methodS in Patient-centered outcomes and HEalth ResEarch

Importance: Coronavirus disease 2019 (COVID-19) is associated with severe lung damage. Corticosteroids are a possible therapeutic option. Objective: To determine the effect of hydrocortisone on treatment failure on day 21 in critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute respiratory failure. Design, Setting, and Participants: Multicenter randomized double-blind sequential trial conducted in France, with interim analyses planned every 50 patients. Patients admitted to the intensive care unit (ICU) for COVID-19-related acute respiratory failure were enrolled from March 7 to June 1, 2020, with last follow-up on June 29, 2020. The study intended to enroll 290 patients but was stopped early following the recommendation of the data and safety monitoring board. Interventions: Patients were randomized to receive low-dose hydrocortisone (n = 76) or placebo (n = 73). Main Outcomes and Measures: The primary outcome, treatment failure on day 21, was defined as death or persistent dependency on mechanical ventilation or high-flow oxygen therapy. Prespecified secondary outcomes included the need for tracheal intubation (among patients not intubated at baseline); cumulative incidences (until day 21) of prone position sessions, extracorporeal membrane oxygenation, and inhaled nitric oxide; Pao2:Fio2 ratio measured daily from day 1 to day 7, then on days 14 and 21; and the proportion of patients with secondary infections during their ICU stay. Results: The study was stopped after 149 patients (mean age, 62.2 years; 30.2% women; 81.2% mechanically ventilated) were enrolled. One hundred forty-eight patients (99.3%) completed the study, and there were 69 treatment failure events, including 11 deaths in the hydrocortisone group and 20 deaths in the placebo group. The primary outcome, treatment failure on day 21, occurred in 32 of 76 patients (42.1%) in the hydrocortisone group compared with 37 of 73 (50.7%) in the placebo group (difference of proportions, -8.6% [95.48% CI, -24.9% to 7.7%]; P = .29). Of the 4 prespecified secondary outcomes, none showed a significant difference. No serious adverse events were related to the study treatment. Conclusions and Relevance: In this study of critically ill patients with COVID-19 and acute respiratory failure, low-dose hydrocortisone, compared with placebo, did not significantly reduce treatment failure (defined as death or persistent respiratory support) at day 21. However, the study was stopped early and likely was underpowered to find a statistically and clinically important difference in the primary outcome. Trial Registration: ClinicalTrials.gov Identifier: NCT02517489.

BACKGROUND: Whether the antiinflammatory and immunomodulatory effects of glucocorticoids may decrease mortality among patients with severe community-acquired pneumonia is unclear. METHODS: In this phase 3, multicenter, double-blind, randomized, controlled trial, we assigned adults who had been admitted to the intensive care unit (ICU) for severe community-acquired pneumonia to receive intravenous hydrocortisone (200 mg daily for either 4 or 7 days as determined by clinical improvement, followed by tapering for a total of 8 or 14 days) or to receive placebo. All the patients received standard therapy, including antibiotics and supportive care. The primary outcome was death at 28 days. RESULTS: A total of 800 patients had undergone randomization when the trial was stopped after the second planned interim analysis. Data from 795 patients were analyzed. By day 28, death had occurred in 25 of 400 patients (6.2%; 95% confidence interval [CI], 3.9 to 8.6) in the hydrocortisone group and in 47 of 395 patients (11.9%; 95% CI, 8.7 to 15.1) in the placebo group (absolute difference, -5.6 percentage points; 95% CI, -9.6 to -1.7; P = 0.006). Among the patients who were not undergoing mechanical ventilation at baseline, endotracheal intubation was performed in 40 of 222 (18.0%) in the hydrocortisone group and in 65 of 220 (29.5%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.40 to 0.86). Among the patients who were not receiving vasopressors at baseline, such therapy was initiated by day 28 in 55 of 359 (15.3%) of the hydrocortisone group and in 86 of 344 (25.0%) in the placebo group (hazard ratio, 0.59; 95% CI, 0.43 to 0.82). The frequencies of hospital-acquired infections and gastrointestinal bleeding were similar in the two groups; patients in the hydrocortisone group received higher daily doses of insulin during the first week of treatment. CONCLUSIONS: Among patients with severe community-acquired pneumonia being treated in the ICU, those who received hydrocortisone had a lower risk of death by day 28 than those who received placebo. (Funded by the French Ministry of Health; CAPE COD ClinicalTrials.gov number, NCT02517489.).

