Operative trends following the adoption of nonoperative management of rectal cancer.

BACKGROUND: Differentiating clinical near-complete and complete responses (cCR) after neoadjuvant therapy (NT) is challenging in rectal cancer patients. We hypothesized that magnetic resonance imaging staging limitations for low rectal cancers may increase the proportion of abdominoperineal resection (APR) with permanent colostomy for those without a cCR. METHODS: Single institution retrospective analysis of rectal cancer cases before and after adoption of nonoperative "watch and wait" (W&W) pathway. APR as a percentage of rectal resections was the primary outcome. RESULTS: There were 76 total mesorectal excisions (TME) in the pre-W&W group and 98 in the post-W&W group. NT was significantly more common in the post-W&W group. There was no significant difference in the APR primary outcome (pre-W&W APR 33.3% vs. post-W&W APR 26.5%, p = 0.482). APR patients had fewer complete TME grades (69.2% vs. 46.2%) and more pathologic complete responses (0% vs. 26.9%) in the post-W&W period. The cCR rate for patients with nonoperative management was 51.4% (n = 37) and 13.5% (n = 5) had regrowths, all of whom underwent salvage surgery. CONCLUSION: APR for those without a cCR to NT has not increased in the nonoperative management era. Balancing the pathologic complete response rate may require restaging some patients with clinical near-complete responses.

Early discharge after enhanced recovery rectal resection does not increase emergency department visits and readmissions: a single institution analysis.

BACKGROUND: Same-day discharge after colectomy in enhanced recovery pathways has been shown to be feasible. It is not clear how early patients with rectal resections may be safely discharged. The study aim was to determine if patients discharged ≤ 3 days after rectal resections are associated with increased rates of emergency department (ED) visits and hospital readmissions. METHODS: Retrospective analysis of enhanced recovery low anterior resection, abdominoperineal resection, and proctocolectomy patients in a prospectively maintained single institution colorectal surgery database from 01/01/2018 to 07/15/2022. Clinic visits were scheduled within 4-7 days and at 30 days after discharge, and every 1-2 weeks for stoma patients until no longer needed. Logistic regression models were used to analyze the association of discharge on postoperative days (POD)-1-3, POD-4-5, and POD ≥ 6 days with incidence of ED visits and readmissions. RESULTS: A total of 118 patients met inclusion criteria, 76 with stomas. Median postoperative length of stay was 5 [IQR 6.5] days. Mean age was 58.6 years; 59.3% were ASA-3; and 69.5% had a minimally invasive surgical approach. ED visits were not significantly different between discharge-day groups (p = 0.096). No patients were discharged same-day, one without a stoma was discharged on POD-1, ten patients (2 with stomas) on POD-2, and twenty-four patients (13 with stomas) on POD-3. ED visits were lowest for the POD-1-3 group (14.3%) but not significantly different than later discharge groups (p = 0.166). Readmission rate was also lowest for the POD-1-3 group (11.4%) and also not significantly different than later discharge groups (p = 0.261) and this was confirmed with logistic regression. Complication rate was lowest in the POD-1-3 group (p < 0.001). CONCLUSION: Early discharge after enhanced recovery partial or complete proctectomy is not associated with increased ED visits and readmissions. Follow up studies should identify post-discharge resources that allow safe early discharge and that may be standardized and generalizable.

Quantification of Brucella abortus population structure in a natural host.

Cattle are natural hosts of the intracellular pathogen Brucella abortus, which inflicts a significant burden on the health and reproduction of these important livestock. The primary routes of infection in field settings have been described, but it is not known how the bovine host shapes the structure of B. abortus populations during infection. We utilized a library of uniquely barcoded B. abortus strains to temporally and spatially quantify population structure during colonization of cattle through a natural route of infection. Introducing 108 bacteria from this barcoded library to the conjunctival mucosa resulted in expected levels of local lymph node colonization at a 1-wk time point. We leveraged variance in strain abundance in the library to demonstrate that only 1 in 10,000 brucellae introduced at the site of infection reached a parotid lymph node. Thus, cattle restrict the overwhelming majority of B. abortus introduced via the ocular conjunctiva at this dose. Individual strains were spatially restricted within the host tissue, and the total B. abortus census was dominated by a small number of distinct strains in each lymph node. These results define a bottleneck that B. abortus must traverse to colonize local lymph nodes from the conjunctival mucosa. The data further support a model in which a small number of spatially isolated granulomas founded by unique strains are present at 1 wk postinfection. These experiments demonstrate the power of barcoded transposon tools to quantify infection bottlenecks and to define pathogen population structure in host tissues.

