Surgical restabilization reduces the progression of post-traumatic osteoarthritis initiated by ACL rupture in mice.

OBJECTIVE: People who sustain joint injuries such as anterior cruciate ligament (ACL) rupture often develop post-traumatic osteoarthritis (PTOA). In human patients, ACL injuries are often treated with ACL reconstruction. However, it is still unclear how effective joint restabilization is for reducing the progression of PTOA. The goal of this study was to determine how surgical restabilization of a mouse knee joint following non-invasive ACL injury affects PTOA progression. DESIGN: In this study, 187 mice were subjected to non-invasive ACL injury or no injury. After injury, mice underwent restabilization surgery, sham surgery, or no surgery. Mice were then euthanized on day 14 or day 49 after injury/surgery. Functional analyses were performed at multiple time points to assess voluntary movement, gait, and pain. Knees were analyzed ex vivo with micro-computed tomography, RT-PCR, and whole-joint histology to assess articular cartilage degeneration, synovitis, and osteophyte formation. RESULTS: Both ACL injury and surgery resulted in loss of epiphyseal trabecular bone (-27-32%) and reduced voluntary movement at early time points. Joint restabilization successfully lowered OA score (-78% relative to injured at day 14, p < 0.0001), and synovitis scores (-37% relative to injured at day 14, p = 0.042), and diminished the formation of chondrophytes/osteophytes (-97% relative to injured at day 14, p < 0.001, -78% at day 49, p < 0.001). CONCLUSIONS: This study confirmed that surgical knee restabilization was effective at reducing articular cartilage degeneration and diminishing chondrophyte/osteophyte formation after ACL injury in mice, suggesting that these processes are largely driven by joint instability in this mouse model. However, restabilization was not able to mitigate the early inflammatory response and the loss of epiphyseal trabecular bone, indicating that these processes are independent of joint instability.

A prospective longitudinal analysis of the predictors of amenorrhea after breast cancer chemotherapy: Impact of BRCA pathogenic variants.

BACKGROUND: Better tools for post-chemotherapy amenorrhea risk assessment are needed for fertility preservation decision-making. Our aim was to determine the predictors of amenorrhea risk at 12 and 18 months post-chemotherapy in women with breast cancer. METHODS: 142 women with breast cancer were longitudinally followed for their menstrual changes at 6, 12, and 18 months after the completion of adjuvant chemotherapy with an Anthracycline-Cyclophosphamide-based (AC-based) or Cyclophosphamide-Methotrexate +5-Fluorouracil regimen. Pre- and/or post-chemo AMH levels, age, BMI, tamoxifen use, regimen type, and germline BRCA pathogenic variant (gBRCApv) status were evaluated for the prediction of amenorrhea at 6-18 months. RESULTS: In multivariable-adjusted logistic regression, age (p = 0.03) and AMH (p = 0.03) at 12 months, and gBRCApv status (p = 0.03) at 18 months were significant predictors of amenorrhea (areas under the ROC curve of 0.77 and 0.76, for 12 and 18 months, respectively) among 102 evaluable subjects. An undetectable AMH immediately post-chemotherapy was predictive of amenorrhea with <18 month follow-up. In longitudinal analysis estimating time trends, baseline AMH and gBRCApv status was associated with the risk of amenorrhea over 6-18 months; the AMH >2.0 ng/mL group showed attenuated time-trend risk of amenorrhea versus AMH ≤2.0 group (ratio of ORs = 0.91, 95% CI = 0.86-0.97, p = 0.002), while the gBRCApv + showed a steeper time trend, versus the controls (ratio of ORs = 1.12, 95% CI = 1.04-1.20, p = 0.003). CONCLUSIONS: In addition to the pre- and post-treatment AMH levels, gBRCApv status is a novel potential predictor of amenorrhea at 12 and 18 months after chemotherapy. The higher likelihood of amenorrhea in women gBRCApv suggests that they are more prone to losing their fertility post-chemotherapy.

Outcomes of random-start letrozole protocol with PGT-A in women with breast cancer undergoing fertility preservation.