BACKGROUND: The management of prosthetic joint infection usually consists of a combination of surgery and antimicrobial therapy. The appropriate duration of antimicrobial therapy for this indication remains unclear. METHODS: We performed an open-label, randomized, controlled, noninferiority trial to compare 6 weeks with 12 weeks of antibiotic therapy in patients with microbiologically confirmed prosthetic joint infection that had been managed with an appropriate surgical procedure. The primary outcome was persistent infection (defined as the persistence or recurrence of infection with the initial causative bacteria, with an antibiotic susceptibility pattern that was phenotypically indistinguishable from that at enrollment) within 2 years after the completion of antibiotic therapy. Noninferiority of 6 weeks of therapy to 12 weeks of therapy would be shown if the upper boundary of the 95% confidence interval for the absolute between-group difference (the value in the 6-week group minus the value in the 12-week group) in the percentage of patients with persistent infection within 2 years was not greater than 10 percentage points. RESULTS: A total of 410 patients from 28 French centers were randomly assigned to receive antibiotic therapy for 6 weeks (205 patients) or for 12 weeks (205 patients). Six patients who withdrew consent were not included in the analysis. In the main analysis, 20 patients who died during follow-up were excluded, and missing outcomes for 6 patients who were lost to follow-up were considered to be persistent infection. Persistent infection occurred in 35 of 193 patients (18.1%) in the 6-week group and in 18 of 191 patients (9.4%) in the 12-week group (risk difference, 8.7 percentage points; 95% confidence interval, 1.8 to 15.6); thus, noninferiority was not shown. Noninferiority was also not shown in the per-protocol and sensitivity analyses. We found no evidence of between-group differences in the percentage of patients with treatment failure due to a new infection, probable treatment failure, or serious adverse events. CONCLUSIONS: Among patients with microbiologically confirmed prosthetic joint infections that were managed with standard surgical procedures, antibiotic therapy for 6 weeks was not shown to be noninferior to antibiotic therapy for 12 weeks and resulted in a higher percentage of patients with unfavorable outcomes. (Funded by Programme Hospitalier de Recherche Clinique, French Ministry of Health; DATIPO ClinicalTrials.gov number, NCT01816009.).

Class probabilities predicted by most multiclass classifiers are uncalibrated, often tending towards over-confidence. With neural networks, calibration can be improved by temperature scaling, a method to learn a single corrective multiplicative factor for inputs to the last softmax layer. On non-neural models the existing methods apply binary calibration in a pairwise or one-vs-rest fashion. We propose a natively multiclass calibration method applicable to classifiers from any model class, derived from Dirichlet distributions and generalising the beta calibration method from binary classification. It is easily implemented with neural nets since it is equivalent to log-transforming the uncalibrated probabilities, followed by one linear layer and softmax. Experiments demonstrate improved probabilistic predictions according to multiple measures (confidence-ECE, classwise-ECE, log-loss, Brier score) across a wide range of datasets and classifiers. Parameters of the learned Dirichlet calibration map provide insights to the biases in the uncalibrated model.

