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Improving survival in metastatic renal cell carcinoma (mRCC) patients: do elderly patients benefit from expanded targeted therapeutic options?

World J Urol. 2022 Aug 2. doi: 10.1007/s00345-022-04110-3. Online ahead of print.

ABSTRACT

INTRODUCTION: Treatment advances in metastatic renal cell carcinoma (mRCC) have improved overall survival (OS) in mRCC patients over the last two decades. This single center retrospective analysis assesses if the purported survival benefits are also applicable in elderly mRCC patients.

METHODS: 401 patients with mRCC treated at Hannover Medical School from 01/2003-05/2016 were identified and evaluated by chart review. Treatment periods were defined as 01.01.2003-31.12.2009 (P1) and 01.01.2010-31.05.2016 (P2). Age groups were defined according to WHO classes (≤ 60 years: younger, > 60-75 years: elderly and > 75 years: old). Descriptive statistics, Kaplan-Meier analysis and logistic regression were performed.

RESULTS: Median OS improved from 35.1 months in P1 to 59.1 months in P2. Sub-division into the respective age groups revealed median survival of 38.1 (95%-CI: 28.6-47.6) months in younger patients, 42.9 (95%-CI: 29.5-56.3) months among elderly patients and 27.3 (95%-CI: 12.8-41.8) months among old patients. Risk reduction for death between periods was most evident among old patients (young: HR 0.71 (95%-CI: 0.45-1.13, p = 0.2); elderly: HR 0.62 (95%-CI: 0.40-0.97, p = 0.04); old: HR 0.43 (95%-CI: 0.18-1.05, p = 0.06)). Age ≥ 75 years was an independent risk factor for death in P1 but not in P2.

CONCLUSION: Improved OS in the targeted treatment period was confirmed. Surprisingly elderly and old patients seem to profit the most form expansion of therapeutic armamentarium, within the TKI-dominated observation period.

PMID:35916904 | DOI:10.1007/s00345-022-04110-3

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Can transperineal ultrasound improve the diagnosis of obstetric anal sphincter injuries?

Int Urogynecol J. 2022 Aug 2. doi: 10.1007/s00192-022-05290-7. Online ahead of print.

ABSTRACT

INTRODUCTION AND HYPOTHESIS: Women with missed obstetric anal sphincter injuries (OASIs) are at an increased risk of anal incontinence. Our aim was to assess the accuracy of three-dimensional (3D) transperineal ultrasound (TPUS) compared with clinical examination for detecting OASIs.

METHODS: A cross-sectional study of women undergoing their first vaginal delivery. Perineal trauma was initially assessed by the doctor or midwife performing the delivery (accoucheur) and women were then re-examined by the trained research fellow (KW). A 3D TPUS was performed immediately after delivery before suturing to identify OASIs. The research fellow’s clinical diagnosis was used as the reference standard. A power calculation determined that 216 women would be required for the study.

RESULTS: Two hundred and sixty-four women participated and 226 (86%) delivered vaginally. Twenty-one (9%) sustained OASIs. Six (29%) of these tears were missed by the accoucheur but were identified by the research fellow. TPUS identified 19 of the 21 (90.5%) OASIs. One percent (n = 2) had sonographic appearances of an anal sphincter defect that was not seen clinically. The positive and negative predictive value of TPUS to detect OASIs was 91% and 99% respectively. TPUS identified 91% of OASIs compared with 71% detected by the accoucheur, which was not statistically significant.

CONCLUSIONS: The detection rate of OASIs with TPUS and with the clinical findings of the accoucheur was similar. Given the training and financial implications needed for TPUS, attention needs to be focused on the training of midwives and doctors to identify anal sphincter injuries by clinical examination.

PMID:35916899 | DOI:10.1007/s00192-022-05290-7

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Course Prerequisites: Here, There, and Everywhere. Time to Standardize?

J Physician Assist Educ. 2022 Jul 1. doi: 10.1097/JPA.0000000000000436. Online ahead of print.

ABSTRACT

INTRODUCTION: This study’s aim was to examine prerequisite course requirements and compare them to previous studies with a secondary aim to examine potential differences relative to program characteristics.

