Impact of Daily Growth Hormone Adherence on Height Velocity Among Children With Growth Hormone Deficiency (GHD).

OBJECTIVE: To describe adherence to daily somatropin treatment and impact on height velocity within 1 year of treatment start among patients with pediatric growth hormone deficiency in a real-world US population. METHODS: This retrospective cohort study included pediatric patients aged ≥3 years to <16 years with pediatric growth hormone deficiency prescribed somatropin by a pediatric endocrinologist at a US-based center of excellence between January 1, 2015 and December 31, 2020. Patient data were collected using hospital electronic health records linked to a specialty pharmacy patient prescription records. Adherence, evaluated over 12 months, was measured using the proportion of days covered metric and patients were categorized as adherent if their proportion of days covered ≥80%. Height velocity was annualized to compare across adherent and nonadherent patients. RESULTS: One hundred eighty-one patients were identified and included in this study, of which 70.2% were male,73.5% were white, and mean age (standard deviation [SD]) at index was 12.1 (2.8). In the height velocity analysis, 174 patients were included and the mean (SD) annualized change in height was 10.2 (5.7) cm/y in the adherent group (n = 108) and 9.8 (7.6) in the nonadherent group (n = 66). The difference in height velocity between the groups was not statistically significant. CONCLUSIONS: Minor improvements in average height velocity were observed in the patient group who were adherent to somatropin therapy, although not statistically significant. Lack of observed significance may be due to small sample sizes, short observation period, a likely heterogenous population in terms of growth hormone prescribing, data bias due to single-center origin, or potential patient misclassification.

Five-Year Structural Changes in the Knee Among Patients With Meniscal Tear and Osteoarthritis: Data From a Randomized Controlled Trial of Arthroscopic Partial Meniscectomy Versus Physical Therapy.

OBJECTIVE: To estimate the risk of magnetic resonance imaging (MRI)-based structural changes in knee osteoarthritis (OA) among individuals with meniscal tear and knee OA, using MRIs obtained at baseline and 18 and 60 months after randomization in a randomized controlled trial of arthroscopic partial meniscectomy (APM) versus physical therapy (PT). METHODS: We used data from the Meniscal Tear in Osteoarthritis Research (METEOR) trial. MRIs were read using the MRI OA Knee Score (MOAKS). We used linear mixed-effects models to examine the association between treatment group and continuous MOAKS summary scores, and Poisson regression to assess categorical changes in knee joint structure. Analyses assessed changes in OA between baseline and month 18 and between months 18 and 60. We performed both intention-to-treat and as-treated analyses. RESULTS: The analytic sample included 302 participants. For both treatment groups, more OA changes were seen during the early interval than during the later interval. ITT analysis revealed that, between baseline and month 18, APM was significantly associated with an increased risk of having a worsening cartilage surface area score, involving both any worsening across all knee joint subregions (risk ratio [RR] 1.35 [95% confidence interval (95% CI) 1.14, 1.61]) and the number of subregions damaged (RR 1.44 [95% CI 1.13, 1.85]) having a worsening effusion-synovitis score (RR 2.62 [95% CI 1.32, 5.21]), and having ≥1 additional subregion with osteophytes (RR 1.24 [95% CI 1.02, 1.50]). Significant associations were detected between months 18 and 60 only for having any subregion with a worsening osteophyte score (RR 1.28 [95% CI 1.04, 1.58]). CONCLUSION: These findings suggest that the association between APM and MRI-based structural changes in knee OA is most apparent during the initial 18 months after surgery. The reason for attenuation of this association over longer follow-up merits further investigation.

Predicting Remission Among Patients With Rheumatoid Arthritis Starting Tocilizumab Monotherapy: Model Derivation and Remission Score Development.

