Oxygen-Saturation Targets and Cognitive and Functional Outcomes in Mechanically Ventilated Adults.

Rationale: Among mechanically ventilated critically ill adults, the PILOT (Pragmatic Investigation of Optimal Oxygen Targets) trial demonstrated no difference in ventilator-free days among lower, intermediate, and higher oxygen-saturation targets. The effects on long-term cognition and related outcomes are unknown.Objectives: To compare the effects of lower (90% [range, 88-92%]), intermediate (94% [range, 92-96%]), and higher (98% [range, 96-100%]) oxygen-saturation targets on long-term outcomes.Methods: Twelve months after enrollment in the PILOT trial, blinded neuropsychological raters conducted assessments of cognition, disability, employment status, and quality of life. The primary outcome was global cognition as measured using the Telephone Montreal Cognitive Assessment. In a subset of patients, an expanded neuropsychological battery measured executive function, attention, immediate and delayed memory, verbal fluency, and abstraction.Measurements and Main Results: A total of 501 patients completed follow-up, including 142 in the lower, 186 in the intermediate, and 173 in the higher oxygen target groups. Median (interquartile range) peripheral oxygen saturation values in the lower, intermediate, and higher target groups were 94% (91-96%), 95% (93-97%), and 97% (95-99%), respectively. Telephone Montreal Cognitive Assessment score did not differ between lower and intermediate (adjusted odds ratio [OR], 1.36 [95% confidence interval (CI), 0.92-2.00]), intermediate and higher (adjusted OR, 0.90 [95% CI, 0.62-1.29]), or higher and lower (adjusted OR, 1.22 [95% CI, 0.83-1.79]) target groups. There was also no difference in individual cognitive domains, disability, employment, or quality of life.Conclusions: Among mechanically ventilated critically ill adults who completed follow-up at 12 months, oxygen-saturation targets were not associated with cognition or related outcomes.

Randomized controlled trial of urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE): Rationale and design.

Diuresis to achieve decongestion is a central aim of therapy in patients hospitalized for acute decompensated heart failure (ADHF). While multiple clinical trials have investigated initial diuretic strategies for a designated period of time, there is a paucity of evidence to guide diuretic titration strategies continued until decongestion is achieved. The use of urine chemistries (urine sodium and creatinine) in a natriuretic response prediction equation accurately estimates natriuresis in response to diuretic dosing, but a randomized clinical trial is needed to compare a urine chemistry-guided diuresis strategy with a strategy of usual care. The urinE chemiStry guided aCute heArt faiLure treATmEnt (ESCALATE) trial is designed to test the hypothesis that protocolized diuretic therapy guided by spot urine chemistry through completion of intravenous diuresis will be superior to usual care and improve outcomes over the 14 days following randomization. ESCALATE will randomize and obtain complete data on 450 patients with acute heart failure to a diuretic strategy guided by urine chemistry or a usual care strategy. Key inclusion criteria include an objective measure of hypervolemia with at least 10 pounds of estimated excess volume, and key exclusion criteria include significant valvular stenosis, hypotension, and a chronic need for dialysis. Our primary outcome is days of benefit over the 14 days after randomization. Days of benefit combines patient symptoms captured by global clinical status with clinical state quantifying the need for hospitalization and intravenous diuresis. CLINICAL TRIAL REGISTRATION: NCT04481919.

'Will I wear purple?'-a school arts-based research project in the UK to disseminate findings from a qualitative evidence synthesis about living to an extreme age.