PURPOSE: The extant response shift definitions and theoretical response shift models, while helpful, also introduce predicaments and theoretical debates continue. To address these predicaments and stimulate empirical research, we propose a more specific formal definition of response shift and a revised theoretical model. METHODS: This work is an international collaborative effort and involved a critical assessment of the literature. RESULTS: Three main predicaments were identified. First, the formal definitions of response shift need further specification and clarification. Second, previous models were focused on explaining change in the construct intended to be measured rather than explaining the construct at multiple time points and neglected the importance of using at least two time points to investigate response shift. Third, extant models do not explicitly distinguish the measure from the construct. Here we define response shift as an effect occurring whenever observed change (e.g., change in patient-reported outcome measures (PROM) scores) is not fully explained by target change (i.e., change in the construct intended to be measured). The revised model distinguishes the measure (e.g., PROM) from the underlying target construct (e.g., quality of life) at two time points. The major plausible paths are delineated, and the underlying assumptions of this model are explicated. CONCLUSION: It is our hope that this refined definition and model are useful in the further development of response shift theory. The model with its explicit list of assumptions and hypothesized relationships lends itself for critical, empirical examination. Future studies are needed to empirically test the assumptions and hypothesized relationships.

As the population ages, the global cardiovascular disease burden will continue to increase, particularly among older adults. Increases in life expectancy and better cardiovascular care have significantly reshaped the epidemiology of cardiovascular disease and have created new patient profiles. The combination of older age, multiple comorbidities, polypharmacy, frailty, and adverse noncardiovascular outcomes is challenging our routine clinical practice in this field. In this review, we examine noncardiovascular factors that statistically interact in a relevant way with health status and quality of life in older people with cardiovascular disease. We focused on specific geriatric conditions (multimorbidity, polypharmacy, geriatric syndromes, and frailty) that are responsible for a major risk of functional decline and have an important impact on the overall prognosis in this patient population.

Importance: Fluid therapy is an important component of care for patients with traumatic brain injury, but whether it modulates clinical outcomes remains unclear. Objective: To determine whether continuous infusion of hypertonic saline solution improves neurological outcome at 6 months in patients with traumatic brain injury. Design, Setting, and Participants: Multicenter randomized clinical trial conducted in 9 intensive care units in France, including 370 patients with moderate to severe traumatic brain injury who were recruited from October 2017 to August 2019. Follow-up was completed in February 2020. Interventions: Adult patients with moderate to severe traumatic brain injury were randomly assigned to receive continuous infusion of 20% hypertonic saline solution plus standard care (n = 185) or standard care alone (controls; n = 185). The 20% hypertonic saline solution was administered for 48 hours or longer if patients remained at risk of intracranial hypertension. Main Outcomes and Measures: The primary outcome was Extended Glasgow Outcome Scale (GOS-E) score (range, 1-8, with lower scores indicating worse functional outcome) at 6 months, obtained centrally by blinded assessors and analyzed with ordinal logistic regression adjusted for prespecified prognostic factors (with a common odds ratio [OR] >1.0 favoring intervention). There were 12 secondary outcomes measured at multiple time points, including development of intracranial hypertension and 6-month mortality. Results: Among 370 patients who were randomized (median age, 44 [interquartile range, 27-59] years; 77 [20.2%] women), 359 (97%) completed the trial. The adjusted common OR for the GOS-E score at 6 months was 1.02 (95% CI, 0.71-1.47; P = .92). Of the 12 secondary outcomes, 10 were not significantly different. Intracranial hypertension developed in 62 (33.7%) patients in the intervention group and 66 (36.3%) patients in the control group (absolute difference, -2.6% [95% CI, -12.3% to 7.2%]; OR, 0.80 [95% CI, 0.51-1.26]). There was no significant difference in 6-month mortality (29 [15.9%] in the intervention group vs 37 [20.8%] in the control group; absolute difference, -4.9% [95% CI, -12.8% to 3.1%]; hazard ratio, 0.79 [95% CI, 0.48-1.28]). Conclusions and Relevance: Among patients with moderate to severe traumatic brain injury, treatment with continuous infusion of 20% hypertonic saline compared with standard care did not result in a significantly better neurological status at 6 months. However, confidence intervals for the findings were wide, and the study may have had limited power to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT03143751.