Arthralgia in female Masters weightlifters.

BACKGROUND: Arthralgia or joint pain is a heterogeneous condition including organic and nonorganic joint pain. It is common in older populations, particularly in females. There is evidence that menopausal changes are associated with increased prevalence of arthralgia. While physical activities have been recommended to mitigate osteoarthritis (OA) and arthralgia, sport participation also carries risk factors due to excessive loading of some joints and possible injuries. The aim was to evaluate the association of training patterns, prior injuries, and severity of menopausal symptoms with arthralgia in female Masters weightlifters. METHODS: Competitive female Masters weightlifters (n=868, 30-78 years) from 30 countries completed an online survey including joint pain for different anatomical sites, weightlifting training and performance, sport history, and menopausal symptoms. Logistic regression models were used to estimate the association of training patterns, prior sport participation, and menopausal symptom severity with arthralgia separately for shoulders, spine, hips, knees, ankles, elbows, and hands. RESULTS: Arthralgia was most reported in knees (38.8%), shoulders (29.8%), hands/wrists (28.8%), and hips (24.9%). The prevalence of arthralgia was 51.5% in pre-menopausal women, 62.4% in women post natural menopause and 73.3% in women post medical or surgical menopause. Lifting heavier weights was associated with arthralgia in hips (OR=1.05, p=0.03), knees (OR=1.06, p=0.01), and hands/wrists (OR=1.05, p=0.04), but prior strength training was protective for arthralgia in the shoulders (OR=0.66, p=0.02). Prior injuries and psychological menopausal symptom severity were associated with an increased risk for arthralgia (p<0.01). CONCLUSIONS: Arthralgia was common in competitive female weightlifters. Training frequency was not associated with arthralgia, but lifting heavier weights relative to age and body mass was. Prior injuries and menopausal symptoms were associated with arthralgia, but prior strength training was protective of arthralgia in the shoulders. Athletes, coaches and sports medicine professionals should be aware that prevalence of polyarthralgia increases in post-menopausal athletes.

Structured reporting to improve transparency of analyses in prognostic marker studies.

BACKGROUND: Factors contributing to the lack of understanding of research studies include poor reporting practices, such as selective reporting of statistically significant findings or insufficient methodological details. Systematic reviews have shown that prognostic factor studies continue to be poorly reported, even for important aspects, such as the effective sample size. The REMARK reporting guidelines support researchers in reporting key aspects of tumor marker prognostic studies. The REMARK profile was proposed to augment these guidelines to aid in structured reporting with an emphasis on including all aspects of analyses conducted. METHODS: A systematic search of prognostic factor studies was conducted, and fifteen studies published in 2015 were selected, three from each of five oncology journals. A paper was eligible for selection if it included survival outcomes and multivariable models were used in the statistical analyses. For each study, we summarized the key information in a REMARK profile consisting of details about the patient population with available variables and follow-up data, and a list of all analyses conducted. RESULTS: Structured profiles allow an easy assessment if reporting of a study only has weaknesses or if it is poor because many relevant details are missing. Studies had incomplete reporting of exclusion of patients, missing information about the number of events, or lacked details about statistical analyses, e.g., subgroup analyses in small populations without any information about the number of events. Profiles exhibit severe weaknesses in the reporting of more than 50% of the studies. The quality of analyses was not assessed, but some profiles exhibit several deficits at a glance. CONCLUSIONS: A substantial part of prognostic factor studies is poorly reported and analyzed, with severe consequences for related systematic reviews and meta-analyses. We consider inadequate reporting of single studies as one of the most important reasons that the clinical relevance of most markers is still unclear after years of research and dozens of publications. We conclude that structured reporting is an important step to improve the quality of prognostic marker research and discuss its role in the context of selective reporting, meta-analysis, study registration, predefined statistical analysis plans, and improvement of marker research.

Facilitating harmonized data quality assessments. A data quality framework for observational health research data collections with software implementations in R.

