Estimated glomerular filtration rate slopes on tenofovir alafenamide.

OBJECTIVES: The aim of the study was to analyse and compare estimated glomerular filtration rate (eGFR) slopes during exposure to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in individuals who initiated TAF, regardless of prior regimen, before October 2016. METHODS: An observational cohort study was conducted at 11 clinics in the UK and Ireland. Mixed effects models with random intercept and time terms fitted were used to generate and compare eGFR slopes while participants were exposed to TDF and TAF, with adjustment for age, eGFR at TDF/TAF initiation, gender, ethnicity, and time-updated CD4 cell count and HIV RNA measurements. RESULTS: Data were available for 357 subjects (median age 50 years; 80% male; 82% white/other ethnicity; 51% men who have sex with men; median nadir CD4 count 216 cells/µL). The median duration of exposure to TAF was 2.0 (interquartile range 1.6, 2.3) years. At TAF initiation, the median CD4 count was 557 cells/µL, the median eGFR was 80 mL/min/1.73 m2, and 86% had suppressed HIV infection. The mean adjusted eGFR slope during TDF and TAF exposure was -2.08 [95% confidence interval (CI) -2.24, -1.92] and 1.18 (95% CI 0.20, 1.52) mL/min/1.73 m2/year, respectively (P < 0.001). Individuals who experienced rapid eGFR decline (> 3 or 5 mL/min/1.73 m2/year) while receiving TDF experienced significant eGFR recovery while on TAF (P < 0.001). CONCLUSIONS: Significant improvement in eGFR slope was observed in patients who switched from TDF- to TAF-containing antiretroviral regimens. These data provide further support for the renal safety of TAF, and for switching those who experience progressive worsening of renal function from TDF to TAF.

Pattern of failure in anaplastic glioma patients with an IDH1/2 mutation.

PURPOSE: The current study aimed to assess patterns of failure (PoF) in anaplastic glioma (AG) patients managed with intensity-modulated radiation therapy (IMRT) and their relationship to molecular subtype. METHODS: The outcomes of AG patients managed between 2008 and 2014 and entered into a prospective database were assessed, including PoF. AG was initially defined using the WHO 2007 classification, but for analysis, patients were subsequently recategorised based on WHO 2016 as anaplastic oligodendroglioma (AOD), astrocytoma isocitrate dehydrogenase (IDH) mutant (AAmut) or astrocytoma IDH wildtype (AAwt). Management involved IMRT and temozolomide (TMZ), including from 2011 patients with an IDH mutation (IDHmut) planned with 18F-fluoroethyltyrosine (FET) and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET). PoF was local, marginal or distant in relation to the IMRT volume. Relapse-free survival (RFS) was calculated from the start of IMRT. RESULTS: A total of 156 patients were assessed, with median follow-up of 5.1 years. Of these patients, 75% were IDHmut, 44% were managed at first or later relapse and 73% received TMZ. Relapse occurred in 68 patients, with 6­year RFS of 75.0, 48.8 and 2.5% for AOD, AAmut and AAwt, respectively (p < 0.001). There was a component of local relapse in 63%, of marginal relapse in 19% and of distant relapse in 37% of relapses. Isolated local, marginal and distant relapse was evident in 51, 9 and 22%, respectively. A distant relapse pattern was more frequent in IDHmut compared to IDHwt patients (26% vs. 45%, p = 0.005), especially within the first 2 years post-IMRT. In multivariate analysis, distant relapse remained associated with AAmut (p < 0.002) and delayed IMRT until the second relapse (p < 0.001). CONCLUSION: Although patients with IDH-mutated AG have improved outcomes, there was a higher proportion of distant relapses occurring during the 2 years after IMRT.

Diagnosis of upper limb lymphedema: development of an evidence-based approach.

BACKGROUND: The diagnosis of secondary upper limb lymphedema (LE) is complicated by the lack of an agreed-upon measurement tool and diagnostic threshold. The aim of this study was to determine which of the many commonly used and normatively determined clinical diagnostic thresholds has the best diagnostic accuracy of secondary upper limb LE, when compared to diagnosis by an appropriate reference standard, lymphoscintigraphy. MATERIAL AND METHODS: The arms of women treated for breast cancer with and without a previous diagnosis of LE, as well as healthy controls, were assessed using lymphoscintigraphy, bioimpedance spectroscopy (BIS) and perometry. Dermal backflow score determined from lymphoscintigraphy imaging assessment (reference standard) was compared with diagnosis by both commonly used and normatively determined diagnostic thresholds for volume and circumference measurements as well as BIS. RESULTS: For those with established dermal backflow, all commonly used and normatively determined diagnostic thresholds accurately identified presence of LE compared with lymphoscintigraphy diagnosis. In participants with mild to moderate changes in dermal backflow, only a normatively determined diagnostic threshold, set at two standard deviations above the norm, for arm circumference and full arm BIS were found to have both high sensitivity (81% and 76%, respectively) and specificity (96% and 93%, respectively). For this group, strong, and clinically useful, positive (23 and 10, respectively) and negative likelihood (0.2 and 0.3) ratios were found for both the circumference and bioimpedance diagnostic thresholds. CONCLUSION: For the first time, evidence-based clinical diagnostic thresholds have been established for secondary LE. With mild LE, normatively determined circumference and BIS thresholds are superior to the commonly used thresholds.

