Chelsea and Westminster Hospital NHS Foundation Trust

INTRODUCTION: The SCARE Guidelines were published in 2016 to provide a structure for reporting surgical case reports. Since their publication, SCARE guidelines have been widely endorsed by authors, journal editors, and reviewers, and have helped to improve reporting transparency of case reports across a range of surgical specialties. In order to encourage further progress in reporting quality, the SCARE guidelines must themselves be kept up to date. We completed a Delphi consensus exercise to update the SCARE guidelines. METHODS: A Delphi consensus exercise was undertaken. All members of the previous Delphi group were invited to participate, in addition to researchers who have previously studied case reports, and editors from the International Journal of Surgery Case Reports. The expert group was sent an online questionnaire where they were asked to rate their agreement with proposed changes to each of the 24 items. RESULTS: 56 people agreed to participate and 45 (80%) invitees completed the survey which put forward modifications to the original guideline. The collated responses resulted in modifications. There was high agreement amongst the expert group. CONCLUSION: A modified and improved SCARE checklist is presented, after a Delphi consensus exercise was completed. The SCARE 2018 Statement: Updating Consensus Surgical CAse REport (SCARE) Guidelines.

Ulcerative colitis and Crohn's disease are the principal forms of inflammatory bowel disease. Both represent chronic inflammation of the gastrointestinal tract, which displays heterogeneity in inflammatory and symptomatic burden between patients and within individuals over time. Optimal management relies on understanding and tailoring evidence-based interventions by clinicians in partnership with patients. This guideline for management of inflammatory bowel disease in adults over 16 years of age was developed by Stakeholders representing UK physicians (British Society of Gastroenterology), surgeons (Association of Coloproctology of Great Britain and Ireland), specialist nurses (Royal College of Nursing), paediatricians (British Society of Paediatric Gastroenterology, Hepatology and Nutrition), dietitians (British Dietetic Association), radiologists (British Society of Gastrointestinal and Abdominal Radiology), general practitioners (Primary Care Society for Gastroenterology) and patients (Crohn's and Colitis UK). A systematic review of 88 247 publications and a Delphi consensus process involving 81 multidisciplinary clinicians and patients was undertaken to develop 168 evidence- and expert opinion-based recommendations for pharmacological, non-pharmacological and surgical interventions, as well as optimal service delivery in the management of both ulcerative colitis and Crohn's disease. Comprehensive up-to-date guidance is provided regarding indications for, initiation and monitoring of immunosuppressive therapies, nutrition interventions, pre-, peri- and postoperative management, as well as structure and function of the multidisciplinary team and integration between primary and secondary care. Twenty research priorities to inform future clinical management are presented, alongside objective measurement of priority importance, determined by 2379 electronic survey responses from individuals living with ulcerative colitis and Crohn's disease, including patients, their families and friends.

BACKGROUND: Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir-emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. METHODS: PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). FINDINGS: We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64-96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3-11·3). 13 men (90% CI 9-23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. INTERPRETATION: In this high incidence population, daily tenofovir-emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. FUNDING: MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.

BACKGROUND: To explore and describe the current literature surrounding bacterial/fungal coinfection in patients with coronavirus infection. METHODS: MEDLINE, EMBASE, and Web of Science were searched using broad-based search criteria relating to coronavirus and bacterial coinfection. Articles presenting clinical data for patients with coronavirus infection (defined as SARS-1, MERS, SARS-CoV-2, and other coronavirus) and bacterial/fungal coinfection reported in English, Mandarin, or Italian were included. Data describing bacterial/fungal coinfections, treatments, and outcomes were extracted. Secondary analysis of studies reporting antimicrobial prescribing in SARS-CoV-2 even in absence of coinfection was performed. RESULTS: 1007 abstracts were identified. Eighteen full texts reporting bacterial/fungal coinfection were included. Most studies did not identify or report bacterial/fungal coinfection (85/140; 61%). Nine of 18 (50%) studies reported on COVID-19, 5/18 (28%) on SARS-1, 1/18 (6%) on MERS, and 3/18 (17%) on other coronaviruses. For COVID-19, 62/806 (8%) patients were reported as experiencing bacterial/fungal coinfection during hospital admission. Secondary analysis demonstrated wide use of broad-spectrum antibacterials, despite a paucity of evidence for bacterial coinfection. On secondary analysis, 1450/2010 (72%) of patients reported received antimicrobial therapy. No antimicrobial stewardship interventions were described. For non-COVID-19 cases, bacterial/fungal coinfection was reported in 89/815 (11%) of patients. Broad-spectrum antibiotic use was reported. CONCLUSIONS: Despite frequent prescription of broad-spectrum empirical antimicrobials in patients with coronavirus-associated respiratory infections, there is a paucity of data to support the association with respiratory bacterial/fungal coinfection. Generation of prospective evidence to support development of antimicrobial policy and appropriate stewardship interventions specific for the COVID-19 pandemic is urgently required.

BACKGROUND: Early, goal-directed therapy (EGDT) is recommended in international guidelines for the resuscitation of patients presenting with early septic shock. However, adoption has been limited, and uncertainty about its effectiveness remains. METHODS: We conducted a pragmatic randomized trial with an integrated cost-effectiveness analysis in 56 hospitals in England. Patients were randomly assigned to receive either EGDT (a 6-hour resuscitation protocol) or usual care. The primary clinical outcome was all-cause mortality at 90 days. RESULTS: We enrolled 1260 patients, with 630 assigned to EGDT and 630 to usual care. By 90 days, 184 of 623 patients (29.5%) in the EGDT group and 181 of 620 patients (29.2%) in the usual-care group had died (relative risk in the EGDT group, 1.01; 95% confidence interval [CI], 0.85 to 1.20; P=0.90), for an absolute risk reduction in the EGDT group of -0.3 percentage points (95% CI, -5.4 to 4.7). Increased treatment intensity in the EGDT group was indicated by increased use of intravenous fluids, vasoactive drugs, and red-cell transfusions and reflected by significantly worse organ-failure scores, more days receiving advanced cardiovascular support, and longer stays in the intensive care unit. There were no significant differences in any other secondary outcomes, including health-related quality of life, or in rates of serious adverse events. On average, EGDT increased costs, and the probability that it was cost-effective was below 20%. CONCLUSIONS: In patients with septic shock who were identified early and received intravenous antibiotics and adequate fluid resuscitation, hemodynamic management according to a strict EGDT protocol did not lead to an improvement in outcome. (Funded by the United Kingdom National Institute for Health Research Health Technology Assessment Programme; ProMISe Current Controlled Trials number, ISRCTN36307479.).