BACKGROUND: No standards exist for the handling and reporting of data quality in health research. This work introduces a data quality framework for observational health research data collections with supporting software implementations to facilitate harmonized data quality assessments. METHODS: Developments were guided by the evaluation of an existing data quality framework and literature reviews. Functions for the computation of data quality indicators were written in R. The concept and implementations are illustrated based on data from the population-based Study of Health in Pomerania (SHIP). RESULTS: The data quality framework comprises 34 data quality indicators. These target four aspects of data quality: compliance with pre-specified structural and technical requirements (integrity); presence of data values (completeness); inadmissible or uncertain data values and contradictions (consistency); unexpected distributions and associations (accuracy). R functions calculate data quality metrics based on the provided study data and metadata and R Markdown reports are generated. Guidance on the concept and tools is available through a dedicated website. CONCLUSIONS: The presented data quality framework is the first of its kind for observational health research data collections that links a formal concept to implementations in R. The framework and tools facilitate harmonized data quality assessments in pursue of transparent and reproducible research. Application scenarios comprise data quality monitoring while a study is carried out as well as performing an initial data analysis before starting substantive scientific analyses but the developments are also of relevance beyond research.

Prognostic associations of circulating phytoestrogens and biomarker changes in long-term survivors of postmenopausal breast cancer.

Lignans are associated with improved postmenopausal breast cancer (BC) survival, but whether these associations, particularly with enterolactone (major lignan metabolite), persist over time is unclear. Little is known about other phytoestrogens on prognosis in long-term survivors. The study examines associations of prognosis with 1) circulating postdiagnosis enterolactone, 2) eight circulating phytoestrogen metabolites, and 3) changes in enterolactone and genistein. In a German cohort of 2,105 postmenopausal BC patients with blood samples collected at recruitment 2002-2005 (baseline) and re-interview in 2009 (follow-up), delay-entry Cox proportional hazards regression was used. Landmark analysis showed that circulating enterolactone (log2) associations with 5-year survival changed over time, with strongest hazard ratios of 0.89 (95% CI, 0.80-0.99) at blood draw (BD) and 0.86 (0.77-0.97) at 2 years post-BD for BC mortality, and 0.87 (0.80-0.95) at BD and 0.84 (0.76-0.92) at 3 years post-BD for all-cause mortality, which attenuated thereafter. In long-term survivors, increasing concentrations of genistein (1.17, 1.01-1.36), resveratrol (1.19, 1.02-1.40), and luteolin (1.96, 1.07-3.58) measured in follow-up blood samples were associated with poorer subsequent prognosis. Neither enterolactone at follow-up nor changes in enterolactone/genistein were associated with prognosis. Large long-term longitudinal studies with multiple phytoestrogen measurements are required to understand long-term effects of phytoestrogens after BC.

Hidden analyses: a review of reporting practice and recommendations for more transparent reporting of initial data analyses.

BACKGROUND: In the data pipeline from the data collection process to the planned statistical analyses, initial data analysis (IDA) typically takes place between the end of the data collection and do not touch the research questions. A systematic process for IDA and clear reporting of the findings would help to understand the potential shortcomings of a dataset, such as missing values, or subgroups with small sample sizes, or shortcomings in the collection process, and to evaluate the impact of these shortcomings on the research results. A clear reporting of findings is also relevant when making datasets available to other researchers. Initial data analyses can provide valuable insights into the suitability of a data set for a future research study. Our aim was to describe the practice of reporting of initial data analyses in observational studies in five highly ranked medical journals with focus on data cleaning, screening, and reporting of findings which led to a potential change in the analysis plan. METHODS: This review was carried out using systematic search strategies with eligibility criteria for articles to be reviewed. A total of 25 papers about observational studies were selected from five medical journals published in 2018. Each paper was reviewed by two reviewers and IDA statements were further discussed by all authors. The consensus was reported. RESULTS: IDA statements were reported in the methods, results, discussion, and supplement of papers. Ten out of 25 papers (40%) included a statement about data cleaning. Data screening statements were included in all articles, and 18 (72%) indicated the methods used to describe them. Item missingness was reported in 11 papers (44%), unit missingness in 15 papers (60%). Eleven papers (44%) mentioned some changes in the analysis plan. Reported changes referred to missing data treatment, unexpected values, population heterogeneity and aspects related to variable distributions or data properties. CONCLUSION: Reporting of initial data analyses were sparse, and statements on IDA were located throughout the research articles. There is a lack of systematic reporting of IDA. We conclude the article with recommendations on how to overcome shortcomings in the practice of IDA reporting in observational studies.