PURPOSE  : To compare the cycle characteristics and outcomes of random-start-controlled ovarian stimulation (RSCOS) protocols to the outcomes of standard-start-controlled ovarian stimulation (SSCOS) cycles and to report the utility of PGT-A in these cycles. METHODS: One hundred and seventeen who underwent SSCOS and 39 who underwent RSCOS for oocyte and/or embryo cryopreservation before breast cancer chemotherapy were retrospectively evaluated. Mean number of embryos and blastocyst euploidy rates were the main outcome measures. RESULTS: A majority of RSCOS cycles were initiated in the luteal phase (66.6% luteal vs. 33.3% follicular). While the total dose of gonadotropins was significantly higher in the RSCOS (3720.8 ± 1230.0 vs. 2345.1 ± 803.6 IU; P < 0.001), the mean number of mature oocytes and embryos was similar to SSCOS. However, there was a trend for a higher number of mean embryos with luteal start RSCOS (6.9 ± 2.7 in late follicular start vs. 9.4 ± 4.2 in luteal start, P = 0.08). PGT-A was performed in 48% of the cases that underwent embryo cryopreservation in RSCOS (12 women, mean age = 35.3 ± 4.1; 87 blastocysts), revealing a euploidy rate of 36.2 ± 22.3% per patient. This rate was comparable to a 45% aneuploidy rate from similarly aged published data. Of the 7 RSCOS patients who returned for frozen embryo transfer, 5 delivered and one has an ongoing pregnancy, while in SSCOS, 18 out of 40 cycles resulted in live birth. CONCLUSION: Our data suggests that RSCOS fertility preservation cycle outcomes are similar to those with SSCOS and result in age-appropriate euploidy rates.

Evaluation of pharmacist guided intervention using procalcitonin and respiratory virus testing.

INTRODUCTION: Acute respiratory infections make up a sizable percentage of emergency department (ED) visits and many result in antibiotics being prescribed. Procalcitonin (PCT) has been found to reduce antibiotic use in both outpatient and critical care settings, yet remains underused in the ED. This study aimed to evaluate whether point of care molecular influenza and Respiratory Syncytial Virus (RSV) testing, PCT, and a pharmacist driven educational intervention in aggregate optimizes antibiotic and antiviral prescribing in the ED setting. METHODS: A randomized trial of the Cobas Liat Flu/RSV Assay, procalcitonin, and the use of pharmacist-led education in patients 0-50 years of age being seen in the ED for Influenza Like Illness (ILI) or acute respiratory illness. The study enrolled 200 ED patients between March 2018 and April 2022. RESULTS: There was little difference in antibiotic or antiviral prescribing between the intervention and control groups in this study (39%-32% = 7.0%, 95% CI: -6.2, 20.2, P = 0.30). However, a post-hoc analysis of the use of procalcitonin showed results were used as indicated in the ED (P = 0.001). CONCLUSION: PCT can be used in both adult and pediatric populations to help guide the decision of whether to treat with antibiotics in the ED setting. Pharmacist guided education may not be a driving factor.

GFR Estimation in Potential Living Kidney Donors: Race- and Nonrace-based Equations and Measured GFR.

