The first patients treated with MR-CBCT soft-tissue matching in a MR-only prostate radiotherapy pathway.

INTRODUCTION: Magnetic Resonance (MR)-only radiotherapy for prostate cancer has previously been reported using fiducial markers for on-treatment verification. MR-Cone Beam Computed Tomography (CBCT) soft-tissue matching does not require invasive fiducial markers and enables MR-only treatments to other pelvic cancers. This study evaluated the first clinical implementation of MR-only prostate radiotherapy using MR-CBCT soft-tissue matching. METHODS: Twenty prostate patients were treated with MR-only radiotherapy using a synthetic (s)CT-optimised plan with MR-CBCT soft-tissue matching. Two MR sequences were acquired: small Field Of View (FOV) for target delineation and large FOV for organs at risk delineation, sCT generation and on-treatment verification. Patients also received a CT for validation. The prostate was independently contoured on the small FOV MR, copied to the registered CT and modified if there were MR-CT soft-tissue alignment differences (MR-CT volume). This was compared to the MR-only volume with a paired t-test. The treatment plan was recalculated on CT and the doses compared. Independent offline CT-CBCT matches for 5/20 fractions were performed by three therapeutic radiographers using the MR-only contours and compared to the online MR-CBCT matches using two one-sided paired t-tests for equivalence within ±1 mm. RESULTS: The MR-only volumes were significantly smaller than MR-CT (p = 0.003), with a volume ratio 0.92 ± 0.02 (mean ± standard error). The sCT isocentre dose difference to CT was 0.2 ± 0.1%. MR-CBCT soft-tissue matching was equivalent to CT-CBCT (p < 0.001), with differences of 0.1 ± 0.2 mm (vertical), -0.1 ± 0.2 mm (longitudinal) and 0.0 ± 0.1 mm (lateral). CONCLUSIONS: MR-only radiotherapy with soft-tissue matching has been successfully clinically implemented. It produced significantly smaller target volumes with high dosimetric and on-treatment matching accuracy. IMPLICATIONS FOR PRACTICE: MR-only prostate radiotherapy can be safely delivered without using invasive fiducial markers. This enables MR-only radiotherapy to be extended to other pelvic cancers where fiducial markers cannot be used.

Is stopping secondary prophylaxis safe in HIV-positive talaromycosis patients? Experience from Myanmar.

OBJECTIVES: The aim of the study was to determine whether it is safe to stop secondary prophylaxis in patients with talaromycosis after immune reconstitution with a sustained increase in CD4 count to ≥ 100 cells/µL after antiretroviral therapy (ART). METHODS: A retrospective cohort analysis was performed in HIV-infected patients treated for talaromycosis between June 2009 and June 2017 in Medical Action Myanmar (MAM) clinics. RESULTS: Among a cohort of 5466 HIV-infected patients, 41 patients were diagnosed with and treated for clinical talaromycosis. All the patients were on ART and had a CD4 count < 100 cells/µL. Of these 41 patients, 24 patients (71%) were skin smear positive for talaromycosis, while results were negative in 17 patients. Median CD4 count and haemoglobin concentration were 24 cells/µL and 7.7 g/dL, respectively. Seventy-three per cent (30) were male. Among the 41 patients, 11 (27%) died and six (15%) were transferred to other centres. Twenty-four patients (58% of the total diagnosed) stopped itraconazole secondary prophylaxis after starting active ART with CD4 counts > 100 cells/µL for at least 1 year. Throughout the duration of follow-up post itraconazole cessation, the observed incidence of relapse was zero with a total follow-up of 93.8 person-years (95% confidence interval 0-4 per 100 person-years). The median (25th, 75th percentile) duration of follow-up post-prophylaxis discontinuation was 2.8 (2.1, 6.3) years. CONCLUSIONS: Secondary prophylaxis can be safely stopped in patients with talaromycosis after immune reconstitution with a sustained increase in CD4 count to ≥ 100 cells/µL after highly active antiretroviral therapy.

Integration of HIV services with primary care in Yangon, Myanmar: a retrospective cohort analysis.