OBJECTIVE: Most patients with rheumatoid arthritis (RA) strive to consolidate their treatment from methotrexate combinations. The objective of this analysis was to identify patients with RA most likely to achieve remission with tocilizumab (TCZ) monotherapy by developing and validating a prediction model and associated remission score. METHODS: We identified four TCZ monotherapy randomized controlled trials in RA and chose two for derivation and two for internal validation. Remission was defined as a Clinical Disease Activity Index score less than 2.8 at 24 weeks post randomization. We used logistic regression to assess the association between each predictor and remission. After selecting variables and assessing model performance in the derivation data set, we assessed model performance in the validation data set. The cohorts were combined to calculate a remission prediction score. RESULTS: The variables selected included younger age, male sex, lower baseline Clinical Disease Activity Index score, shorter RA disease duration, region of the world (Europe and South America [increased odds of remission] versus Asia and North America), no previous exposure to disease-modifying antirheumatic drugs and/or methotrexate, lower baseline Health Assessment Questionnaire Disability Index score, and baseline hematocrit. The area under the receiver operating characteristic curve was 0.739 in the derivation data set and 0.756 in the validation data set. Patients were categorized into three remission prediction categories based on the remission prediction score: 40% in the low (less than 10% probability of remission), 45% in the intermediate (10%-25% probability), and 15% in the moderate remission prediction category (greater than 25% probability). CONCLUSION: We used easily accessible factors to develop a remission prediction score to predict RA remission at 24 weeks after initializing TCZ monotherapy. These results may provide guidance to clinicians tailoring treatment options based on clinical characteristics.

Association between changes in muscle strength and pain in persons with meniscal tear and osteoarthritis.

Objective: Strengthening-based physical therapy (PT) is frequently recommended for persons with knee osteoarthritis (OA) and meniscal tear. On average, knee OA patients experience pain improvement while undergoing PT, but whether these changes are accompanied by changes in muscle strength remains an important research question. Design: We used data from subjects randomized to PT in the Meniscal Tear in Osteoarthritis Research (MeTeOR) trial. Key elements, measured at baseline and 3 months, included quadriceps and hamstrings strength (in pounds) and Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain subscale (0-100; 100 worst). We examined the linear association between change in strength and change in pain over 3 months. Results: 111 subjects (mean age 57.1, average baseline hamstrings strength 27.5 (SD 14.7), average baseline KOOS 48.0 (SD 17.0)) experienced an average increase in hamstring strength of 3.5 lbs (SD 9.4) and an average decrease in KOOS Pain of 17.1 points (SD 17.4). The correlation between change in hamstrings strength and change in KOOS Pain was weak (Pearson r = 0.17; 95% CI-0.016-0.345). A multivariable linear regression model adjusting for baseline pain showed that a 10-pound increase in hamstrings strength was associated with a 2.9-point (95% CI-0.05-5.9) reduction in KOOS Pain. The association between changes in quadriceps strength and pain was even weaker than that for hamstrings pain. Conclusion: We observed small increases in strength and weak associations between strengthening and pain relief, suggesting that pain relief achieved during PT likely arises from multiple factors beyond strengthening alone.

Quality-Adjusted Life-Years Lost Due to Physical Inactivity in a US Population With Osteoarthritis.

OBJECTIVE: One-half of the 14 million persons in the US with knee osteoarthritis (OA) are not physically active, despite evidence that physical activity (PA) is associated with improved health. We undertook this study to estimate both the quality-adjusted life-year (QALY) losses in a US population with knee OA due to physical inactivity and the health benefits associated with higher PA levels. METHODS: We used data from the Osteoarthritis Initiative and the Centers for Disease Control and Prevention to estimate the proportions of a US population with knee OA ages ≥45 years that are inactive, insufficiently active, and active, and the likelihood of a shift in their PA level. We used the OA Policy Model, a computer simulation of knee OA, to determine QALYs lost due to inactivity and to measure potential benefits of increased PA (comorbidities averted and QALYs saved). RESULTS: Among 13.7 million persons with knee OA, a total of 7.5 million QALYs, or 0.55 QALYs per person, were lost due to inactivity or insufficient PA relative to activity over their remaining lifetimes. Black Hispanic women experienced the highest losses, at 0.76 QALYs per person. Women of all races/ethnicities had ~20% higher loss burdens than men. According to our model, if 20% of the inactive population were instead active, 95,920 cases of cancer, 222,413 of cardiovascular disease, and 214,725 of diabetes mellitus would potentially be averted, and 871,541 potential QALYs would be saved. CONCLUSION: Physical inactivity leads to substantial QALY losses in a US population with knee OA. Increases in the activity levels in even a fraction of this population may have considerable collateral health benefits, potentially averting cases of cancer, cardiovascular disease, and diabetes mellitus.