IMPORTANCE: Sirolimus is increasingly being used to treat various vascular anomalies, although evidence of its efficacy is lacking. OBJECTIVE: To assess the efficacy and safety of sirolimus for children with slow-flow vascular malformations to better delineate the indications for treatment. DESIGN, SETTING AND PARTICIPANTS: This multicenter, open-label, observational-phase randomized clinical trial included 59 children aged 6 to 18 years with a slow-flow vascular malformation who were recruited between September 28, 2015, and March 22, 2018, in 11 French tertiary hospital centers. Statistical analysis was performed on an intent-to-treat basis from December 4, 2019, to November 10, 2020. INTERVENTIONS: Patients underwent an observational period, then switched to an interventional period when they received oral sirolimus (target serum levels, 4-12 ng/mL). The switch time was randomized from month 4 to month 8, and the whole study period lasted 12 months for each patient. MAIN OUTCOMES AND MEASURES: The primary outcome was change in the volume of vascular malformations detected on magnetic resonance imaging scan (with centralized interpretation) per unit of time (ie, between the interventional period and the observational period). Secondary outcomes included subjective end points: pain, bleeding, oozing, quality of life, and safety. RESULTS: Among the participants (35 girls [59.3%]; mean [SD] age, 11.6 [3.8] years), 22 (37.3%) had a pure venous malformation, 18 (30.5%) had a cystic lymphatic malformation, and 19 (32.2%) had a combined malformation, including syndromic forms. Variations in the volume of vascular malformations detected on magnetic resonance imaging scans associated with the duration period were not overall significantly different between the interventional period and the observational period (all vascular malformations: mean [SD] difference, -0.001 [0.007]; venous malformations: mean [SD] difference, 0.001 [0.004]; combined malformations: mean [SD] difference, 0.001 [0.009]). However, a significant decrease in volume was observed for children with pure lymphatic malformations (mean [SD] difference, -0.005 [0.005]). Overall, sirolimus had positive effects on pain, especially for combined malformations, and on bleeding, oozing, self-assessed efficacy, and quality of life. During sirolimus treatment, 56 patients experienced 231 adverse events (5 serious adverse events, none life-threatening). The most frequent adverse event was an oral ulcer (29 patients [49.2%]). CONCLUSIONS AND RELEVANCE: This observational-phase randomized clinical trial allows for clarifying the goals of patients and families when starting sirolimus therapy for children older than 6 years. Pure lymphatic malformations seem to be the best indication for sirolimus therapy because evidence of decreasing lymphatic malformation volume per unit of time, oozing, and bleeding and increasing quality of life was found. In combined malformations, sirolimus significantly reduced pain, oozing, and bleeding. Benefits seemed lower for pure venous malformations than for the 2 other subgroups, also based on symptoms. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02509468; clinicaltrialsregister.eu Identifier: 2015-001096-43.

BACKGROUND: Whether preventive inhaled antibiotics may reduce the incidence of ventilator-associated pneumonia is unclear. METHODS: In this investigator-initiated, multicenter, double-blind, randomized, controlled, superiority trial, we assigned critically ill adults who had been undergoing invasive mechanical ventilation for at least 72 hours to receive inhaled amikacin at a dose of 20 mg per kilogram of ideal body weight once daily or to receive placebo for 3 days. The primary outcome was a first episode of ventilator-associated pneumonia during 28 days of follow-up. Safety was assessed. RESULTS: A total of 850 patients underwent randomization, and 847 were included in the analyses (417 assigned to the amikacin group and 430 to the placebo group). All three daily nebulizations were received by 337 patients (81%) in the amikacin group and 355 patients (83%) in the placebo group. At 28 days, ventilator-associated pneumonia had developed in 62 patients (15%) in the amikacin group and in 95 patients (22%) in the placebo group (difference in restricted mean survival time to ventilator-associated pneumonia, 1.5 days; 95% confidence interval [CI], 0.6 to 2.5; P = 0.004). An infection-related ventilator-associated complication occurred in 74 patients (18%) in the amikacin group and in 111 patients (26%) in the placebo group (hazard ratio, 0.66; 95% CI, 0.50 to 0.89). Trial-related serious adverse effects were seen in 7 patients (1.7%) in the amikacin group and in 4 patients (0.9%) in the placebo group. CONCLUSIONS: Among patients who had undergone mechanical ventilation for at least 3 days, a subsequent 3-day course of inhaled amikacin reduced the burden of ventilator-associated pneumonia during 28 days of follow-up. (Funded by the French Ministry of Health; AMIKINHAL ClinicalTrials.gov number, NCT03149640; EUDRA Clinical Trials number, 2016-001054-17.).

