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Background : Lefamulin, a pleuromutilin antibiotic approved for community-acquired bacterial pneumonia (CABP), was evaluated for microbiological efficacy in a prespecified pooled analysis of LEAP 1 and 2 phase 3 clinical trial data in patients with CABP. Methods : In LEAP 1, adults (Pneumonia Outcomes Research Team [PORT] risk class III‒V) received intravenous (IV) lefamulin 150 mg every 12 hours (q12h; 5‒7 days) or moxifloxacin 400 mg every 24 hours (q24h; 7 days), with optional IV-to-oral switch. In LEAP 2, adults (PORT II‒IV) received oral lefamulin 600 mg q12h (5 days) or moxifloxacin 400 mg q24h (7 days). Primary outcomes were early clinical response (ECR) 96±24 hours after treatment start and investigator assessment of clinical response (IACR) 5‒10 days after last dose. Secondary outcomes included ECR and IACR in patients with a baseline CABP pathogen (detected via culture, urinary antigen test, serology, and/or real-time PCR). Results : Baseline CABP pathogens were detected in 709/1289 patients (55.0% [microbiological intent-to-treat population]). The most frequently identified pathogens in this population were Streptococcus pneumoniae (61.9% of patients) and Haemophilus influenzae (29.9%); 25.1% had atypical pathogens and 33.1% had polymicrobial infections. Pathogens were identified most frequently by PCR from sputum, followed by culture from respiratory specimens. In patients with baseline CABP pathogens, ECR rates were 89.3% (lefamulin) and 93.0% (moxifloxacin); IACR success rates were 83.2% and 86.7%, respectively. Results were consistent across CABP pathogens, including drug-resistant isolates and polymicrobial infections. Conclusions : Lefamulin is a valuable IV and oral monotherapy option for empiric and directed CABP treatment in adults.

Background and aims The role of laparoscopic rectal cancer resection remains controversial. Thus, we aimed to conduct a one-stage meta-analysis with reconstructed patient-level data using randomized trial data to compare long-term oncologic efficacy of laparoscopic and open surgical resection for rectal cancer. Methods Medline, EMBASE and Scopus were searched for articles comparing laparoscopic with open surgery for rectal cancer. Primary outcome was disease free survival (DFS) while secondary outcome was overall survival (OS). One-stage meta-analysis was conducted using patient-level survival data reconstructed from Kaplan-Meier curves with Web Plot Digitizer. Shared-frailty and stratified Cox models were fitted to compare survival endpoints. Results Seven randomized trials involving 1767 laparoscopic and 1293 open resections for rectal cancer were included. There were no significant differences between both groups for DFS and OS with respective hazard ratio estimates of 0.91 (95% CI: 0.78–1.06, p = 0.241) and 0.86 (95% CI:0.73–1.02, p = 0.090). Sensitivity analysis for non-metastatic patients and patients with mid and lower rectal cancer showed no significant differences in OS and DFS between both surgical approaches. In the laparoscopic arm, improved DFS was noted for stage II (HR: 0.73, 95% CI:0.54–0.98, p = 0.036) and stage III rectal cancers (HR: 0.74, 95% CI:0.55–0.99, p = 0.041). Conclusions This meta-analysis concludes that laparoscopic rectal cancer resection does not compromise long-term oncologic outcomes compared with open surgery with potential survival benefits for a minimal access approach in patients with stage II and III rectal cancer.

OBJECTIVE Catheter-based cerebral angiography is commonly used for neurovascular diagnosis in children. In this work, the authors aimed to quantify the complication rate of cerebral angiography in children, characterize these complications, and identify risk factors for complications. METHODS Relevant clinical data were retrospectively obtained for 587 consecutive cerebral angiography procedures performed in 390 children from March 2002 to March 2020. Complications were categorized as neurological or nonneurological, and severity was graded using a standard schema. Incidences of complications were reported as point estimates. Associations between risk factors and complications were characterized in univariate analysis using the two-tailed Fisher exact test and in multivariate analysis using multiple logistic regression with bidirectional elimination based on the Akaike information criterion. In both univariate and multivariate analyses, statistical significance was corrected for multiple comparisons using the Benjamini-Hochberg method. RESULTS Complications occurred in 6.5% of procedures, including neurological complications in 1.9% and nonneurological complications in 4.8%. Permanent deficits occurred in only 0.2% of cases. Overall, 0.5% of procedures resulted in major complications, while 6.0% resulted in minor complications. Female sex and a history of hypertension or ischemic stroke were associated with an increased risk of complications, while femoral artery access was associated with a decreased risk of complications. CONCLUSIONS Pediatric cerebral angiography was shown to have a low rate of major or permanent complications. Children who were female and those with a history of hypertension or ischemic stroke were shown to be at higher risk of complications, while the use of femoral access carried a lower risk of complications.