Rationale & Objective: Recent studies evaluated and proposed new race-neutral, creatinine-based glomerular filtration rate (GFR) estimation equations. The performance of these equations in diverse potential living kidney donors requires study. Study Design: Cross-sectional study. Setting & Participants: 637 potential living kidney donors from one tertiary hospital with serum creatinine concentration measurement and GFR measurement by iohexol plasma clearance between October 2016 and December 2020. Exposure: Creatinine-based estimation of GFR by Chronic Kidney Disease Epidemiology Collaboration (2009, CKDEPI09; 2021, CKDEPI21) and Modification of Diet in Renal Disease equations with and without inclusion of race coefficient, where applicable. Outcomes: Equation bias, precision, accuracy, and accurate classification of GFR as equal to and above or below 80 mL/min/1.73 m2. Analytical Approach: GFR estimation equation performance compared to measured GFR (mGFR) by iohexol clearance. Results: The median bias of the CKDEPI21 equation underestimated mGFR by 2.8 mL/min/1.73 m2. The bias in the Black subgroup underestimated mGFR by 9.0 mL/min/1.73 m2. Compared to CKDEPI09 with and without race adjustment, the accuracy of CKDEPI21 increased across all subgroups. On average, 3.9% of individuals were misclassified by CKDEPI21 as having a GFR greater than, and 8.9% misclassified less than, 80 mL/min/1.73 m2, compared to 3.1% and 13.2% for CKDEPI09 with race adjustment, respectively. Total misclassification (either above or below 80 mL/min/1.73 m2) was 16.3% for CKDEPI21 and 16.0% for CKDEPI09 (with race adjustment). Limitations: Limited sample of individuals identifying as Black. Lack of cystatin C data. Conclusions: In our potential living donor sample, GFR estimation by creatinine-based CKDEPI21 is less biased and more accurate than previous creatinine-based estimated GFR equations. When evaluated by race, this summative improvement remains in individuals identifying as Asian, Hispanic, or White. More external validation is needed to assess whether the new equation is an improvement over the previous CKDEPI equation with a race coefficient.

Serum MicroRNA Transcriptomics and Acute Rejection or Recurrent Hepatitis C Virus in Human Liver Allograft Recipients: A Pilot Study.

BACKGROUND: Acute rejection (AR) and recurrent hepatitis C virus (R-HCV) are significant complications in liver allograft recipients. Noninvasive diagnosis of intragraft pathologies may improve their management. METHODS: We performed small RNA sequencing and microRNA (miRNA) microarray profiling of RNA from sera matched to liver allograft biopsies from patients with nonimmune, nonviral (NINV) native liver disease. Absolute levels of informative miRNAs in 91 sera matched to 91 liver allograft biopsies were quantified using customized real-time quantitative PCR (RT-qPCR) assays: 30 biopsy-matched sera from 26 unique NINV patients and 61 biopsy-matched sera from 41 unique R-HCV patients. The association between biopsy diagnosis and miRNA abundance was analyzed by logistic regression and calculating the area under the receiver operating characteristic curve. RESULTS: Nine miRNAs-miR-22, miR-34a, miR-122, miR-148a, miR-192, miR-193b, miR-194, miR-210, and miR-885-5p-were identified by both sRNA-seq and TLDA to be associated with NINV-AR. Logistic regression analysis of absolute levels of miRNAs and goodness-of-fit of predictors identified a linear combination of miR-34a + miR-210 (P < 0.0001) as the best statistical model and miR-122 + miR-210 (P < 0.0001) as the best model that included miR-122. A different linear combination of miR-34a + miR-210 (P < 0.0001) was the best model for discriminating NINV-AR from R-HCV with intragraft inflammation, and miR-34a + miR-122 (P < 0.0001) was the best model for discriminating NINV-AR from R-HCV with intragraft fibrosis. CONCLUSIONS: Circulating levels of miRNAs, quantified using customized RT-qPCR assays, may offer a rapid and noninvasive means of diagnosing AR in human liver allografts and for discriminating AR from intragraft inflammation or fibrosis due to R-HCV.

Ovarian transplantation with robotic surgery and a neovascularizing human extracellular matrix scaffold: a case series in comparison to meta-analytic data.

