GRADE summary of findings tables enhanced understanding of values and preferences evidence.

OBJECTIVES: We conceptualize patient values and preferences as the relative importance of health outcomes (RIO) which are often obtained through utility elicitation research. A transparent and structured approach to present synthesized RIO evidence and the certainty of this evidence is needed. This study aims to adapt the summary of findings (SoF) table to describe the RIO. STUDY DESIGN AND SETTING: We performed three interactive workshops with a protype version of the SoF table for RIO, evidence adapted from the SoF table for intervention effects. We then tested the new format through semi-structured interviews with professionals who interpret RIO evidence (e.g., systematic review authors and guideline developers). RESULTS: We adapted the SoF table for the presentation of RIO evidence. This SoF table may be easy to use, but bears one risk: some participants misunderstood the utility information and the variability around the RIO. We added a visual analogue scale to clarify the concept of utilities. CONCLUSION: Through a multi-stage process including brainstorming sessions and interviews, we adapted the SoF table to present RIO evidence. This table may enhance understanding of evidence synthesis of values and preferences, facilitating the incorporation of this type of evidence in decision-making.

The Intersection of HIV and Syphilis: Update on the Key Considerations in Testing and Management.

PURPOSE OF REVIEW: To highlight recent trends in the epidemiology of HIV and syphilis, the impact of the COVID epidemic, our approach to care of co-infected patients, and our views on important next steps in advancing the field. RECENT FINDINGS: HIV and syphilis co-infection has been on the rise in recent years although since the COVID pandemic there is a decrease in new diagnoses-it remains unclear if this represents a true decline or inadequate testing or under-reporting. Standard HIV care should include regular syphilis serology .Treatment and serological follow-up of syphilis in HIV positive and negative patients can be conducted similarly. Challenges remain in the diagnosis and management of neurosyphilis. New models for testing and prevention will be crucial next steps in controlling co-infection. The intersection of HIV and syphilis infections continues to pose new and unique challenges in diagnosis, treatment, and prevention.

Deciphering the serological response to syphilis treatment in men living with HIV.

OBJECTIVE: To examine syphilis serology after treatment in people living with HIV. No unanimous guidelines exist in the era of increasing coinfection. DESIGN: Retrospective review using a tertiary care clinic in Toronto from 2000 to 2017. METHODS: The 2015 Centers for Diseases Control and Prevention syphilis guidelines were used to define an adequate serologic response. Cumulative distribution estimates and proportional hazards models accounting for interval censoring estimated the time to serologic response and seroreversion. Multistate models were used to investigate extended periods of serofast serology. RESULTS: A total of 171 patients with syphilis met our inclusion criteria (16 primary, 53 secondary, 26 early latent, 46 late latent, 30 neurosyphilis). Serologic response was achieved by 12 months for 65 (94%) patients and by 12-18 months for four (6%) patients with primary/secondary syphilis. For latent and neurosyphilis, 94 (92%) achieved serologic response by 24 months and one (1%) at 24.1 months. 84 (49%) patients achieved seroreversion with a median (95% confidence interval) time of 2 (1.44, 2.68) years. Latent syphilis was associated with a lower likelihood of achieving serologic response [hazard ratio (HR) = 0.52, P = 0.05] and seroreversion (HR = 0.27, P < 0.001) compared with primary/secondary syphilis. The probability of moving from a new infection state to a serofast state within 1 year was high (0.65) but the 1-year probability of transitioning from a serofast state to seroreversion was low (0.27). CONCLUSION: The majority of people living with HIV infected with syphilis will achieve an adequate serologic response as per the Centers for Diseases Control and Prevention guidelines. Seroreversion was observed in about half but can take years to occur.

Pilot study assessing the Rotterdam Healthy Aging Score in a cohort of HIV-positive adults in Toronto, Canada.