What makes a biostatistician?

Biostatisticians play an important role in medical research. They are co-responsible for an appropriate and efficient study design, they are involved in monitoring the study conduct, they plan and perform the data analysis, and they are involved in interpreting and publishing the results. However, how are the biostatisticians prepared for their tasks and responsibilities? Graduate programs in biostatistics are being offered, but some practicing biostatisticians completed their studies in a mathematical or epidemiological program, or obtained their degree in subject-specific fields (such as medicine or biology). Therefore, the expertise and the competencies can vary widely between the individual biostatisticians, also depending on the application field. In this article, focusing on European and US practices, we discuss the required professional expertise for the main areas of applications in the medical field as well as the necessary soft skill competencies of a biostatistician.

The MIDA Mortality Risk Score: development and external validation of a prognostic model for early and late death in degenerative mitral regurgitation.

Aims: In degenerative mitral regurgitation (DMR), lack of mortality scores predicting death favours misperception of individual patients' risk and inappropriate decision-making. Methods and results: The Mitral Regurgitation International Database (MIDA) registries include 3666 patients (age 66 ± 14 years; 70% males; follow-up 7.8 ± 5.0 years) with pure, isolated, DMR consecutively diagnosed by echocardiography at tertiary (European/North/South-American) centres. The MIDA Score was derived from the MIDA-Flail-Registry (2472 patients with DMR and flail leaflet-Derivation Cohort) by weighting all guideline-provided prognostic markers, and externally validated in the MIDA-BNP-Registry (1194 patients with DMR and flail leaflet/prolapse-Validation Cohort). The MIDA Score ranged from 0 to 12 depending on accumulating risk factors. In predicting total mortality post-diagnosis, the MIDA Score showed excellent concordance both in Derivation Cohort (c = 0.78) and Validation Cohort (c = 0.81). In the whole MIDA population (n = 3666 patients), 1-year mortality with Scores 0, 7-8, and 11-12 was 0.4, 17, and 48% under medical management and 1, 7, and 14% after surgery, respectively (P < 0.001). Five-year survival with Scores 0, 7-8, and 11-12 was 98 ± 1, 57 ± 4, and 21 ± 10% under medical management and 99 ± 1, 82 ± 2, and 57 ± 9% after surgery (P < 0.001). In models including all guideline-provided prognostic markers and the EuroScoreII, the MIDA Score provided incremental prognostic information (P ≤ 0.002). Conclusion: The MIDA Score may represent an innovative tool for DMR management, being able to position a given patient within a continuous spectrum of short- and long-term mortality risk, either under medical or surgical management. This innovative prognostic indicator may provide a specific framework for future clinical trials aiming to compare new technologies for DMR treatment in homogeneous risk categories of patients.

Twenty-Year Outcome After Mitral Repair Versus Replacement for Severe Degenerative Mitral Regurgitation: Analysis of a Large, Prospective, Multicenter, International Registry.

BACKGROUND: Mitral valve (MV) repair is preferred over replacement in clinical guidelines and is an important determinant of the indication for surgery in degenerative mitral regurgitation. However, the level of evidence supporting current recommendations is low, and recent data cast doubts on its validity in the current era. Accordingly, the aim of the present study was to analyze very long-term outcome after MV repair and replacement for degenerative mitral regurgitation with a flail leaflet. METHODS: MIDA (Mitral Regurgitation International Database) is a multicenter registry enrolling patients with degenerative mitral regurgitation with a flail leaflet in 6 tertiary European and US centers. We analyzed the outcome after MV repair (n=1709) and replacement (n=213) overall, by propensity score matching, and by inverse probability-of-treatment weighting. RESULTS: At baseline, patients undergoing MV repair were younger, had more comorbidities, and were more likely to present with a posterior leaflet prolapse than those undergoing MV replacement. After propensity score matching and inverse probability-of-treatment weighting, the 2 treatments groups were balanced, and absolute standardized differences were usually <10%, indicating adequate match. Operative mortality (defined as a death occurring within 30 days from surgery or during the same hospitalization) was lower after MV repair than after replacement in both the entire population (1.3% versus 4.7%; P<0.001) and the propensity-matched population (0.2% versus 4.4%; P<0.001). During a mean follow-up of 9.2 years, 552 deaths were observed, of which 207 were of cardiovascular origin. Twenty-year survival was better after MV repair than after MV replacement in both the entire population (46% versus 23%; P<0.001) and the matched population (41% versus 24%; P<0.001). Similar superiority of MV repair was obtained in patient subsets on the basis of age, sex, or any stratification criteria (all P<0.001). MV repair was also associated with reduced incidence of reoperations and valve-related complications. CONCLUSIONS: Among patients with degenerative mitral regurgitation with a flail leaflet referred to mitral surgery, MV repair was associated with lower operative mortality, better long-term survival, and fewer valve-related complications compared with MV replacement.