STUDY QUESTION Do extrinsic factors including lifestyle, psychosocial factors and healthcare professional engagement independently contribute to weight gain in women with and without polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Women with PCOS had a higher rate of weight gain than women without PCOS which was most marked in those with unhealthy lifestyles. WHAT IS KNOWN ALREADY Women with PCOS have a higher prevalence of overweight/obesity and greater weight gain than women without PCOS. The association of lifestyle factors with weight change in PCOS is not known. STUDY DESIGN, SIZE, DURATION The study was a population-based observational study with data collected from seven surveys over 19 years (N = 14 127; Survey 1) involving women with and without PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS We used data from the 1973–1978 birth cohort of the Australian Longitudinal Study on Women’s Health. MAIN RESULTS AND THE ROLE OF CHANCE Women with PCOS gained more weight annually (0.26 kg/year; 95% CI 0.12, 0.39; P < 0.0001) and over 19 years (4.62 kg; 95% CI 3.04, 6.21; P < 0.0001) than women without PCOS (adjusted analyses). For all women, there were positive associations between weight gain and energy intake, sitting time and stress; inverse associations with fibre intake and physical activity (PA); and no associations with diet quality, glycaemic index, healthcare utilization, depression or anxiety. There were interactions between lifestyle factors (energy intake P = 0.006, glycaemic index P = 0.025, sitting time P = 0.041 and PA P = 0.021), PCOS status and time such that weight gain varied between women with and without PCOS according to these factors. LIMITATIONS, REASONS FOR CAUTION The limitations of this study include the use of self-reported measures such as diet, PA, sitting time, psychological factors and health care utilization. WIDER IMPLICATIONS OF THE FINDINGS While women with PCOS are more prone to weight gain, lifestyle factors have a more profound impact on weight gain in women with PCOS than without PCOS. These study findings have implications for understanding the mechanisms of weight gain in women with PCOS. They also highlight the importance of early lifestyle intervention as soon as PCOS is diagnosed to address modifiable extrinsic factors and prevent excess weight gain and worsening of the clinical features of PCOS. STUDY FUNDING/COMPETING INTEREST(S) M.A.A. is funded by the Monash International Tuition Scholarship and Monash Graduate Scholarship and L.J.M. is funded by a National Heart Foundation Future Leader Fellowship. The authors declared no conflict of interest. TRIAL REGISTRATION NUMBER N/A.

International Classification of Diseases (ICD)-10 codes may correspond to cirrhosis diagnosis. However, these codes have not been as well studied as ICD-9 codes. We aimed to evaluate the positive predictive value (PPV) and specificity of ICD-10 codes for cirrhosis. We conducted a single-center retrospective study of patients in Michigan Medicine (Ann Arbor, MI, USA). We evaluated patients with at least one of 28 ICD-10 codes for cirrhosis and randomly selected controls for the presence of cirrhosis and/or portal hypertensive complications. Among 1317 patients with at least one ICD-10 code consistent with cirrhosis and/or portal hypertension, 796 had confirmed cirrhosis. After excluding ICD-10 codes found in 80%), including codes for cirrhosis itself, gastroesophageal varices, hepatic encephalopathy, and other portal hypertensive complications. Specificity of ICD codes for cirrhosis for these 15 codes was high (> 94% for all). PPV and specificity were high across liver disease etiologies. Among patients without portal hypertension, PPVs of ICD-10 codes for cirrhosis were lower but still > 80% for the most common codes. PPVs of most codes for portal hypertensive complications were > 70%. Defining cirrhosis based on the presence of any of the 15 codes resulted in a PPV of 86% and by two different codes, a PPV 94%. ICD-10 codes for cirrhosis can accurately identify patients with cirrhosis with or without portal hypertensive complications.

