Nonsteroidal anti-inflammatory drug "allergy" labeling is associated with increased postpartum opioid utilization.

BACKGROUND: Current guidelines recommend a stepwise approach to postpartum pain management, beginning with acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), with opioids added only if needed. Report of a prior NSAID-induced adverse drug reaction (ADR) may preclude use of first-line analgesics, despite evidence that many patients with this allergy label may safely tolerate NSAIDs. OBJECTIVE: We assessed the association between reported NSAID ADRs and postpartum opioid utilization. METHODS: We performed a retrospective cohort study of birthing people who delivered within an integrated health system (January 1, 2017, to December 31, 2020). Study outcomes were postpartum inpatient opioid administrations and opioid prescriptions at discharge. Statistical analysis was performed on a propensity score-matched sample, which was generated with the goal of matching to the covariate distributions from individuals with NSAID ADRs. RESULTS: Of 38,927 eligible participants, there were 883 (2.3%) with an NSAID ADR. Among individuals with reported NSAID ADRs, 49.5% received inpatient opioids in the postpartum period, compared to 34.5% of those with no NSAID ADRs (difference = 15.0%, 95% confidence interval 11.4-18.6%). For patients who received postpartum inpatient opioids, those with NSAID ADRs received a higher total cumulative dose between delivery and hospital discharge (median 30.0 vs 22.5 morphine milligram equivalents [MME] for vaginal deliveries; median 104.4 vs 75.0 MME for cesarean deliveries). The overall proportion of patients receiving an opioid prescription at the time of hospital discharge was higher for patients with NSAID ADRs compared to patients with no NSAID ADRs (39.3% vs 27.2%; difference = 12.1%, 95% confidence interval 8.6-15.6%). CONCLUSION: Patients with reported NSAID ADRs had higher postpartum inpatient opioid utilization and more frequently received opioid prescriptions at hospital discharge compared to those without NSAID ADRs, regardless of mode of delivery.

Impact of depressive symptoms on direct medical cost among medicare recipients with knee osteoarthritis.

OBJECTIVE: Depressive symptoms are prevalent among knee osteoarthritis (KOA) patients and may lead to additional medical costs. We compared medical costs in Medicare Current Beneficiary Survey (MCBS) respondents with KOA with and without self-reported depressive symptoms. METHODS: We identified a KOA cohort using ICD-9/10 diagnostic codes in both Part A and Part B claims among community-dwelling MCBS respondents from 2003 to 2019. We determined the presence of depressive symptoms using self-reported data on sadness or anhedonia. We considered three groups: 1) without depressive symptoms, 2) with depressive symptoms, no billable services, and 3) with depressive symptoms and billable services. We used a generalized linear model with log-transformed outcomes to compare annual total direct medical costs among the three groups, adjusting for age, gender, race, history of fall, Total Joint Replacement, comorbidities, and calendar year. RESULTS: The analysis included 4118 MCBS respondents with KOA. Of them, 27% had self-reported depressive symptoms, and 6% reported depressive symptoms and received depression-related billable services. The adjusted mean direct medical costs were $8598/year for those without depressive symptoms, $9239/year for those who reported depressive symptoms and received no billable services, and $14,229/year for those who reported depressive symptoms and received billable services. CONCLUSION: While over one quarter of Medicare beneficiaries with KOA self-reported depressive symptoms, only 6% received billable medical services. The presence of depressive symptoms led to higher direct medical costs, even among those who did not receive depression-related billable services.

The Association of Sacro-Femoro-Pubic Angle and Postoperative Dislocation Following Total Hip Arthroplasty.

BACKGROUND: Spino-pelvic orientation may affect dislocation risk following total hip arthroplasty (THA). It can be measured on lateral lumbo-pelvic radiographs. The sacro-femoro-pubic (SFP) angle, measured on an antero-posterior (AP) pelvis radiograph, is a reliable proxy for pelvic tilt, a measurement of spino-pelvic orientation measured on a lateral lumbo-pelvic radiograph. The purpose of this study was to investigate the relationship between SFP angle and dislocation following THA. METHODS: An Institutional Review Board-approved retrospective case-control study was conducted at a single academic center. We matched 71 dislocators (cases) to 71 nondislocators (controls) following THA performed by 1 of 10 surgeons between September 2001 and December 2010. Two authors (readers) independently calculated SFP angle from single preoperative AP pelvis radiographs. Readers were blinded to cases and controls. Conditional logistic regressions were used to identify factors differentiating cases and controls. RESULTS: The data did not show a clinically relevant or statistically significant difference in SFP angles after adjusting for gender, American Society of Anesthesiologists classification, prosthetic head size, age at time of THA, measurement laterality, and surgeon. CONCLUSION: We did not find an association between preoperative SFP angle and dislocation following THA in our cohort. Based on our data, SFP angle as measured on a single AP pelvis radiograph should not be used to assess dislocation risk prior to THA.