OBJECTIVE: The Rotterdam Healthy Aging Score (HAS) is a validated multidimensional index constructed from five health domains. We describe the HAS distribution in a cohort of HIV-positive adults and correlate it with health outcomes. DESIGN: A cross-sectional pilot study of 101 adults aged at least 40 years, on suppressive antiretroviral therapy attending a tertiary HIV clinic in Toronto, Canada. METHODS: Participants completed questionnaires to calculate their HAS (range 0-14). Demographics, HAS and sub-scores were compared by age and sex. The HAS was compared with results of the Fried Frailty Score, Short Performance Physical Battery score (SPPB) and measures of health utilization. Kruskal--Wallis Rank-Sum and Fisher's exact tests were used for all comparisons. RESULTS: Median (IQR) age was 56 (50--62), 81 (80%) men and 50 (50%) born in Canada. Median (IQR) CD4 cell count was 574 (417--794) cells/µl. Median (IQR) HAS was 12 (10--13) with 39 (39%) achieving a score more than 12 (considered healthy aging). Younger participants experienced more depression, whereas women had greater pain. The HAS score correlated with the Fried Frailty Score (P = 0.008) and trended with the SPPB Score (P = 0.077). Those with the poorest HAS scores were more likely to have been hospitalized in the preceding 6 months (P = 0.034). CONCLUSION: The HAS ranged from 5 to 14 in this cohort of older HIV adults with 39% attaining scores in the 'healthy' range. The HAS correlated with measures of physical performance and health utilization. Further validation of an objective outcome in HIV-positive patients will facilitate evaluation of interventional studies to improve healthy aging.

Antibiotic Prophylaxis in the Management of Open Fractures: A Systematic Survey of Current Practice and Recommendations.

BACKGROUND: Evidence with regard to antibiotic prophylaxis for patients with open fractures of the extremities is limited. We therefore conducted a systematic survey addressing current practice and recommendations. METHODS: We included publications from January 2007 to June 2017. We searched Embase, MEDLINE, CINAHL, the Cochrane Central Registry of Controlled Trials (CENTRAL), and the Cochrane Database of Systematic Reviews for clinical studies and surveys of surgeons; WorldCat for textbooks; and web sites for guidelines and institutional protocols. RESULTS: We identified 223 eligible publications that reported 100 clinical practice patterns and 276 recommendations with regard to systemic antibiotic administration, and 3 recommendations regarding local antibiotic administration alone. Most publications of clinical practice patterns used regimens with both gram-positive and gram-negative coverage and continued the administration for 2 to 3 days. Most publications recommended prophylactic systemic antibiotics. Most recommendations suggested gram-positive coverage for less severe injuries and administration duration of 3 days or less. For more severe injuries, most recommendations suggested broad antimicrobial coverage continued for 2 to 3 days. Most publications reported intravenous administration of antibiotics immediately. CONCLUSIONS: Current practice and recommendations strongly support early systemic antibiotic prophylaxis for patients with open fractures of the extremities. Differences in antibiotic regimens, doses, and durations of administration remain in both practice and recommendations. Consensus with regard to optimal practice will likely require well-designed randomized controlled trials. CLINICAL RELEVANCE: The current survey of literature systematically provides surgeons' practice and the available expert recommendations from 2007 to 2017 on the use of prophylactic antibiotics in the management of open fractures of extremities.

Assessing Patient Perspectives on Receiving Bad News: A Survey of 1337 Patients With Life-Changing Diagnoses.

BACKGROUND: Guidelines for breaking bad news are largely directed at and validated in oncology patients, based on expert opinion, and neglect those with other diagnoses. We sought to determine whether existing guidelines for breaking bad news, particularly SPIKES, are consistent with patient preferences across patient populations. METHODS: Patients from an online community responded to 5 open-ended and 11 Likert-scale questions identifying their preferences in having bad news delivered. Patient participants received a diagnosis of cancer, lupus, amyotrophic lateral sclerosis, multiple sclerosis, HIV/AIDS, or Parkinson's disease. Additionally, we surveyed all 14 English-curriculum Canadian medical schools regarding resources used to teach breaking bad news. RESULTS: Ten of 12 responding schools used the SPIKES model. Preferences of 1337 patients were consistent with the recommendations of SPIKES. There was one exception: Most patients disagree that empathetic physical touch is important and some described apprehension. Responses were consistent across disease states. Content analysis of 220 open-ended patient responses revealed 16 patient-important themes. Themes were largely addressed by the SPIKES guidelines, but five were not: ensuring timely follow-up is planned; offering informational sheets about the diagnosis; offering contact information of support organizations, with some patients preferring patient support groups while others preferring counselors; and conveying a sense of determination to aid the patient through the diagnosis. The four most patient-important components of SPIKES were physicians conveying empathy, taking their time, explaining the diagnosis and its implications, and asking the patient if they understand. CONCLUSION: SPIKES is the most commonly taught framework for breaking bad news in Canadian medical schools. This is the first work to demonstrate that the existing guidelines in breaking bad news such as SPIKES largely reflect the perspectives of many patient groups, as assessed by quantitative and qualitative measures. We highlight the most important components of SPIKES to patients and identify five additional suggestions to aid clinicians in breaking bad news.