Background The benefit of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) in patients with large vessel occlusion (LVO) stroke is uncertain. Conventional metrics of final modified thrombolysis in cerebral ischemia (mTICI) score and 90-d modified Rankin Scale may be insensitive to IVT effects on procedural complexity and duration. Objective To study the effect of IVT prior to MT on clot survival. Methods We performed a single-center retrospective analysis of 257 acute stroke patients with LVO undergoing MT and analyzed the effect of IVT prior to MT using a novel, pass-by-pass clot survival methodology. Results The use of IVT was associated with a significantly lower number of passes to attain mTICI 2B or greater (P = .002) or mTICI 3 (P = .039) reperfusion. The number of patients who achieved mTICI 2B or greater after the first pass was significantly higher in the IVT group (P = .003). This increased rate of reperfusion persisted into subsequent passes. Conclusion IVT prior to MT reduces the number of thrombectomy passes required to achieve mTICI 2B or mTICI 3 reperfusion. This information should be considered as the merits of IVT prior to MT are debated.

BackgroundConflicting evidence surrounds the effect of dietary macronutrient intake (fat, carbohydrate and protein) on cardiovascular disease (CVD), particularly in women.MethodsWomen (aged 50–55 years) were recruited into the Australian Longitudinal Study on Women’s Health. Women were divided into quintiles according to their carbohydrate and saturated fat intake as a percentage of total energy intake (TEI). The primary endpoint was new-onset CVD (heart disease/stroke). Secondary endpoints included all-cause mortality, incident hypertension, obesity and/or diabetes mellitus. Multivariate logistic regression models assessed for associations with the primary and secondary endpoints, with adjustment for confounders.ResultsA total of 9899 women (mean age 52.5±1.5 years) were followed for 15 years, with 1199 incident CVD and 470 deaths. On multivariable analysis, higher carbohydrate intake was associated with lower CVD risk (ptrendtrend=0.69) or between saturated fat intake and CVD (ptrend=0.29) or mortality (ptrend=0.25). Both increasing saturated fat and carbohydrate intake were significantly inversely associated with hypertension, diabetes mellitus and obesity (ptrendConclusionsIn middle-aged Australian women, moderate carbohydrate intake (41.0%–44.3% of TEI) was associated with the lowest risk of CVD, without an effect on total mortality. Increasing saturated fat intake was not associated with CVD or mortality and instead correlated with lower rates of diabetes, hypertension and obesity.

Polycystic ovary syndrome (PCOS) is a heterogeneous disorder and many women are dissatisfied with their healthcare under the current fragmented health services. Here, we review existing literature on PCOS healthcare services and qualitatively evaluate an integrated PCOS service based on experiences of women with PCOS. Limited prior PCOS-dedicated services have been studied and their quantitative and efficacy-focused evaluations are summarized. Here, we also provide a broader PCOS service evaluation via semistructured interviews and surveys, with thematic analysis based on a predetermined evaluation framework. Fifteen women completed interviews and surveys. Overall the integrated, evidence-based PCOS service was well-received and women were generally satisfied with appropriateness, effectiveness, and reported positive health impact resulting from the service. Integrated care, tailored treatments, education, lifestyle support, and laser therapy were highly valued. Patients reported improvements on symptoms, understanding and confidence in managing PCOS, and emotional well-being. Elements of efficiency in the initial stages, awareness and communication, and the need for service expansion and tensions between evidence-based treatments and patient preferences were also captured to guide improvement. Further research into models of care is recommended to meet the needs of women with PCOS.

Objective:Household food insecurity is associated with CVD risk factors in low-income adults, but research on these associations among adolescents is inconsistent. This study investigates whether household and child food insecurity is associated with CVD risk factors in lower-income adolescents.Design:Cross-sectional. Multivariable linear regression assessed the association between household and child food security and CVD risk factors. Household and child food security was measured using the US Food Security Survey Module. The analyses were adjusted for adolescent’s age, sex, race/ethnicity, smoking status, physical activity and sedentary time, as well as household income and the head-of-household’s education and marital status.Setting:The USA.Participants:The sample was comprised of 2876 adolescents, aged 12–17 years, with household incomes at or below 300 % federal poverty line from the National Health and Nutrition Examination Survey cycles 2007–2016.Results:The weighted prevalence of household food insecurity in the analytic sample was 33·4 %, and the weighted prevalence of child food insecurity was 17·4 %. After multivariable adjustment, there were no significant associations between household and child food insecurity and BMI-for-age Z-score, systolic and diastolic blood pressure, HDL-cholesterol, total cholesterol, fasting TAG, fasting LDL-cholesterol and fasting plasma glucose.Conclusions:Despite observed associations in adults, household food insecurity was not associated with CVD risk factors in a national sample of lower-income adolescents. Child food insecurity was also not associated with CVD risk factors. More research should be conducted to confirm these associations.