The Value of Total Knee Replacement in Patients With Knee Osteoarthritis and a Body Mass Index of 40 kg/m2 or Greater : A Cost-Effectiveness Analysis.

BACKGROUND: Total knee replacement (TKR) is an effective and cost-effective strategy for treating end-stage knee osteoarthritis. Greater risk for complications among TKR recipients with a body mass index (BMI) of 40 kg/m2 or greater has raised concerns about the value of TKR in this population. OBJECTIVE: To assess the value of TKR in recipients with a BMI of 40 kg/m2 or greater using a cost-effectiveness analysis. DESIGN: Osteoarthritis Policy Model to assess long-term clinical benefits, costs, and cost-effectiveness of TKR in patients with a BMI of 40 kg/m2 or greater. DATA SOURCES: Total knee replacement parameters from longitudinal studies and published literature, and costs from Medicare Physician Fee Schedules, the Healthcare Cost and Utilization Project, and published data. TARGET POPULATION: Recipients of TKR with a BMI of 40 kg/m2 or greater in the United States. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: Total knee replacement. OUTCOME MEASURES: Cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), discounted at 3% annually. RESULTS OF BASE-CASE ANALYSIS: Total knee replacement increased QALYs by 0.71 year and lifetime medical costs by $25 200 among patients aged 50 to 65 years with a BMI of 40 kg/m2 or greater, resulting in an ICER of $35 200. Total knee replacement in patients older than 65 years with a BMI of 40 kg/m2 or greater increased QALYs by 0.39 year and costs by $21 100, resulting in an ICER of $54 100. RESULTS OF SENSITIVITY ANALYSIS: In TKR recipients with a BMI of 40 kg/m2 or greater and diabetes and cardiovascular disease, ICERs were below $75 000 per QALY. Results were most sensitive to complication rates and preoperative pain levels. In the probabilistic sensitivity analysis, at a $55 000-per-QALY willingness-to-pay threshold, TKR had a 100% and 90% likelihood of being a cost-effective strategy for patients aged 50 to 65 years and patients older than 65 years, respectively. LIMITATION: Data are derived from several sources. CONCLUSION: From a cost-effectiveness perspective, TKR offers good value in patients with a BMI of 40 kg/m2 or greater, including those with multiple comorbidities. PRIMARY FUNDING SOURCE: National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health.

College Campuses and COVID-19 Mitigation: Clinical and Economic Value.

BACKGROUND: Colleges in the United States are determining how to operate safely amid the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To examine the clinical outcomes, cost, and cost-effectiveness of COVID-19 mitigation strategies on college campuses. DESIGN: The Clinical and Economic Analysis of COVID-19 interventions (CEACOV) model, a dynamic microsimulation model, was used to examine alternative mitigation strategies. The CEACOV model tracks infections accrued by students and faculty, accounting for community transmissions. DATA SOURCES: Data from published literature were used to obtain parameters related to COVID-19 and contact-hours. TARGET POPULATION: Undergraduate students and faculty at U.S. colleges. TIME HORIZON: One semester (105 days). PERSPECTIVE: Modified societal. INTERVENTION: COVID-19 mitigation strategies, including social distancing, masks, and routine laboratory screening. OUTCOME MEASURES: Infections among students and faculty per 5000 students and per 1000 faculty, isolation days, tests, costs, cost per infection prevented, and cost per quality-adjusted life-year (QALY). RESULTS OF BASE-CASE ANALYSIS: Among students, mitigation strategies reduced COVID-19 cases from 3746 with no mitigation to 493 with extensive social distancing and masks, and further to 151 when laboratory testing was added among asymptomatic persons every 3 days. Among faculty, these values were 164, 28, and 25 cases, respectively. Costs ranged from about $0.4 million for minimal social distancing to about $0.9 million to $2.1 million for strategies involving laboratory testing ($10 per test), depending on testing frequency. Extensive social distancing with masks cost $170 per infection prevented ($49 200 per QALY) compared with masks alone. Adding routine laboratory testing increased cost per infection prevented to between $2010 and $17 210 (cost per QALY gained, $811 400 to $2 804 600). RESULTS OF SENSITIVITY ANALYSIS: Results were most sensitive to test costs. LIMITATION: Data are from multiple sources. CONCLUSION: Extensive social distancing with a mandatory mask-wearing policy can prevent most COVID-19 cases on college campuses and is very cost-effective. Routine laboratory testing would prevent 96% of infections and require low-cost tests to be economically attractive. PRIMARY FUNDING SOURCE: National Institutes of Health.