Surgical Site Infection in Colorectal Surgery: A Study in Antibiotic Duration.

BACKGROUND: Despite distant historical studies that demonstrated the adequacy of preoperative antibiotic prophylaxis, current surgical practice continues to use antibiotics for postoperative coverage up to 24 hours. OBJECTIVE: The aim of this study was to evaluate a change in antibiotic prophylaxis duration and its effect on surgical site infection in a high-volume modern colorectal practice. DESIGN: A case-controlled series retrospectively reviewed outcomes through a prospective validated data base. SETTING: The study was conducted at Mayo Clinic, Rochester, Minnesota. PATIENTS: A total of 965 patients were evaluated. Our study analyzed patient outcomes related to surgical site infection comparing cohort 1 (2012-2013), which had the same antibiotic coverage preoperatively up to 24 hours postoperatively, and cohort 2 (2014-2015), which eliminated postoperative doses and relied solely on pre- and intraoperative dosing duration. MAIN OUTCOME MEASURES: The primary outcomes of this study are superficial and deep surgical site infection. RESULTS: There were no differences identified for superficial or deep surgical site infection rates between cohorts. Before the change in antibiotic dosing duration (2012-2013), 28 of 493 patients (5.7%) vs after the practice change (2014-2015), 25 of 472 patients (5.3%) were reported to have superficial or deep surgical site infection (p = 0.794). LIMITATIONS: This study is limited by its retrospective design within a single institution. CONCLUSION: These equivalent results present an opportunity for surgeons to reconsider optimal antibiotic duration and minimize unnecessary antibiotic dosing. See Video Abstract at http://links.lww.com/DCR/A322.

Randomized trial on the physiologic impact of NOTES.

BACKGROUND: Our previous work revealed significantly less acidosis in swine undergoing natural orifice translumenal endoscopic surgery (NOTES) using endoscopic air insufflation than swine undergoing standard laparoscopy. We wanted to evaluate the differential effects of CO2 versus intra-abdominal pressure as source for this finding. In addition, we investigated the endocrine stress response between swine undergoing NOTES peritoneoscopy with CO2 insufflation and animals undergoing standard diagnostic laparoscopy with CO2. MATERIALS AND METHODS: Twenty-eight (28) female 50-kg domestic pigs were randomly assigned to one of four groups using a permuted block randomization table: Group 1: NOTES using CO2 insufflation, Group 2: NOTES using air insufflation, Group 3: laparoscopy max pressure 12 mmHg and Group 4: laparoscopy with max pressure 7 mmHg. Invasive monitoring lines were placed. Pneumoperitoneum was established by the respective method and maintained for 90 min, visualizing liver, spleen and colon. Arterial blood gas was obtained at baseline and four additional time points. Serum TNF-α for POD (postoperative day) 1 and cumulative urine adrenaline for the procedure were determined by ELISA. ANOVA and t test were used for statistical comparison. The study was Institutional Animal Care and Use Committees approved. RESULTS: All experiments were completed as outlined. Blood pH showed a significant difference between groups. Serum TNF-α revealed higher levels for NOTES CO2 on POD 1 than standard laparoscopy (p = 0.03). CONCLUSION: NOTES animals with CO2 insufflation initially experienced similar pH compared to standard laparoscopy but recovered to levels seen in low-pressure laparoscopy and NOTES with air. NOTES with CO2 appears to elicit a stronger stress response in this study than standard or low-pressure laparoscopy or NOTES with air.

Predictors of recurrence free survival for patients with stage II and III colon cancer.

