted to an intensive care unit. We conducted a prospective observational cohort study in 78 consecutive patients. Demographics, clinical details and clinical outcomes were recorded. Admission and 24 h B-type natriuretic peptide and cardiac troponin I levels were measured. B-type natriuretic peptide and cardiac troponin I levels taken on intensive care admission and 24 h after admission did not accurately predict hospital mortality for all patients, including patients with severe sepsis or septic shock (all p > 0.05). B-type natriuretic peptide levels were higher in patients with severe sepsis and septic shock (p = 0.02), in patients > or = 65 years (p = 0.04) and in patients with raised creatinine > or = 110 micromol.l(-1) (p = 0.02). We concluded that B-type natriuretic peptide, measured soon after admission to intensive care, does not usefully predict outcome after intensive care.

Dynamic function after anterior cruciate ligament reconstruction with autologous patellar tendon.

The purpose of this study was to dynamically assess the functional outcome of patients who had undergone successful anterior cruciate ligament reconstruction using an autologous patellar tendon technique and to determine whether their dynamic knee function was related to quadriceps and hamstring muscle strength. The knee kinematics and kinetics of 22 subjects who had undergone anterior cruciate ligament reconstruction (mean age, 27 +/- 11 years) and of 22 age- and sex-matched healthy control subjects were determined during various dynamic activities using a computerized motion analysis and force plate system. The differences in the sagittal plane angles and external moments between the two groups during light (walking), moderate (climbing and descending stairs), and higher-demand (jogging, jog and cut, jog and stop) activities were related to isokinetic strength measurements. Although patients who are asymptomatic and functioning well after anterior cruciate ligament reconstruction can perform normally in light activities, higher-demand activities reveal persistent functional adaptations that require further study.

Reassessment of the incidence of complex regional pain syndrome type 1 following stroke.

Previous literature has suggested that reflex sympathetic dystrophy, also known as complex regional pain syndrome (CRPS) type 1, is a relatively common finding after a stroke. However, much of this data was obtained before patients routinely received early intensive inpatient rehabilitation. The purpose of this study is to reevaluate the incidence of CRPS type 1 following an acute first stroke. Subjects admitted to an acute rehabilitation setting for stroke with no other concomitant neurologic or orthopedic injuries between October 1, 1996, and May 31, 1997, were studied. At admission and once a week until discharge, subjects were evaluated for shoulder pain, decreased passive range of motion of the shoulder, wrist/hand pain, edema, and skin changes. If three of these five criteria were positive, the subjects underwent a triple-phase bone scan (TPBS). Bone scan findings consistent with CRPS type 1 were taken as confirming the diagnosis. Of 64 subjects, 13 underwent bone scans, with only one positive result. Thus our study revealed a 1.56 percent incidence of CRPS type 1 following a first stroke. This incidence is much lower than the historically accepted 12.5 percent. We speculate that this low figure is related to early comprehensive rehabilitation that included proper upper extremity positioning and early mobilization with sensory stimulation.