We estimated the degree to which language used in the high-profile medical/public health/epidemiology literature implied causality using language linking exposures to outcomes and action recommendations; examined disconnects between language and recommendations; identified the most common linking phrases; and estimated how strongly linking phrases imply causality. We searched for and screened 1,170 articles from 18 high-profile journals (65 per journal) published from 2010-2019. Based on written framing and systematic guidance, 3 reviewers rated the degree of causality implied in abstracts and full text for exposure/outcome linking language and action recommendations. Reviewers rated the causal implication of exposure/outcome linking language as none (no causal implication) in 13.8%, weak in 34.2%, moderate in 33.2%, and strong in 18.7% of abstracts. The implied causality of action recommendations was higher than the implied causality of linking sentences for 44.5% or commensurate for 40.3% of articles. The most common linking word in abstracts was "associate" (45.7%). Reviewers' ratings of linking word roots were highly heterogeneous; over half of reviewers rated "association" as having at least some causal implication. This research undercuts the assumption that avoiding "causal" words leads to clarity of interpretation in medical research.

Public health strategies for malaria in endemic countries aim to prevent transmission of the disease and control the vector. This historical analysis considers the strategies for vector control developed during the first four decades of the twentieth century. In 1925, policies and technological advances were debated internationally for the first time after the outbreak of malaria in Europe which followed World War I. This dialogue had implications for policies in Europe, Russia and the Middle East, and influenced the broader international control agenda. The analysis draws on the advances made before 1930, and includes the effects of mosquito-proofing of houses; the use of larvicides (Paris Green) and larvivorous fish (Gambusia); the role of large-scale engineering works; and the emergence of biological approaches to malaria. The importance of strong government and civil servant support was outlined. Despite best efforts of public health authorities, it became clear that it was notoriously difficult to interrupt transmission in areas of moderately high transmission. The importance of combining a variety of measures to achieve control became clear and proved successful in Palestine between 1923 and 1925, and improved education, economic circumstances and sustained political commitment emerge as key factors in the longer term control of malaria. The analysis shows that the principles for many of the present public health strategies for malaria have nearly all been defined before 1930, apart from large scale usage of pesticides, which came later at the end of the Second World War. No single intervention provided an effective single answer to preventing transmission, but certainly approaches taken that are locally relevant and applied in combination, are relevant to today's efforts at elimination.

Many drugs are responsible, through different mechanisms, for peripheral oedema. Severity is highly variable, ranging from slight oedema of the lower limbs to anasarca pictures as in the capillary leak syndrome. Although most often noninflammatory and bilateral, some drugs are associated with peripheral oedema that is readily erythematous (eg, pemetrexed) or unilateral (eg, sirolimus). Thus, drug-induced peripheral oedema is underrecognized and misdiagnosed, frequently leading to a prescribing cascade. Four main mechanisms are involved, namely precapillary arteriolar vasodilation (vasodilatory oedema), sodium/water retention (renal oedema), lymphatic insufficiency (lymphedema) and increased capillary permeability (permeability oedema). The underlying mechanism has significant impact on treatment efficacy. The purpose of this review is to provide a comprehensive analysis of the main causative drugs by illustrating each pathophysiological mechanism and their management through an example of a drug.