Background Safe and effective oral antibiotics are needed for outpatient management of moderate to severe community-acquired bacterial pneumonia (CABP). Objective We describe a post-hoc analysis of adults with CABP managed as outpatients from the Lefamulin Evaluation Against Pneumonia (LEAP) 2 double-blind, noninferiority, phase 3 clinical trial. Methods LEAP 2 compared the efficacy and safety of oral lefamulin 600 mg every 12 h (5 days) vs. oral moxifloxacin 400 mg every 24 h (7 days) in adults (inpatients and outpatients) with Pneumonia Outcomes Research Team (PORT) risk classes II‒IV. Results Overall, 41% (151 of 368) of patients receiving lefamulin and 43% (159 of 368) of patients receiving moxifloxacin started treatment as outpatients—44% and 40%, respectively, were PORT risk class III/IV, and 21% in both groups had CURB-65 scores of 2‒3. Early clinical response (at 96 ± 24 h) and investigator assessment of clinical response success rates at test of cure (5‒10 days after last study drug dose) were high and similar in both groups among all (lefamulin, 91% vs. moxifloxacin, 89‒90%), PORT risk class III/IV (89‒91% vs. 88‒91%), and CURB-65 score 2‒3 (87‒90% vs. 82‒88%) outpatients. Few outpatients (lefamulin, 2.6%; moxifloxacin, 2.5%) discontinued the study drug because of treatment-emergent adverse events (TEAEs). No outpatient in the lefamulin group was hospitalized for a TEAE, compared with 5 patients (3%), including two deaths, in the moxifloxacin group. Conclusions These data suggest that 5 days of oral lefamulin can be given in lieu of fluoroquinolones for outpatient treatment of adults with CABP and PORT risk class III/IV or CURB-65 scores of 2‒3.

Decades of neurobiological research have disclosed the diverse manners in which the response properties of neurons are dynamically modulated to support adaptive cognitive functions. This neuromodulation is achieved through alterations in the biophysical properties of the neuron. However, changes in cognitive function do not arise directly from the modulation of individual neurons, but are mediated by population dynamics in mesoscopic neural ensembles. Understanding this multiscale mapping is an important but nontrivial issue. Here, we bridge these different levels of description by showing how computational models parametrically map classic neuromodulatory processes onto systems-level models of neural activity. The ensuing critical balance of systems-level activity supports perception and action, although our knowledge of this mapping remains incomplete. In this way, quantitative models that link microscale neuronal neuromodulation to systems-level brain function highlight gaps in knowledge and suggest new directions for integrating theoretical and experimental work.

Background and purpose Flow diversion of aneurysms located in the M1 segment and middle cerebral artery bifurcation with Pipeline embolization device is sometimes performed, but further study is needed to support its regular use in aneurysm treatment. Here, we report measures of safety and efficacy for Pipeline embolization in the proximal middle cerebral artery in a multi-center cohort. Materials and methods Clinical and angiographic data of eligible patients were retrospectively obtained from participating centers and assessed for key clinical and angiographic outcomes. Additional details were extracted for patients with complications. Results In our multi-center cohort, complete aneurysm occlusion was achieved in 71% (17/24) of treated aneurysms. There were no deaths or disabling strokes, but non-disabling ischemic strokes occurred in 8% (2/24) of patients. For aneurysms in the M1 segment, complete aneurysm occlusion was observed in 75% (12/16) of aneurysms, aneurysm volume reduction was observed in 100% (16/16) of aneurysms, and non-disabling ischemic strokes occurred in 13% (2/16) of patients. For aneurysms at the middle cerebral artery bifurcation, complete aneurysm occlusion was observed in 63% (5/8) of aneurysms, aneurysm volume reduction occurred in 88% (7/8) of aneurysms, and ischemic or hemorrhagic complications occurred in 0% (0/8) of patients. Conclusion Pipeline embolization of cerebral aneurysms in the M1 segment and middle cerebral artery bifurcation demonstrated a 71% rate of complete aneurysm occlusion. There were no deaths or disabling strokes, but there was an 8% rate of non-disabling ischemic strokes.

