The core outcomes for open lower limb fracture study.

Aims: A core outcome set for adult, open lower limb fracture has been established consisting of 'Walking, gait and mobility', 'Being able to return to life roles', 'Pain or discomfort', and 'Quality of life'. This study aims to identify which outcome measurement instruments (OMIs) should be recommended to measure each core outcome. Methods: A systematic review and quality assessment were conducted to identify existing instruments with evidence of good measurement properties in the open lower limb fracture population for each core outcome. Additionally, shortlisting criteria were developed to identify suitable instruments not validated in the target population. Candidate instruments were presented, discussed, and voted on at a consensus meeting of key stakeholders. Results: The Wales Lower Limb Trauma Recovery scale was identified, demonstrating validation evidence in the target population. In addition, ten candidate OMIs met the shortlisting criteria. Six patients, eight healthcare professionals, and 11 research methodologists attended the consensus meeting. Consensus was achieved for the EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and the Lower Extremity Functional Scale (LEFS) to measure 'Quality of life' and 'Walking, gait and mobility' in future research trials, audit, and clinical assessment, respectively. No instrument met consensus criteria to measure 'Being able to return to life roles' and 'Pain or discomfort'. However, the EQ-5D-5L was found to demonstrate good face validity and could also be used pragmatically to measure these two outcomes, accepting limitations in sensitivity. Conclusion: This study recommends the LEFS and EQ-5D-5L to measure the core outcome set for adult open lower limb fracture.

What outcomes have been reported on patients following open lower limb fracture, and how have they been measured?

Open lower limb fracture is a life-changing injury affecting 11.5 per 100,000 adults each year, and causes significant morbidity and resource demand on trauma infrastructures. This study aims to identify what, and how, outcomes have been reported for people following open lower limb fracture over ten years. Systematic literature searches identified all clinical studies reporting outcomes for adults following open lower limb fracture between January 2009 and July 2019. All outcomes and outcome measurement instruments were extracted verbatim. An iterative process was used to group outcome terms under standardized outcome headings categorized using an outcome taxonomy. A total of 532 eligible studies were identified, reporting 1,803 outcomes with 786 unique outcome terms, which collapsed to 82 standardized outcome headings. Overall 479 individual outcome measurement instruments were identified, including 298 outcome definitions, 27 patient- and 18 clinician-reported outcome measures, and six physical performance measures. The most-reported outcome was 'bone union/healing' reported in over 50% of included studies, while health-related quality of life was only measured in 6% of included studies. Outcomes reported for people recovering from open lower limb fracture are heterogeneous, liable to outcome reporting bias, and vary widely in the definitions and the measurement tools used to collect them. Outcomes likely to be important to patients, such as quality of life and measures of physical functioning, have been neglected. This systematic review identifies the need to unify outcome measures reported on patients recovering from open lower limb fracture; this may be addressed by creating a core outcome set.

Development of a core outcome set for open lower limb fracture.

Open lower limb fracture is life-changing, resulting in substantial morbidity and resource demand, while inconsistent outcome-reporting hampers systematic review and meta-analysis. A core outcome set establishes consensus among key stakeholders for the recommendation of a minimum set of outcomes. This study aims to define a core outcome set for adult open lower limb fracture. Candidate outcomes were identified from a previously published systematic review and a secondary thematic analysis of 25 patient interviews exploring the lived experience of recovery from open lower limb fracture. Outcomes were categorized and sequentially refined using healthcare professional and patient structured discussion groups. Consensus methods included a multi-stakeholder two-round online Delphi survey and a consensus meeting attended by a purposive sample of stakeholders, facilitated discussion, and voting using a nominal group technique. Thematic analysis and systematic review identified 121 unique outcomes, reduced to 68 outcomes following structured discussion groups. Outcomes were presented to 136 participants who completed a two-round online Delphi survey. The Delphi survey resulted in 11 outcomes identified as consensus 'in' only. All outcomes were discussed at a consensus meeting attended by 15 patients, 14 healthcare professionals, 11 researchers, and one patient-carer. Consensus was achieved for a four-core outcome set: 'Walking, gait and mobility', 'Being able to return to life roles', 'Pain or discomfort', and 'Quality of life'. This study used robust consensus methods to establish a core outcome set that should be measured in all future research studies and audits of clinical practice without precluding the measurement of additional outcomes.

Longitudinal study of body composition of 101 HIV men with lipodystrophy: dual-energy X-ray criteria for lipodystrophy evolution.

