Objectives
The incidence of sexually transmitted infections (STIs) and HIV infection remains high in gay, bisexual, and other men who have sex with men (MSM) in the UK, and sexualized drug use ...(“chemsex”) and injecting drug use (“slamsex”) may play a part in this. We aimed to characterize HIV‐positive MSM engaging in chemsex/slamsex and to assess the associations with self‐reported STI diagnoses and sexual behaviours.
Methods
Data from a 2014 survey of people attending HIV clinics in England and Wales were linked to clinical data from national HIV surveillance records and weighted to be nationally representative. Multivariable logistic regression assessed the associations of chemsex and slamsex with self‐reported unprotected anal intercourse (UAI), serodiscordant UAI (sdUAI) (i.e. UAI with an HIV‐negative or unknown HIV status partner), sdUAI with a detectable viral load (>50 HIV‐1 RNA copies/mL), hepatitis C, and bacterial STIs.
Results
In the previous year, 29.5% of 392 sexually active participants engaged in chemsex, and 10.1% in slamsex. Chemsex was significantly associated with increased odds of UAI adjusted odds ratio (AOR) 5.73; P < 0.001, sdUAI (AOR 2.34; P < 0.05), sdUAI with a detectable viral load (AOR 3.86; P < 0.01), hepatitis C (AOR 6.58; P < 0.01), and bacterial STI diagnosis (AOR 2.65; P < 0.01). Slamsex was associated with increased odds of UAI (AOR 6.11; P < 0.05), hepatitis C (AOR 9.39; P < 0.001), and bacterial STI diagnosis (AOR 6.11; P < 0.001).
Conclusions
Three in ten sexually active HIV‐positive MSM engaged in chemsex in the past year, which was positively associated with self‐reported depression/anxiety, smoking, nonsexual drug use, risky sexual behaviours, STIs, and hepatitis C. Chemsex may therefore play a role in the ongoing HIV and STI epidemics in the UK.
Objectives
Community HIV testing represents an opportunity for diagnosing HIV infection among individuals who may not have contact with health services, especially in hard‐to‐reach groups. The aim of ...this review was to assess the evidence for feasibility, acceptability and effectiveness of HIV testing strategies in community settings in resource‐rich countries.
Methods
The PubMed database was searched for English language studies of outreach HIV testing in resource‐rich countries. Studies were included if they reported one of the following outcome measures: uptake of testing; seropositivity; client acceptability; or provider acceptability.
Results
Forty‐four studies were identified; the majority took place in the USA and targeted men who have sex with men. Uptake of HIV testing varied between 9 and 95% (in 14 studies). Seropositivity was ≥ 1% in 30 of 34 studies. In 16 studies the proportion of patients who received their test results varied from 29 to 100% and rapid testing resulted in a higher proportion of clients receiving their results. Overall, client satisfaction with community HIV testing was high. However, concern remained over confidentiality, professional standards and the need for post‐test counselling. Staff reported positive attitudes towards community testing.
Conclusions
In the majority of studies, the reported seropositivity was higher than 1/1000, the threshold deemed to be cost‐effective for routinely offering testing. Rapid testing improved the return of HIV test results to clients. HIV testing in outreach settings may be important in identifying undiagnosed infections in at‐risk populations, but appropriate data to evaluate these initiatives must be collected.
Of the 58,186 coronavirus deaths among adults in England during March-December 2020, 77% occurred in hospitals, 93% were in patients >60 years, and 91% occurred within 28 days of positive specimen. ...Cumulative mortality rates were highest among persons of Black, Asian, other, or mixed ethnicities and in socioeconomically deprived areas.