Objectives Emergency department (ED) patients with serious skin and soft tissue infections (SSTIs) are often hospitalized to receive intravenous (IV) antibiotics. Appropriate patients may avoid admission following a single‐dose, long‐acting IV antibiotic. Methods We conducted a preintervention versus postintervention design trial at 11 U.S. EDs comparing hospitalization rates under usual care to those using a clinical pathway that included a single IV dalbavancin dose. We enrolled adults with cellulitis, abscess, or wound infection with an infected area of ≥75 cm2 without other indications for hospitalization. Clinical pathway participants discharged from the ED received a 24‐hour follow‐up telephone call and had a 48‐ to 72‐hour in‐person visit. We hypothesized that, compared to usual care, the clinical pathway would result in a significant reduction in the initial hospitalization rate. Results Of 156 and 153 participants in usual care and clinical pathway periods, median infection areas were 255.0 (interquartile range [IQR] = 150.0 to 500.0) cm2 and 289.0 (IQR = 161.3 to 555.0) cm2, respectively. During their initial care, 60 (38.5%) usual care participants were hospitalized and 27 (17.6%) pathway participants were hospitalized (difference = 20.8 percentage points [PP], 95% confidence interval [CI] = 10.4 to 31.2 PP). Over 44 days, 70 (44.9%) usual care and 44 (28.8%) pathway participants were hospitalized (difference = 16.1 PP, 95% CI = 4.9 to 27.4 PP). Conclusions Implementation of an ED SSTI clinical pathway for patient selection and follow‐up that included use of a single‐dose, long‐acting IV antibiotic was associated with a significant reduction in hospitalization rate for stable patients with moderately severe infections. Registration: NCT02961764.

Background Lefamulin, a first-in-class pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia (CABP), was noninferior to moxifloxacin in the Lefamulin Evaluation Against Pneumonia (LEAP) 1 intravenous-to-oral switch study and the LEAP 2 oral-only study. Using pooled LEAP 1/2 data, we examined lefamulin efficacy/safety overall and within subgroups of patients presenting with comorbidities typical in CABP management. Methods In LEAP 1, adults with CABP were randomized to receive intravenous lefamulin (150 mg every 12 h) for 5‒7 days or moxifloxacin (400 mg every 24 h) for 7 days, with optional intravenous-to-oral switch if predefined improvement criteria were met. In LEAP 2, adults with CABP were randomized to receive oral lefamulin (600 mg every 12 h) for 5 days or moxifloxacin (400 mg every 24 h) for 7 days. Both studies assessed early clinical response (ECR) at 96 ± 24 h after first study drug dose and investigator assessment of clinical response (IACR) at test-of-cure (5‒10 days after last dose). Pooled analyses of the overall population used a 10% noninferiority margin. Results Lefamulin (n = 646) was noninferior to moxifloxacin (n = 643) for ECR (89.3% vs 90.5%, respectively; difference − 1.1%; 95% CI − 4.4 to 2.2); IACR success rates at test-of-cure were similarly high (≥ 85.0%). High efficacy with both lefamulin and moxifloxacin was also demonstrated across all well-represented patient subgroups, including those with advanced age, diabetes mellitus, a history of cardiovascular diseases (e.g., hypertension, congestive heart failure, or arrhythmia) or chronic lung diseases (e.g., asthma or chronic obstructive pulmonary disease), elevated liver enzymes, or mild-to-moderate renal dysfunction. No new safety signals were identified. Conclusions Lefamulin may provide a valuable intravenous/oral monotherapy alternative to fluoroquinolones or macrolides for empiric treatment of patients with CABP, including cases of patients at risk for poor outcomes due to age or various comorbidities. Trial registration ClinicalTrials.gov LEAP 1 (NCT02559310; Registration Date: 24/09/2015) and LEAP 2 (NCT02813694; Registration Date: 27/06/2016).

Background and purpose Flow diversion is commonly used to treat intracranial aneurysms in various regions of the cerebral vasculature, but is only approved for use in the internal carotid arteries. Treatment of distal PICA aneurysms with PED is sometimes performed but has not been well studied. Here, we report our experience with flow diversion of distal PICA aneurysms with PED. Materials and methods Clinical and angiographic data of eligible patients was retrospectively obtained and assessed for key demographic characteristics and clinical and angiographic outcomes. Principal outcomes included rates of aneurysm occlusion, ischemic or hemorrhagic complication, technical complication, and in-stent stenosis. Results Three female and 2 male patients underwent placement of PED in the PICA for treatment of 5 distal PICA aneurysms. Clinical and angiographic follow-up was obtained for all patients. Complete aneurysm occlusion was observed in 100% (5/5) of treated aneurysms at 6 month and longest angiographic follow-up. While there were no ischemic or device-related complications, delayed hemorrhagic complications occurred in 20% (1/5) of patients. Conclusion Pipeline embolization of distal PICA aneurysms can be performed in select patients. Further study is necessary in larger cohorts to better define clinical scenarios in which flow diversion in the distal PICA should be considered.