OBJECTIVE: To report our experience with robot-assisted (RA) autologous cryopreserved ovarian tissue transplantation (ACOTT) with the use of a neovascularizing extracellular matrix scaffold. DESIGN: Case series with meta-analytic update. SETTING: Academic. PATIENT(S): Seven recipients of RA-ACOTT. INTERVENTION(S): Before or shortly after initiating chemotherapy, ovarian tissue was cryopreserved from 7 women, who then underwent RA-ACOTT 9.9 ± 1.8 years (range, 7-12 years) later. Perioperatively, they received transdermal estrogen and low-dose aspirin to enhance graft vascularization. Ovarian cortical pieces were thawed and sutured on an extracellular matrix scaffold, which was then robotically anastomosed to the bivalved remaining ovary in 6 cases and retroperitoneally (heterotopic) to the lower abdomen in 1 case. MAIN OUTCOME MEASURE(S): Ovarian function return, the number of oocytes/embryos, aneuploidy %, live births, and neonatal outcomes were recorded. Graft longevity was compared with the mean from the meta-analytic data. RESULT(S): Ovarian function returned 13.9 ± 2.7 weeks (11-16.2 weeks) after ACOTT, and oocytes were retrieved in all cases with 12.3 ± 6.9 embryos generated. In contrast to orthotopic, the heterotopic ACOTT demonstrated low embryo quality and an 80% aneuploidy rate. A recipient did not attempt to conceive and 2 needed a surrogate, whereas 4 of 4 delivered 6 healthy children, compared with 115 of 460 (25% pregnancy rate) from the meta-analytic data (n = 79). The mean graft longevity (43.2 ± 23.6/47.4 ± 22.8 months with/without sensitivity analysis) trended longer than the meta-analytic mean (29.4 ± 22.7), even after matching age at cryopreservation. CONCLUSION(S): In this series, RA-ACOTT resulted in extended graft longevity, with ovarian functions restored in all cases, even when the tissues were cryopreserved after chemotherapy exposure.

Association of Germline BRCA Pathogenic Variants With Diminished Ovarian Reserve: A Meta-Analysis of Individual Patient-Level Data.

PURPOSE: To determine whether germline BRCA (gBRCA) pathogenic variants are associated with decreased ovarian reserve. MATERIALS AND METHODS: An individual patient-level data meta-analysis was performed using five data sets on 828 evaluable women who were tested for gBRCA. Of those, 250 carried gBRCA, whereas 578 had tested negative and served as controls. Of the women with gBRCA, four centers studied those affected with breast cancer (n = 161) and one studied unaffected individuals (n = 89). The data were adjusted for the center, age, body mass index, smoking, and oral contraceptive pill use before the final analysis. Anti-Müllerian hormone (AMH) levels in affected women were drawn before presystemic therapy. RESULTS: The mean age of women with versus without gBRCA1/2 (34.1 ± 4.9 v 34.3 ± 4.8 years; P = .48) and with gBRCA1 versus gBRCA2 (33.7 ± 4.9 v 34.6 ± 4.8 years; P = .16) was similar. After the adjustments, women with gBRCA1/2 had significantly lower AMH levels compared with controls (23% lower; 95% CI, 4 to 38; P = .02). When the adjusted analysis was limited to affected women (157 with gBRCA v 524 without, after exclusions), the difference persisted (25% lower; 95% CI, 9 to 38; P = .003). The serum AMH levels were lower in women with gBRCA1 (33% lower; 95% CI, 12 to 49; P = .004) but not gBRCA2 compared with controls (7% lower; 95% CI, 31% lower to 26% higher; P = .64). CONCLUSION: Young women with gBRCA pathogenic variants, particularly those affected and with gBRCA1, have lower serum AMH levels compared with controls. They may need to be preferentially counseled about the possibility of shortened reproductive lifespan because of diminished ovarian reserve.

Impact of adjuvant chemotherapy or tamoxifen-alone on the ovarian reserve of young women with breast cancer.