METHODS: Data were extracted from the websites of 265 entry-level physician assistant (PA) programs from October 2020 until December 2020. Course prerequisites as well as number of courses and semester hours required were described and examined according to program location, phase, Carnegie Classification, association with a medical school, and the public/private status of the sponsoring institution.

RESULTS: Of 264 PA programs, more than 50% of programs required 6 common prerequisites: anatomy, physiology, microbiology, statistics, general chemistry, and psychology. The total number of unique prerequisite courses was 28 for all programs with a reduction in humanities and social sciences semester hours compared to previous studies and a slight increase in credit hours required for the common 6 courses. Total prerequisite hours and courses required were higher for master’s programs; private, not-for-profit programs; newly established programs; and those not associated with a medical school. Newer programs are generally located in private, not-for-profit educational institutions that are not associated with a medical school. Programs in the Mountain Division required a lower number of prerequisites, and the South Region required the greatest number of prerequisite courses and semester hours.

DISCUSSION: The present study demonstrates a difference in prerequisite requirements across the country. This could translate to increased cost and a potential barrier to those considering a career as a PA.

PMID:35916887 | DOI:10.1097/JPA.0000000000000436

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Comparison of Countermovement Jump and Squat Jump Performance Between 627 State and Non-State Representative Junior Australian Football Players

J Strength Cond Res. 2022 Jul 1. doi: 10.1519/JSC.0000000000004299. Online ahead of print.

ABSTRACT

Edwards, T, Weakley, J, Woods, CT, Breed, R, Benson, AC, Suchomel, TJ, and Banyard, HG. Comparison of countermovement jump and squat jump performance between 627 state and non-state representative junior Australian football players. J Strength Cond Res XX(X): 000-000, 2022-This cross-sectional study investigated differences in lower-body power of state and nonstate representative junior Australian football (AF) players through countermovement jump (CMJ) and squat jump (SJ) performance. A total of 627 players performed the CMJ and SJ at the end of the preseason phase over a 2-week period, with each player grouped according to their age (under 18 [U18] or under 16 [U16]), and highest competition level played (state representation and nonstate representation). One-way multivariate analysis of variance (MANOVA), follow up ANOVA’s, and Cohen’s d effect sizes were used to identify significant main effects and between-group differences. Statistical significance was set at α < 0.05. Significant small-to-moderate effect size differences were observed between competition level, with state U18 and U16 players recording greater CMJ and SJ height, and peak power (PP), compared with their nonstate representative peers, respectively. Similarly, significant small-to-moderate effect size differences existed between age groups, with nonstate U18 players recording greater CMJ and SJ height and PP than nonstate U16 counterparts. However, state U18 and state U16 only differed in CMJ PP. No differences were found between competition level or age groups for the difference between CMJ and SJ jump height (CMJSJdiff). Together, these findings suggest that state and nonstate representative junior AFs may have a similar ability to use the stretch-shortening cycle, despite state representative players jumping higher in the CMJ and SJ.

PMID:35916875 | DOI:10.1519/JSC.0000000000004299

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Effect of Graded Sensorimotor Retraining on Pain Intensity in Patients With Chronic Low Back Pain: A Randomized Clinical Trial

JAMA. 2022 Aug 2;328(5):430-439. doi: 10.1001/jama.2022.9930.

ABSTRACT

IMPORTANCE: The effects of altered neural processing, defined as altering neural networks responsible for perceptions of pain and function, on chronic pain remains unclear.

OBJECTIVE: To estimate the effect of a graded sensorimotor retraining intervention (RESOLVE) on pain intensity in people with chronic low back pain.

DESIGN, SETTING, AND PARTICIPANTS: This parallel, 2-group, randomized clinical trial recruited participants with chronic (>3 months) nonspecific low back pain from primary care and community settings. A total of 276 adults were randomized (in a 1:1 ratio) to the intervention or sham procedure and attention control groups delivered by clinicians at a medical research institute in Sydney, Australia. The first participant was randomized on December 10, 2015, and the last was randomized on July 25, 2019. Follow-up was completed on February 3, 2020.