Impact of reported NSAID "allergies" on opioid use disorder in back pain.

BACKGROUND: It is crucial to identify patients at highest risk for opioid use disorder (OUD) and to address challenges in reducing opioid use. Reported nonsteroidal anti-inflammatory drug (NSAID) allergies may predispose to use of stronger pain medications and potentially to OUD. OBJECTIVE: We sought to investigate the clinical impact of reported NSAID allergy on OUD in patients with chronic back pain. METHODS: We conducted a retrospective study of adults receiving care at a tertiary health care system from January 1, 2013, to December 31, 2018. Back pain and OUD were identified using administrative data algorithms. We used propensity score matching and logistic regression to estimate the impact of self-reported NSAID adverse drug reactions (ADRs) on risk of OUD, adjusting for other relevant clinical information. RESULTS: Of 47,114 patients with chronic back pain, 3,620 (7.7%) had a reported NSAID ADR. In an adjusted propensity score-matched analysis, patients with NSAID ADRs had higher odds (odds ratio, 1.34; 95% CI, 1.07-1.67) of developing OUD as compared with those without NSAID ADRs. Additional risk factors for OUD included younger age, male sex, Medicaid insurance, Medicare insurance, higher number of inpatient and outpatient visits in the previous year, and comorbid anxiety and depression. Patients with listed NSAID ADRs also had higher odds of a documented opioid prescription during the study period (odds ratio, 1.22; 95% CI, 1.11-1.34). CONCLUSIONS: Adults with chronic back pain and reported NSAID ADRs are at a higher risk of developing OUD and receiving opioid analgesics, even after accounting for comorbidities and health care utilization. Allergy evaluation is critical for potential delabeling of patients with reported NSAID allergies and chronic pain.

Effect of Diet and Exercise on Knee Pain in Patients With Osteoarthritis and Overweight or Obesity: A Randomized Clinical Trial.

Importance: Some weight loss and exercise programs that have been successful in academic center-based trials have not been evaluated in community settings. Objective: To determine whether adaptation of a diet and exercise intervention to community settings resulted in a statistically significant reduction in pain, compared with an attention control group, at 18-month follow-up. Design, Setting, and Participants: Assessor-blinded randomized clinical trial conducted in community settings in urban and rural counties in North Carolina. Patients were men and women aged 50 years or older with knee osteoarthritis and overweight or obesity (body mass index ≥27). Enrollment (N = 823) occurred between May 2016 and August 2019, with follow-up ending in April 2021. Interventions: Patients were randomly assigned to either a diet and exercise intervention (n = 414) or an attention control (n = 409) group for 18 months. Main Outcomes and Measures: The primary outcome was the between-group difference in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) knee pain score (range, 0 [none] to 20 [severe]; minimum clinically important difference, 1.6) over 18 months, tested using a repeated-measures mixed linear model with adjustments for covariates. There were 7 secondary outcomes including body weight. Results: Among the 823 randomized patients (mean age, 64.6 years; 637 [77%] women), 658 (80%) completed the trial. At 18-month follow-up, the adjusted mean WOMAC pain score was 5.0 in the diet and exercise group (n = 329) compared with 5.5 in the attention control group (n = 316) (adjusted difference, -0.6; 95% CI, -1.0 to -0.1; P = .02). Of 7 secondary outcomes, 5 were significantly better in the intervention group compared with control. The mean change in unadjusted 18-month body weight for patients with available data was -7.7 kg (8%) in the diet and exercise group (n = 289) and -1.7 kg (2%) in the attention control group (n = 273) (mean difference, -6.0 kg; 95% CI, -7.3 kg to -4.7 kg). There were 169 serious adverse events; none were definitely related to the study. There were 729 adverse events; 32 (4%) were definitely related to the study, including 10 body injuries (9 in diet and exercise; 1 in attention control), 7 muscle strains (6 in diet and exercise; 1 in attention control), and 6 trip/fall events (all 6 in diet and exercise). Conclusions and Relevance: Among patients with knee osteoarthritis and overweight or obesity, diet and exercise compared with an attention control led to a statistically significant but small difference in knee pain over 18 months. The magnitude of the difference in pain between groups is of uncertain clinical importance. Trial Registration: ClinicalTrials.gov Identifier: NCT02577549.