PURPOSE: To determine the longitudinal impact of adjuvant chemotherapy and tamoxifen-only treatments on the reproductive potential of women with breast cancer by using a sensitive ovarian reserve marker anti-Mullerian hormone (AMH) as a surrogate. METHODS: One-hundred-and-forty-two women with a primary diagnosis of breast cancer were prospectively followed with serum AMH assessments before the initiation, and 12, 18 and 24 months after the completion of adjuvant chemotherapy or the start of tamoxifen-only treatment. The chemotherapy regimens were classified into Anthracycline-Cyclophosphamide-based (AC-based) and Cyclophosphamide-Methotrexate + 5-Fluorouracil (CMF). Longitudinal data were analyzed by mixed effects model for treatment effects over time, adjusting for baseline age and BMI. RESULTS: Both chemotherapy regimens resulted in significant decline in ovarian reserve compared to the tamoxifen-only treatment (p < 0.0001 either regimen vs. tamoxifen for overall trend). AMH levels sharply declined at 12 months but did not show a significant recovery from 12 to 18 and 18 to 24 months after the completion of AC-based or CMF regimens. The degree of decline did not differ between the two chemotherapy groups (p = 0.53). In contrast, tamoxifen-only treatment did not significantly alter the age-adjusted serum AMH levels over the 24-month follow up. Likewise, the use of adjuvant tamoxifen following AC-based regimens did not affect AMH recovery. CONCLUSIONS: Both AC-based regimens and CMF significantly compromise ovarian reserve, without a recovery beyond 12 months post-chemotherapy. In contrast, tamoxifen-only treatment does not seem to alter ovarian reserve. These data indicate that the commonly used chemotherapy regimens but not the hormonal therapy compromise future reproductive potential.

The US Supplemental Nutrition Assistance Program - Education improves nutrition-related behaviors.

The aim of this study was to measure whether participating in Supplemental Nutrition Assistance Program - Education (SNAP-Ed) interventions is associated with changes in meeting recommendations for healthy eating and food resource management behaviours, such as shopping, among low-income children, adolescents, and adults in eight states in the US Southeast. The study used a one-group pre-test post-test design, analysing aggregate data on nutrition and shopping behaviours collected during Federal Fiscal Year 17 from SNAP-Ed direct education in community settings. Twenty-five implementing agencies in Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee provided aggregated data on program participants. Because survey questions differed, agencies followed standard recoding guidelines. The number of participants varied depending on the indicator; the maximum number was n 43 303 pre-tests, n 43 256 post-test. Participants were significantly more likely to consume more than one kind of fruit (pooled relative risk (RR), 1⋅10; 95% confidence interval (CI), 1⋅09-1⋅11) and more than one kind of vegetable (pooled RR, 1⋅14; 95% CI, 1⋅12-1⋅15) after the intervention than before. On average, participants consumed 0⋅34 cups more of fruit per day (95% CI, 0⋅31-0⋅37), and 0⋅22 cups more of vegetables per day (95% CI, 0⋅19-0⋅25) after the intervention, compared to before. About 701 policy, systems, and environmental changes for nutrition supports were reported. This study suggests that SNAP-Ed direct education is associated with positive behaviour changes in the US Southeast. It provides a methodology that can inform data aggregation efforts across unique SNAP-Ed programs or other similar nutrition education programs to report on the collective impact.

5-0 Polypropylene versus 5-0 fast absorbing plain gut for cutaneous wound closure: a randomized evaluator blind trial.

Mixed opinions exist regarding cosmetic outcomes of 5-0 fast absorbing plain (FG) gut relative to nonabsorbable suture material, such as 5-0 polypropylene (PP). High quality randomized trials comparing these two suture materials are lacking. To determine whether the use of PP during layered repair of linear cutaneous surgery wounds improves scar cosmesis compared to wound closure with FG. A randomized, split wound, comparative effectiveness trial was undertaken. Patients were evaluated 3 months after the intervention by two blinded physicians using the validated patient observer scar assessment scale (POSAS). Patient assessments were also captured using the same instrument as well as scar width and complications. The mean sum of the six components of the POSAS was 10.26 vs 12.74 for PP and FG, respectively, significantly (p < 0.001) in favor of PP. Mean observer overall opinion similarly showed better outcomes for PP than for FG [1.88 vs 2.52, respectively (p < 0.006)]. The mean sum of the patient assessed components of the POSAS for PP and FG was 12.3 vs 14.34, respectively (p = 0.11). Patient overall opinion significantly favored PP (2.41 vs 3.14, p = 0.043). PP resulted in small but statistically significant better cosmetic outcomes than FG. Pain experienced during suture removal was minimal for most patients.

Comparison of Endoscopic Ultrasound Biopsy Needles for Endoscopic Ultrasound-Guided Liver Biopsy.