The Internet as a diagnostic aid: the patients' perspective.

A questionnaire-based cross-sectional study was conducted in order to determine how frequently patients attending a genitourinary (GU) medicine clinic use the Internet to diagnose their own symptoms, and to assess the accuracy of their diagnosis. Out of 223 symptomatic patients attending a GU clinic, 101 (45.3%) looked up their symptoms on the Internet. The age difference between those who looked up their symptoms and those who did not was not statistically significant (P = 0.77). Twenty (19.8%) out of 101 patients diagnosed their own symptoms, and 14 (13.9%) patients made the correct diagnosis. Ninety-one (90.1%) patients used the Google((R)) search engine as the starting point for their search. Although the Internet plays an important role in providing health information, the variable quality of health information available limits its use as a diagnostic tool by patients.

Sexual behaviours and sexually transmitted infection outcomes in a cohort of HIV-negative men who have sex with men attending sexual health clinics in England.

Men who have sex with men (MSM) attending sexual health (SH) clinics are at high risk for HIV acquisition and are disproportionately affected by sexually transmitted infections (STIs). We collected standardised behavioural data from MSM attending clinics to characterise sexual behaviours and identify predictors for HIV and STIs. In 2012­2013, HIV-negative MSM attending five SH clinics in England reported sexual behaviours in the previous three months via a self-administered questionnaire. Behaviours were linked to the individual's clinical records using national surveillance. The prevalence and incidence of bacterial STIs (gonorrhoea, Chlamydia, lymphogranuloma venereum and syphilis) and incidence of HIV were calculated. Adjusted odds ratios and hazard ratios with 95% confidence interval (CI) were reported for significant predictors. Of 1278 HIV-negative MSM, 54% were of white ethnicity and UK-born and 43% were 25­34 years old. Almost all men reported at least one partner in the last three months. Half reported condomless anal sex and 36% condomless receptive anal intercourse (CRAI). Incidence of bacterial STIs was 46/100 (95%CI 39­54) person years (py) and of HIV was 3.1/100 (95%CI 1.7­5.6) py. A STI at baseline and CRAI with increasing numbers of partners were associated with both incident infections. In this cohort of MSM high-risk behaviours and STIs were prevalent. Engagement in CRAI increased the likelihood of subsequent infection, while men diagnosed with a bacterial STI were at increased risk of a future STI. Clinical and behavioural risk assessments to determine an individual's risk of infection could allow a more nuanced prevention approach that has greater success in reducing transmission.

Setting up the first genitourinary clinic in Malta and an audit of the initial performance.

BACKGROUND: The first genitourinary (GU) clinic was set up in Malta in January 2000. An audit was conducted to evaluate the demand for such a service and its effectiveness during the first 6 years after its introduction. METHOD: Case notes from the first 6 years were reviewed, and data were collected for gender, age, sexual orientation, symptoms, diagnosis, condom use, referral source, total number of attendances, and contact tracing. RESULTS: The total number of attendances increased from 760 in the first year to 1832 in 2005. The male to female ratio decreased from 2.3 in 2000 to 1.6 in 2005, as more females attended. The number of partners treated per index case was 0.25. Eighty per cent of attendees were self-referred; 16% were referred by their general practitioner (GP). Only 10% admitted to using a condom regularly. Twenty-nine per cent of asymptomatic attendees in 2005 were diagnosed with a sexually transmitted infection (STI). Fifty-three cases of gonorrhoea were diagnosed by the GU clinic during the first 6 years, with 17% of isolates showing resistance to ciprofloxacin in 2005. A total of 38 cases of syphilis were diagnosed compared to only a handful of cases reported in the 25 years prior to the introduction of the service. CONCLUSIONS: The increasing attendance, as revealed by this audit, reflects a growing demand for the service offered by the GU clinic in Malta. Numerous STIs are being diagnosed and treated, including syphilis, which has re-emerged in Malta as it has in the rest of Europe. The prevalence of ciprofloxacin-resistant gonorrhoea has been increasing, a trend that has also been documented in other European countries. In addition to successful management of STIs, the GU clinic would further benefit from a public health campaign aimed at encouraging asymptomatic sexually active individuals to attend for an STI screen, while simultaneously promoting responsible sexual behaviour.

An elimination diet for chronic urticaria of childhood.

Twenty-three children with chronic urticaria were treated with an elimination diet for two weeks. Eighteen completed the period of dietary elimination; in seven of the 18 children there was a marked remission of the urticaria during the second week of the diet. The administration of challenge capsules provoked an exacerbation of urticaria in five of the 14 (36%) children given aspirin. The incidence of reactions to tartrazine, sodium benzoate and yeast (7%) was not significantly different from those to the lactose placebo (9%). In selected cases, elimination diets with controlled reintroduction of foods have a role in the management of chronic urticaria in childhood.