People living with HIV experience burdensome multidimensional symptoms and concerns requiring person-centred care. Routine use of patient reported outcome measures can improve outcomes. There is no ...brief patient reported outcome measure (PROM) that currently reflects the breadth of concerns for people living with HIV. This study aimed to develop and cognitively test a brief novel patient reported outcome measure for use within routine adult HIV care- the "Positive Outcomes" HIV PROM. Development followed the COSMIN taxonomy and guidance for relevance and comprehensiveness, and Rothrock guidance on development of valid patient reported outcome measures. The Positive Outcomes HIV PROM was developed by a steering group (people living with HIV, HIV professionals and health services researchers) using findings from a previously reported qualitative study of priority outcomes for people living with HIV. The prototype measure was cognitively tested with a purposive sample of people living with HIV. The Positive Outcomes HIV PROM consists of 23 questions (22 structured, and one open question) informed by the priorities of key stakeholders (n = 28 people living with HIV, n = 21 HIV professionals and n = 8 HIV commissioners) to ensure face and content validity, and refined through cognitive testing (n = 6 people living with HIV). Cognitive testing demonstrated high levels of acceptability and accessibility. The Positive Outcomes HIV PROM is the first brief patient reported outcome measure reflecting the diverse needs of people living with HIV designed specifically for use in the clinical setting to support patient assessment and care, and drive service quality improvement. It is derived from primary data on the priority outcomes for people living with HIV and is comprehensive and acceptable. Further psychometric testing is required to ensure reliability and responsiveness.
Background
Sequential synchronized atrioventricular (AV) pacing provides enhanced electrophysiologic parameters which contribute to improved hemodynamic parameters and increased cardiac performance ...to subsequently confer a clinical advantage over traditional ventricular pacing. Current temporary transvenous pacemaker catheters are limited to only one electrode which paces solely the right ventricle, thus lacking the capability to provide the optimal pacing mode. A new multilead pacemaker device was developed in response to the need for improved temporary pacing through the utilization of sequential synchronized atrioventricular pacing (TAVSP). It consists of seven preformed, preshaped nitinol wires electrodes, of which four are for intra‐atrial and three for intraventricular positioning and endocardial contact, respectively. Each wire carries a ball tip designed to minimize tissue trauma and provide a high current density for adequate myocardial capture. The device is not yet Food and Drug Administration approved.
Objective
To present the unique structural components and mechanical properties of a novel sequential synchronized AV pacing device for temporary insertion and to report its first‐in‐human application with an analysis of the early clinical experience.
Methods
Following a process of development and proof of concept of the novel pacing modality in an animal model which demonstrated feasibility and safety, a series of patients who were candidates for the device application was identified. During left and right heart catheterization, the novel temporary pacing catheter was inserted transvenously and delivered in most patients under fluoroscopy or echocardiography. The catheter was deployed to its target right heart anatomic sites and then activated in an AV sequential mode. The technical aspects, the corresponding clinical utilization, and device performance were documented and analyzed.
Results
The series included 10 enrolled subjects. During planned left and right heart catheterization, the novel TAVSP device was inserted transvenously and then delivered and deployed successfully in a timely fashion in all patients. The pacing catheter achieved proper threshold and impedance in all (100%) patients. The performance of all ventricular leads was adequate; however, in 1 (10%) patient poor performance of the atrial leads was detected. The device was successfully retrieved in all patients. No adverse arrhythmia, impaired hemodynamics, or clinical adverse events occurred. No technical difficulties, component failure, or wires thrombosis were detected. All patients sustained the device application without sequala and were discharged home.
Conclusion
Initial clinical experience with the utilization of a novel TAVSP demonstrates feasibility and safety in humans. The TAVSP modality potentially offers improved pacing capability and subsequent hemodynamic benefits over the current temporary pacing catheters. Further experience with the clinical application of this pacing catheter is warranted.
BACKGROUND AND PURPOSE Intestinal absorption via membrane transporters may determine the pharmacokinetics of drug compounds. The hypothesis is that oral absorption of gaboxadol ...(4,5,6,7‐tetrahydroisoxazolo 5,4‐c pyridine‐3‐ol) in rats occurs via the proton‐coupled amino acid transporter, rPAT1 (encoded by the gene rSlc36a1). Consequently, we aimed to elucidate the in vivo role of rPAT1 in the absorption of gaboxadol from various intestinal segments obtained from Sprague‐Dawley rats.