BACKGROUND/AIMS: To compare the performance of latest commercially available endoscopic ultrasound biopsy needles. METHODS: Six latest commercially available needles were tested on a freshly harvested bovine liver; the tested needles included three 19 G, one 20 G, and two 22 G needles. Five biopsies were performed per needle with 10 mL of wet suction. The primary outcome was the number of complete portal tracts (CPTs) per needle aspirate. The secondary outcomes were the mean specimen length and mean fragment length. Analysis of variance and Tukey's test were applied. RESULTS: All 19 G needles and the 20 G needle yielded similar mean CPTs and were superior to the SharkCore 22 G needle (p<0.001 adjusted for multiplicity). There was no statistically significant difference in total specimen length among the three 19 G needles and the 20 G needle tested. The two 22 G needles performed similarly with respect to the number of CPTs, mean fragment length, and mean specimen length (adjusted p=0.07, p=0.59, and p=0.10, respectively). CONCLUSION: The specimen adequacy was similar among the 3 latest commercially available 19 G needles. The endoscopist may choose a larger-bore needle based on availability without concerns of specimen adequacy. Further studies are needed to assess the ease of needle use in various anatomical locations and to confirm the optimal needle design.

Prolonged QTc in HIV-Infected Patients: A Need for Routine ECG Screening.

BACKGROUND: With HIV-infected patients living longer, there is an increased burden of comorbidities related to aging, HIV itself, and polypharmacy. Cardiac morbidity is of particular importance. METHODS: This 2-group comparison study (156 HIV-positive and 105 HIV-negative patients) investigated the prevalence of abnormalities in and factors associated with an electrocardiogram (ECG) measure, corrected QT interval (QTc), where prolongation can lead to arrhythmia and sudden death. Medications prescribed (antiretroviral therapy, psychiatric medications, methadone, and antibiotics) at the time of ECG were noted. Patient characteristics, medications, QTc, and ECG characteristics were compared between the 2 groups. RESULTS: Prolongation (29% versus 19%) and extreme prolongation (6% versus 1%) in QTc were more frequent in those with HIV. Antiretroviral therapy was associated with lower odds of prolonged QTc (odds ratio [OR] = 0.35; P = .04), while methadone with higher odds (OR = 4.6; P = .01) in HIV-positive patients. With methadone and medication groups adjusted, HIV status was still associated with 17-millisecond longer QTc ( P = .04). CONCLUSION: This study provides evidence that patients with HIV may have clinically relevant longer QTc interval on ECG. Baseline and routine ECG monitoring may be warranted among patients living with HIV in clinical practice based on cumulative evidence.

Potentially High Number of Ineffective Drugs with the Standard Shorter Course Regimen for Multidrug-Resistant Tuberculosis Treatment in Haiti.

Multidrug-resistant tuberculosis (MDR-TB) outcomes are poor partly because of the long treatment duration; the World Health Organization conditionally recommends a shorter course regimen to potentially improve treatment outcomes. Here, we describe the drug susceptibility patterns of a cohort of MDR-TB patients in Haiti and determine the number of likely effective drugs if they were treated with the recommended shorter course regimen. We retrospectively examined drug susceptibility patterns of adults initiating MDR-TB treatment between 2008 and 2015 at the Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic Infections in Port-au-Prince, Haiti. First- and second-line drug susceptibility testing (DST) was analyzed and used to determine the number of presumed effective drugs. Of the 239 patients analyzed, 226 (95%), 183 (77%), 135 (57%), and 38 (16%) isolates were resistant to high-dose isoniazid, ethambutol, pyrazinamide, and ethionamide, respectively. Eight patients (3%) had resistance to either a fluoroquinolone or a second-line injectable and none had extensively resistant TB. Of the 239 patients, 132 (55%) would have fewer than five likely effective drugs in the intensive phase of the recommended shorter course regimen and 121 (51%) would have two or fewer likely effective drugs in the continuation phase. Because of the high rates of resistance to first-line TB medications, about 50% of MDR-TB patients would be left with only two effective drugs in the continuation phase of the recommended shorter course regimen, raising concerns about the effectiveness of this regimen in Haiti and the importance of using DST to guide treatment.