Significance Statement Identifying biomarkers for predicting kidney transplant failure requires better understanding of the immune response to chronic allogeneic stimulation. The authors demonstrated that 1 year after kidney transplantation, the composition of CD8 + memory T cell subsets in blood—specifically the ratio of terminally differentiated effector memory (TEMRA) and effector memory CD8 + T cells—is associated with risk for subsequent graft failure and adds predictive value to a previously reported eight-variable clinical risk score. They also found that TEMRA CD8 + T cells display a novel T cell receptor–independent mechanism of activation that is mediated through CD16 engagement and results in inflammation and antibody-dependent cellular cytotoxicity. These findings suggest a pivotal role for TEMRA CD8 + T cells in chronic humoral and cellular rejection leading to kidney transplant failure. Future clinical benefits may include the use of CD8 + memory T cell monitoring to improve risk prediction for graft failure and development of therapeutic strategies targeting TEMRA CD8 + T cells. Background Identifying biomarkers to predict kidney transplant failure and to define new therapeutic targets requires more comprehensive understanding of the immune response to chronic allogeneic stimulation. Methods We investigated the frequency and function of CD8 + T cell subsets—including effector memory (EM) and terminally differentiated EM (TEMRA) CD8 + T cells—in blood samples from 284 kidney transplant recipients recruited 1 year post-transplant and followed for a median of 8.3 years. We also analyzed CD8 + T cell reactivity to donor-specific PBMCs in 24 patients who had received living-donor kidney transplants. Results Increased frequency of circulating TEMRA CD8 + T cells at 1 year post-transplant associated with increased risk of graft failure during follow-up. This association remained after adjustment for a previously reported composite of eight clinical variables, the Kidney Transplant Failure Score. In contrast, increased frequency of EM CD8 + T cells associated with reduced risk of graft failure. A distinct TEMRA CD8 + T cell subpopulation was identified that was characterized by expression of Fc γ RIIIA (CD16) and by high levels of proinflammatory cytokine secretion and cytotoxic activity. Although donor-specific stimulation induced a similar rapid, early response in EM and TEMRA CD8 + T cells, CD16 engagement resulted in selective activation of TEMRA CD8 + T cells, which mediated antibody-dependent cytotoxicity. Conclusions At 1 year post-transplant, the composition of memory CD8 + T cell subsets in blood improved prediction of 8-year kidney transplant failure compared with a clinical-variables score alone. A subpopulation of TEMRA CD8 + T cells displays a novel dual mechanism of activation mediated by engagement of the T-cell receptor or of CD16. These findings suggest that TEMRA CD8 + T cells play a pivotal role in humoral and cellular rejection and reveal the potential value of memory CD8 + T cell monitoring for predicting risk of kidney transplant failure.

STUDY OBJECTIVE: The QoR-15 scale is a validated tool to assess the quality of postoperative recovery (QoR). Our objective was to assess the association between the early QoR-15 values and the occurrence of one-month postoperative complications. DESIGN: We used the data from a prospective single-centre cohort study conducted in the Angers University Hospital from July 2019 to February 2020 that validated the French version of the QoR-15 (FQoR-15). SETTING: Preoperative room, ward, and home. PATIENTS: 363 French-speaking adult patients, undergoing elective surgery, were enrolled (217 (59,8%) men, median age 60 (range 44 to 71) years old), including 139 (38.3%) ambulatory surgeries. INTERVENTION: Patients completed the QoR-15 scale the day before, at 24 and 48 h after surgery. MEASUREMENTS: Postoperative complications were recorded according to the PostOperative Morbidity Survey (POMS) classification till 30 days after surgery. The QoR was classified as excellent (QoR-15 > 135), good (122 ≤ QoR-15 ≤ 135), moderate (90 ≤ QoR-15 ≤ 121) or poor (QoR-15 < 90). Days alive and out of hospital up to 30 days after surgery was also recorded. MAIN RESULTS: According to the POMS classification, 176 (48.5%) patients had at least one complication up to 30 days after surgery. Among the 69 (19.0%) patients with a poor recovery at H24, 58 (84.1%) had at least one complication up to 30 days after surgery compared to 10 (23.8%) among the 42 (11.6%) in the excellent recovery group (p < 0.0001). The QoR-15 score at H24 allowed suitable discrimination of the occurrence of at least one complication up to 30 days after surgery (AUC 0.732 (95% CI 0.680 to 0.784)). CONCLUSION: The early QoR-15 scale after surgery is moderately associated with the occurrence of postoperative complications up to 30 days after elective surgeries (i.e. it has predictive validity).