OBJECTIVES: Integration of HIV care with general healthcare may improve patient engagement. We assessed patient outcomes in four clinics offering HIV care integrated into primary care clinics in Yangon, Myanmar. METHODS: We carried out a retrospective cohort analysis of 4551 patients who started antiretroviral therapy between 2009 and 2017. Mortality and disengagement from care were assessed using Cox regression. RESULTS: People living with HIV presented late with low CD4 counts [median (25th , 75th percentile) = 178 (65, 308) from 4216 patients] and advanced HIV (69% with stage 3 or 4). Survival was 0.95 at 1 year and 0.90 at 5 years. Males were at a higher risk of mortality than females [unadjusted hazard ratio (uHR) = 1.6 (95% CI: 1.3-2.0). Patients linked to HIV care via antenatal care or partner/parent notification were at reduced risk of mortality [uHR = 0.4 (95% CI: 0.1-1.0) and uHR = 0.5 (95% CI: 0.3-0.7)] relative to patients who presented for HIV testing. The cumulative incidence of disengagement was 0.06 at 1 year and 0.15 at 5 years. Young adults had a higher risk of disengagement than did children and older patients. Women linked to HIV care via antenatal care services were at increased risk of disengagement relative to patients who came for HIV testing (uHR = 2.4; 95% CI: 1.7-3.4). Mortality and disengagement remained steady over calendar time as the programme scaled up. CONCLUSIONS: HIV care within a primary care model is effective to attain early linkage to care, with high survival. However, close attention should be given to disengagement from care, in particular for pregnant women.

Assessing diet in a university student population: a longitudinal food card transaction data approach.

Starting university is an important time with respect to dietary changes. This study reports a novel approach to assessing student diet by utilising student-level food transaction data to explore dietary patterns. First-year students living in catered accommodation at the University of Leeds (UK) received pre-credited food cards for use in university catering facilities. Food card transaction data were obtained for semester 1, 2016 and linked with student age and sex. k-Means cluster analysis was applied to the transaction data to identify clusters of food purchasing behaviours. Differences in demographic and behavioural characteristics across clusters were examined using χ2 tests. The semester was divided into three time periods to explore longitudinal changes in purchasing patterns. Seven dietary clusters were identified: 'Vegetarian', 'Omnivores', 'Dieters', 'Dish of the Day', 'Grab-and-Go', 'Carb Lovers' and 'Snackers'. There were statistically significant differences in sex (P < 0·001), with women dominating the Vegetarian and Dieters, age (P = 0·003), with over 20s representing a high proportion of the Omnivores and time of day of transactions (P < 0·001), with Dieters and Snackers purchasing least at breakfast. Many students (n 474, 60·4 %) changed dietary cluster across the semester. This study demonstrates that transactional data present a feasible method for dietary assessment, collecting detailed dietary information over time and at scale, while eliminating participant burden and possible bias from self-selection, observation and attrition. It revealed that student diets are complex and that simplistic measures of diet, focusing on narrow food groups in isolation, are unlikely to adequately capture dietary behaviours.

Associations between food environment typologies and body mass index: Evidence from Yorkshire, England.

International research linking food outlets and body mass index (BMI) is largely cross-sectional, yielding inconsistent findings. However, addressing the exposure of food outlets is increasingly considered as an important adult obesity prevention strategy. Our study investigates associations between baseline food environment types and change in BMI over time. Survey data were used from the Yorkshire Health Study (n=8,864; wave one: 2010-2012, wave two: 2013-2015) for adults aged 18-86. BMI was calculated using self-reported height (cm) and weight (kg). Restaurants, cafés, fast-food, speciality, convenience and large supermarkets were identified from the Ordnance Survey Point of Interest database within 1600m radial buffer of home postcodes. K-means cluster analysis developed food environment typologies based on food outlets and population density. Large supermarkets, restaurants, cafés, fast-food, speciality and convenience food outlets all clustered together to some extent. Three neighbourhood typologies were identified. However, multilevel models revealed that relative to cluster one all were unrelated to change in BMI (cluster 2, b= -0.146 [-0.274, 0.566]; cluster 3, b= 0.065 [-0.224, 0.356]). There was also little evidence of gender-based differences in these associations when examined in a three-way interaction. Policymakers may need to begin to consider multiple types of food outlet clusters, while further research is needed to confirm how these relate to changed BMI.