Five-Year Outcome of Operative and Nonoperative Management of Meniscal Tear in Persons Older Than Forty-Five Years.

OBJECTIVE: To determine the 5-year outcome of treatment for meniscal tear in osteoarthritis. METHODS: We examined 5-year follow-up data from the Meniscal Tear in Osteoarthritis Research trial (METEOR) of physical therapy versus arthroscopic partial meniscectomy. We performed primary intent-to-treat (ITT) and secondary as-treated analyses. The primary outcome measure was the Knee Injury and Osteoarthritis Outcome Score (KOOS) pain scale; total knee replacement (TKR) was a secondary outcome measure. We used piecewise linear mixed models to describe change in KOOS pain. We calculated 5-year cumulative TKR incidence and used a Cox model to estimate hazard ratios (HRs) for TKR, with 95% confidence intervals (95% CIs). RESULTS: Three hundred fifty-one participants were randomized. In the ITT analysis, the KOOS pain scores were ~46 (scale of 0 [no pain] to 100 [most pain]) at baseline in both groups. Pain scores improved substantially in both groups over the first 3 months, continued to improve through the next 24 months (to ~18 in each group), and were stable at 24-60 months. Results of the as-treated analyses of the KOOS pain score were similar. Twenty-five participants (7.1% [95% CI 4.4-9.8%]) underwent TKR over 5 years. In the ITT model, the HR for TKR was 2.0 (95% CI 0.8-4.9) for subjects randomized to the arthroscopic partial meniscectomy group, compared to those randomized to the physical therapy group. In the as-treated analysis, the HR for TKR was 4.9 (95% CI 1.1-20.9) for subjects ultimately treated with arthroscopic partial meniscectomy, compared to those treated nonoperatively. CONCLUSION: Pain improved considerably in both groups over 60 months. While ITT analysis revealed no statistically significant differences following TKR, greater frequency of TKR in those undergoing arthroscopic partial meniscectomy merits further study.

Medical Tent Utilization at 10-km Road Races: Injury, Illness, and Influencing Factors.

PURPOSE: To increase awareness of the need for coordinated medical care at 10-km races and to help direct future medical planning for these events. METHODS: We related medical encounter data from nineteen 10-km road races to runner, race, and environmental characteristics. We quantified the most commonly used resources and described the disposition of runners in these encounters. RESULTS: Across the 19 races and 90,265 finishers, there were 562 medical events for a cumulative incidence of 6.2 events per 1000 finishers (95% confidence interval, 5.7-6.8). Race size was associated with an increased incidence of medical events. Overall, the most common diagnosis was heat-related illness (1.6 per 1000 finishers), followed by musculoskeletal complaints (1.3 per 1000 finishers) and fluid-electrolyte imbalances (1.2 per 1000 finishers). For all diagnoses, runners with finishing times in the first performance quintile and in the fifth performance quintile had greater representation in the medical tent than mid-pack runners. Most runners were treated with supportive care, basic first aid, and oral rehydration. Ninety-four runners (1.0 per 1000 finishers) required ice water immersion for exertional heat stroke. There were low rates of hospital transport (0.2 per 1000 finishers), and no fatalities. CONCLUSIONS: In 10-km road races, injury rates are low compared with longer races in similar weather conditions. Common medical issues can be managed with basic resources in the on-site medical tent. Green flag start race conditions may not predict race safety with regard to exertional heat stroke risk. There were no deaths in nearly 100,000 finishers.

Cross-Cultural Comparison of Postoperative Discharge Opioid Prescribing After Orthopaedic Trauma Surgery.