IMPORTANCE: A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. OBJECTIVE: To evaluate the rate of within-couple HIV transmission (heterosexual and men who have sex with men [MSM]) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL. DESIGN, SETTING, AND PARTICIPANTS: The prospective, observational PARTNER (Partners of People on ART-A New Evaluation of the Risks) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex (September 2010 to May 2014). Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples' HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions. EXPOSURES: Condomless sexual activity with an HIV-positive partner taking virally suppressive ART. MAIN OUTCOMES AND MEASURES: Risk of within-couple HIV transmission to the HIV-negative partner. RESULTS: Among 1166 enrolled couples, 888 (mean age, 42 years [IQR, 35-48]; 548 heterosexual [61.7%] and 340 MSM [38.3%]) provided 1238 eligible couple-years of follow-up (median follow-up, 1.3 years [IQR, 0.8-2.0]). At baseline, couples reported condomless sex for a median of 2 years (IQR, 0.5-6.3). Condomless sex with other partners was reported by 108 HIV-negative MSM (33%) and 21 heterosexuals (4%). During follow-up, couples reported condomless sex a median of 37 times per year (IQR, 15-71), with MSM couples reporting approximately 22,000 condomless sex acts and heterosexuals approximately 36,000. Although 11 HIV-negative partners became HIV-positive (10 MSM; 1 heterosexual; 8 reported condomless sex with other partners), no phylogenetically linked transmissions occurred over eligible couple-years of follow-up, giving a rate of within-couple HIV transmission of zero, with an upper 95% confidence limit of 0.30/100 couple-years of follow-up. The upper 95% confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up. CONCLUSIONS AND RELEVANCE: Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex, during median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up). Additional longer-term follow-up is necessary to provide more precise estimates of risk.

The redefinition of neuropathic pain as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system," which was suggested by the International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) in 2008, has been widely accepted. In contrast, the proposed grading system of possible, probable, and definite neuropathic pain from 2008 has been used to a lesser extent. Here, we report a citation analysis of the original NeuPSIG grading paper of 2008, followed by an analysis of its use by an expert panel and recommendations for an improved grading system. As of February, 2015, 608 eligible articles in Scopus cited the paper, 414 of which cited the neuropathic pain definition. Of 220 clinical studies citing the paper, 56 had used the grading system. The percentage using the grading system increased from 5% in 2009 to 30% in 2014. Obstacles to a wider use of the grading system were identified, including (1) questions about the relative significance of confirmatory tests, (2) the role of screening tools, and (3) uncertainties about what is considered a neuroanatomically plausible pain distribution. Here, we present a revised grading system with an adjusted order, better reflecting clinical practice, improvements in the specifications, and a word of caution that even the "definite" level of neuropathic pain does not always indicate causality. In addition, we add a table illustrating the area of pain and sensory abnormalities in common neuropathic pain conditions and propose areas for further research.

Abstract The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-19 1,2 , host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal relationships of modifiable environmental risk factors for SARS-CoV-2 infection and outcomes. We formed a global network of researchers to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity. Here we describe the results of three genome-wide association meta-analyses that consist of up to 49,562 patients with COVID-19 from 46 studies across 19 countries. We report 13 genome-wide significant loci that are associated with SARS-CoV-2 infection or severe manifestations of COVID-19. Several of these loci correspond to previously documented associations to lung or autoimmune and inflammatory diseases 3–7 . They also represent potentially actionable mechanisms in response to infection. Mendelian randomization analyses support a causal role for smoking and body-mass index for severe COVID-19 although not for type II diabetes. The identification of novel host genetic factors associated with COVID-19 was made possible by the community of human genetics researchers coming together to prioritize the sharing of data, results, resources and analytical frameworks. This working model of international collaboration underscores what is possible for future genetic discoveries in emerging pandemics, or indeed for any complex human disease.

BACKGROUND: The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships. METHODS: The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods. FINDINGS: Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1-3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33-46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4-2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up). INTERPRETATION: Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV. FUNDING: National Institute for Health Research.

Abstract Machine learning methods offer great promise for fast and accurate detection and prognostication of coronavirus disease 2019 (COVID-19) from standard-of-care chest radiographs (CXR) and chest computed tomography (CT) images. Many articles have been published in 2020 describing new machine learning-based models for both of these tasks, but it is unclear which are of potential clinical utility. In this systematic review, we consider all published papers and preprints, for the period from 1 January 2020 to 3 October 2020, which describe new machine learning models for the diagnosis or prognosis of COVID-19 from CXR or CT images. All manuscripts uploaded to bioRxiv, medRxiv and arXiv along with all entries in EMBASE and MEDLINE in this timeframe are considered. Our search identified 2,212 studies, of which 415 were included after initial screening and, after quality screening, 62 studies were included in this systematic review. Our review finds that none of the models identified are of potential clinical use due to methodological flaws and/or underlying biases. This is a major weakness, given the urgency with which validated COVID-19 models are needed. To address this, we give many recommendations which, if followed, will solve these issues and lead to higher-quality model development and well-documented manuscripts.

