The mortality rate after surgery for acute diverticular disease remains excessive and a high-risk group can be identified before operation. A policy of resection and anastomosis appears justified for selected patients. Adopting a practice of interval elective sigmoid colectomy after admission with acute diverticulitis might prevent readmission with further complications.
Background Lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is a novel technology formulated as a low dose vaccine against COVID-19.Methods A phase I first-in-human dose-ranging trial of a saRNA COVID-19 vaccine candidate LNP-nCoVsaRNA, was conducted at Imperial Clinical Research Facility, and participating centres in London, UK, between 19 th June to 28 th October 2020. Participants received two intramuscular (IM) injections of LNP-nCoVsaRNA at six different dose levels, 0.1-10.0mg, given four weeks apart. An open-label dose escalation was followed by a dose evaluation. Solicited adverse events (AEs) were collected for one week from enrolment, with follow-up at regular intervals (1-8 weeks). The binding and neutralisation capacity of anti-SARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, immunoblot, SARS-CoV-2 pseudoneutralisation and wild type neutralisation assays. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20).Findings 192 healthy individuals with no history or serological evidence of COVID-19, aged 18-45 years were enrolled. The vaccine was well tolerated with no serious adverse events related to vaccination. Seroconversion at week six whether measured by ELISA or immunoblot was related to dose (both p<0.001), ranging from 8% (3/39; 0.1mg) to 61% (14/23; 10.0mg) in ELISA and 46% (18/39; 0.3mg) to 87% (20/23; 5.0mg and 10.0mg) in a post-hoc immunoblot assay. Geometric mean (GM) anti-S IgG concentrations ranged from 74 (95% CI, 45-119) at 0.1mg to 1023 (468-2236) ng/mL at 5.0mg (p<0.001) and was not higher at 10.0mg. Neutralisation of SARS-CoV-2 by participant sera was measurable in 15% (6/39; 0.1mg) to 48% (11/23; 5.0mg) depending on dose level received.Interpretation Encapsulated saRNA is safe for clinical development, is immunogenic at low dose levels but failed to induce 100% seroconversion. Modifications to optimise humoral responses are required to realise its potential as an effective vaccine against SARS-CoV-2.
Introduction Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV‐status unawareness represents a significant challenge for achieving zero new HIV infections and deaths. In order to enhance knowledge of HIV status, the World Health Organisation (WHO) recommends a testing strategy that includes the use of HIV‐specific antibody point‐of‐care tests (POCT). These POCTs do not detect acute HIV infection, the stage of disease when viral load is highest but HIV antibodies are undetectable. Complicating things further, in the presence of antiretroviral therapy (ART) for pre‐exposure prophylaxis (PrEP) or post‐exposure prophylaxis (PEP), other currently available testing technologies, such as viral load detection for diagnosis of acute HIV infection, may yield false‐negative results. In this scoping review, we evaluate the evidence and discuss alternative HIV testing algorithms that may mitigate diagnostic dilemmas in the setting of increased utilization of ART for immediate treatment and prevention of HIV infection. Discussion Missed acute HIV infection prevents people living with HIV (PLHIV) from accessing early treatment, increases likelihood of onward transmission, and allows for inappropriate initiation or continuation of PrEP, which may result in HIV drug resistance. While immediate ART is recommended for all PLHIV, studies have shown that starting ART in the setting of acute HIV infection may result in a delayed or complete absence of development of HIV‐specific antibodies, posing a diagnostic challenge that is particularly pertinent to resource‐limited, high HIV burden settings where HIV‐antibody POCTs are standard of care. Similarly, ART used as PrEP or PEP may supress HIV RNA viral load, complicating current HIV testing algorithms in resource‐wealthy settings where viral detection is included. As rollout of PrEP continues, HIV testing algorithms may need to be modified. Conclusions With increasing use of PrEP and ART in acute infection we anticipate diagnostic challenges using currently available HIV testing strategies. Research and surveillance are needed to determine the most appropriate assays and optimal testing algorithms that are accurate, affordable and sustainable.
Objective To assess the acceptability and preferences of HPV screening with self‐sampling and mobile phone results delivery among women living with HIV (WLWH) in Botswana, as an alternative to traditional speculum screening. Methods WLWH aged 25 years or older attending an infectious disease clinic in Gaborone were enrolled in a cross‐sectional study between March and April 2017. Women self‐sampled with a flocked swab, had a speculum exam, and completed an interviewer‐administered questionnaire about screening acceptability, experiences, and preferences. Results Of the 104 WLWH recruited, 98 (94%) had a history of traditional screening. Over 90% agreed self‐sampling was easy and comfortable. Ninety‐five percent were willing to self‐sample again; however, only 19% preferred self‐sampling over speculum exam for future screening. Preferences differed by education and residence with self‐sampling being considered more convenient, easier, less embarrassing, and less painful. Speculum exams were preferred because of trust in providers’ skills and women's low self‐efficacy to sample correctly. Almost half (47%) preferred to receive results via mobile phone call. Knowledge of cervical cancer did not affect preferences. Conclusion HPV self‐sampling is acceptable among WLWH in Botswana; however, preferences vary. Although self‐sampling is an important alternative to traditional speculum screening, education and support will be critical to address women's low self‐efficacy to self‐sample correctly.
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