BACKGROUND: The extent of variation in analgesic prescribing following musculoskeletal injury among countries and cultural contexts is poorly understood. Such an understanding can inform both domestic prescribing and future policy. The aim of our survey study was to evaluate how opioid prescribing by orthopaedic residents varies by geographic context. METHODS: Orthopaedic residents in 3 countries in which residents are the primary prescribers of postoperative analgesia in academic medical centers (Haiti, the Netherlands, and the U.S.) responded to surveys utilizing vignette-based musculoskeletal trauma case scenarios. The residents chose which medications they would prescribe for post-discharge analgesia. We standardized opioid prescriptions in the surveys by conversion to morphine milligram equivalents (MMEs). We then constructed multivariable regressions with generalized estimating equations to describe differences in opiate prescription according to country, the resident's sex and training year, and the injury site and age in the test cases. RESULTS: U.S. residents prescribed significantly more total MMEs per case (mean [95% confidence interval] = 383 [331 to 435]) compared with residents from the Netherlands (229 [160 to 297]) and from Haiti (101 [52 to 150]) both overall (p < 0.0001) and for patients treated for injuries of the femur (452 [385 to 520], 315 [216 to 414], and 103 [37 to 169] in the U.S., the Netherlands, and Haiti, respectively), tibial plateau (459 [388 to 531], 280 [196 to 365], and 114 [46 to 183]), tibial shaft (440 [380 to 500], 294 [205 to 383], and 141 [44 to 239]), wrist (239 [194 to 284], 78 [36 to 119], and 63 [30 to 95]), and ankle (331 [270 to 393], 190 [100 to 280], and 85 [42 to 128]) (p = 0.0272). U.S. residents prescribed significantly more MMEs for patients <40 years old (432 [374 to 490]) than for those >70 years old (327 [270 to 384]) (p = 0.0019). CONCLUSIONS: Our results demonstrate greater prescribing of postoperative opioids at discharge in the U.S. compared with 2 other countries, 1 low-income and 1 high-income. Our findings highlight the high U.S. reliance on opioid prescribing for postoperative pain control after orthopaedic trauma. CLINICAL RELEVANCE: Our findings point toward a need for careful reassessment of current opioid prescribing habits in the U.S. and demand reflection on how we can maximize effectiveness in pain management protocols and reduce provider contributions to the ongoing opioid crisis.

Increased postoperative dexamethasone and gabapentin reduces opioid consumption after total knee arthroplasty.

PURPOSE: Dexamethasone and gabapentin are used in multimodal pain management protocols to reduce postoperative pain after total knee arthroplasty. For both analgesic adjuvants, the optimal dose regimen to reduce opioid usage is still unclear. METHODS: The opioid consumption of patients undergoing primary TKA before and after a change of the analgesic adjuvant medication in our protocol (old protocol: 4 mg of dexamethasone daily for 2 days, 600 mg gabapentin daily for 1 week; new protocol: 10 mg dexamethasone daily for 2 days, 300 mg gabapentin every 8 h for 1 week) were retrospectively compared. All surgeries were performed under spinal anesthesia. Peri- and postoperative pain medication remained unchanged. RESULTS: A total of 186 patients who received TKA between 11/29/2016 and 06/09/2017 were screened. Six patients who received general anesthesia, 4 patients who underwent simultaneous bilateral TKA, and 16 patients with ongoing opioid consumption at the time of surgery were excluded, leaving 80 patients in each group. Opioid consumption within 24 h [morphine equivalents in mg: mean 50.5, standard deviation (SD) 30.0 (old) vs. 39.8, SD 24.2 (new); P = 0.0470], cumulative consumption over 48 h (97.3, SD 64.4 vs. 70.4, SD 51.2; P = 0.0040) and cumulative consumption over 72 h (108.1, SD 79.5 vs. 82.5, SD 72.6; P = 0.0080), were all significantly lower in the new protocol. CONCLUSION: Increased postoperative administration of dexamethasone and gabapentin after TKA is associated with lower opioid consumption. Within the first 48 h, up to about 25% of opioids can be spared, comparing high-dose to low-dose protocols. LEVEL OF EVIDENCE: Therapeutic Level III.

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.

Financial incentives for objectively-measured physical activity or weight loss in adults with chronic health conditions: A meta-analysis.