The preconception period provides a significant opportunity to engage women in healthy behaviour change for improved maternal and child health outcomes. However, there is limited research exploring women's pregnancy planning in Australia.This study investigated associations between pregnancy planning, socio-demographics and preconception health behaviours in Australian women.A retrospective cross-sectional survey of pregnant women ≥18-years-of-age recruited through a Victorian public maternity service and a national private health insurer.Overall 317 women (30±4.7 years) participated (public: n=225, private: n=92). Planned pregnancies were reported by 74% of women and were independently associated with marital status (AOR=5.71 95% CI 1.92-17.00, p=0.002); having ≤2 children (AOR=3.75 95% CI 1.28-11.05, p=0.016); and having private health insurance (AOR=2.51 95% CI 1.08-5.81, p=0.03). Overall, women reported preconception: any folic-acid supplementation (59%), up-to-date cervical screening (68%), weight management attempts (75%), accessing information from health professionals (57%) and immunisation reviews (47%). Pregnancy planners were more likely to use folic-acid (AOR=17.13 95% CI 7.67-38.26, p0.001), review immunisations (AOR=2.09 95% CI 1.07-4.10, p=0.03) and access information (AOR=3.24 95% CI 1.75-6.00, p0.001) compared to non-planners. Women25-years-of-age were less likely to access information (AOR=0.38 95% CI 0.16-0.89, p=0.03) and take folic-acid (AOR=0.23 95% CI 0.09-0.59, p=0.002) and were more likely to smoke 3-months preconception (AOR=6.68 95% CI 1.24-36.12, p=0.03).Women with planned and unplanned pregnancies reported variable preconception health behaviour uptake and limited healthcare engagement. Opportunities exist to improve awareness and healthcare engagement for optimising preconception health and pregnancy planning benefits including collaborative health promotion. Population-based and targeted approaches reaching pregnancy planners and non-planners are required.

Aim Cytoreductive surgery (CRS) for peritoneal malignancy has traditionally included umbilical excision with no published evidence on the incidence of umbilical involvement. The primary aim of this work was to determine the incidence of umbilical involvement in patients undergoing CRS for peritoneal malignancy of appendiceal origin. The secondary aim was to investigate the relationship of umbilical involvement with prior surgery affecting the umbilicus, such as diagnostic laparoscopy and midline laparotomy. Method This study is from a national referral centre in the United Kingdom for appendiceal tumours and peritoneal malignancy. It is a retrospective analysis from a dedicated prospective database. We evaluated the most recent 200 consecutive patients who underwent CRS for peritoneal malignancy of appendiceal origin where all pathology specimens were reported by a recognized expert pathologist in appendiceal tumours and peritoneal malignancy. Results From June 2016 to September 2019, 200 consecutive patients had CRS and 178 had umbilical excision. Of these 54/178 (30.3%) had disease involving the umbilicus. The pathological findings in the 178 patients were low-grade mucinous carcinoma peritonei in 90/178 (50.6%), high-grade mucinous carcinoma peritonei in 31/178 (17.4%), metastatic appendiceal adenocarcinoma in 29/178 (16.4%) and diffuse acellular mucin in 28/178 (15.7%). Umbilical involvement was found in 25/90 (27.8%) with low-grade, 11/31 (35.5%) with high-grade, 8/29 (27.6%) with adenocarcinoma and 10/28 (35.7%) of patients with acellular mucin. In the 54 patients with umbilical disease, 30/54 (55.6%) had previous diagnostic surgery affecting the umbilicus. In the 124 patients without umbilical disease, 76/124 (61.2%) had prior surgery involving the umbilicus. The difference between the groups was not significant (p = 0.24). Conclusion In patients with peritoneal malignancy of appendiceal origin, approximately 30% have umbilical involvement, irrespective of the primary appendiceal pathology. Umbilical involvement was not associated with prior surgery involving the umbilicus. This is the first report to document the incidence of umbilical pathology and supports consideration of routine umbilical excision in CRS for peritoneal malignancy.