Effects of Antibiotic Prophylaxis in Patients with Open Fracture of the Extremities: A Systematic Review of Randomized Controlled Trials.

BACKGROUND: The purpose of the present study was to perform a systematic review and meta-analysis of the use of alternative antibiotic regimens-including (A) antibiotic prophylaxis versus no prophylaxis, (B) longer versus shorter duration of antibiotic prophylaxis, and (C) alternative drugs-for patients with open fracture of the extremities. METHODS: Data sources included CINAHL, EMBASE, MEDLINE, the Cochrane Central Registry of Controlled Trials (CENTRAL), and the Cochrane database of systematic reviews from 1965 to December 2013. All randomized controlled trials comparing the effectiveness of antibiotic prophylaxis in patients with open fracture of the extremities were eligible. RESULTS: We identified 329 potentially eligible articles, of which seventeen proved to be eligible. In four randomized controlled trials involving 472 patients, we found a significantly lower infection rate in patients receiving antibiotic prophylaxis compared with those not receiving antibiotic prophylaxis (risk ratio = 0.37 [95% confidence interval, 0.21 to 0.66]; absolute risk reduction = 9.6% [95% confidence interval, 5.2% to 12.1%]). In three studies involving 1104 patients, we found no difference in the infection rate when a longer duration of antibiotics (three to five days) was compared with a shorter duration (one day) (risk ratio = 0.97; 95% confidence interval, 0.69 to 1.37). Confidence in the estimates for both questions was low to moderate. Individual comparisons of alternative drugs yielded estimates warranting only low to very low confidence. CONCLUSIONS: Results of randomized controlled trials performed to date provide evidence that antibiotic prophylaxis reduces subsequent infection and that courses as short as one day are as effective as courses of three to five days, although the evidence warrants only low to moderate confidence. Given current practice, a large, multicenter, low risk of bias, randomized controlled trial enrolling representative populations and addressing the duration of antibiotics may be the next optimum step in investigation. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

Lectin-induced activation of plasma membrane NADPH oxidase in cholesterol-depleted human neutrophils.

The gp91phox subunit of flavocytochrome b(558) is the catalytic core of the phagocyte plasma membrane NADPH oxidase. Its activation occurs within lipid rafts and requires translocation of four subunits to flavocytochrome b(558). gp91phox is the only glycosylated subunit of NADPH oxidase and no data exist about the structure or function of its glycans. Glycans, however, bind to lectins and this can stimulate NADPH oxidase activity. Given this information, we hypothesized that lectin-gp91phox interactions would facilitate the assembly of a functionally active NADPH oxidase in the absence of lipid rafts. To test this, we used lectins with different carbohydrate-binding specificity to examine the effects on H(2)O(2) generation by human neutrophils treated with the lipid raft disrupting agent methyl-ß-cyclodextrin (MßCD). MßCD treatment removed membrane cholesterol, caused changes in cell morphology, inhibited lectin-induced cell aggregation, and delayed lectin-induced assembly of the NADPH oxidase complex. More importantly, MßCD treatment either stimulated or inhibited H(2)O(2) production in a lectin-dependent manner. Together, these results show selectivity in lectin binding to gp91phox, and provide evidence for the biochemical structures of the gp91phox glycans. Furthermore, the data also indicate that in the absence of lipid rafts, neutrophil NADPH oxidase activity can be altered by these select lectins.