BACKGROUND: The aim of this study was to evaluate clinico-pathologic specific predictors of recurrence for stage II/III disease. Improving recurrence prediction for resected stage II/III colon cancer patients could alter surveillance strategies, providing opportunities for more informed use of chemotherapy for high risk individuals. METHODS: 871 stage II and 265 stage III patients with colon cancers were included. Features studied included surgery date, age, gender, chemotherapy, tumor location, number of positive lymph nodes, tumor differentiation, and lymphovascular and perineural invasion. Time to recurrence was evaluated, using Cox's proportional hazards models. The predictive ability of the multivariable models was evaluated using the concordance (c) index. RESULTS: For stage II cancer patients, estimated recurrence-free survival rates at one, three, five, and seven years following surgery were 98%, 92%, 90%, and 89%. Only T stage was significantly associated with recurrence. Estimated recurrence-free survival rates for stage III patients at one, three, five, and seven years following surgery were 94%, 78%, 70%, and 66%. Higher recurrence rates were seen in patients who didn't receive chemotherapy (p = 0.023), with a higher number of positive nodes (p < 0.001). The c-index for the stage II model was 0.55 and 0.68 for stage III. CONCLUSIONS: Current clinic-pathologic information is inadequate for prediction of colon cancer recurrence after resection for stage II and IIII patients. Identification and clinical use of molecular markers to identify the earlier stage II and III colon cancer patients at elevated risk of recurrence are needed to improve prognostication of early stage colon cancers.

Improving conventional recovery with enhanced recovery in minimally invasive surgery for rectal cancer.

BACKGROUND: Enhanced recovery pathways have been shown to decrease the length of hospital stay in patients undergoing colorectal surgery. Few reports have studied patients undergoing minimally invasive surgery for rectal cancer. OBJECTIVE: Our aim was to review our experience in minimally invasive rectal cancer surgery. We report short-term outcomes and evaluate the potential advantages of the enhanced recovery protocol compared with our less intensive conventional pathway. DESIGN: This is a consecutive retrospective study of all minimally invasive rectal cancers treated from February 2005 to December 2011. Multivariable logistic regression models were constructed to identify factors contributing to a short length of stay. SETTINGS: This study was performed at Mayo Clinic, Rochester, Minnesota, between 2005 and 2011. PATIENTS: A total of 346 patients were retrospectively reviewed. Seventy-eight patients were managed under the enhanced recovery pathway. Patients underwent either laparoscopic-, robotic-, or hand-assisted laparoscopic surgery for rectal cancer. INTERVENTIONS: All patients followed either a standardized conventional pathway or an enhanced recovery pathway for perioperative care. MAIN OUTCOME MEASURES: The primary outcome was the length of stay. Secondary outcomes were postoperative complications and 30-day readmissions. RESULTS: Hospital stay was significantly decreased for patients who underwent minimally invasive surgery for rectal cancer and were managed with an enhanced recovery protocol, 4.1 days, vs 6.1 days for the conventional pathway (95% CI, -2.9 to -1.2 days; p < 0.0001). Rates of complications were similar between the 2 groups. Factors associated with shorter length of stay included the enhanced recovery protocol and laparoscopic or robotic surgery compared with hand-assisted laparoscopic surgery. LIMITATIONS: This was a retrospective study at a single institution. Additional limitations include the comparison with historical controls and the potential for selection bias. CONCLUSION: The enhanced recovery pathway is associated with a significantly decreased length of hospital stay after minimally invasive surgery for rectal cancer in this series. Decreased hospital stay was achieved without affecting short-term outcomes.

Modeling trajectories of perceived leg exertion during maximal cycle ergometer exercise in children and adolescents.