Accuracy of self-report of HIV viral load among people with HIV on antiretroviral treatment.

OBJECTIVES: The aim of the study was to assess, among people living with HIV, knowledge of their latest HIV viral load (VL) and CD4 count. METHODS: Agreement between self-report and clinic record was assessed among 2771 HIV-diagnosed individuals on antiretroviral treatment (ART) in the UK Antiretrovirals, Sexual Transmission Risk and Attitudes Study (2011-2012). A confidential self-completed questionnaire collected information on demographic, socioeconomic, HIV-related and health-related factors. Participants were asked to self-report their latest VL [undetectable (≤ 50 copies/mL), detectable (> 50 copies/mL) or "don't know"] and CD4 count (< 200, 200-350, 351-500 or > 500 cells/µL, or "don't know"). Latest clinic-recorded VL and CD4 count were documented. RESULTS: Of 2678 participants on ART, 434 (16.2%) did not accurately report whether their VL was undetectable. Of 2334 participants with clinic-recorded VL ≤ 50 copies/mL, 2061 (88.3%) correctly reported undetectable VL; 49 (2.1%) reported detectable VL; 224 (9.6%) did not know their VL. Of 344 participants with clinic-recorded VL > 50 copies/mL, 183 (53.2%) correctly reported detectable VL; 76 (22.1%) reported undetectable VL; 85 (24.7%) did not know their VL. Of 2137 participants who reported undetectable VL, clinic-recorded VL was ≤ 50 copies/mL for 2061 (96.4%) and <1000 copies/mL for 2122 (99.3%). In analyses adjusted for gender/sexual orientation, ethnicity, age and time since starting ART, factors strongly associated with inaccurate self-report of VL (including "don't know") included socioeconomic disadvantage [prevalence ratio (95% CI) for "not" vs. "always" having enough money for basic needs: 2.4 (1.9, 3.1)], poor English fluency [3.5 (2.4, 5.1) vs. UK born], nondisclosure of HIV status [1.7 (1.3, 2.1)], ART nonadherence [2.1 (1.7, 2.7) for three or more missed doses vs. none in the past 2 weeks] and depressive symptoms (PHQ-9 score ≥ 10) [1.9 (1.6, 2.2)]. Overall, 612 (22.9%) of 2667 participants on ART did not accurately self-report whether or not their CD4 count was ≤ 350 cells/µL. CONCLUSIONS: There is a high level of accuracy of a self-report of undetectable VL in people on ART in the UK. Overall, accurate knowledge of personal VL level varied according to demographic, socioeconomic, HIV-related and health-related factors. Active identification of people who may benefit from increased levels of support and engagement in care is important.

Cost-effectiveness analysis of tenofovir/emtricitabine and abacavir/lamivudine in combination with efavirenz or atazanavir/ritonavir for treatment-naïve adults with HIV-1 infection in the UK, based on the AIDS Clinical Trials Group 5202 clinical trial.