INTERVENTIONS: Participants randomized to the intervention group (n = 138) were asked to participate in 12 weekly clinical sessions and home training designed to educate them about and assist them with movement and physical activity while experiencing lower back pain. Participants randomized to the control group (n = 138) were asked to participate in 12 weekly clinical sessions and home training that required similar time as the intervention but did not focus on education, movement, and physical activity. The control group included sham laser and shortwave diathermy applied to the back and sham noninvasive brain stimulation.

MAIN OUTCOMES AND MEASURES: The primary outcome was pain intensity at 18 weeks, measured on an 11-point numerical rating scale (range, 0 [no pain] to 10 [worst pain imaginable]) for which the between-group minimum clinically important difference is 1.0 point.

RESULTS: Among 276 randomized patients (mean [SD] age, 46 [14.3] years; 138 [50%] women), 261 (95%) completed follow-up at 18 weeks. The mean pain intensity was 5.6 at baseline and 3.1 at 18 weeks in the intervention group and 5.8 at baseline and 4.0 at 18 weeks in the control group, with an estimated between-group mean difference at 18 weeks of -1.0 point ([95% CI, -1.5 to -0.4]; P = .001), favoring the intervention group.

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial conducted at a single center among patients with chronic low back pain, graded sensorimotor retraining, compared with a sham procedure and attention control, significantly improved pain intensity at 18 weeks. The improvements in pain intensity were small, and further research is needed to understand the generalizability of the findings.

TRIAL REGISTRATION: ANZCTR Identifier: ACTRN12615000610538.

PMID:35916848 | DOI:10.1001/jama.2022.9930

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Risk factors of delayed post-polypectomy bleeding after treatment of gastrointestinal polyps with snare-assisted endoscopic sub-mucosal dissection

J Minim Access Surg. 2022 Jul 20. doi: 10.4103/jmas.jmas_6_22. Online ahead of print.

ABSTRACT

CONTEXT: Gastrointestinal polyps are common gastrointestinal diseases that involve localised hyperplastic masses derived from gastrointestinal mucosa.

AIMS: To investigate the risk factors of delayed post-polypectomy bleeding (DPPB) after the treatment of gastrointestinal polyps with snare-assisted endoscopic sub-mucosal dissection (ESD) and to construct a nomogram model to predict the risk of DPPB.

SETTINGS AND DESIGN: A total of 226 patients who underwent snare-assisted ESD for gastrointestinal polyps from May 2018 to November 2020 were divided into DPPB group (n = 10) and non-DPPB group (n = 216).

SUBJECTS AND METHODS: The correlations of clinical data and endoscopic data with DPPB were compared. Univariate analysis was performed to screen the influencing factors of DPPB. Multivariate logistic regression analysis was used to screen the risk factors of DPPB, which was employed to construct a nomogram prediction model.

STATISTICAL ANALYSIS USED: SPSS 16.0 software was utilised for statistical analysis. Numerical data were expressed as percentage (n [%]), and Chi-square test was performed for univariate analysis. The significant factors (P < 0.05) in univariate analysis were included in multivariate logistic regression analysis, and the variables with statistical significance (P < 0.05) were considered as independent risk factors. The factors were used to construct a nomogram model for predicting the risk of DPPB. Bootstrap method was employed to perform repeated sampling 1000 times for internal verification. The consistency index (C-index) was used to evaluate the discrimination of the model, and C-index ≥0.70 represented a good discrimination. Two-tailed P < 0.05 indicated that a difference was statistically significant.

RESULTS: Univariate and multivariate logistic regression analyses revealed that hypertension, polyp location, polyp diameter, polyp morphology and intra-operative bleeding were the independent risk factors for DPPB (P < 0.05). The C-index of the nomogram model for predicting the risk of DPPB was 0.791, indicating a good discrimination. The calibration curve showed that the mean absolute error between predicted and actual DPPB occurrence risks was 0.014, indicating a high accuracy.