The aim of this study was to define evolution profiles of body composition among human immunodeficiency virus (HIV)-infected men with lipodystrophy. The design is a retrospective analysis using observational data collected longitudinally. We included 101 HIV-infected men with lipodystrophy managed in routine practice and who had 2 dual energy X-ray absorptiometry scans within a minimum interval of 18 mo. Lipodystrophy was defined as a fat mass ratio (FMR, defined as the ratio of the percentage of the trunk fat mass over the percentage of the lower limbs fat mass) equal or superior to 1.5. Patients were classified in "improved" group (IG: increase of lower limbs fat mass >/= 10%) or "nonimproved" group (NIG). Body composition, immunovirological and epidemiological data were collected and compared between the 2 groups. In the whole population, over a 4-yr period, a significant increase was observed for total fat mass, trunk fat mass, and lower limbs fat mass, whereas total lean mass was stable. Total body mineral density decreased. Fifty-nine patients (IG), less exposed to zidovudine than the NIG, had an increase of lower limbs fat mass higher than 10%. But only 13 (22%) regained a normal distribution of fat mass (FMR < 1.5), showing that lipodystrophy was slowly reversible. Among the NIG, 5 patients (11.9%), less exposed to zidovudine and with a higher mean of viral load, reached an FMR below 1.5. It was mainly because of a loss of trunk fat mass, which could be the sign of a lipodystrophy worsening. Lipodystrophy improved for 58.4% of men. The improvement was very slow. Recovery was observed only in patients with an earlier intervention. No correlation was observed between lipodystrophy and total body bone mineral density. The loss of trunk fat mass without gain of lower limbs fat mass may indicate a worsening of HIV disease.

Integrated multidisciplinary approach to hidradenitis suppurativa in clinical practice,.

BACKGROUND: The European hidradenitis suppurativa (HS) guidelines recommend a multidisciplinary approach for patients with HS and management of comorbidities. OBJECTIVE: We aimed to describe the organization of a multidisciplinary HS program and characterize the patient population. METHODS: We conducted a retrospective study of patients with HS undergoing prospectively defined multidisciplinary work-up including examinations by a dermatologist, plastic surgeon, smoking specialist, and nutritionist in our outpatient unit between October 2015 and January 2017. RESULTS: The study included 49 patients with a sex ratio of 1:1. A total of 73.4% of patients were smokers, 20.4% were overweight, 48.9% were obese, and 30.6% had symptoms of depression. The mean Sartorius score was 30.4 (±17.6). The outcome of plastic surgery consultation was as follows: 16 patients had operations, 5 were excluded based on medical history, 9 refused surgery, and 16 remained undecided. The refusal rates for consulting with the smoking cessation and nutrition specialists were 55.8% and 69.5%, respectively. Twelve patients received antibiotics, 9 received biologics, 9 underwent medico-surgical treatment, 9 underwent surgery, and 10 were lost to follow-up. The mean visual analogue scale score for satisfaction was 8.3 (±1.6; n = 28). CONCLUSION: An integrated multidisciplinary care model for HS is associated with high patient satisfaction. Adherence to the proposed comorbidity management was higher in female patients and related to empathetic interactions with physicians.

Effects of discontinuing stavudine or protease inhibitor therapy on human immunodeficiency virus-related fat redistribution evaluated by dual-energy x-ray absorptiometry.

STUDY OBJECTIVE: To determine whether discontinuation of stavudine or protease inhibitor therapy improves human immunodeficiency virus (HIV)-related fat distribution in men. DESIGN: Observational, retrospective study consisting of a cross-sectional (part 1) and a longitudinal (part 2) study. DATA SOURCE: Medical records from Purpan University Hospital and La Grave University Hospital, Toulouse, France. Subjects. Eighty men with HIV infection treated with antiretrovirals and 151 healthy male controls matched for age. MEASUREMENTS AND MAIN RESULTS: In part 1, body composition and fat distribution of the HIV-infected men were compared by dual energy x-ray absorptiometry (DEXA) with those of the controls to determine whether body fat distribution is altered in HIV-infected men. In part 2, we analyzed modifications of body composition and fat distribution in 45 of the 80 patients. These 45 had been exposed to antiretroviral drugs, including stavudine and a protease inhibitor, for at least 5 months before the first of two DEXA assessments. They received three different treatment strategies for several months. In group 1, stavudine was withdrawn; in group 2, protease inhibitor was discontinued, and in group 3, stavudine plus protease inhibitor were continued. Group 1 showed a significant fat gain in the lower extremities 31.7 +/- 5.9 months after stavudine discontinuation (p<0.0001). Group 2 did not show any significant modification of total body, lower limb, or trunk fat despite protease inhibitor discontinuation for 35.2 +/- 6.6 months. Findings were similar for group 3, who continued receiving stavudine-protease inhibitor therapy for 21.2 +/- 12.8 months. CONCLUSION: These data suggest that long-term withdrawal of stavudine from the antiretroviral therapy regimen may be associated with significant improvement in lipoatrophy in the lower extremities, whereas long-term protease inhibitor withdrawal did not modify fat distribution.