OBJECTIVES: The aim of the study was to assess the cost-effectiveness of the four regimens studied in the AIDS Clinical Trials Group (ACTG) 5202 clinical trial, tenofovir/emtricitabine (TDF/FTC) or abacavir/lamivudine (ABC/3TC) in combination with efavirenz (EFV) or atazanavir/ritonavir (ATV/r), for treatment-naïve adults with HIV-1 infection in the UK. METHODS: A Markov model with six health states based on CD4 cell count ranges was developed to predict long-term costs and health outcomes for individuals on first-line therapy. Head-to-head efficacy data comparing TDF/FTC + EFV, TDF/FTC + ATV/r, ABC/3TC + EFV, and ABC/3TC + ATV/r were obtained from ACTG 5202 for up to 192 weeks. Antiretroviral drug costs were based on current list prices. Other medical costs (2013 UK pounds sterling), utility values, and mortality rates were obtained from published sources. Base-case, sensitivity, and subgroup analyses (by baseline viral load) were conducted. RESULTS: Individuals using TDF/FTC-based regimens were predicted to remain on first-line therapy longer and accrue more quality-adjusted life-years (QALYs) than individuals using ABC/3TC-based regimens. At a willingness-to-pay threshold of £30 000 per QALY gained, TDF/FTC-based regimens were predicted to be cost-effective compared with ABC/3TC-based regimens, with incremental cost-effectiveness ratios of £23 355 for TDF/FTC + EFV vs. ABC/3TC + EFV and £23 785 for TDF/FTC + ATV/r vs. ABC/3TC + ATV/r. Results were generally robust in subgroup, sensitivity, and scenario analyses. CONCLUSIONS: In an analysis of the regimens studied in ACTG 5202 for treatment-naïve adults with HIV-1 infection in the UK, TDF/FTC-based regimens yielded more favourable health outcomes and were generally predicted to be cost-effective compared with ABC/3TC-based regimens. These results confirm that TDF/FTC-based regimens are not only clinically effective but also cost-effective.

Screening for chronic comorbid diseases in people with HIV: the need for a strategic approach.

Among people living with HIV, the proportion of deaths attributed to chronic noninfectious comorbid diseases has increased over the past 15 years. This is partly a result of increased longevity in the era of highly active antiretroviral therapy (HAART), and also because HIV infection is related, causally or otherwise, to several chronic conditions. These comorbidities include conditions that are strongly associated with modifiable risk factors, such as cardiovascular disease (CVD), diabetes, and renal and bone diseases, and increasingly management guidelines for HIV recommend risk evaluation for these conditions. The uptake of these screening approaches is often limited by the resources required for their application, and hence the management of risk reduction in most HIV-infected populations falls below a reasonable standard. The situation is compounded by the fact that few risk calculators have been adjusted for specific use in HIV infection. There is substantial overlap of risk factors for the four common comorbid diseases listed above that are especially relevant in HIV infection, and this offers an opportunity to develop a simple screening approach that encompasses the key risk factors for lifestyle-related chronic disease in people with HIV infection. This would identify those patients who require more in-depth investigation, and facilitate a stepwise approach to targeted management. Such a tool could improve communication between patient and clinician. A significant proportion of people with HIV are sufficiently engaged with their care to participate in health promotion and take the lead in using patient-centric screening measures. Health-based social networking offers a mechanism for dissemination of such a tool and is able to embed educational messages and support within the process.

British HIV Association guidelines for the management of HIV infection in pregnant women 2012.

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of human immunodeficiency virus (HIV)-positive pregnant women in the UK. The scope includes guidance on the use of antiretroviral therapy (ART) both to prevent HIV mother-to-child transmission (MTCT) and for the welfare of the mother herself, guidance on mode of delivery and recommendations in specific patient populations where other factors need to be taken into consideration,such as coinfection with other agents. The guidelines are aimed at clinical professionals directly involved with, and responsible for, the care of pregnant women with HIV infection.

A DNA resequencing array for genes involved in Parkinson's disease.

Parkinson's disease (PD) is aetiologically complex with both familial and sporadic forms. Familial PD results from rare, highly penetrant pathogenic mutations whereas multiple variants of low penetrance may contribute to the risk of sporadic PD. Common variants implicated in PD risk appear to explain only a minor proportion of the familial clustering observed in sporadic PD. It is therefore plausible that combinations of rare and/or common variants in genes already implicated in disease pathogenesis may help to explain the genetic basis of PD. We have developed a CustomSeq Affymetrix resequencing array to enable high-throughput sequencing of 13 genes (44 kb) implicated in the pathogenesis of PD. Using the array we sequenced 269 individuals, including 186 PD patients and 75 controls, achieving an overall call rate of 96.5% and 93.6%, for two respective versions of the array, and >99.9% accuracy for five samples sequenced by capillary sequencing in parallel. We identified modest associations with common variants in SNCA and LRRK2 and a trend suggestive of an overrepresentation of rare variants in cases compared to controls for several genes. We propose that this technology offers a robust and cost-effective alternative to targeted sequencing using traditional sequencing methods, and here we demonstrate the potential of this approach for either routine clinical investigation or for research studies aimed at understanding the genetic aetiology of PD.