Clinical Impact, Costs, and Cost-effectiveness of Expanded Severe Acute Respiratory Syndrome Coronavirus 2 Testing in Massachusetts.

BACKGROUND: We projected the clinical and economic impact of alternative testing strategies on coronavirus disease 2019 (COVID-19) incidence and mortality in Massachusetts using a microsimulation model. METHODS: We compared 4 testing strategies: (1) hospitalized: polymerase chain reaction (PCR) testing only for patients with severe/critical symptoms warranting hospitalization; (2) symptomatic: PCR for any COVID-19-consistent symptoms, with self-isolation if positive; (3) symptomatic + asymptomatic once: symptomatic and 1-time PCR for the entire population; and (4) symptomatic + asymptomatic monthly: symptomatic with monthly retesting for the entire population. We examined effective reproduction numbers (Re = 0.9-2.0) at which policy conclusions would change. We assumed homogeneous mixing among the Massachusetts population (excluding those residing in long-term care facilities). We used published data on disease progression and mortality, transmission, PCR sensitivity/specificity (70%/100%), and costs. Model-projected outcomes included infections, deaths, tests performed, hospital-days, and costs over 180 days, as well as incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]). RESULTS: At Re = 0.9, symptomatic + asymptomatic monthly vs hospitalized resulted in a 64% reduction in infections and a 46% reduction in deaths, but required >66-fold more tests/day with 5-fold higher costs. Symptomatic + asymptomatic monthly had an ICER <$100 000/QALY only when Re ≥1.6; when test cost was ≤$3, every 14-day testing was cost-effective at all Re examined. CONCLUSIONS: Testing people with any COVID-19-consistent symptoms would be cost-saving compared to testing only those whose symptoms warrant hospital care. Expanding PCR testing to asymptomatic people would decrease infections, deaths, and hospitalizations. Despite modest sensitivity, low-cost, repeat screening of the entire population could be cost-effective in all epidemic settings.

Changing contextual factors from baseline to 9-months post-HIV diagnosis predict 5-year mortality in Durban, South Africa.

Changes in an individual's contextual factors following HIV diagnosis may influence long-term outcomes. We evaluated how changes to contextual factors between HIV diagnosis and 9-month follow-up predict 5-year mortality among HIV-infected individuals in Durban, South Africa enrolled in the Sizanani Trial (NCT01188941). We used random survival forests to identify 9-month variables and changes from baseline predictive of time to mortality. We incorporated these into a Cox proportional hazards model including age, sex, and starting ART by 9 months a priori, 9-month social support and competing needs, and changes in mental health between baseline and 9 months. Among 1,154 participants with South African ID numbers, 900 (78%) had baseline and 9-month data available of whom 109 (12%) died after 9-month follow-up. Those who reported less social support at 9 months had a 16% higher risk of mortality. Participants who went without basic needs or healthcare at 9 months had a 2.6 times higher hazard of death compared to participants who did not. Low social support and competing needs at 9-month follow-up substantially increase long-term mortality risk. Reassessing contextual factors during follow-up and targeting interventions to increase social support and affordability of care may reduce long-term mortality for HIV-infected individuals in South Africa.

Epidemiology of abdominal wall and groin hernia repairs in children.