BACKGROUND: a change in attitude towards ageing is needed. Arts-based research (ABR) refers to the use of any creative art in research. ABR can provide an environment to reflect on challenging social issues and has the potential to make lasting impressions. OBJECTIVE: we aimed to explore the use of ABR to disseminate findings from a qualitative evidence synthesis exploring what it means to live well beyond the age of 80. DESIGN: ABR using art as a stimulus for recorded discussions and written annotations. SETTING: a mixed catchment state secondary school in the UK. SUBJECTS: fifty-four secondary school pupils aged 14-15. The majority identified as female (ratio 5:1). METHODS: school pupils created artwork to represent themes about ageing drawn from a qualitative evidence synthesis. The artwork was a stimulus for recorded discussions. We used thematic analysis to develop themes about children's response to ageing. RESULTS: we developed six themes. Pupils found comfort in recognising that old age can be lived well; they began to see themselves in the older person; they explored the ambiguous nature of memory; they highlighted the dangers of disconnection; they affirmed a need to restore connection with elders and they recognised the need to cherish time and live meaningfully. CONCLUSIONS: this project encouraged pupils to think about what it means to grow old. ABR has the potential to contribute to a more positive relationship with older people and towards ageing. Research stakeholders should not undervalue the potential power of shifts in perspective for powering social change.

Less pain reported 5 years after cementless compared to cemented unicompartmental knee replacement: an analysis of pain, neuropathy, and co-morbidity scores.

PURPOSE: To compare patient-reported pain scores and assess the influence of neuropathy and co-morbidity, on knee pain following cemented and cementless medial unicompartmental knee replacement (UKR) 5 years after surgery. METHOD: In this longitudinal study, 262 cemented and 262 cementless Oxford UKR performed for the same indications and with the same techniques were recruited. Patients were reviewed at five years, evaluating patient-reported pain and association with clinical outcomes. Intermittent and Constant Osteoarthritis Pain (ICOAP), PainDETECT (PD), Charnley score, Oxford Knee Score (OKS) and American Knee Society Score (AKSS) were compared. RESULTS: In both cohorts, intermittent pain was more common than constant pain (47% vs 21%). Cementless knees reported significantly less pain than cemented (ICOAP-Total 5/100 vs 11/100, p < 0.0001). A greater proportion of cementless knees experienced no pain at all (ICOAP = 0/100, 61% vs 43%, p < 0.0001) and 75% fewer experienced severe or extreme pain. Pain sub-scores in PD, OKS and AKSS follow this trend. Pain was unlikely to be neuropathic (PD positive: 5.26%), but patients reporting high levels of 'strongest' pain were three times more likely to be neuropathic. Patients with co-morbidities (Charnley C) experienced greater pain than those without (Charnley A+B) across all knee-specific scores, despite scores being knee specific. CONCLUSION: Both cemented and cementless UKR in this study had substantially less pain than that reported in literature following TKR. Cementless UKR had significantly less pain than cemented UKR in all scores. Two-thirds of patients with a cementless UKR had no pain at all at 5 years, and pain experienced was most likely to be mild and intermittent with no patients in severe or extreme pain. Patients with cementless UKR that had higher levels of pain were more likely to have co-morbidity or evidence or neuropathic pain. It is unclear why cementless UKR have less pain than cemented; further study is necessary.

Fixed lateral unicompartmental knee replacement is a reliable treatment for lateral compartment osteoarthritis after mobile-bearing medial unicompartmental replacement.

PURPOSE: Lateral osteoarthritis following medial unicompartmental knee replacement (UKR) is usually treated with total knee replacement, however, lateral UKR is a less invasive option that preserves a well-functioning medial UKR. This study aimed to determine the 5-year outcome of the cemented Fixed Lateral Oxford UKR (FLO) when used for the treatment of severe lateral disease after medial Oxford unicompartmental knee replacement. METHODS: Forty-four knees with lateral bone-on-bone osteoarthritis (n = 43) and avascular necrosis (n = 1) treated with the FLO following medial Oxford UKR were followed up prospectively. The Oxford Knee Score (OKS) and Tegner Activity Score (TAS) were collected pre- and post-operatively. Life-table analysis was used to determine survival rates. RESULTS: The mean patient age at the time of FLO surgery was 74.4 years with a mean time of 12.1 years between the primary medial UKR and the conversion to a bi-UKR with a FLO. Mean follow-up of the FLO was 3.5 years. After FLO no intra-operative or medical complications, re-admissions, or mortality occurred. There was one reoperation in which a bearing was exchanged for a medial bearing dislocation. There were no revisions of the FLO, so the FLO survival rate at 5 years was 100% (24 at risk). The mean pre-operative OKS was 22, which significantly (p < 0.0001) improved to a mean of 42, 42, and 40 at 1, 2, and 5 years, respectively. The median TAS had a non-significant improvement from 2.5 (Range 0-8) pre-operatively to 2 (Range 1-6) at 5 years postoperatively. CONCLUSION: The FLO is a reliable treatment for lateral osteoarthritis following medial UKR. At 5 years there was a 100% survival of the FLO with a mean OKS of 40. LEVEL OF EVIDENCE: IV, Prospective Case Series.