Autoimmune encephalitis: a case series and comprehensive review of the literature.

Encephalitic syndromes are a common medical emergency. The importance of early diagnosis and appropriate treatment is paramount. If initial investigations for infectious agents prove negative, other diagnoses must be considered promptly. Autoimmune encephalitides are being increasingly recognized as important (and potentially reversible) non-infectious causes of an encephalitic syndrome. We describe four patients with autoimmune encephalitis--3 auto-antibody positive, 1 auto-antibody negative--treated during the last 18 months. A comprehensive review of the literature in this expanding area will be of interest to the infectious diseases, general medical and neurology community.

Relationship of larval desiccation to Anopheles gambiae Giles and An. arabiensis Patton survival.

The relationship between mosquito 4th instar larval desiccation and survival to adulthood was explored by three methods in the laboratory. Two colonies of Anopheles arabiensis and one of Anopheles gambiae were studied. We found significant differences in tolerance to desiccation among all three stocks suggesting an intra- and interspecific genetic component to desiccation tolerance. An. arabiensis KGB, originating from Zimbabwe about 1975, had a much-reduced desiccation tolerance compared to An. gambiae G3, colonized in the Gambia in 1975, and An. arabiensis DONGOLA which originated in Sudan in 2004. Individuals of the G3 stock survived desiccation of times up to 40 min with survival of 0.52. The degree of difference in tolerance between G3 and DONGOLA was smallest and was detected by one of three experimental methods. Mass losses of individuals that were weighed individually and survived to adulthood averaged 27% and 29% for G3 and DONGOLA and 20% for the less tolerant KGB stock, respectively. Such differences in survival in transiently dry larval habitats may account in part for differences in the distribution of these species and karyotypes.

Epidemiology and severity of paediatric burn injuries occurring during camping and caravanning holidays.

BACKGROUND: Due to its unique location, the South West England Paediatric Burns Service based in Bristol admits an interesting cohort of holiday-makers, who have sustained their burns whilst on camping and caravanning holidays. AIM: We aimed to establish whether burns sustained during camping and caravanning holidays are more severe and require more extensive intervention compared to burns sustained in other situations. METHODS: We undertook a retrospective, observational study of admissions to the South West Paediatric Burns Service between June, and August from 2003 to 2005. Our primary outcome was to assess the severity of the burns as defined by percentage total body surface area of partial and full thickness burns. We used secondary outcomes of indirect indicators of burn severity: length of hospital stay, number of general anaesthetics, and need for surgical debridement, artificial skin dressing and/or skin grafting. Analysis of the data was undertaken using Mann-Whitney test, Fisher's exact test, and Chi-squared test. RESULTS: 151 patients were included in the study, 30 (20%) of which were campers. Our results show that burns sustained during camping and caravanning holidays are significantly more likely to be of larger surface area than burns sustained in other environments. Campers' burns also required more frequent surgical intervention (in 87% versus 66%) and had longer inpatient admissions (5.3 days versus 3.8 days). CONCLUSIONS: Our results have implications for clinicians and campsite owners. Access to free flowing water is often not immediately available on campsites and time taken to reach the nearest Emergency Department is often prolonged with a further delay before reaching the tertiary centre. The general public needs to be aware of the risks of burn during camping and caravanning holidays. Campsite owners should consider improving first aid facilities and clinicians need to be aware of the need for early referral and timely transfer to tertiary facilities.

Sensorineural hearing loss due to secondary syphilis.

We present a case of sudden sensorineural hearing loss occurring as a complication of secondary syphilis. Syphilis affecting the inner ear, or otosyphilis, is well described in historical literature, but has rarely been reported in recent times. However, following the resurgence of syphilis in the UK, unusual manifestations such as otosyphilis are likely to be seen increasingly commonly.