Data concordance between ESRD Medical Evidence Report and Medicare claims: is there any improvement?

BACKGROUND: Medicare is one of the world's largest health insurance programs. It provides health insurance to nearly 44 million beneficiaries whose entitlements are based on age, disability, or end-stage renal disease (ESRD). Data of these ESRD beneficiaries are collected in the US Renal Data System (USRDS), which includes comorbidity information entered at the time of dialysis initiation (medical evidence data), and are used to shape health care policy. One limitation of USRDS data is the lack of validation of these medical evidence comorbidities against other comorbidity data sources, such as medical claims data. METHODS: We examined the potential for discordance between USRDS Medical Evidence and medical claims data for 11 comorbid conditions amongst Medicare beneficiaries in 2011-2013 via sensitivity, specificity, kappa and hierarchical logistic regression. RESULTS: Among 61,280 patients, most comorbid conditions recorded on the Medical Evidence forms showed high specificity (>0.9), compared to prior medical claims as reference standard. However, both sensitivity and kappa statistics varied greatly and tended to be low (most <0.5). Only diabetes appeared accurate, whereas tobacco use and drug dependence showed the poorest quality (sensitivity and kappa <0.1). Institutionalization and patient region of residency were associated with data discordance for six and five comorbidities out of 11, respectively, after conservative adjustment of multiple testing. Discordance appeared to be non-informative for congestive heart failure but was most varied for drug dependence. CONCLUSIONS: We conclude that there is no improvement in comorbidity data quality in incident ESRD patients over the last two decades. Since these data are used in case-mix adjustment for outcome and quality of care metrics, the findings in this study should press regulators to implement measures to improve the accuracy of comorbidity data collection.

Prostate-Specific Antigen-Based Screening for Prostate Cancer: Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Prostate cancer is the second leading cause of cancer death among US men. Objective: To systematically review evidence on prostate-specific antigen (PSA)-based prostate cancer screening, treatments for localized prostate cancer, and prebiopsy risk calculators to inform the US Preventive Services Task Force. Data Sources: Searches of PubMed, EMBASE, Web of Science, and Cochrane Registries and Databases from July 1, 2011, through July 15, 2017, with a surveillance search on February 1, 2018. Study Selection: English-language reports of randomized clinical trials (RCTs) of screening; cohort studies reporting harms; RCTs and cohort studies of active localized cancer treatments vs conservative approaches (eg, active surveillance, watchful waiting); external validations of prebiopsy risk calculators to identify aggressive cancers. Data Extraction and Synthesis: One investigator abstracted data; a second checked accuracy. Two investigators independently rated study quality. Main Outcomes and Measures: Prostate cancer and all-cause mortality; false-positive screening results, biopsy complications, overdiagnosis; adverse effects of active treatments. Random-effects meta-analyses were conducted for treatment harms. Results: Sixty-three studies in 104 publications were included (N = 1 904 950). Randomization to PSA screening was not associated with reduced risk of prostate cancer mortality in either a US trial with substantial control group contamination (n = 76 683) or a UK trial with low adherence to a single PSA screen (n = 408 825) but was associated with significantly reduced prostate cancer mortality in a European trial (n = 162 243; relative risk [RR], 0.79 [95% CI, 0.69-0.91]; absolute risk reduction, 1.1 deaths per 10 000 person-years [95% CI, 0.5-1.8]). Of 61 604 men screened in the European trial, 17.8% received false-positive results. In 3 cohorts (n = 15 136), complications requiring hospitalization occurred in 0.5% to 1.6% of men undergoing biopsy after abnormal screening findings. Overdiagnosis was estimated to occur in 20.7% to 50.4% of screen-detected cancers. In an RCT of men with screen-detected prostate cancer (n = 1643), neither radical prostatectomy (hazard ratio [HR], 0.63 [95% CI, 0.21-1.93]) nor radiation therapy (HR, 0.51 [95% CI, 0.15-1.69]) were associated with significantly reduced prostate cancer mortality vs active monitoring, although each was associated with significantly lower risk of metastatic disease. Relative to conservative management, radical prostatectomy was associated with increased risk of urinary incontinence (pooled RR, 2.27 [95% CI, 1.82-2.84]; 3 trials; n = 1796) and erectile dysfunction (pooled RR, 1.82 [95% CI, 1.62-2.04]; 2 trials; n = 883). Relative to conservative management (8 cohort studies; n = 3066), radiation therapy was associated with increased risk of erectile dysfunction (pooled RR, 1.31 [95% CI, 1.20-1.42]). Conclusions and Relevance: PSA screening may reduce prostate cancer mortality risk but is associated with false-positive results, biopsy complications, and overdiagnosis. Compared with conservative approaches, active treatments for screen-detected prostate cancer have unclear effects on long-term survival but are associated with sexual and urinary difficulties.