EXPERIMENTAL APPROACH The absorption of gaboxadol was investigated following its administration into four different intestinal segments. The intestinal expression of rSlc36a1 mRNA was measured by quantitative real‐time PCR. Furthermore, the hPAT1‐/rPAT1‐mediated transport of gaboxadol or L‐proline was studied in hPAT1‐expressing Xenopus laevis oocytes, Caco‐2 cell monolayers and excised segments of the rat intestine.
KEY RESULTS The absorption fraction of gaboxadol was high (81.3–91.3%) following its administration into the stomach, duodenum and jejunum, but low (4.2%) after administration into the colon. The pharmacokinetics of gaboxadol were modified by the co‐administration of L‐tryptophan (an hPAT1 inhibitor) and L‐proline (an hPAT1 substrate). The in vitro carrier‐mediated uptake rate of L‐proline in the excised intestinal segments was highest in the mid jejunum and lowest in the colon. The in vitro uptake and the in vivo absorption correlated with the expression of rSlc36a1 mRNA along the rat intestine.
CONCLUSIONS AND IMPLICATIONS These results suggest that PAT1 mediates the intestinal absorption of gaboxadol and therefore determines its oral bioavailability. This has implications for the in vivo role of PAT1 and may have an influence on the design of pharmaceutical formulations of PAT1 substrates.
Objectives
We present national trends in death rates and the proportion of deaths attributable to AIDS in the era of effective antiretroviral therapy (ART), and examine risk factors associated with ...an AIDS‐related death.
Methods
Analyses of the national HIV‐infected cohort for England and Wales linked to death records from the Office of National Statistics were performed. Annual all‐cause mortality rates were calculated by age group and sex for the years 1999–2008 and rates for 2008 were compared with death rates in the general population. Risk factors associated with an AIDS‐related death were investigated using a case–control study design.
Results
The all‐cause mortality rate among persons diagnosed with HIV infection aged 15–59 years fell over the decade: from 217 per 10 000 in 1999 to 82 per 10 000 in 2008, with declines in all age groups and exposure categories except women aged 50–59 years and persons who inject drugs (rate fluctuations in both of these groups were probably a result of small numbers). Compared with the general population (15 per 10 000 in 2008), death rates among persons diagnosed with HIV infection remained high, especially in younger persons (aged 15–29 years) and persons who inject drugs (13 and 20 times higher, respectively). AIDS‐related deaths accounted for 43% of all deaths over the decade (24% in 2008). Late diagnosis (CD4 count < 350 cells/μL) was the most important predictor of dying of AIDS odds ratio (OR) 10.55; 95% confidence interval (CI) 8.22–13.54. Sixty per cent of all‐cause mortality and 81% of all AIDS‐related deaths were attributable to late diagnosis.
Conclusions
Despite substantial declines, death rates among persons diagnosed with HIV infection continue to exceed those of the general population in the ART era. Earlier diagnosis could have prevented 1600 AIDS‐related deaths over the decade. These findings highlight the need to intensify efforts to offer and recommend an HIV test in a wider range of clinical and community settings.
Objectives
Involvement of people living with HIV (PLHIV) in the design of HIV cure studies is important, given the potential risks to participants. We present results of an international survey of ...PLHIV to define these issues and inform cure research.
Methods
PLHIV were recruited in June−November 2014 through HIV websites, advocacy forums, social media and 12 UK HIV clinics. The survey included questions concerning demographics, HIV disease history, the desirability of types of cure and the patient's willingness to accept potential toxicity and treatment interruption (TI). We examined factors associated with TI and willingness to accept substantial risks.