[Analysis of antiretroviral drugs-induced adverse effects]. / Analyse des effets indésirables des médicaments du VIH.

In 1999, The Regional Center of Pharmacogilance and the Department of Infectious Disease of the Toulouse University Hospital set up a system to improve the data collection about antiretroviral-induced adverse reactionss (ADRs). From November 1999 to April 2003, a resident of pharmacovigilance collected ADRs reported with antiretroviral drugs during 2 weekly medical consultations. A total of 613 ADRs corresponding to 428 patients were reported, classified as "non serious" in 88.6% of cases and required the withdrawal of suspected drugs in 57% of cases. Our data show an improvement of antiretroviral drug-induced ADRs reporting.

[Not Available]. / Analyse des effets indésirables des médicaments du VIH.

Analysis of Antiretroviral Drugs-Induced Adverse Elfects. In 1999, The Regional Center of Pharmacogilance and the Department of Infectious Disease of the Toulouse University Hospital set up a system to improve the data collection about antiretroviral-induced adverse reactionss (ADRs). From November 1999 to April 2003, a resident of pharmacovigilance collected ADRs reported with antiretroviral drugs during 2 weekly medical consultations. A total of 613 ADRs corresponding to 428 patients were reported, classified as "non serious" in 88.6% of cases and required the withdrawal of suspected drugs in 57% of cases. Our data show an improvement of antiretroviral drug-induced ADRs reporting.

Persistence of distinct HIV-1 populations in blood monocytes and naive and memory CD4 T cells during prolonged suppressive HAART.

OBJECTIVE: Reservoirs of HIV-1 are a major obstacle to virus eradication. There is therefore a need to clearly understand the molecular nature of the virus populations that persist in patients with sustained suppression of plasma viraemia on highly active antiretroviral therapy (HAART). DESIGN: We performed a detailed analysis of the genotypes of HIV-1 quasispecies isolated from highly purified blood cell types taken from three selected patients with sustained undetectable viral loads on HAART for 7 years. METHODS: We used polychromatic flow cytometry to sort naive and memory CD4 T cells, CD14 monocytes, and CD56+CD3- natural killer (NK) cells from the total peripheral blood mononuclear cells after 7 years of HAART. Clonal analysis was used to determine coreceptor use and drug-resistance genotypes of HIV-1 quasispecies in the sorted blood cell types. RESULTS: We detected HIV-1 DNA in memory and naive CD4 T cells and in CD14 monocytes, but not in the CD56+CD3- NK cells. Phylogenetic analysis demonstrated that the various blood cells types of two of the three patients harboured genetically distinct HIV-1 quasispecies. Drug-resistance mutations were also distributed differently from one cell type to another. This compartmentalization suggests a minimal virus trafficking between blood cell types during suppressive HAART. CONCLUSIONS: We observed a cell-specific compartmentalization of the residual virus populations during prolonged suppressive HAART. The coexistence of numerous HIV-1 quasispecies with different resistance genotypes and coreceptor use in cellular reservoirs may be relevant for future antiretroviral treatment strategies.

Rapid onset of acute carcinoma of the glans penis arising three years after a lichen sclerosus.

Lichen sclerosus and atrophicus (LSA) is an inflammatory disease of incompletely characterised pathogenesis. If the development of squamous cell carcinoma (SCC) during the evolution of LSA is well described in women, this complication is a matter of discussion in men. We report an unusual case of acute and aggressive SCC which complicated the evolution of an LSA of the glans penis within three years. This type of observation is rarely reported in the medical literature.

Triple nucleoside combination zidovudine/lamivudine/abacavir versus zidovudine/lamivudine/nelfinavir as first-line therapy in HIV-1-infected adults: a randomized trial.