Anticytomegalovirus CD4+ T Cells Are Associated With Subclinical Atherosclerosis in Persons With HIV.

[Figure: see text].

Tuberculosis treatment intermittency in the continuation phase and mortality in HIV-positive persons receiving antiretroviral therapy.

BACKGROUND: Some tuberculosis (TB) treatment guidelines recommend daily TB treatment in both the intensive and continuation phases of treatment in HIV-positive persons to decrease the risk of relapse and acquired drug resistance. However, guidelines vary across countries, and treatment is given 7, 5, 3, or 2 days/week. The effect of TB treatment intermittency in the continuation phase on mortality in HIV-positive persons on antiretroviral therapy (ART), is not well-described. METHODS: We conducted an observational cohort study among HIV-positive adults treated for TB between 2000 and 2018 and after enrollment into the Caribbean, Central, and South America network for HIV epidemiology (CCASAnet; Brazil, Chile, Haiti, Honduras, Mexico and Peru). All received standard TB therapy (2-month initiation phase of daily isoniazid, rifampin or rifabutin, pyrazinamide ± ethambutol) and continuation phase of isoniazid and rifampin or rifabutin, administered concomitantly with ART. Known timing of ART and TB treatment were also inclusion criteria. Kaplan-Meier and Cox proportional hazards methods compared time to death between groups. Missing model covariates were imputed via multiple imputation. RESULTS: 2303 patients met inclusion criteria: 2003(87%) received TB treatment 5-7 days/week and 300(13%) 2-3 days/week in the continuation phase. Intermittency varied by site: 100% of patients from Brazil and Haiti received continuation phase treatment 5-7 days/week, followed by Honduras (91%), Peru (42%), Mexico (7%), and Chile (0%). The crude risk of death was lower among those receiving treatment 5-7 vs. 2-3 days/week (HR = 0.68; 95% CI = 0.51-0.91; P = 0.008). After adjusting for age, sex, CD4, ART use at TB diagnosis, site of TB disease (pulmonary vs. extrapulmonary), and year of TB diagnosis, mortality risk was lower, but not significantly, among those treated 5-7 days/week vs. 2-3 days/week (HR 0.75, 95%CI 0.55-1.01; P = 0.06). After also stratifying by study site, there was no longer a protective effect (HR 1.42, 95%CI 0.83-2.45; P = 0.20). CONCLUSIONS: TB treatment 5-7 days/week was associated with a marginally decreased risk of death compared to TB treatment 2-3 days/week in the continuation phase in multivariable, unstratified analyses. However, little variation in TB treatment intermittency within country meant the results could have been driven by other differences between study sites. Therefore, randomized trials are needed, especially in heterogenous regions such as Latin America.

Risk of Incident Diabetes Mellitus, Weight Gain, and Their Relationships With Integrase Inhibitor-Based Initial Antiretroviral Therapy Among Persons With Human Immunodeficiency Virus in the United States and Canada.