Excess Readmission-Based Penalty: Is Arthroplasty Different From the Other Outcomes?

Whether factors not under a hospital's control affect readmissions remains intensely debated in the context of the Centers for Medicare & Medicaid Services' Hospital Readmission Reduction Program. This study aimed to evaluate the potential effects of poverty, race, and hospital volume on excess readmissions, with >3000 hospitals participating in "Hospital Compare." Correlations between excess readmission ratios for five eligible outcomes (including hip and knee arthroplasty) were assessed with the three area and hospital-level factors: poverty, race (percent of black population), and hospital volume (number of discharges). Correlation coefficients of the ratios with race were approximately r = 0.2, consistently larger than those with poverty (r = 0-0.1), and those with volume were r = 0 to -0.5. Hip and knee arthroplasty had unique findings: null correlation with poverty (r ≈ 0), largest variability, and strong monotonicity with volume (r ≈ -0.5). The percent of Hispanic population showed negligible correlations in secondary analysis. Penalty assessment and hospital profiling should consider areas with high percentages of black population and a small volume of hospitals and providers of hip and knee surgery. (Journal of Surgical Orthopaedic Advances 27(4):286-294, 2018).

Comparison of screening scores for diabetes and prediabetes.

AIMS: There are numerous risk or screening scores for the prediction of type-2 diabetes mellitus (DM). In contrast, few scores are available for preDM. In this paper, we compare the two screening scores from the American Diabetes Association (ADA) and Centers for Disease Control and Prevention (CDC) that can be used for DM as well as preDM. METHODS: Adult participants (N=9391) without known DM from the National Health and Nutrition Examination Surveys 2009-12 were included. We fitted the factors/items in the ADA and CDC scores in logistic regression with the outcomes of undiagnosed DM, preDM, and combination, and assessed the association and discrimination accuracy. We also evaluated the suggested cutpoints that define high risk individuals. We mimicked the original models/settings but also tested various deviations/modifications often encountered in practice. RESULTS: Both scores performed well and robustly, while the ADA score performed somewhat better (e.g., AUC=0.77 for ADA and 0.73-0.74 for CDC for DM; 0.72-0.74 and 0.70-0.71 for preDM). The same predictors and scoring rules seem to be reasonably justified with different cutpoints for DM and preDM, which can make usage easier and consistent. Some factors such as race and HDL/LDL cholesterols may be useful additions to health education. CONCLUSIONS: Current DM education and screening focus on the prevention and management of DM. The ADA and CDC scores could further help when we identify individuals at high risk for preDM, and teach the importance of preDM during which lifestyle intervention can be effective and urgently needed.

Factors associated with abnormal pulmonary function test among subjects with normal chest radiography: The Korean National Health and Nutrition Examination Survey.

Determinants of abnormal lung function among subjects with normal chest radiography have not been widely evaluated. We investigated 12 109 participants with normal chest radiographs from the Korean National Health and Nutrition Examination Survey. Factors associated with abnormal pulmonary function were male gender, age ≥50, smoking history and a clinical history of cough or sputum production. Pulmonary function tests should be considered in population-based screening, especially in men over 50 years old with a smoking history.