Purpose Iodine-125 (125I) is the most commonly used isotope for prostate brachytherapy (BT). Cesium-131 (131Cs) has a higher dose rate and shorter dose delivery time resulting in decreased duration of acute urinary morbidity. Long-term data suggest excellent oncologic outcomes; it is not known how outcomes compare. A prospective randomized trial comparing the two isotopes was initiated. Materials and Methods Patients with low- or intermediate-risk disease were treated with a BT in a single outpatient facility. Prescription dose was 144 Gy for 125I and 115 Gy for 131Cs. Androgen deprivation or supplemental EBRT was not allowed. The primary study objective was comparison of the mean EPIC Urinary Domain Score. Secondary objective was biochemical relapse-free survival (BRFS) comparison. Time-to-event for all outcomes of interest was measured from implant date. Results One hundred forty men were enrolled; 81.4% were low-risk and 18.6% were intermediate-risk. The median followup was 97 months. Urinary and sexual health-related quality of life did not differ between isotopes at any recorded time point. At 2 months after implantation, bowel health-related quality of life was worse with 125I; however, this difference was lost at subsequent time points. The 9-year BRFS was 87.2% and 84.0% for the 125I and 131Cs group, respectively (p = 0.897). There was no statistically significant difference in BRFS based on initial T stage, PSA, or Gleason score. Conclusions Short- and long-term urinary, sexual, and bowel quality of life, as well as long-term biochemical control were comparable between 125I and 131Cs. This report therefore supports the continued use of 131Cs as an effective and comparable alternative isotope.

Study objective Enterobacteriaceae resistant to ceftriaxone, mediated through extended-spectrum β-lactamases (ESBLs), commonly cause urinary tract infections worldwide, but have been less prevalent in North America. Current US rates are unknown. We determine Enterobacteriaceae antimicrobial resistance rates among US emergency department (ED) patients hospitalized for urinary tract infection. Methods We prospectively enrolled adults hospitalized for urinary tract infection from 11 geographically diverse university-affiliated hospital EDs during 2018 to 2019. Among participants with culture-confirmed infection, we evaluated prevalence of antimicrobial resistance, including that caused by ESBL-producing Enterobacteriaceae, resistance risk factors, and time to in vitro–active antibiotics. Results Of 527 total participants, 444 (84%) had cultures that grew Enterobacteriaceae; 89 of 435 participants (20.5%; 95% confidence interval 16.9% to 24.5%; 4.6% to 45.4% by site) whose isolates had confirmatory testing had bacteria that were ESBL producing. The overall prevalence of ESBL-producing Enterobacteriaceae infection among all participants with urinary tract infection was 17.2% (95% confidence interval 14.0% to 20.7%). ESBL-producing Enterobacteriaceae infection risk factors were hospital, long-term care, antibiotic exposure within 90 days, and a fluoroquinolone- or ceftriaxone-resistant isolate within 1 year. Enterobacteriaceae resistance rates for other antimicrobials were fluoroquinolone 32.3%, gentamicin 13.7%, amikacin 1.3%, and meropenem 0.3%. Ceftriaxone was the most common empirical antibiotic. In vitro–active antibiotics were not administered within 12 hours of presentation to 48 participants (53.9%) with ESBL-producing Enterobacteriaceae infection, including 17 (58.6%) with sepsis. Compared with other Enterobacteriaceae infections, ESBL infections were associated with longer time to in vitro–active treatment (17.3 versus 3.5 hours). Conclusion Among adults hospitalized for urinary tract infection in many US locations, ESBL-producing Enterobacteriaceae have emerged as a common cause of infection that is often not initially treated with an in vitro–active antibiotic.

Objectives Endoscopic mucosal improvement is the gold standard for assessing treatment efficacy in clinical trials of Crohn’s disease. Current endoscopic indices are not routinely used in clinical practice. The lack of endoscopic information in large clinical registries limits their use for research. A quick, easy, and accurate method is needed for assessing mucosal improvement for clinicians in real-world practice. We developed and tested a novel simplified endoscopic mucosal assessment for Crohn’s disease (SEMA-CD). Methods We developed a 5-point scale for ranking endoscopic severity of ileum and colon based on Simple Endoscopic Score for Crohn’s disease (SES-CD). Central readers were trained to perform SES-CD and SEMA-CD. Pediatric patients with Crohn’s disease undergoing colonoscopy were enrolled. Video recordings of colonoscopies were de-identified and randomly assigned to blinded central readers. The SES-CD and SEMA-CD were scored for each video. The SES-CD was considered the validated standard for comparison. Correlation was assessed with Spearman rho, inter- and intrarater reliability with kappa statistics. Results Fifty-seven colonoscopies were read a total of 212 times. Correlation between SEMA-CD and SES-CD was strong (rho = 0.98, P < 0.0001). Inter-rater reliability for SEMA-CD was 0.80, and intrarater reliability was 0.83. Central readers rated SEMA-CD as easier than SES-CD. Conclusion The SEMA-CD accurately and reproducibly correlates with the standard SES-CD. Central readers viewed SEMA-CD as easier than SES-CD. Use of SEMA-CD in practice should enable collecting mucosal improvement information in large populations of patients. This will improve the quality of research that can be conducted in clinical registries. External validation is needed.