BACKGROUND: Integrase strand transfer inhibitor (INSTI)-based combination antiretroviral therapy (cART) is associated with greater weight gain among persons with human immunodeficiency virus (HIV), though metabolic consequences, such as diabetes mellitus (DM), are unclear. We examined the impact of initial cART regimen and weight on incident DM in a large North American HIV cohort (NA-ACCORD). METHODS: cART-naive adults (≥18 years) initiating INSTI-, protease inhibitor (PI)-, or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimens from January 2007 through December 2017 who had weight measured 12 (±6) months after treatment initiation contributed time until clinical DM, virologic failure, cART regimen switch, administrative close, death, or loss to follow-up. Multivariable Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for incident DM by cART class. Mediation analyses, with 12-month weight as mediator, similarly adjusted for all covariates. RESULTS: Among 22 884 eligible individuals, 47% started NNRTI-, 30% PI-, and 23% INSTI-based cART with median follow-up of 3.0, 2.3, and 1.6 years, respectively. Overall, 722 (3%) developed DM. Persons starting INSTIs vs NNRTIs had incident DM risk (HR, 1.17 [95% CI, .92-1.48]), similar to PI vs NNRTI initiators (HR, 1.27 [95% CI, 1.07-1.51]). This effect was most pronounced for raltegravir (HR, 1.42 [95% CI, 1.06-1.91]) vs NNRTI initiators. The INSTI-DM association was attenuated (HR, 1.03 [95% CI, .71-1.49] vs NNRTIs) when accounting for 12-month weight. CONCLUSIONS: Initiating first cART regimens with INSTIs or PIs vs NNRTIs may confer greater risk of DM, likely mediated through weight gain.

Efficacy and safety of dapagliflozin in acute heart failure: Rationale and design of the DICTATE-AHF trial.

BACKGROUND: Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, reduces cardiovascular death and worsening heart failure in patients with chronic heart failure and reduced ejection fraction. Early initiation during an acute heart failure (AHF) hospitalization may facilitate decongestion, improve natriuresis, and facilitate safe transition to a beneficial outpatient therapy for both diabetes and heart failure. OBJECTIVE: The objective is to assess the efficacy and safety of initiating dapagliflozin within the first 24 hours of hospitalization in patients with AHF compared to usual care. METHODS: DICTATE-AHF is a prospective, multicenter, open-label, randomized trial enrolling a planned 240 patients in the United States. Patients with type 2 diabetes hospitalized with hypervolemic AHF and an estimated glomerular filtration rate of at least 30 mL/min/1.73m2 are eligible for participation. Patients are randomly assigned 1:1 to dapagliflozin 10 mg once daily or structured usual care until day 5 or hospital discharge. Both treatment arms receive protocolized diuretic and insulin therapies. The primary endpoint is diuretic response expressed as the cumulative change in weight per cumulative loop diuretic dose in 40 mg intravenous furosemide equivalents. Secondary and exploratory endpoints include inpatient worsening AHF, 30-day hospital readmission for AHF or diabetic reasons, change in NT-proBNP, and measures of natriuresis. Safety endpoints include the incidence of hyper/hypoglycemia, ketoacidosis, worsening kidney function, hypovolemic hypotension, and inpatient mortality. CONCLUSIONS: The DICTATE-AHF trial will establish the efficacy and safety of early initiation of dapagliflozin during AHF across both AHF and diabetic outcomes in patients with diabetes.

Understanding the experience of living well, beyond the age of 85 years: a qualitative analysis using themes from a meta-ethnography.

BACKGROUND: Increase in life-expectancy is not necessarily matched by an increase in quality of life. OBJECTIVE: (1) To explore the quality of life of patients over the age of 85 in the second decade following unicompartmental knee replacement surgery (2) To understand the usefulness of a priori themes from an evidence synthesis as a framework for primary qualitative analysis. DESIGN: Qualitative Research. A hermeneutic phenomenological approach, using a priori themes as sensitising concepts. PARTICIPANTS: Adults over the age of 85 who were part of an outcomes study in the second decade following unicompartmental knee joint replacement. METHODS: Semi-structured interviews in people's homes. Transcripts were coded and data sorted using a priori themes as sensitising concepts. Data that did not fit these themes, or that added nuance, were analysed thematically through constant comparison. RESULTS: We interviewed seven white women and five white men, aged 85-100. Data resonated with a priori themes and supported additional themes that help us to understand older peoples' experience: (1) losing our autonomy can be challenging, so be kind; (2) we must take care of our own bodies and the NHS; (3) I am more afraid of not dying. CONCLUSIONS: Findings indicate that health outcomes for older people should incorporate measures of participation and well-being; they highlight the importance of kindness in healthcare; they indicate that older people do not want to place additional burden on the NHS, and this can act as a barrier to care; they support the need for open conversations about dying well.