OBJECTIVE: To compare the efficacy and safety of a triple nucleoside combination to a protease inhibitor-containing triple regimen as first-line antiretroviral therapy (ART) in HIV-1-infected patients. DESIGN: Open-label study in HIV-1-infected ART-naive adults, randomized to receive either Combivir (lamivudine 150 mg/zidovudine 300 mg twice daily) + abacavir (300 mg twice daily), or Combivir + nelfinavir (750 mg every 8 h) for 48 weeks. Plasma HIV-1 RNA, CD4 cell count and adverse events were assessed at baseline and weeks 4, 8, 16, 24, 32, 40 and 48. RESULTS: 195 subjects (131 men, 64 women), median age 34 years, were randomized: 98 received combivir/abacavir and 97 combivir/nelfinavir. Baseline median plasma HIV-1 RNA was 4.2 log10 copies/ml [Interquartile range (IQR): 3.7-4.5.2] and 4.1 log10 copies/ml (IQR: 3.8-4.6), respectively. Baseline median CD4 cell count was 387 cells/mm3 (IQR: 194-501) and 449 cells/mm3 (IQR: 334-605), respectively. Nine patients (3 vs 6, respectively) did not start treatment or did not have any available efficacy data. At week 48, using the intent to treat analysis (switch/missing equals failure), plasma HIV-1 RNA was <50 copies/ml in 54/95 (57%) and 53/91 (58%) of subjects, respectively. Median CD4 increase was +110 and +120 cells/mm3, respectively. Possible hypersensitivity reactions to abacavir were reported in four subjects (4%). CONCLUSION: The triple nucleoside combination combivir/abacavir is well tolerated as a first-line ART regimen in HIV-1-infected adults, with comparable antiviral activity to a nelfinavir-containing regimen at week 48.

Nickel-induced systemic contact dermatitis and intratubal implants: the baboon syndrome revisited.

Permanent sterilization using intratubal implants is becoming increasingly popular worldwide. We report the first case of a 40-year-old woman presenting a systemic contact dermatitis due to nickel-containing intratubal implants: the Essure system. The diagnosis was confirmed with positive patch test result for nickel and total clearance of dermatitis after removing the implants that contain a metallic spiral of nitinol (alloy of 55% nickel and 45% titanium). Systemic contact dermatitis to the intratubal implants could be explained by the corrosion of nitinol after implantation resulting in the release of nickel. In the literature, no similar case has been reported despite the introduction of intratubal implants since 2002. Dermatologists and gynecologists need to be aware of this type of complication. In practice, a thorough assessment for possible nickel contact dermatitis in a woman undergoing sterilization with Essure is recommended. Preoperative patch testing must be carried out if there is any doubt.

Secondary syphilis simulating oral hairy leukoplakia.

We describe a case of secondary syphilis of the tongue in which the main clinical presentation of the disease was similar to oral hairy leukoplakia. In a man who was HIV seronegative, the first symptom was a dryness of the throat followed by a feeling of foreign body in the tongue. Lesions were painful without cutaneous manifestations of secondary syphilis. IgM-fluorescent treponemal antibody test and typical serologic parameters promptly led to the diagnosis of secondary syphilis. We initiated an appropriate antibiotic therapy using benzathine penicillin, which induced healing of the tongue lesions. The differential diagnosis of this lesion may include oral squamous carcinoma, leukoplakia, candidosis, lichen planus, and, especially, hairy oral leukoplakia. This case report emphasizes the importance of considering secondary syphilis in the differential diagnosis of hairy oral leukoplakia. Depending on the clinical picture, the possibility of syphilis should not be overlooked in the differential diagnosis of many diseases of the oral mucosa.

HIV therapy after treatment interruption in patients with multiple failure and more than 200 CD4+ T lymphocyte count.

The aim of the study was to investigate the safety and efficacy of a salvage therapy initiated after interrupting treatment in patients with virological failure and more than 200 CD4(+) T lymphocyte count. In this prospective study, 77 patients who received failing regimens had stopped completely all medication for 3 months before starting an optimised regimen consisting of 3-5 drugs. Patients were tested for HIV resistance before and after treatment interruption. Discontinuation of therapy for 3 months was associated with a median increase in HIV RNA of 1.1 log(10), a median decrease in CD4(+) T cell count of 136 x 10(6)/L and five clinical events related to HIV, but no AIDS-defining event. Eighty-seven percent of patients showed a shift from a drug resistant genotype to a wild-type genotype based on the major resistance mutations. Forty-seven percent of patients with a genotype shift reached fewer than 200 HIV RNA copies/ml of plasma 6 and 12 months after treatment resumption whereas none of those without a genotype shift did so (P = 0.03). However, the genotypic shift was not associated with a sustained virological response by multivariate analysis. The use of a new therapeutic class of compound in the salvage regimen was the only predictor of the sustained virological response. Salvage therapy with 3-5 drugs after interrupting treatment for 3 months can be a safe and effective strategy provided the HIV disease is not too advanced. Randomised trials in this population are needed to assess the clinical benefit of this strategy.