BACKGROUND: Borg developed scales for rating pain and perceived exertion in adults that have also been used in pediatric populations. Models describing functional relationships between perceived exertion and work capacity have not been studied in children. We compared different models and their fits to individual trajectories and assessed the variability in these trajectories. METHODS: Ratings of perceived exertion (RPE) were collected from 79 children. Progressive cycle ergonometric testing was performed to maximal work capacity with test duration ranging from 6- 12 minutes. Ratings were obtained during each 1-minute increment. Work was normalized to individual maximal work capacity (Wmax). A delay was defined as the fraction of Wmax at which point an increase in ratings of leg fatigue occurred. Such a delay term allows the characterization of trajectories for children whose ratings were initially constant with increasing work. Two models were considered, a delay model and a power model that is commonly used to analyze Borg ratings. Individual model fit was assessed with root mean squared error (RMSE). Functional clustering algorithms were used to identify patterns. RESULTS: Leg tiredness developed quickly for some children while for others there was a delay before an in- creased ratings of leg exertion occurred with increasing work. Models for individual trajectories with the smallest RMSE included a delay and a quadratic term (quadratic-delay model), or a power function and a delay term (power-delay model) compared to a simple power function. The median delay was 40% Wmax (interquartile range (IQR): 26-49%) in a quadratic-delay model, while the median exponent was 1.03 (IQR: 0.83-1.78) in a power-delay model. Nine clusters were identified showing linear or quadratic patterns with or without a delay. Cluster membership did not depend on age, gender or diagnosis. CONCLUSION: Children and adolescents vary widely in their capacity to rate their perceptions and exhibit different functional relationships between ratings of perceived exertion and work capacity normalized across individuals. Models including a delay term, a linear component, or a power function can describe these individual trajectories of perceived leg exertion during incremental exercise to voluntary exhaustion.

Evaluating implementation of a rapid response team: considering alternative outcome measures.

OBJECTIVE: Determine the prolonged effect of rapid response team (RRT) implementation on failure to rescue (FTR). DESIGN: Longitudinal study of institutional performance with control charts and Bayesian change point (BCP) analysis. SETTING: Two academic hospitals in Midwest, USA. PARTICIPANTS: All inpatients discharged between 1 September 2005 and 31 December 2010. INTERVENTION: Implementation of an RRT serving the Mayo Clinic Rochester system was phased in for all inpatient services beginning in September 2006 and was completed in February 2008. MAIN OUTCOME MEASURE: Modified version of the AHRQ FTR measure, which identifies hospital mortalities among medical and surgical patients with specified in-hospital complications. RESULTS: A decrease in FTR, as well as an increase in the unplanned ICU transfer rate, occurred in the second-year post-RRT implementation coinciding with an increase in RRT calls per month. No significant decreases were observed pre- and post-implementation for cardiopulmonary resuscitation events or overall mortality. A significant decrease in mortality among non-ICU discharges was identified by control charts, although this finding was not detected by BCP or pre- vs. post-analyses. CONCLUSIONS: Reduction in the FTR rate was associated with a substantial increase in the number of RRT calls. Effects of RRT may not be seen until RRT calls reach a sufficient threshold. FTR rate may be better at capturing the effect of RRT implementation than the rate of cardiac arrests. These results support prior reports that short-term studies may underestimate the impact of RRT systems, and support the need for ongoing monitoring and assessment of outcomes to facilitate best resource utilization.

Correction: The Masters athlete in Olympic weightlifting: Training, lifestyle, health challenges, and gender differences.

[This corrects the article DOI: 10.1371/journal.pone.0243652.].

The short- and long-term effect of osteopathic manipulative treatment on pain, and psychosocial factors in adults with chronic low back pain.

CONTEXT: Chronic low back pain (CLBP) has long plagued mankind, but little progress has been made in finding a rational and effective treatment, let alone a common cause. This study is an attempt to fill that void by measuring short- and long-term effects of osteopathic manipulative treatment (OMT), including psychosocial and pain reduction in CLBP patients. OBJECTIVES: The objectives of this study were to investigate the effectiveness of neuromusculoskeletal medicine/osteopathic manipulative medicine (OMM) in treating CLBP, with a focus on biopsychosocial (pain sensitivity questionnaire [PSQ]) and pain control in chronic conditions. METHODS: The study involved a large, single cohort observational design of 101 patients. The inclusion criteria for selecting patients targeted those with "nonspecific" CLBP. The National Institutes of Health (NIH) Minimum Dataset for Chronic Low Back Pain (NMD) was the measurement tool and was administered at consent (baseline), 2, 4, and 8 weeks and at 6 and 12 months. Time trends were analyzed as overall mean. Pairwise differences were compared between time points. Mixed-effects models were utilized to test the association of time with pain and biopsychosocial scores. RESULTS: Pain and PSQ scores decreased over the study timeline. The most significant change for both pain and biopsychosocial scores occurred at 6 months compared to baseline, with a further reduction at 12 months. CONCLUSIONS: OMT has been demonstrated to significantly reduce pain and psychosocial factors related to CLBP in both the short and long term.