CONCLUSIONS: Hypertension, polyp location, polyp diameter, polyp morphology and intra-operative bleeding are the independent risk factors for DPPB, and the nomogram model established based on these factors for prediction has good discrimination and accuracy. Therefore, it is recommended to perform targeted intervention for high-risk groups to reduce the incidence of DPPB.

PMID:35915538 | DOI:10.4103/jmas.jmas_6_22

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Clinical outcome of endoscopic balloon dilatations employed in benign paediatric oesophageal pathologies

J Minim Access Surg. 2022 Jul 6. doi: 10.4103/jmas.jmas_79_22. Online ahead of print.

ABSTRACT

BACKGROUND: Oesophageal dilatations can be done either by bougies or balloons for differing aetiologies in children. We investigated the efficacy and safety of endoscopic balloon dilatations (EBDs) employed by a single surgeon.

PATIENTS AND METHODS: Relevant data over 12 years were retrospectively evaluated with an ethical committee approval.

RESULTS: Ninety-seven children underwent 514 EBD with a median EBD of 3 (1-50). The primary diagnoses were oesophageal atresia (OA) in 51 children, corrosive ingestion in 21, peptic strictures in 13, achalasia in 8 and congenital oesophageal stenosis in 4. The balloon size varied between 3 and 30 mm. The EBD was successfully ended in 72 patients and unsuccessful in six patients. Six children are still under EBD and 13 are lost to follow-up. The overall success rate was 92%. The age at the time of first dilatation was the youngest in OA group followed by corrosive strictures. The balloon sizes differed regarding the age of the patients with larger balloons used as the patient age increased. The sizes of the balloons used at the first and the last EBD differed among diagnostic groups. The total number of dilatations or the time interval between the first and the last EBD dilatation did not show a statistically significant difference among groups. The anatomical type of OA or the height of corrosive stricture revealed no significant difference in any of the above parameters. A transmural oesophageal perforation occurred during 2 (0.4%) EBD sessions.

CONCLUSIONS: EBD is an effective mean in relieving paediatric oesophageal pathologies with a variety of aetiologies and has a low complication rate.

PMID:35915522 | DOI:10.4103/jmas.jmas_79_22

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A newer method of seroma reduction by fenestration of pseudo-sac during laparoscopic repair of direct inguinal hernia: A randomised, controlled pilot study

J Minim Access Surg. 2022 Jul 6. doi: 10.4103/jmas.jmas_391_21. Online ahead of print.

ABSTRACT

BACKGROUND: Minimally invasive surgeries for inguinal hernia repair have been reduced post-operative morbidity. However, certain complications such as seroma formation are unavoidable. In this study, we introduce a newer technique of reducing seroma formation by fenestration of the pseudo-sac (thickened transversalis fascia) in patients undergoing laparoscopic hernia repair for uncomplicated direct inguinal hernia.

PATIENTS AND METHODS: A randomised, controlled pilot study was conducted from January 2019 to December 2020 for the patients undergoing laparoscopic hernia repair for uncomplicated direct inguinal hernia. Study participants were randomised into interventional group and control groups. Demographics, operative duration and complications including post-operative pain and seroma on days 1, 10 and 30 were analysed between both the groups.

RESULTS: A total of 20 cases with 30 hernias were included in the study. Demographic data were comparable between the two groups. The intervention group showed a statistically significant decrease in the incidence of seroma formation on the post-operative day 10 (13.3% vs. 46.6%, P = 0.046). The mean volume of seroma on day 10 was also less compared to the non-fenestration group (2.5 vs. 6.58 ml, P = 0.048). After the 30th day, no patient had a presence of seroma. There were no statistically significant differences in terms of mean operative duration, post-operative pain and other complications.

CONCLUSION: Fenestration of pseudo-sac in laparoscopic hernia repair for uncomplicated direct inguinal hernia is a simple and effective technique. It has reduced the incidence and volume of seroma formation without any increased risk of infection, acute or chronic pain and recurrence.

PMID:35915521 | DOI:10.4103/jmas.jmas_391_21

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Linking physical activity to personal values: feasibility and acceptability randomized pilot of a behavioral intervention for older adults with osteoarthritis pain

Pilot Feasibility Stud. 2022 Aug 1;8(1):164. doi: 10.1186/s40814-022-01121-0.