PURPOSE: We sought to estimate the prevalence, incidence, and timing of surgery for elective and non-elective hernia repairs. METHODS: We performed a retrospective cohort study, abstracting data on children < 18 years from the 2005-2014 DoD Military Health System Data Repository, which includes > 3 million dependents of U.S. Armed Services members. Our primary outcome was initial hernia repair (inguinal, umbilical, ventral, or femoral), stratified by elective versus non-elective repair and by age. We calculated prevalence, incidence rate, and time from diagnosis to repair. RESULTS: 19,398 children underwent hernia repair (12,220 inguinal, 5761 umbilical, 1373 ventral, 44 femoral). Prevalence of non-elective repairs ranged from 6% (umbilical) to 22% (ventral). Incidence rates of elective repairs ranged from 0.03 [95% CI: 0.02-0.04] (femoral) to 8.92 [95% CI: 8.76-9.09] (inguinal) per 10,000 person-years, while incidence rates of non-elective repairs ranged from 0.005 [95% CI: 0.002-0.01] (femoral) to 0.68 [95% CI: 0.64-0.73] (inguinal) per 10,000 person-years. Inguinal (median = 20, interquartile range [IQR] = 0-46 days), ventral (median = 23, IQR = 5-62 days), and femoral hernias (median = 0, IQR = 0-12 days) were repaired more promptly and with less variation than umbilical hernias (median = 66, IQR = 23-422 days). CONCLUSIONS: These data describe the burden of hernia repair in the U.S. The large variation in time between diagnosis and repair by hernia type identifies an important area of research to understand mechanisms underlying such heterogeneity and determine the ideal timing for repair. LEVEL OF EVIDENCE: Prognosis study II.

Ambulatory status after surgical and nonsurgical treatment for spinal metastasis.

BACKGROUND: Decisions for operative or nonoperative management remain challenging for patients with spinal metastases, especially when life expectancy and quality of life are not easily predicted. This study evaluated the effects of operative and nonoperative management on maintenance of ambulatory function and survival for patients treated for spinal metastases. METHODS: Propensity matching was used to yield an analytic sample in which operatively and nonoperatively treated patients were similar with respect to key baseline covariates. The study included patients treated for spinal metastases between 2005 and 2017 who were 40 to 80 years old, were independent ambulators at presentation, and had fewer than 5 medical comorbidities. It evaluated the influence of operative care and nonoperative care on ambulatory function 6 months after presentation as the primary outcome. Survival at 6 months and survival at 1 year were secondary outcomes. RESULTS: Nine hundred twenty-nine individuals eligible for inclusion were identified, with 402 (201 operative patients and 201 nonoperative patients) retained after propensity score matching. Patients treated operatively had a lower likelihood than those treated nonoperatively of being nonambulatory 6 months after presentation (3% vs 16%; relative risk [RR], 0.16; 95% confidence interval [CI], 0.06-0.46) as well as a reduced risk of 6-month mortality (20% vs 29%; RR, 0.69; 95% CI, 0.49-0.98). CONCLUSIONS: These results indicate that in a group of patients with similar demographic and clinical characteristics, those treated operatively were less likely to lose ambulatory function 6 months after presentation than those managed nonoperatively. For patients with spinal metastases, our data can be incorporated into discussions about the treatments that align best with patients' preferences regarding surgical risk, mortality, and ambulatory status.

Management of Reducible Ventral Hernias: Clinical Outcomes and Cost-effectiveness of Repair at Diagnosis Versus Watchful Waiting.

OBJECTIVE: To compare long-term clinical and economic outcomes associated with 3 management strategies for reducible ventral hernia: repair at diagnosis (open or laparoscopic) and watchful waiting. BACKGROUND: There is variability in ventral hernia management. Recent data suggest watchful waiting is safe; however, long-term clinical and economic outcomes for different management strategies remain unknown. METHODS: We built a state-transition microsimulation model to forecast outcomes for individuals with reducible ventral hernia, simulating a cohort of 1 million individuals for each strategy. We derived cohort characteristics (mean age 58 years, 63% female), hospital costs, and perioperative mortality from the Nationwide Inpatient Sample (2003-2011), and additional probabilities, costs, and utilities from the literature. Outcomes included prevalence of any repair, emergent repair, and recurrence; lifetime costs; quality-adjusted life years (QALYs); and incremental cost-effectiveness ratios. We performed stochastic and probabilistic sensitivity analyses to identify parameter thresholds that affect optimal management, using a willingness-to-pay threshold of $50,000/QALY. RESULTS: With watchful waiting, 39% ultimately required repair (14% emergent) and 24% recurred. Seventy per cent recurred with repair at diagnosis. Laparoscopic repair at diagnosis was cost-effective compared with open repair at diagnosis (incremental cost-effectiveness ratio $27,700/QALY). The choice of operative strategy (open vs laparoscopic) was sensitive to cost and postoperative quality of life. When perioperative mortality exceeded 5.2% or yearly recurrence exceeded 19.2%, watchful waiting became preferred. CONCLUSIONS: Ventral hernia repair at diagnosis is very cost-effective. The choice between open and laparoscopic repair depends on surgical costs and postoperative quality of life. In patients with high risk of perioperative mortality or recurrence, watchful waiting is preferred.