Quality of physician care coordination during inter-facility transfer for cardiac arrest patients.

AIM: We sought to evaluate whether the quality of coordination between physicians transferring comatose cardiac arrest survivors to a high-volume cardiac arrest center for targeted temperature management (TTM) was associated with timeliness of care. METHODS: We conducted a retrospective analysis of inter-facility transfers to Vanderbilt University Medical Center for TTM between October 2016 and October 2018. We examined the relationship between Relational Coordination (RC) - a measure of communication and relationship quality - during phone conversations between transferring physicians and time-to-acceptance. RESULTS: We identified 18 patients meeting criteria. TTM was initiated or continued in 72%, and in-hospital mortality was 75%. Median time-to-acceptance was 2.77 (interquartile range [IQR] 2.0, 4.1) minutes, and duration of calls was 3.95 (IQR 2.7, 5.2) minutes. Interrater reliability for overall RC was high (rho = 0.87). The correlation between RC and the time-to-acceptance was significant in univariate analyses (adjusted relative risk = 0.96, 95%CI 0.93, 1.0, p = 0.05). Secondary analyses did not find a significant relationship between RC and timeliness measures. CONCLUSION: In this sample of patients transferred for TTM, we found that RC as a measure of care coordination, was reliable. Higher quality care coordination for cardiac arrest survivors was associated with faster physician acceptance. Future work using a larger cohort should explore if higher RC among a broader set of stakeholders (physicians, EMS, families, etc.) is associated with timeliness measures after adjusting for other factors, to better understand how the quality of care coordination impacts timeliness of care and patient outcomes.

The Experience of Living to an Extreme Age: A Meta-Ethnography.

Advances in health care mean that we can now treat diseases that once cut lives short. However, the increase in life expectancy has not been matched by improvements in quality of life. The World Health Organization warns us that all countries should prepare to meet the challenges of an aging population and this is integral to the United Nations 2030 Agenda for Sustainable Development. This may require a shift in attitude toward aging. We aimed to use meta-ethnography to explore the experience of adults living beyond the age of 80. Our conceptual model illuminates the phenomenon of connection in older age and reflects on the paradox of time: ephemeral, yet interminable. Our findings encourage us to reflect on the influence of enlightenment philosophies that underpin the desire for autonomy at all costs. Our study challenges the stereotypes of old age and has the potential to influence people's perspectives toward aging.

Emergency department provider and facility variation in opioid prescriptions for discharged patients.

STUDY OBJECTIVE: To study the variation in opioid prescribing among emergency physicians and facilities for discharged adult ED patients. METHODS: We conducted a retrospective analysis of ED visits from five U.S. hospitals between January and May 2014 using records from Data to Intelligence (D2i). We examined physician- and facility-level variation in opioid prescription rates for discharged ED patients. We calculated unadjusted opioid prescription rates at the physician and facility levels and used a multivariable mixed-effect logistic regression model to examine within-facility physician variation in opioid prescription adjusting for patient and situational factors including time of presentation, ED census, and physician workload. RESULTS: In 47,304 visits across five EDs, median patient age was 40 years old (IQR 28,55), and 89% had some form of insurance. There were 17,098 (36%) ED discharges with at least one opioid prescription. The unadjusted facility-level opioid prescription rate ranged from 24%-46%. Among 253 ED physicians, the adjusted opioid prescription rate varied from 22%-76%. Increased physician workload is related to decreased odds of opioid prescription at ED discharge for the lowest (<3 patients) and moderate (6-9 patients) physician workload levels, while the association weakened with increasing levels of workload. CONCLUSION: There was substantial physician and facility variation in opioid prescription for discharged adult ED patients. Emergency physicians were less likely to prescribe opioids when their workload was lower, and this effect diminished at high workload levels. Understanding situational and other factors that explain this variation is important given the rising U.S. opioid epidemic and the need for urgent intervention.