INTRODUCTION: The PROCESS guidelines were published in 2016 to provide a structure for reporting surgical case series. The PROCESS guidelines have since been widely endorsed by a number of journals. The requirement to report compliance with each item outlined in the PROCESS statement has improved the reporting transparency of case series across a number of surgical specialties. Here, we undertook a new Delphi consensus exercise to update the PROCESS guidelines. METHODS: All members of the previous Delphi group were invited to participate. In addition, researchers, editors, and reviewers who have previously published or reviewed case series with the International Journal of Surgery were invited to collaborate. An online questionnaire was sent to participants asking them to rate their agreement with amendments to each of the 29 items. RESULTS: 140 experts were invited to participate, 56 people agreed to participate, and 45 (80%) recipients completed the survey. There was a high level of agreement amongst the expert group, and unanimous consensus was reached in the first round. All except three proposed items were accepted, and the original guidelines were modified accordingly. CONCLUSION: A modified and improved PROCESS checklist is presented, after a Delphi consensus exercise was completed.

Pandemics rarely affect all people in a uniform way. The Black Death in the 14th century reduced the global population by a third, with the highest number of deaths observed among the poorest populations.1Duncan CJ Scott S (2005). What caused the black death?.Postgrad Med J. 2005; 81: 315-320Crossref PubMed Scopus (99) Google Scholar Densely populated with malnourished and overworked peasants, medieval Europe was a fertile breeding ground for the bubonic plague. Seven centuries on—with a global gross domestic product of almost US$100 trillion—is our world adequately resourced to prevent another pandemic?2Roser M The short history of global living conditions and why it matters that we know it.https://ourworldindata.org/a-history-of-global-living-conditions-in-5-chartsDate: 2019Date accessed: March 23, 2020Google Scholar Current evidence from the coronavirus disease 2019 (COVID-19) pandemic would suggest otherwise. Estimates indicate that COVID-19 could cost the world more than $10 trillion,3International Food Policy Research InstituteHow much will poverty increase because of COVID-19?.https://www.ifpri.org/blog/how-much-will-global-poverty-increase-because-covid-19Date accessed: March 23, 2020Google Scholar although considerable uncertainty exists with regard to the reach of the virus and the efficacy of the policy response. For each percentage point reduction in the global economy, more than 10 million people are plunged into poverty worldwide.3International Food Policy Research InstituteHow much will poverty increase because of COVID-19?.https://www.ifpri.org/blog/how-much-will-global-poverty-increase-because-covid-19Date accessed: March 23, 2020Google Scholar Considering that the poorest populations are more likely to have chronic conditions, this puts them at higher risk of COVID-19-associated mortality. Since the pandemic has perpetuated an economic crisis, unemployment rates will rise substantially and weakened welfare safety nets further threaten health and social insecurity. Working should never come at the expense of an individual's health nor to public health. In the USA, instances of unexpected medical billings for uninsured patients treated for COVID-19 and carriers continuing to work for fear of redundancy have already been documented.4Hoadley J Fuchs B Lucia K Update on federal surprise billing legislation: new bills contain key differences.https://www.commonwealthfund.org/blog/2020/update-surprise-billing-legislation-new-bills-contain-key-differencesDate: Feb 20, 2020Date accessed: March 23, 2020Google Scholar Despite employment safeguards recently being passed into law in some high-income countries, such as the UK and the USA, low-income groups are wary of these assurances since they have experience of long-standing difficulties navigating complex benefits systems,4Hoadley J Fuchs B Lucia K Update on federal surprise billing legislation: new bills contain key differences.https://www.commonwealthfund.org/blog/2020/update-surprise-billing-legislation-new-bills-contain-key-differencesDate: Feb 20, 2020Date accessed: March 23, 2020Google Scholar and many workers (including the self-employed) can be omitted from such contingency plans. The implications of inadequate financial protections for low-wage workers are more evident in countries with higher levels of extreme poverty, such as India. In recent pandemics, such as the Middle East respiratory syndrome, doctors were vectors of disease transmission due to inadequate testing and personal protective equipment.5Bedford J Enria D Giesecke J et al.COVID-19: towards controlling of a pandemic.Lancet. 2020; (published online March 17.)https://doi.org/10.1016/S0140-6736(20)30673-5Summary Full Text Full Text PDF PubMed Scopus (1015) Google Scholar History seems to be repeating itself, with clinicians comprising more than a tenth of all COVID-19 cases in Spain and Italy. With a projected global shortage of 15 million health-care workers by 2030, governments have left essential personnel exposed in this time of need. Poor populations lacking access to health services in normal circumstances are left most vulnerable during times of crisis. Misinformation and miscommunication disproportionally affect individuals with less access to information channels, who are thus more likely to ignore government health warnings.6Pirisi A Low health literacy prevents equal access to care.Lancet. 2000; 3561828Summary Full Text Full Text PDF PubMed Scopus (34) Google Scholar With the introduction of physical distancing measures, household internet coverage should be made ubiquitous. The inequitable response to COVID-19 is already evident. Healthy life expectancy and mortality rates have historically been markedly disproportionate between the richest and poorest populations. The full effects of COVID-19 are yet to be seen, while the disease begins to spread across the most fragile settings, including conflict zones, prisons, and refugee camps. As the global economy plunges deeper into an economic crisis and government bailout programmes continue to prioritise industry, scarce resources and funding allocation decisions must aim to reduce inequities rather than exacerbate them. We declare no competing interests. COVID-19 puts societies to the testAs of April 21, the coronavirus outbreak has infected more than 2·3 million people and taken 162 956 lives—35 884 in the USA, 24 114 in Italy, 20 852 in Spain, 20 233 in France, 16 509 in the UK, 5209 in Iran, 4642 in China—all underestimates most probably. Beyond these numbers are people, families, communities, societies that have been affected in unprecedented ways. The coronavirus pandemic puts societies to the test: it is a test of political leadership, of national health systems, of social care services, of solidarity, of the social contract—a test of our very own fabric. Full-Text PDF Open Access