Assessing rates and contextual predictors of 5-year mortality among HIV-infected and HIV-uninfected individuals following HIV testing in Durban, South Africa.

BACKGROUND: Little is known about contextual factors that predict long-term mortality following HIV testing in resource-limited settings. We evaluated the impact of contextual factors on 5-year mortality among HIV-infected and HIV-uninfected individuals in Durban, South Africa. METHODS: We used data from the Sizanani trial (NCT01188941) in which adults (≥18y) were enrolled prior to HIV testing at 4 outpatient sites. We ascertained vital status via the South African National Population Register. We used random survival forests to identify the most influential predictors of time to death and incorporated these into a Cox model that included age, gender, HIV status, CD4 count, healthcare usage, health facility type, mental health, and self-identified barriers to care (i.e., service delivery, financial, logistical, structural and perceived health). RESULTS: Among 4816 participants, 39% were HIV-infected. Median age was 31y and 49% were female. 380 of 2508 with survival information (15%) died during median follow-up of 5.8y. For both HIV-infected and HIV-uninfected participants, each additional barrier domain increased the HR of dying by 11% (HR 1.11, 95% CI 1.05-1.18). Every 10-point increase in mental health score decreased the HR by 7% (HR 0.93, 95% CI 0.89-0.97). The hazard ratio (HR) for death of HIV-infected versus HIV-uninfected varied by age: HR of 6.59 (95% CI: 4.79-9.06) at age 20 dropping to a HR of 1.13 (95% CI: 0.86-1.48) at age 60. CONCLUSIONS: Independent of serostatus, more self-identified barrier domains and poorer mental health increased mortality risk. Additionally, the impact of HIV on mortality was most pronounced in younger persons. These factors may be used to identify high-risk individuals requiring intensive follow up, regardless of serostatus. TRIAL REGISTRATION: Clinical Trials.gov Identifier NCT01188941. Registered 26 August 2010.

Test and Treat TB: a pilot trial of GeneXpert MTB/RIF screening on a mobile HIV testing unit in South Africa.

BACKGROUND: Community-based GeneXpert MTB/RIF testing may increase detection of prevalent TB in the community and improve rates of TB treatment completion. METHODS: We conducted a pilot randomized trial to evaluate the impact of GeneXpert screening on a mobile HIV testing unit. Adults (≥18y) underwent rapid HIV testing and TB symptom screening and were randomized to usual mobile unit care (providing sputum on the mobile unit sent out for GeneXpert testing) or the "Test & Treat TB" intervention with immediate GeneXpert testing. Symptomatic participants in usual care produced sputum that was sent for hospital-based GeneXpert testing; participants were contacted ~ 7 days later with results. In the "Test & Treat TB" intervention, HIV-infected or HIV-uninfected/TB symptomatic participants underwent GeneXpert testing on the mobile unit. GeneXpert+ participants received expedited TB treatment initiation, monthly SMS reminders and non-cash incentives. We assessed 6-month TB treatment outcomes. RESULTS: 4815 were eligible and enrolled; median age was 27 years (IQR 22 to 35). TB symptoms included cough (5%), weight loss (4%), night sweats (4%), and fever (3%). 42% of eligible participants produced sputum (intervention: 56%; usual care: 26%). Seven participants tested GeneXpert+, six in the intervention (3%, 95% CI 1%, 5%) and one in usual care (1%, 95% CI 0%, 6%). 5 of 6 intervention participants completed TB treatment; the GeneXpert+ participant in usual care did not. CONCLUSION: GeneXpert MTB/RIF screening on a mobile HIV testing unit is feasible. Yield for GeneXpert+ TB was low, however, the "Test & Treat TB" strategy led to high rates of TB treatment completion. TRIAL REGISTRATION: This study was registered on November 21, 2014 at ClinicalTrials.gov ( NCT02298309 ).

A consensus-based process identifying physical therapy and exercise treatments for patients with degenerative meniscal tears and knee OA: the TeMPO physical therapy interventions and home exercise program.