AIMS: Negative and positive urgency are emotion-related impulsivity traits that are thought to be transdiagnostic factors in psychopathology. However, it has recently been claimed that these two traits are closely related to each other and that considering them separately might have limited conceptual and methodological value. The present study aimed to examine whether positive and negative urgency constructs constitute separate impulsivity traits. METHODS: In contrast to previous studies that have used latent variable approaches, this study employed an item-based network analysis conducted in two different samples: a large sample of non-clinical participants (N = 18,568) and a sample of clinical participants with psychiatric disorders (N = 385). RESULTS: The network analysis demonstrated that items denoting both positive and negative urgency cohere as a single cluster of items termed "general urgency" in both clinical and non-clinical samples, thereby suggesting that differentiating positive and negative urgency as separate constructs is not necessary. CONCLUSION: These findings have important implications for the conceptualization and assessment of urgency and, more broadly, for future research on impulsivity, personality, and psychopathology.

BACKGROUND: While peritoneal dialysis (PD) can offer patients more independence and flexibility compared with in-center hemodialysis, managing the ongoing and technically demanding regimen can impose a burden on patients and caregivers. Patient empowerment can strengthen capacity for self-management and improve treatment outcomes. We aimed to describe patients' and caregivers' perspectives on the meaning and role of patient empowerment in PD. METHODS: Adult patients receiving PD (n = 81) and their caregivers (n = 45), purposively sampled from nine dialysis units in Australia, Hong Kong and the USA, participated in 14 focus groups. Transcripts were thematically analyzed. RESULTS: We identified six themes: lacking clarity for self-management (limited understanding of rationale behind necessary restrictions, muddled by conflicting information); PD regimen restricting flexibility and freedom (burden in budgeting time, confined to be close to home); strength with supportive relationships (gaining reassurance with practical assistance, comforted by considerate health professionals, supported by family and friends); defying constraints (reclaiming the day, undeterred by treatment, refusing to be defined by illness); regaining lost vitality (enabling physical functioning, restoring energy for life participation); and personal growth through adjustment (building resilience and enabling positive outlook, accepting the dialysis regimen). CONCLUSIONS: Understanding the rationale behind lifestyle restrictions, practical assistance and family support in managing PD promoted patient empowerment, whereas being constrained in time and capacity for life participation outside the home undermined it. Education, counseling and strategies to minimize the disruption and burden of PD may enhance satisfaction and outcomes in patients requiring PD.

Herpes zoster pain and postherpetic neuralgia (PHN) particularly affect older persons. This literature review presents how quality of life is evaluated and the consequences of shingles and PHN on the quality of life of older persons. Although more than 150 articles have been published on herpes zoster and its consequences, specific studies focusing on the older population are needed, in several domains like epidemiology, preventive medicine, neuropsychology, and pharmacology.