This is the first European Crohn’s and Colitis Organisation [ECCO] consensus guideline that addresses extra-intestinal manifestations [EIMs] in inflammatory bowel disease [IBD]. It has been drafted by 21 ECCO members from 13 European countries. Although this is the first ECCO consensus guideline that primarily addresses EIMs, it is partly derived from, updates, and replaces previous ECCO consensus advice on EIMs, contained within the consensus guidelines for Crohn’s disease 1 [CD] and ulcerative colitis 2 [UC]. The strategy to define consensus was similar to that previously described in other ECCO consensus guidelines [available at www.ecco-ibd.eu ]. Briefly, topics were selected by the ECCO guidelines committee [GuiCom]. ECCO members were selected to form working groups. Provisional ECCO Statements and supporting text were written following a comprehensive literature review, then refined following two voting rounds which included national representative participation by ECCO’s 35 member countries. The level of evidence was graded according to the Oxford Centre for Evidence-based Medicine [www.cebm.net]. The ECCO Statements were finalised by the authors at a meeting in Vienna in October 2014 and represent consensus with agreement of at least 80% of participants. Complete consensus [100% agreement] was reached for most statements. The supporting text was then finalised under the direction of each working group leader [VA, SV, FC, MH] before being integrated by the two consensus leaders [MH, FC]. This consensus guideline is pictorially represented within the freely available ECCO e-Guide [http://www.e-guide.ecco-ibd.eu/]. Up to 50% of patients with inflammatory bowel disease [IBD] experience at least one extra-intestinal manifestation [EIM], which can present before IBD is diagnosed. 34,5,6 EIMs adversely impact upon patients’ quality of life and some, such as primary sclerosing cholangitis [PSC] or venous thromboembolism [VTE], can be life-threatening. The probability of developing EIMs increases with disease duration and in patients who already have one EIM. 7 EIMs are more common in CD than UC, 7,8 particularly in patients with colonic CD; some EIMs, such as iritis/uveitis, are more common in women whereas PSC and ankylosing spondylitis are more common in males. 3 Most EIMs run in parallel with intestinal disease activity, 4 with the exception of ankylosing spondylitis and uveitis and with uncertainty regarding PSC and pyoderma gangrenosum [PG]. 9 The management of complex EIMs should be discussed in a multidisciplinary team meeting. Both peripheral and axial arthropathies occur in UC and CD, and belong to the spondyloarthritis [SpA] group of conditions (evidence level 2 [EL2]). They should be distinguished from arthralgia, which is more common. The prevalence of axial disease is equal between sexes and forms of IBD, but peripheral arthropathies are more common in CD [particularly affecting the colon] and in females [EL3] Diagnosis of axial SpA is based on the clinical feature of inflammatory low back pain associated with magnetic resonance imaging [MRI ]or radiographic features of sacroiliitis [EL 2]. Human leukocyte antigen B27 [HLA-B27] is associated with axial arthritis, but it has a lower prevalence than in idiopathic ankylosing spondylitis, making it unreliable as a diagnostic test in IBD [EL2] Radiological evidence of sacroiliitis occurs in 20–50% of patients with UC and CD, but progressive ankylosing spondylitis occurs in only 1–10% of patients [EL2]. MRI may identify early sacroiliitis in symptomatic patients with normal plain radiology [non-radiographic SpA] [EL2] Arthropathies associated with IBD belong to the SpA group of conditions. According to the Assessment in Spondyloarthritis International Society [ASAS] classification of 2009, 10 SpA are divided into axial and peripheral SpA, depending on the predominant symptoms. Diagnosis of axial SpA is based on magnetic resonance imaging [MRI] or radiographic features of sacroiliitis associated with clinical features of inflammatory low back pain. Radiological evidence of sacroiliitis is common in both UC and CD, occurring in 20–50 % of patients, 11,12,13 but progressive AS with syndesmophytes occurs in only 1–10 % of patients. 14,15,16 Early assessment using T1-weighted spin-echo [TISE], short tau inversion recovery [STIR], and fat-saturated T2-weighted sequences, are recommended for patients aged less than 40 years with inflammatory back pain lasting more than 3 months, to identify non-radiographic sacroiliitis. 17,18 Human leukocyte antigen [HLA]-B27 is found in 25–75% of patients with IBD and AS 11,19,20,21 but only in 7–15% of patients with isolated sacroiliitis. HLA-B27 positive IBD patients seem to be at risk for the development of AS 21 but, due to a lower prevalence than in idiopathic AS, it is unreliable as a diagnostic test in IBD. 22,23 Diagnosis of peripheral arthropathy and/or enthesitis associated with IBD is based on signs of inflammation and exclusion of other specific forms of arthritis [EL3]. Type I is an acute pauciarticular arthritis, affecting large joints, and is usually associated with active IBD. Type II is polyarticular, affecting a larger number of peripheral joints, and is independent of IBD activity [EL4] The peripheral arthritis of IBD is an inflammatory arthropathy but, unlike psoriatic arthritis and other inflammatory arthropathies, it is generally non-erosive. The ASAS guidelines for peripheral SpA included only six patients with IBD, 24 so the clinical classification of IBD-related peripheral arthropathies is usually based on a larger study of IBD patients. 25 On the basis of articular and two have been Type 1 is as pain with evidence of or affecting than joints, the large of the lower The are usually acute and than 10 and usually with IBD Type 2 more than joints, has a and the for or independent of IBD Diagnosis is on clinical based on features of inflammation and exclusion of other specific forms of in to arthritis, and peripheral arthritis has to be from may to and and have been less in IBD. inflammation at the of a to the to and and or is of SpA, with a prevalence of in IBD. arthritis in IBD is usually and and more common in CD, particularly in with colonic may that of bowel it usually with or the of IBD. prevalence in IBD from to in UC and in the of peripheral arthritis is only and in a of patients. The of axial is less and is to the of AS, and the of IBD. AS is a progressive with and affecting patients’ quality of It is to identify early axial SpA, to the to radiographic axial SpA that occurs in % by 2 years in with an or with active inflammation on The of IBD in the of SpA is by the that sacroiliitis and spondylitis occur in to of patients with IBD, whereas to of patients with AS or SpA have evidence of only The of HLA-B27 with AS is in IBD, but to a than in idiopathic AS This may to the between the of AS and IBD. and have more than for IBD in an and in IBD and of for AS were by IBD with a that and to the to the and and to a common the complex with axial SpA should be with and are [EL but with is recommended [EL2]. [EL2] and [EL2] are of early is the for or to [EL2] of inflammation is to peripheral arthritis or symptomatic are [EL but should be as as arthritis, [EL2] and [EL4] may have a is and in [EL2] for the of IBD-related arthropathy are based on in SpA, in IBD have been only or are with axial SpA should be with of the disease the of and in axial but with is in IBD. Although the risk for a larger study CD patients and UC patients that with low of was of was associated with disease activity with Crohn’s but this was by a in disease The of such as and may be with a lower risk of disease than and in are of is the in patients or to on the of on radiographic are less may of early axial SpA, of large are of inflammation is to peripheral is for the of and for symptomatic Although and are or only in ankylosing spondylitis, a 2014 of in patients with peripheral and recommended the for patients with short disease duration and a in that was to study the that be an in SpA patients with peripheral are with seem to can be in has been to be in 35 in patients with disease on quality of pain is common in IBD and may be associated with the of or the of associated with is associated with and usually the first 3 of to is usually Diagnosis of in is from a on radiographic is a risk for and patients who should [EL2] and are common in and patients with IBD disease or low activity, and The of in is based on assessment of by is as a at least lower than the for the between and risk is and to the has been should be as for and the for in the of risk low previous IBD is to and so can be to and peripheral and are and recommended as for IBD patients from for the and are based on risk such as 3 months, of and have been recommended in in the of risk the the for with patients at risk for of the and peripheral should the risk increases for each in the have been in patients with both and normal the that is the risk for in patients with IBD. between and risk The of is a previous by of the is in the of patients with IBD, who are patients aged between and 40 of patients have with a and has been in of IBD patients. of IBD patients can 3 years in a have in with have that in are similar in IBD to in the The of each risk to be has been of the of can be a of IBD. is common in IBD patients, and so may to risk of