ABSTRACT

BACKGROUND: Osteoarthritis (OA) pain is common and leads to functional impairment for many older adults. Physical activity can improve OA outcomes for older adults, but few are appropriately active. Behavioral interventions can reduce physical activity barriers. We developed and tested a brief, novel behavioral intervention (i.e., Engage-PA) for older adults combining values to enhance motivation and strategic activity pacing to improve arthritis-related pain and functioning and increase physical activity.

METHODS: A randomized feasibility and acceptability pilot trial compared Engage-PA to treatment-as-usual plus fitness tracker (TAU+) in N = 40 adults age 65+ with OA pain in the knee or hip. Engage-PA involved two 60-min telephone sessions. All participants wore a fitness tracker to collect daily steps throughout the study and completed baseline and post-treatment assessments of secondary outcomes (arthritis-related pain and physical functioning, physical activity, psychological distress, psychological flexibility, and valued living). The impact of COVID-19 on general well-being and physical activity was also assessed. Descriptive statistics were conducted for feasibility and acceptability outcomes. Indicators of improvement in secondary outcomes were examined via change scores from baseline to post-treatment and performing independent samples t-tests to assess for between-group differences.

RESULTS: Feasibility was high; 100% accrual, low (5%) attrition, and 100% completion of study sessions. Acceptability was high, with 89% finding the intervention “mostly” or “very” helpful. Engage-PA participants demonstrated improvements in arthritis pain severity (Mdiff = 1.68, p = 0.044, 95% CI [- 0.26, 3.62]) and self-reported activity (Mdiff = 0.875, p = 0.038, 95% CI [- 1.85, 0.98]) from baseline to post-treatment as compared to TAU+. Due to pandemic-related challenges, there was a high level of missing data (43%) for daily steps, but available data showed no significant change in steps over time or between the groups. COVID-19 added an additional burden to participants, such that 50% were exercising less, 68% were more sedentary, and 72% lost access to spaces and social support to be active.

CONCLUSIONS: Engage-PA is a promising brief, novel behavioral intervention with the potential to support older adults in improving arthritis-related pain and functioning and increasing physical activity. The feasibility and acceptability of Engage-PA are particularly notable as most participants reported COVID-19 added more barriers to physical activity.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT04490395 . Registered on July 29, 2020.

PMID:35915512 | DOI:10.1186/s40814-022-01121-0

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Differential richness inference for 16S rRNA marker gene surveys

Genome Biol. 2022 Aug 1;23(1):166. doi: 10.1186/s13059-022-02722-x.

ABSTRACT

BACKGROUND: Individual and environmental health outcomes are frequently linked to changes in the diversity of associated microbial communities. Thus, deriving health indicators based on microbiome diversity measures is essential. While microbiome data generated using high-throughput 16S rRNA marker gene surveys are appealing for this purpose, 16S surveys also generate a plethora of spurious microbial taxa.

RESULTS: When this artificial inflation in the observed number of taxa is ignored, we find that changes in the abundance of detected taxa confound current methods for inferring differences in richness. Experimental evidence, theory-guided exploratory data analyses, and existing literature support the conclusion that most sub-genus discoveries are spurious artifacts of clustering 16S sequencing reads. We proceed to model a 16S survey’s systematic patterns of sub-genus taxa generation as a function of genus abundance to derive a robust control for false taxa accumulation. These controls unlock classical regression approaches for highly flexible differential richness inference at various levels of the surveyed microbial assemblage: from sample groups to specific taxa collections. The proposed methodology for differential richness inference is available through an R package, Prokounter.

CONCLUSIONS: False species discoveries bias richness estimation and confound differential richness inference. In the case of 16S microbiome surveys, supporting evidence indicate that most sub-genus taxa are spurious. Based on this finding, a flexible method is proposed and is shown to overcome the confounding problem noted with current approaches for differential richness inference. Package availability: https://github.com/mskb01/prokounter.

PMID:35915508 | DOI:10.1186/s13059-022-02722-x