Obesity should not be considered a contraindication to medial Oxford UKA: long-term patient-reported outcomes and implant survival in 1000 knees.

PURPOSE: Some health providers ration knee arthroplasty on the basis of body mass index (BMI). There is no long-term data on the outcome of medial mobile-bearing unicompartmental knee arthroplasty (UKA) in different BMI groups. This study aimed to determine the effect of patient body mass index (BMI) on patient-reported outcomes and long-term survival of medial UKA in a large non-registry cohort. Our hypothesis is that increasing BMI would be associated with worse outcomes. METHODS: Data were analysed from a prospective cohort of 1000 consecutive medial mobile-bearing Oxford UKA with mean 10-year follow-up. Patients were grouped: BMI < 25, BMI 25 to < 30, BMI 30 to < 35 and BMI 35+. Oxford Knee Score (OKS) and Tegner Activity Score were assessed at 1, 5 and 10 years. Kaplan-Meier survivorship was calculated and compared between BMI groups. RESULTS: All groups had significant improvement in OKS and Tegner scores. BMI 35 + kg/m2 experienced the greatest overall increase in mean OKS of 17.3 points (p = 0.02). There was no significant difference in ten-year survival, which was, from lowest BMI group to highest 92%, 95%, 94% and 93%. CONCLUSION: There was no difference in implant survival between groups, and although there was no consistent trend in postoperative OKS, the BMI 35+ group benefited the most from UKA. Therefore, when UKA is used for appropriate indications, high BMI should not be considered to be a contraindication. Furthermore rationing based on BMI seems unjustified, particularly when the commonest threshold (BMI 35) is used. LEVEL OF EVIDENCE: III.

Knee Arthroplasty Patients Predicted Versus Actual Recovery: What Are Their Expectations About Time of Recovery After Surgery and How Long Before They Can Do the Tasks They Want to Do?

OBJECTIVES: (1) To determine evidence-based guidance for the length of time to return to specific valued functional and leisure activities after knee arthroplasty (KA). (2) To determine what patients feel are the most important functional or leisure activities to recover after KA. (3) To collect information about patients' expectations and compare them to the actual time it takes to return. DESIGN: Prospective longitudinal cohort observational survey. SETTING: Specialist orthopedic hospital. PARTICIPANTS: Patients (N=99) with osteoarthritis or rheumatoid arthritis (mean=69.9y [range 44-88]) listed for total knee arthroplasty (TKA) or unicompartmental knee arthroplasty. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Valued activities list (VAL) used to select activities patients expect to return to and report the actual time taken to return. RESULTS: Participants in unicompartmental knee arthroplasty group returned to the 6 most popular valued activities (walking >1km, stair climbing, housework, driving, gardening, and kneeling) 8%-33% more quickly than TKA group, and they were satisfied with performing these activities sooner on average (4%-18%) than the TKA group. The percentage of participants satisfied at 12 months postsurgery ranged from 96% returning to housework to 36% returning to kneeling. The Wilcoxon signed-rank test was used to compare the expected time and the actual time to return: Housework (Z=-5.631, P<.05, effect size=0.64) and swimming (Z=-3.209, P<.05, effect size=0.59) were quicker than expected, and walking >1 km (Z=-2.324, P<.05, effect size=0.27) was slower than expected. CONCLUSIONS: A more tailored and personalized approach with consideration of prior level of activity and comorbidities must be taken into account and adequately discussed to help bridge the gap between the expected and actual recovery time.

The impact of patient-specific instrumentation on unicompartmental knee arthroplasty: a prospective randomised controlled study.