IBD. study a for in IBD women in a lower risk of CD and UC than in are with previous a in disease to a of and [EL2] are in should and for for the duration of is a for and are recommended the is less than patients, a of should for more [EL4] of disease activity is particularly in the in women or with previous of and other can [EL2] should be in patients with low and/or risk such as which risk in the of a of may be in who has been in IBD in aged to to and/or should be or and and from and/or should be should be in the recommended this usually at a of or should be only is with and increases in patients with IBD. large study in CD that of disease activity and of and were associated with a in of 4 The of and in has been in patients with IBD, in or is common in patients with IBD and should be as should and for that are for the of low in IBD and the risk of but and can be recommended for in IBD patients. to the of a for with is in women or of the is a and should be in patients with or patients, a before be are and have using or as are associated with only increases in and in is evidence that or other peripheral The evidence for and of in patients is patients with active disease should be according to guidelines with to and inflammatory activity, in to or should be in patients with IBD before can be an risk for patients with with more should be to a to an This should be from uveitis and based upon the of and this is or in patients with manifestations and patients should be by an with in inflammatory disease uveitis and are the most common manifestations of IBD. manifestations in IBD can be to and/or of the intestinal disease The classification of uveitis has been in the of guidelines 1 ]. of The most manifestations are or and or uveitis are more to be are occurring in less than but may to of uveitis a of 13 a of features from to to disease activity in the bowel and other extra-intestinal uveitis can be independent of bowel and other EIMs and may the of bowel symptoms. of with to and may be with and and and may as to which is is less common but has more to CD, uveitis is in and acute uveitis with may of a of the features of and The of to of should to an with in the management of and the of and the and the between and pain associated with of the and to be from to or other should for using a to for the of inflammatory and/or both the guidelines and of the International are in disease assessment may be in and of the of manifestations from of IBD in some this to of is to be to of patients in are study of only that patients with IBD are more to of with and and inflammatory disease as EIMs of IBD represent associated with and of both and into the or this may be associated with with and supporting in uveitis with and on I and are by may or or can be for symptomatic for or uveitis should be by an and or and [EL4] a is the of most is may be with following management of the bowel and to the of and uveitis should be with and uveitis and other the level of evidence with the evidence for of being in patients with uveitis but IBD. of and or have been from 3 or 4 the of and in uveitis and but is based upon evidence from the of only a IBD. and have each been to be in CD and or It is associated with disease and has a CD of and associated with UC, have been has been described in with IBD, particularly in patients with UC, and may be due to by T2-weighted is a disease that in and that to It can be associated with IBD. Diagnosis of is on clinical a be [EL3]. is usually based on that of the IBD. are in and forms can be with or [EL4] is and by or of in It the of the particularly the and usually occurs at of IBD in with and The CD, which may at as or or with present can the or 9 clinical can be and is usually the a The prevalence of in IBD from to in CD than UC and more common IBD patients. 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According to and IBD in PSC is as UC and less as of sclerosing cholangitis such as or conditions have to be sclerosing cholangitis has similar and/or but usually in the of IBD. of PSC and pain. are and may be by of IBD. patients with IBD, a clinical for PSC is as this disease patients with in of sclerosing cholangitis have been a of PSC can be magnetic resonance Although common at some it has been that is of to a of PSC the of is and clinical of PSC is The ECCO consensus group that should be to is and/or is patients with should be as is recommended for an or independent of of sclerosing cholangitis should be PSC is normal in a with IBD and a should be to PSC [EL2] of patients, is normal with This group is as a disease which is associated with a of PSC are and may be a is only in patients and features of or PSC is is recommended in PSC patients with features of of and/or an should of sclerosing cholangitis [EL4] should the of PSC in an IBD are normal in of PSC patients. are usually is in of PSC patients and should the of which is found in to of PSC patients. features of are should be but have a low are in of PSC but are found in and IBD patients sclerosing cholangitis be is of sclerosing cholangitis is according to the other and to and is as sclerosing cholangitis in of to may be in PSC patients the for sclerosing patients may a more disease but specific management are The of PSC in an IBD It is to that from is lower than that of The of clinical the risk for at the level is and is a for in and in of PSC and PSC may be associated with such as 1 and PSC to and development in the and affecting and large inflammation the in and with an risk of with IBD have a of with IBD patients PSC or normal patients with PSC and IBD, present with is in in and features that PSC is associated with UC, IBD has specific disease is or the as inflammation This is by the of This be by It that IBD has a that may PSC has a Early that PSC is associated with as in other have The first study in and has been to IBD in to which is in and are in a in and The study was in the authors PSC of European using the and the the number of PSC risk to of a with PSC than with IBD, the of disease in PSC that are from of IBD. has been to to or in PSC or PSC Although should be and/or should be in patients with features of [EL3] the evidence for in PSC is in based on is to clinical has been by most an study to most be should be in patients with and such as or have been is an for and are under PSC patients with clinical or of or an is recommended to that may be to or and for [EL2]. is recommended The and early of such as and are to the management of patients with assessment for the of is are the and imaging may between and in should be in patients with as this may the risk of and particularly in patients in is most is a for in selected of that and PSC patients with disease or with of should be for may be in selected patients with on is the only that can are with to PSC patients with disease should be for according to with and selected with cholangitis can be for The and in PSC patients is due to the disease and the risk of PSC patients with to from this has been is a for that can the diagnostic of in in PSC patients with IBD is recommended 1 to 2 years of PSC with is the recommended strategy [EL2]. PSC patients evidence of IBD, is recommended years PSC is associated with a risk of and in patients with associated IBD, both before and may IBD and PSC have been diagnosed. with is recommended at and 1 to 2 years This should be is to in to is recommended imaging should be is for and in an of antigen and has been but are associated with a risk to of in PSC patients. 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RATIONALE: Bronchial thermoplasty (BT) is a bronchoscopic procedure in which controlled thermal energy is applied to the airway wall to decrease smooth muscle. OBJECTIVES: To evaluate the effectiveness and safety of BT versus a sham procedure in subjects with severe asthma who remain symptomatic despite treatment with high-dose inhaled corticosteroids and long-acting beta(2)-agonists. METHODS: A total of 288 adult subjects (Intent-to-Treat [ITT]) randomized to BT or sham control underwent three bronchoscopy procedures. Primary outcome was the difference in Asthma Quality of Life Questionnaire (AQLQ) scores from baseline to average of 6, 9, and 12 months (integrated AQLQ). Adverse events and health care use were collected to assess safety. Statistical design and analysis of the primary endpoint was Bayesian. Target posterior probability of superiority (PPS) of BT over sham was 95%, except for the primary endpoint (96.4%). MEASUREMENTS AND MAIN RESULTS: The improvement from baseline in the integrated AQLQ score was superior in the BT group compared with sham (BT, 1.35 +/- 1.10; sham, 1.16 +/- 1.23 [PPS, 96.0% ITT and 97.9% per protocol]). Seventy-nine percent of BT and 64% of sham subjects achieved changes in AQLQ of 0.5 or greater (PPS, 99.6%). Six percent more BT subjects were hospitalized in the treatment period (up to 6 wk after BT). In the posttreatment period (6-52 wk after BT), the BT group experienced fewer severe exacerbations, emergency department (ED) visits, and days missed from work/school compared with the sham group (PPS, 95.5, 99.9, and 99.3%, respectively). CONCLUSIONS: BT in subjects with severe asthma improves asthma-specific quality of life with a reduction in severe exacerbations and healthcare use in the posttreatment period. Clinical trial registered with www.clinialtrials.gov (NCT00231114).