BACKGROUND: In a period of change in the organization of primary care, Interprofessional Collaboration (IPC) is presented as one of the solutions to health issues. Although the number of inter-professional interventions grounded in primary care increases in all developed countries, evidence on the effects of these collaborations on patient-centred outcomes is patchy. The objective of our study was to assess the effects of IPC grounded in the primary care setting on patient-centred outcomes. METHODS: We conducted a systematic literature review using the PubMed, Embase, PsycINFO and CINAHL databases from 01/01/1995 to 01/03/2021, according to the PRISMA guidelines. Studies reporting the effects of IPC in primary care on patient health outcomes were included. The quality of the studies was assessed using the revised Downs and Black checklist. RESULTS: Sixty-five articles concerning 61 interventions were analysed. A total of 43 studies were prospective and randomized. Studies were classified into 3 main categories as follows: 1) studies with patients at cardiovascular risk (28 studies)-including diabetes (18 studies) and arterial hypertension (5 studies); 2) studies including elderly and/or polypathological patients (18 studies); and 3) patients with symptoms of mental or physical disorders (15 studies). The number of included patients varied greatly (from 50 to 312,377). The proportion of studies that reported a positive effect of IPC on patient-centred outcomes was as follows: 23 out of the 28 studies including patients at cardiovascular risk, 8 out of the 18 studies of elderly or polypathological patients, and 11 out of the 12 studies of patients with mental or physical disorders. CONCLUSIONS: Evidence suggests that IPC is effective in the management of patients at cardiovascular risk. In elderly or polypathological patients and in patients with mental or physical disorders, the number of studies remains very limited, and the results are heterogeneous. Researchers should be encouraged to perform studies based on comparative designs: it would increase evidence on the positive effect and benefits of IPC on patient variables.

OBJECTIVE: The aims were to review practices concerning Differential Item Functioning (DIF) detection in composite measurement scales, particularly those used in health research, and to provide guidance on how to proceed if statistically significant DIF is detected. METHODS: This work specifically addressed the Rasch model which is the subject of growing interest in the field of health owing to its particularly advantageous properties. There were three steps: 1) Literature review to describe current practices; 2) Simulation study to determine under which conditions encountered in health research studies can erroneous conclusions be drawn from group comparisons when a scale is affected by DIF but which is not considered; 3) Based on steps 1 and 2, formulation of recommendations that were subsequently reviewed by leading internationally recognized experts. RESULTS: Four key recommendations were formulated to help researchers to determine whether statistically significant DIF is meaningful in practice, according to the kind of DIF (uniform or non-uniform) and the DIF effect size. CONCLUSION: This work provides the first recommendations on how to deal in practice with the presence of DIF in composite measurement scales used in health research studies.

INTRODUCTION: Acute respiratory distress syndrome often requires invasive mechanical ventilation, with both mortality and mechanical ventilation duration as outcomes of interest. The concept of ventilator-free days has been proposed as an outcome combining these two outcomes. Here we analyzed the construction of the ventilator-free day outcome and provided a hypothetical scenario to alert physicians that such an outcome can lead to misleading interpretations. METHODS: We proposed the isoventilator-free day curve concept and, using an analytical development, illustrated how a median ventilator-free day value can actually result from very different combinations of death rates and mechanical ventilation durations. We also used a hypothetical example to compare the Student t test, Wilcoxon rank-sum test, and Gray test (which accounts for death as a competing event with extubation) in comparing exposition to mechanical ventilation. RESULTS: A median ventilator-free day value of 10 days may mean that 10% of the patients died while survivors were ventilated during a median of 14 days or that 40% died while survivors were ventilated during a median of 5 days. Changing the time horizon affected the Student t test but not the Wilcoxon rank-sum result. The Gray test was more relevant than both the Student t test and Wilcoxon rank-sum test in identifying differences in groups showing highly different mechanical ventilation duration, despite equal median ventilator-free days. This approach was also illustrated using real data. CONCLUSIONS: Use of ventilator-free days as an outcome appears to have many drawbacks. Suitable methods of analyzing time to extubation should be preferred.