OBJECTIVE: We conducted a meta-analysis and systematic review of published randomized controlled trials (RCTs) to evaluate the impact of financial incentives (FI) on objectively-measured physical activity (PA) and weight loss (WL) in adults with sedentary behavior or chronic health conditions. EVIDENCE REVIEW: We performed a systematic search for RCTs published in English indexed in PubMed, Embase, or Web of Science through July 27, 2017. We limited our search to RCTs that involved an FI intervention with a monetary component, objectively-measured PA or WL outcomes, samples with either sedentary lifestyles or chronic health conditions, and a comparator group that did not receive performance-contingent FI. We calculated the mean difference and standardized mean difference (SMD) for each study and used a random effects model to summarize intervention efficacy. We used the Jadad scoring tool to assess the quality of the identified articles. RESULTS: We abstracted data from 11 RCTs. Two of the 11 included studies focused on PA, totaling 126 intervention and 116 control subjects. Nine RCTs evaluated the effect of FI on WL, totaling 1,799 intervention and 1,483 control subjects. The combined estimate for change in daily steps was 940 (95%CI [306-1,574]) more in PA intervention groups than in control groups and 2.36 (95%CI [1.80-2.93]) more kilograms lost by WL intervention groups compared to control groups. The overall estimated SMD for both outcomes combined was 0.395 (95%CI [0.243-0.546; p<0.001]), favoring FI interventions. CONCLUSION: FI interventions are efficacious in increasing PA and WL in adults with chronic conditions or sedentary adults. Public health programs to increase PA or prevent chronic disease should consider incorporating FI to improve outcomes.

Outcomes of safe patient handling and mobilization programs: A meta-analysis.

BACKGROUND: Variability in patient care settings and the range of patient handling tasks present challenges in developing and evaluating safe patient handling and mobilization (SPHM) programs. OBJECTIVE: We performed a systematic meta-analysis of SPHM program evaluations. METHODS: Systematic literature review identified published SPHM program evaluations. Injury Rate Ratios (IRR), pre- to post-intervention, were used to estimate intervention effects and to examine the influence of patient care level, program components, and follow-up time using meta-regression. RESULTS: 27 articles reported evaluations from 44 sites. Combined effect estimate for all SPHM programs was 0.44 (95% CI 0.36, 0.54), reflecting substantial injury reductions after program implementation. While specific program components were not associated with greater effectiveness, longer follow-up duration was associated with greater injury rate reduction (p = 0.01) and intervention effects varied by level of care (p = 0.01), with the greatest effect in intensive care unit interventions (IRR 0.14; 95% CI 0.07, 0.30). CONCLUSIONS: SPHM programs appear to be highly effective in reducing injuries. More research is needed to identify the most effective interventions for different patient care levels.

Diagnostic accuracy of administrative data algorithms in the diagnosis of osteoarthritis: a systematic review.

BACKGROUND: Administrative health care data are frequently used to study disease burden and treatment outcomes in many conditions including osteoarthritis (OA). OA is a chronic condition with significant disease burden affecting over 27 million adults in the US. There are few studies examining the performance of administrative data algorithms to diagnose OA. The purpose of this study is to perform a systematic review of administrative data algorithms for OA diagnosis; and, to evaluate the diagnostic characteristics of algorithms based on restrictiveness and reference standards. METHODS: Two reviewers independently screened English-language articles published in Medline, Embase, PubMed, and Cochrane databases that used administrative data to identify OA cases. Each algorithm was classified as restrictive or less restrictive based on number and type of administrative codes required to satisfy the case definition. We recorded sensitivity and specificity of algorithms and calculated positive likelihood ratio (LR+) and positive predictive value (PPV) based on assumed OA prevalence of 0.1, 0.25, and 0.50. RESULTS: The search identified 7 studies that used 13 algorithms. Of these 13 algorithms, 5 were classified as restrictive and 8 as less restrictive. Restrictive algorithms had lower median sensitivity and higher median specificity compared to less restrictive algorithms when reference standards were self-report and American college of Rheumatology (ACR) criteria. The algorithms compared to reference standard of physician diagnosis had higher sensitivity and specificity than those compared to self-reported diagnosis or ACR criteria. CONCLUSIONS: Restrictive algorithms are more specific for OA diagnosis and can be used to identify cases when false positives have higher costs e.g. interventional studies. Less restrictive algorithms are more sensitive and suited for studies that attempt to identify all cases e.g. screening programs.