OBJECTIVE: The objective of this study is to estimate life expectancies of HIV-positive patients conditional on response to antiretroviral therapy (ART). METHODS: Patients aged more than 20 years who started ART during 2000-2010 (excluding IDU) in HIV clinics contributing to the UK CHIC Study were followed for mortality until 2012. We determined the latest CD4 cell count and viral load before ART and in each of years 1-5 of ART. For each duration of ART, life tables based on estimated mortality rates by sex, age, latest CD4 cell count and viral suppression (HIV-1 RNA <400 copies/ml), were used to estimate expected age at death for ages 20-85 years. RESULTS: Of 21 388 patients who started ART, 961 (4.5%) died during 110 697 person-years. At start of ART, expected age at death [95% confidence interval (CI)] of 35-year-old men with CD4 cell count less than 200, 200-349, at least 350 cells/μl was 71 (68-73), 78 (74-82) and 77 (72-81) years, respectively, compared with 78 years for men in the general UK population. Thirty-five-year-old men who increased their CD4 cell count in the first year of ART from less than 200 to 200-349 or at least 350 cells/μl and achieved viral suppression gained 7 and 10 years, respectively. After 5 years on ART, expected age at death of 35-year-old men varied from 54 (48-61) (CD4 cell count <200 cells/μl and no viral suppression) to 80 (76-83) years (CD4 cell count ≥350 cells/μl and viral suppression). CONCLUSION: Successfully treated HIV-positive individuals have a normal life expectancy. Patients who started ART with a low CD4 cell count significantly improve their life expectancy if they have a good CD4 cell count response and undetectable viral load.