Results
A total of 982 PLHIV completed the survey; 87% were male, 79% white and 81% men who have sex with men (MSM). Fifty‐one per cent were aged 25–44 years and 69% were UK residents. The median time since diagnosis was 7 years interquartile range (IQR) 2–17 years. Eighty‐eight per cent were receiving antiretrovirals (91% reported undetectable viral load). Health/wellbeing improvements (96%) and an inability to transmit HIV (90%) were more desirable cure characteristics than testing HIV‐negative (69%). Ninety‐five per cent were interested in participating in cure studies, and 59% were willing to accept substantial risks. PLHIV with a low CD4 count 201–350 cells/μL vs. ≥ 350 cells/μL; odds ratio (OR) 2.11; 95% confidence interval (CI) 1.11–4.00 were more likely to accept risks, whereas those with limited knowledge of HIV treatments vs. excellent/good knowledge and those aged ≥ 65 years vs. 45–64 years were less likely to accept risks OR 0.58 (95% CI 0.37–0.90) and OR 0.18 (95% CI 0.07–0.45), respectively. TI was acceptable for 62% of participants, with the main concerns being becoming unwell (82%), becoming infectious (76%) and HIV spreading through the body (76%).
Conclusions
Cure research was highly acceptable to the PLHIV surveyed. Most individuals would accept risks, including TI, even in the absence of personal benefit. An optimal cure would improve health and minimize onward transmission risk.
Objectives
We provide the first estimate of HIV prevalence among trans and gender‐diverse people living in England and compare outcomes of people living with HIV according to gender identity.
Methods
...We analysed a comprehensive national HIV cohort and a nationally representative self‐reported survey of people accessing HIV care in England (Positive Voices). Gender identity was recorded using a two‐step question co‐designed with community members and civil society. Responses were validated by clinic follow‐up and/or self‐report. Population estimates were obtained from national government offices.
Results
In 2017, HIV prevalence among trans and gender‐diverse people was estimated at 0.46–4.78 per 1000, compared with 1.7 (95% credible interval: 1.6–1.7) in the general population. Of 94 885 people living with diagnosed HIV in England, 178 (0.19%) identified as trans or gender‐diverse. Compared with cisgender people, trans and gender‐diverse people were more likely to be London residents (57% vs. 43%), younger (median age 42 vs. 46 years), of white ethnicity (61% vs. 52%), under psychiatric care (11% vs. 4%), to report problems with self‐care (37% vs. 13%), and to have been refused or delayed healthcare (23% vs. 11%). Antiretroviral uptake and viral suppression were high in both groups.
Conclusions
HIV prevalence among trans and gender‐diverse people living in England is relatively low compared with international estimates. Furthermore, no inequalities were observed with regard to HIV care. Nevertheless, trans and gender‐diverse people with HIV report poorer mental health and higher levels of discrimination compared with cisgender people.
To construct a prognostic model based on amyloid positron emission tomography (PET) to predict clinical progression in individual patients with mild cognitive impairment (MCI).
We included 411 MCI ...patients from the Alzheimer's Disease Neuroimaging Initiative. Prognostic models were constructed with Cox regression with demographics, magnetic resonance imaging, and/or amyloid PET to predict progression to Alzheimer's disease dementia. The models were validated in the Amsterdam Dementia Cohort.
The combined model (Harrell's C = 0.82 0.78–0.86) was significantly superior to demographics (β = 0.100, P < .001), magnetic resonance imaging (β = 0.037, P = .011), and PET only models (β = 0.053, P = .003).The models can be used to calculate individualized risk, for example, a female MCI patient (age = 60, APOE ε4 positive, Mini-Mental State Examination = 25, hippocampal volume = 5.8 cm3, amyloid PET positive) has 35% (19–57) risk in one year and 85% (64–97) risk in three years. Model performances in the Amsterdam Dementia Cohort were reasonable.
The present study facilitates the interpretation of an amyloid PET result in the context of a patient's own characteristics and clinical assessment.
•Our models facilitate amyloid PET–based prognosis in light of patient characteristics.•Amyloid PET is the key player in our prognostic models.•Our models are easy to use and can guide clinical decision making.
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