BACKGROUND: Knee osteoarthritis (OA) is prevalent and often associated with meniscal tear. Physical therapy (PT) and exercise regimens are often used to treat OA or meniscal tear, but, to date, few programs have been designed specifically for conservative treatment of meniscal tear with concomitant knee OA. Clinical care and research would be enhanced by a standardized, evidence-based, conservative treatment program and the ability to study the effects of the contextual factors associated with interventions for patients with painful, degenerative meniscal tears in the setting of OA. This paper describes the process of developing both a PT intervention and a home exercise program for a randomized controlled clinical trial that will compare the effectiveness of these interventions for patients with knee pain, meniscal tear and concomitant OA. METHODS: This paper describes the process utilized by an interdisciplinary team of physical therapists, physicians, and researchers to develop and refine a standardized in-clinic PT intervention, and a standardized home exercise program to be carried out without PT supervision. The process was guided in part by Medical Research Council guidance on intervention development. RESULTS: The investigators achieved agreement on an in-clinic PT intervention that included manual therapy, stretching, strengthening, and neuromuscular functional training addressing major impairments in range of motion, musculotendinous length, muscle strength and neuromotor control in the major muscle groups associated with improving knee function. The investigators additionally achieved agreement on a progressive, protocol-based home exercise program (HEP) that addressed the same major muscle groups. The HEP was designed to allow patients to perform and progress the exercises without PT supervision, utilizing minimal equipment and a variety of methods for instruction. DISCUSSION: This multi-faceted in-clinic PT program and standardized HEP provide templates for in-clinic and home-based care for patients with symptomatic degenerative meniscal tear and concomitant OA. These interventions will be tested as part of the Treatment of Meniscal Tear in Osteoarthritis (TeMPO) Trial. TRIAL REGISTRATION: The TeMPO Trial was first registered at clinicaltrials.gov with registration No. NCT03059004 on February 14, 2017. TeMPO was also approved by the Institutional Review Board at Partners HealthCare/Brigham and Women's Hospital.

Associations among knee muscle strength, structural damage, and pain and mobility in individuals with osteoarthritis and symptomatic meniscal tear.

BACKGROUND: Sufficient lower extremity muscle strength is necessary for performing functional tasks, and individuals with knee osteoarthritis demonstrate thigh muscle weakness compared to controls. It has been suggested that lower muscle strength is associated with a variety of clinical features including pain, mobility, and functional performance, yet these relationships have not been fully explored in patients with symptomatic meniscal tear in addition to knee osteoarthritis. Our purpose was to evaluate the associations of quadriceps and hamstrings muscle strength with structural damage and clinical features in individuals with knee osteoarthritis and symptomatic meniscal tear. METHODS: We performed a cross-sectional study using baseline data from the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial. We assessed structural damage using Kellgren-Lawrence grade and the magnetic resonance imaging osteoarthritis knee score (MOAKS) for cartilage damage. We used the Knee Injury and Osteoarthritis Outcomes Score (KOOS) to evaluate pain, symptoms, and activities of daily living (ADL), and the Timed Up and Go (TUG) test to assess mobility. We assessed quadriceps and hamstrings strength using a hand-held dynamometer and classified each into quartiles (Q). We used Chi square tests to evaluate the association between strength and structural damage; and separate analysis of covariance models to establish the association between pain, symptoms, ADL and mobility with strength, after adjusting for demographic characteristics (age, sex and BMI) and structural damage. RESULTS: Two hundred fifty two participants were evaluated. For quadriceps strength, subjects in the strongest quartile scored 14 and 13 points higher on the KOOS Pain and ADL subscales, respectively, and completed the TUG two seconds faster than subjects in the weakest quartile. For hamstrings strength, subjects in the strongest quartile scored 13 and 14 points higher on the KOOS pain and ADL subscales, respectively, and completed the TUG two seconds faster than subjects in the weakest quartile. Strength was not associated with structural damage. CONCLUSIONS: Greater quadriceps and hamstrings muscle strength was associated with less pain, less difficulty completing activities of daily living, and better mobility. These relationships should be evaluated longitudinally.

The TeMPO trial (treatment of meniscal tears in osteoarthritis): rationale and design features for a four arm randomized controlled clinical trial.

BACKGROUND: Meniscal tears often accompany knee osteoarthritis, a disabling condition affecting 14 million individuals in the United States. While several randomized controlled trials have compared physical therapy to surgery for individuals with knee pain, meniscal tear, and osteoarthritic changes (determined via radiographs or magnetic resonance imaging), no trial has evaluated the efficacy of physical therapy alone in these subjects. METHODS: The Treatment of Meniscal Tear in Osteoarthritis (TeMPO) Trial is a four-arm multi-center randomized controlled clinical trial designed to establish the comparative efficacy of two in-clinic physical therapy interventions (one focused on strengthening and one containing placebo) and two protocolized home exercise programs. DISCUSSION: The goal of this paper is to present the rationale behind TeMPO and describe the study design and implementation strategies, focusing on methodologic and clinical challenges. TRIAL REGISTRATION: The TeMPO Trial was first registered at clinicaltrials.gov with registration No. NCT03059004 . on February 14, 2017.