BACKGROUND: This review is an update of 'Topical capsaicin (high concentration) for chronic neuropathic pain in adults' last updated in Issue 2, 2013. Topical creams with capsaicin are used to treat peripheral neuropathic pain. Following application to the skin, capsaicin causes enhanced sensitivity, followed by a period with reduced sensitivity and, after repeated applications, persistent desensitisation. High-concentration (8%) capsaicin patches were developed to increase the amount of capsaicin delivered; rapid delivery was thought to improve tolerability because cutaneous nociceptors are 'defunctionalised' quickly. The single application avoids noncompliance. Only the 8% patch formulation of capsaicin is available, with a capsaicin concentration about 100 times greater than conventional creams. High-concentration topical capsaicin is given as a single patch application to the affected part. It must be applied under highly controlled conditions, often following local anaesthetic, due to the initial intense burning sensation it causes. The benefits are expected to last for about 12 weeks, when another application might be made. OBJECTIVES: To review the evidence from controlled trials on the efficacy and tolerability of topically applied, high-concentration (8%) capsaicin in chronic neuropathic pain in adults. SEARCH METHODS: For this update, we searched CENTRAL, MEDLINE, Embase, two clinical trials registries, and a pharmaceutical company's website to 10 June 2016. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled studies of at least 6 weeks' duration, using high-concentration (5% or more) topical capsaicin to treat neuropathic pain. DATA COLLECTION AND ANALYSIS: Two review authors independently searched for studies, extracted efficacy and adverse event data, and examined issues of study quality and potential bias. Where pooled analysis was possible, we used dichotomous data to calculate risk ratio and numbers needed to treat for one additional event, using standard methods.Efficacy outcomes reflecting long-duration pain relief after a single drug application were from the Patient Global Impression of Change (PGIC) at specific points, usually 8 and 12 weeks. We also assessed average pain scores over weeks 2 to 8 and 2 to 12 and the number of participants with pain intensity reduction of at least 30% or at least 50% over baseline, and information on adverse events and withdrawals.We assessed the quality of the evidence using GRADE and created a 'Summary of findings' table. MAIN RESULTS: We included eight studies, involving 2488 participants, two more studies and 415 more participants than the previous version of this review. Studies were of generally good methodological quality; we judged only one study at high risk of bias, due to small size. Two studies used a placebo control and six used 0.04% topical capsaicin as an 'active' placebo to help maintain blinding. Efficacy outcomes were inconsistently reported, resulting in analyses for most outcomes being based on less than complete data.For postherpetic neuralgia, we found four studies (1272 participants). At both 8 and 12 weeks about 10% more participants reported themselves much or very much improved with high-concentration capsaicin than with 'active' placebo, with point estimates of numbers needed to treat for an additional beneficial outcome (NNTs) of 8.8 (95% confidence interval (CI) 5.3 to 26) with high-concentration capsaicin and 7.0 (95% CI 4.6 to 15) with 'active' placebo (2 studies, 571 participants; moderate quality evidence). More participants (about 10%) had average 2 to 8-week and 2 to 12-week pain intensity reductions over baseline of at least 30% and at least 50% with capsaicin than control, with NNT values between 10 and 12 (2 to 4 studies, 571 to 1272 participants; very low quality evidence).For painful HIV-neuropathy, we found two studies (801 participants). One study reported the proportion of participants who were much or very much improved at 12 weeks (27% with high-concentration capsaicin and 10% with 'active' placebo). For both studies, more participants (about 10%) had average 2 to 12-week pain intensity reductions over baseline of at least 30% with capsaicin than control, with an NNT of 11 (very low quality evidence).For peripheral diabetic neuropathy, we found one study (369 participants). It reported about 10% more participants who were much or very much improved at 8 and 12 weeks. One small study of 46 participants with persistent pain following inguinal herniorrhaphy did not show a difference between capsaicin and placebo for pain reduction (very low quality evidence).We downgraded the quality of the evidence for efficacy outcomes by one to three levels due to sparse data, imprecision, possible effects of imputation methods, and susceptibility to publication bias.Local adverse events were common, but not consistently reported. Serious adverse events were no more common with active treatment (3.5%) than control (3.2%). Adverse event withdrawals did not differ between groups, but lack of efficacy withdrawals were somewhat more common with control than active treatment, based on small numbers of events (six to eight studies, 21 to 67 events; moderate quality evidence, downgraded due to few events). No deaths were judged to be related to study medication. AUTHORS' CONCLUSIONS: High-concentration topical capsaicin used to treat postherpetic neuralgia, HIV-neuropathy, and painful diabetic neuropathy generated more participants with moderate or substantial levels of pain relief than control treatment using a much lower concentration of capsaicin. These results should be interpreted with caution as the quality of the evidence was moderate or very low. The additional proportion who benefited over control was not large, but for those who did obtain high levels of pain relief, there were usually additional improvements in sleep, fatigue, depression, and quality of life. High-concentration topical capsaicin is similar in its effects to other therapies for chronic pain.