PURPOSE: Patient-specific instrumentation (PSI) has been proposed as a means of improving surgical accuracy and ease of implantation during technically challenging procedures such as unicompartmental knee arthroplasty (UKA). The purpose of this prospective randomised controlled trial was to compare the accuracy of implantation and functional outcome of mobile-bearing medial UKAs implanted with and without PSI by experienced UKA surgeons. METHODS: Mobile-bearing medial UKAs were implanted in 43 patients using either PSI guides or conventional instrumentation. Intra-operative measurements, meniscal bearing size implanted, and post-operative radiographic analyses were performed to assess component positioning. Functional outcome was determined using the Oxford Knee Score (OKS). RESULTS: PSI guides could not be used in three cases due to concerns regarding accuracy and registration onto native anatomy, particularly on the tibial side. In general, similar component alignment and positioning was achieved using the two systems (n.s. for coronal/sagittal alignment and tibial coverage). The PSI group had greater tibial slope (p = 0.029). The control group had a higher number of optimum size meniscal bearing inserted (95 vs 52%; p = 0.001). There were no differences in OKS improvements (n.s). CONCLUSION: Component positioning for the two groups was similar for the femur but less accurate on the tibial side using PSI, often with some unnecessarily deep resections of the tibial plateau. Although PSI was comparable to conventional instrumentation based on OKS improvements at 12 months, we continue to use conventional instrumentation for UKA at our institution until further improvements to the PSI guides can be demonstrated. LEVEL OF EVIDENCE: Therapeutic, Level I.

Mortality in Children with Human Immunodeficiency Virus Initiating Treatment: A Six-Cohort Study in Latin America.

OBJECTIVES: To assess the risks of and factors associated with mortality, loss to follow-up, and changing regimens after children with HIV infected perinatally initiate combination antiretroviral therapy (cART) in Latin America and the Caribbean. STUDY DESIGN: This 1997-2013 retrospective cohort study included 1174 antiretroviral therapy-naïve, perinatally infected children who started cART age when they were younger than 18 years of age (median 4.7 years; IQR 1.7-8.8) at 1 of 6 cohorts from Argentina, Brazil, Haiti, and Honduras, within the Caribbean, Central and South America Network for HIV Epidemiology. Median follow-up was 5.6 years (IQR 2.3-9.3). Study outcomes were all-cause mortality, loss to follow-up, and major changes in cART. We used Cox proportional hazards models stratified by site to examine the association between predictors and times to death or changing regimens. RESULTS: Only 52% started cART at younger than 5 years of age; 19% began a protease inhibitor. At cART initiation, median CD4 count was 472 cells/mm3 (IQR 201-902); median CD4% was 16% (IQR 10-23). Probability of death was high in the first year of cART: 0.06 (95% CI 0.04-0.07). Five years after cART initiation, the cumulative mortality incidence was 0.12 (95% CI 0.10-0.14). Cumulative incidences for loss to follow-up and regimen change after 5 years were 0.16 (95% 0.14-0.18) and 0.30 (95% 0.26-0.34), respectively. Younger children had the greatest risk of mortality, whereas older children had the greatest risk of being lost to follow-up or changing regimens. CONCLUSIONS: Innovative clinical and community approaches are needed for quality improvement in the pediatric care of HIV in the Americas.

Lateral osteophytes do not represent a contraindication to medial unicompartmental knee arthroplasty: a 15-year follow-up.

PURPOSE: Lateral osteophytes have been reported to be associated with lateral compartment disease and as such it is unclear whether medial unicompartmental knee arthroplasty should be performed if these are present. METHODS: Using the OARSI classification system, 0 (no osteophyte) to 3 (large osteophyte), radiographs from a series of cemented meniscal-bearing unicompartmental knee arthroplasty implanted in the setting of full-thickness lateral cartilage where lateral osteophytes were not considered a contraindication were identified and factors associated with the presence and size of lateral osteophytes, and their impact on clinical outcomes and implant survival were assessed. RESULTS: Pre-operative radiographs from 458 knees (392 patients), independently followed up for a mean 10.5 years (range 5.3-16.6), were assessed. Lateral osteophytes were present in 62 % of knees with 18 % scored as Grade 3. Inter-observer reliability was good (kappa = 0.70). The presence and size of lateral osteophytes was associated with younger age at joint replacement (p = 0.01) and increasing BMI (p = 0.01). No association was seen with gender, pre-operative status, assessed using the Oxford Knee Score (OKS), American Knee Society (AKSS) Objective or Functional Score, Tegner activity score, or size of medial tibial lesion. Subgroup analysis of Grade 3 Osteophytes revealed that these were associated with a greater degree of macroscopic ACL damage. At 10 years there was no difference in function (n.s.), and at 15 years no difference in implant survival or mechanism of failure between groups (n.s.). Subgroup analysis of Grade 3 osteophytes found no significant difference in functional outcome at 10 years or implant survival at 15 years. CONCLUSION: The presence of lateral osteophytes is not a contraindication to medial meniscal-bearing unicompartmental knee arthroplasty. The clinical relevance of this study is that it highlights the importance of an appropriate pre-operative assessment of the lateral compartment as in the setting of full-thickness cartilage at operation lateral osteophytes do not compromise long-term functional outcome or implant survival. LEVEL OF EVIDENCE: IV.