Projecting 10-year, 20-year, and Lifetime Risks of Cardiovascular Disease in Persons Living With Human Immunodeficiency Virus in the United States.

Background: Cardiovascular disease (CVD) is an increasing cause of morbidity among persons living with human immunodeficiency virus (HIV; PLWH). We projected cumulative CVD risk in PLWH in care compared to the US general population and persons HIV-uninfected, but at high risk for HIV. Methods: We used a mathematical model to project cumulative CVD incidence. We simulated a male and female cohort for each of 3 populations: US general population; HIV-uninfected, at high risk for HIV; and PLWH. We incorporated the higher smoking prevalence and increased CVD risk due to smoking into the HIV-infected and HIV-uninfected, at high risk for HIV populations. We incorporated HIV-attributable CVD risk, independent of smoking. Results: For men, life expectancy ranged from 70.2 to 77.5 years and for women from 67.0 to 81.1 years (PLWH, US general population). Without antiretroviral therapy, lifetime CVD risk for HIV-infected males and females was 12.9% and 9.0%. For males, by age 60, cumulative CVD incidence was estimated at 20.5% in PLWH in care, 14.6% in HIV-uninfected high-risk persons, and 12.8% in the US general population. For females, cumulative CVD incidence was projected to be 13.8% in PLWH in care, 9.7% for high-risk HIV-uninfected persons, and 9.4% in the US general population. Lifetime CVD risk was 64.8% for HIV-infected males compared to 54.8% for males in the US general population, but similar among females. Conclusions: CVD risks should be a part of treatment evaluation among PLWH. CVD prevention strategies could offer important health benefits for PLWH and should be evaluated.

Impact of Medication Adherence on Virologic Failure in A5202: A Randomized, Partially Blinded, Phase 3B Study.

In AIDS Clinical Trials Group A5202, participants who reported missing their medication within the past month or not providing adherence reports at both 8 and 24 weeks had 5 times the hazard of virological failure compared to more adherent participants. Adherence interventions should focus on such patients.

Predictive validity of biochemical biomarkers in knee osteoarthritis: data from the FNIH OA Biomarkers Consortium.

OBJECTIVE: To investigate a targeted set of biochemical biomarkers as predictors of clinically relevant osteoarthritis (OA) progression. METHODS: Eighteen biomarkers were measured at baseline, 12 months (M) and 24 M in serum (s) and/or urine (u) of cases (n=194) from the OA initiative cohort with knee OA and radiographic and persistent pain worsening from 24 to 48 M and controls (n=406) not meeting both end point criteria. Primary analyses used multivariable regression models to evaluate the association between biomarkers (baseline and time-integrated concentrations (TICs) over 12 and 24 M, transposed to z values) and case status, adjusted for age, sex, body mass index, race, baseline radiographic joint space width, Kellgren-Lawrence grade, pain and pain medication use. For biomarkers with adjusted p<0.1, the c-statistic (area under the curve (AUC)), net reclassification index and the integrated discrimination improvement index were used to further select for hierarchical multivariable discriminative analysis and to determine the most predictive and parsimonious model. RESULTS: The 24 M TIC of eight biomarkers significantly predicted case status (ORs per 1 SD change in biomarker): sCTXI 1.28, sHA 1.22, sNTXI 1.25, uC2C-HUSA 1.27, uCTXII, 1.37, uNTXI 1.29, uCTXIα 1.32, uCTXIß 1.27. 24 M TIC of uCTXII (1.47-1.72) and uC2C-Human Urine Sandwich Assay (HUSA) (1.36-1.50) both predicted individual group status (pain worsening, joint space loss and their combination). The most predictive and parsimonious combinatorial model for case status consisted of 24 M TIC uCTXII, sHA and sNTXI (AUC 0.667 adjusted). Baseline uCTXII and uCTXIα both significantly predicted case status (OR 1.29 and 1.20, respectively). CONCLUSIONS: Several systemic candidate biomarkers hold promise as predictors of pain and structural worsening of OA.