Postherpetic neuralgia is more common with older age. Recommended treatments include topical agents (lidocaine or capsaicin) and systemic agents (in particular, gabapentin, pregabalin, or tricyclic antidepressants), but their efficacy tends to be suboptimal.

BACKGROUND: Dolutegravir (GSK1349572), a once-daily HIV integrase inhibitor, has shown potent antiviral response and a favourable safety profile. We evaluated safety, efficacy, and emergent resistance in antiretroviral-experienced, integrase-inhibitor-naive adults with HIV-1 with at least two-class drug resistance. METHODS: ING111762 (SAILING) is a 48 week, phase 3, randomised, double-blind, active-controlled, non-inferiority study that began in October, 2010. Eligible patients had two consecutive plasma HIV-1 RNA assessments of 400 copies per mL or higher (unless >1000 copies per mL at screening), resistance to two or more classes of antiretroviral drugs, and had one to two fully active drugs for background therapy. Participants were randomly assigned (1:1) to once-daily dolutegravir 50 mg or twice-daily raltegravir 400 mg, with investigator-selected background therapy. Matching placebo was given, and study sites were masked to treatment assignment. The primary endpoint was the proportion of patients with plasma HIV-1 RNA less than 50 copies per mL at week 48, evaluated in all participants randomly assigned to treatment groups who received at least one dose of study drug, excluding participants at one site with violations of good clinical practice. Non-inferiority was prespecified with a 12% margin; if non-inferiority was established, then superiority would be tested per a prespecified sequential testing procedure. A key prespecified secondary endpoint was the proportion of patients with treatment-emergent integrase-inhibitor resistance. The trial is registered at ClinicalTrials.gov, NCT01231516. FINDINGS: Analysis included 715 patients (354 dolutegravir; 361 raltegravir). At week 48, 251 (71%) patients on dolutegravir had HIV-1 RNA less than 50 copies per mL versus 230 (64%) patients on raltegravir (adjusted difference 7·4%, 95% CI 0·7 to 14·2); superiority of dolutegravir versus raltegravir was then concluded (p=0·03). Significantly fewer patients had virological failure with treatment-emergent integrase-inhibitor resistance on dolutegravir (four vs 17 patients; adjusted difference -3·7%, 95% CI -6·1 to -1·2; p=0·003). Adverse event frequencies were similar across groups; the most commonly reported events for dolutegravir versus raltegravir were diarrhoea (71 [20%] vs 64 [18%] patients), upper respiratory tract infection (38 [11%] vs 29 [8%]), and headache (33 [9%] vs 31 [9%]). Safety events leading to discontinuation were infrequent in both groups (nine [3%] dolutegravir, 14 [4%] raltegravir). INTERPRETATION: Once-daily dolutegravir, in combination with up to two other antiretroviral drugs, is well tolerated with greater virological effect compared with twice-daily raltegravir in this treatment-experienced patient group. FUNDING: ViiV Healthcare.

BACKGROUND: Deaths in HIV-positive people have decreased since the introduction of highly active antiretroviral therapy (HAART) in 1996. Fewer AIDS-related deaths and an ageing cohort have resulted in an increase in the proportion of HIV patients dying from non-AIDS-related disorders. Here we describe mortality and causes of death in people diagnosed with HIV in the HAART era compared with the general population. METHODS: In this observational analysis, we linked cohort data collected by Public Health England (PHE) for individuals aged 15 years and older, diagnosed with HIV in England and Wales from 1997 to 2012, to the Office for National Statistics (ONS) national mortality register. Cohort inclusion began at diagnosis with follow-up clinical information collected every year from all 220 National Health Service (NHS) HIV outpatient clinics nationwide. To classify causes of death we used a modified Coding Causes of Death in HIV (CoDe) protocol, which uses death certificate data and clinical markers. We applied Kaplan-Meier analysis for survival curves and mortality rate estimation and Cox regression to establish independent predictors of all-cause mortality, adjusting for sex, infection route, age at diagnosis, region of birth, year of diagnosis, late diagnosis, and history of HAART. We used standardised mortality ratios (SMRs) to make comparisons with the general population. FINDINGS: Between 1997 and 2012, 88 994 people were diagnosed with HIV, contributing 448 839 person-years of follow up. By the end of 2012, 5302 (6%) patients had died (all-cause mortality 118 per 10 000 person-years, 95% CI 115-121). In multivariable analysis, late diagnosis was a strong predictor of death (hazard ratio [HR] 3·50, 95% CI 3·13-3·92). People diagnosed more recently had a lower risk of death (2003-07: HR 0·66, 95% CI 0·62-0·70; 2008-12: HR 0·65, 95% CI 0·60-0·71). Cause of death was determinable for 4808 (91%) of 5302 patients; most deaths (2791 [58%] of 4808) were attributable to AIDS-defining illnesses. Cohort mortality was significantly higher than the general population for all causes (SMR 5·7, 95% CI 5·5-5·8), particularly non-AIDS infections (10·8, 9·8-12·0) and liver disease (3·7, 3·3-4·2). All-cause mortality was highest in the year after diagnosis (SMR 24·3, 95% CI 23·4-25·2). INTERPRETATION: Despite the availability of free treatment and care in the UK, AIDS continues to account for the majority of deaths in HIV-positive people, and mortality remains higher in HIV-positive people than in the general population. These findings highlight the importance of prompt diagnosis, care engagement, and optimum management of comorbidities in reducing mortality in people with HIV. FUNDING: Public Health England.

Osteomyelitis is an important cause of morbidity and mortality in children and adults. Imaging plays a crucial role in establishing a timely diagnosis and guiding early management, with the aim of reducing long-term complications. Recognition of the imaging features of osteomyelitis requires a good understanding of its pathogenesis. In this review, the key imaging findings in osteomyelitis are correlated with the underlying pathological processes. There is a particular emphasis on magnetic resonance imaging (MRI), which is the best available imaging modality owing to its high sensitivity for detecting early osteomyelitis, excellent anatomical detail and superior soft tissue resolution. However, other modalities such as nuclear medicine and computed tomography (CT) are also useful in many clinical contexts, and will also be described in this review.