Evidence-Based Indications for Mobile-Bearing Unicompartmental Knee Arthroplasty in a Consecutive Cohort of Thousand Knees.

BACKGROUND: The indications for unicompartmental knee arthroplasty remain controversial. Previously recommended contraindications include the following: age under 60 years, weight 180 lb (82 kg) or over, patients undertaking heavy labor, chondrocalcinosis, and exposed bone in the patellofemoral joint. This study explores whether these contraindications are valid in mobile-bearing unicompartmental knee arthroplasty. METHODS: Using a prospective series of 1000 consecutive medial unicompartmental knee arthroplasties in which the reported contraindications were not applied, the functional outcome and survival in patients with or without contraindications were compared. RESULTS: Of the 1000 consecutive unicompartmental knee arthroplasties (818 patients), 68% (678 knees) would be considered contraindicated based on published contraindications. At a mean follow-up of 10 years (5-17), there was no difference in American Knee Society (AKS) Objective Scores (P = .05) or Oxford Knee Score (P = .08) between groups. However, knees with contraindications had significantly (P = .02) fewer poor outcomes and significantly better AKS Functional Scores (P < .001) and Tegner Activity Scores (P < .001). At 15 years, no difference in implant survival (P = .33) was observed. The 3% of unicompartmental knee arthroplasties performed in young men (age <60) weighing 180 lb or over with high activity levels, who have been reported to have poor outcomes after fixed-bearing unicompartmental knee arthroplasty, had significantly better AKS Functional Scores (P < .001), Oxford Knee Score (P = .01), and Tegner Activity Score (P < .001) at 10 years. No difference in AKS Objective Scores (P = .54) at 10 years or implant survival at 15 years (P = .75) was seen. CONCLUSION: This large case series provides evidence that patients with the previously reported contraindications do as well as, or even better than, those without contraindications. Therefore these contraindications should not apply to mobile-bearing unicompartmental knee arthroplasty.

Comparing results from multiple imputation and dynamic marginal structural models for estimating when to start antiretroviral therapy.

Optimal timing of initiating antiretroviral therapy has been a controversial topic in HIV research. Two highly publicized studies applied different analytical approaches, a dynamic marginal structural model and a multiple imputation method, to different observational databases and came up with different conclusions. Discrepancies between the two studies' results could be due to differences between patient populations, fundamental differences between statistical methods, or differences between implementation details. For example, the two studies adjusted for different covariates, compared different thresholds, and had different criteria for qualifying measurements. If both analytical approaches were applied to the same cohort holding technical details constant, would their results be similar? In this study, we applied both statistical approaches using observational data from 12,708 HIV-infected persons throughout the USA. We held technical details constant between the two methods and then repeated analyses varying technical details to understand what impact they had on findings. We also present results applying both approaches to simulated data. Results were similar, although not identical, when technical details were held constant between the two statistical methods. Confidence intervals for the dynamic marginal structural model tended to be wider than those from the imputation approach, although this may have been due in part to additional external data used in the imputation analysis. We also consider differences in the estimands, required data, and assumptions of the two statistical methods. Our study provides insights into assessing optimal dynamic treatment regimes in the context of starting antiretroviral therapy and in more general settings. Copyright © 2016 John Wiley & Sons, Ltd.