The image quality limitations of echo-planar diffusion-weighted imaging (DWI) are an obstacle to its widespread adoption in the breast. Steady-state DWI is an alternative DWI method with more robust image quality but its contrast for imaging breast cancer is not well-understood. The aim of this study was to develop and evaluate diffusion-weighted double-echo steady-state imaging with a three-dimensional cones trajectory (DW-DESS-Cones) as an alternative to conventional DWI for non-contrast-enhanced MRI in the breast. This prospective study included 28 women undergoing clinically indicated breast MRI and six asymptomatic volunteers. In vivo studies were performed at 3 T and included DW-DESS-Cones, DW-DESS-Cartesian, DWI, and CE-MRI acquisitions. Phantom experiments (diffusion phantom, High Precision Devices) and simulations were performed to establish framework for contrast of DW-DESS-Cones in comparison to DWI in the breast. Motion artifacts of DW-DESS-Cones were measured with artifact-to-noise ratio in volunteers and patients. Lesion-to-fibroglandular tissue signal ratios were measured, lesions were categorized as hyperintense or hypointense, and an image quality observer study was performed in DW-DESS-Cones and DWI in patients. Effect of DW-DESS-Cones method on motion artifacts was tested by mixed-effects generalized linear model. Effect of DW-DESS-Cones on signal in phantom was tested by quadratic regression. Correlation was calculated between DW-DESS-Cones and DWI lesion-to-fibroglandular tissue signal ratios. Inter-observer agreement was assessed with Gwet’s AC. Simulations predicted hyperintensity of lesions with DW-DESS-Cones but at a 3% to 67% lower degree than with DWI. Motion artifacts were reduced with DW-DESS-Cones versus DW-DESS-Cartesian (p < 0.05). Lesion-to-fibroglandular tissue signal ratios were not correlated between DW-DESS-Cones and DWI (r = 0.25, p = 0.38). Concordant hyperintensity/hypointensity was observed between DW-DESS-Cones and DWI in 11/14 lesions. DW-DESS-Cones improved sharpness, distortion, and overall image quality versus DWI. DW-DESS-Cones may be able to eliminate motion artifacts in the breast allowing for investigation of higher degrees of steady-state diffusion weighting. Malignant breast lesions in DW-DESS-Cones demonstrated hyperintensity with respect to surrounding tissue without an injection of contrast. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 1.

Background Calorie labeling is mandated in restaurant chains with ≥20 locations nationwide, but the effect of labeling on the nutritional quality of purchased meals in fast-food settings is unclear, especially for adolescents and children. Objective To estimate the effect of calorie menu labeling on the nutrient content and composition of fast-food meal purchases in McDonald’s restaurants vs control restaurants. Design From 2010 to 2014, customers were sampled during repeated visits to McDonald’s restaurants, which voluntarily labeled menus with calorie information in 2012, and 5 control fast-food restaurant chains that had not labeled their menus over the study period. Participants/setting Restaurant receipts and questionnaires were collected from 2883 adults, 2131 adolescents, and 433 children in 4 New England cities. Main outcome measures Saturated fat, sugar, sodium, and fiber content of purchased meals, as well as nutrient densities (ie, nutrient content adjusted for total calories), were calculated after linking purchases to nutrition data from restaurant websites. Statistical analyses Difference-in-differences analyses and linear mixed models were used to examine whether calorie labeling in McDonald’s was associated with changes in nutrient content and nutrient density of purchased meals separately in adults, adolescents, and children. Results After implementation of calorie labeling at McDonald’s, adult meals contained on average 4.0% fewer calories from sugar (95% confidence interval: −7.5 to −0.5), but 1.8% more calories from saturated fat (95% confidence interval: 0.7 to 2.9) compared with control chains. The fiber content of children’s purchased meals was lower at McDonald’s after calorie labeling (change = −1.4 g, 95% confidence interval: −2.5 to −0.3). Calorie labeling was not associated with changes in nutrient quality of adolescent meals. Conclusions Calorie labeling at McDonald’s was associated with a possibly small positive change in the nutritional quality of meals in adults but not in adolescents or children. Efforts are needed to improve the nutritional quality of restaurant meals.

Background Polycystic ovary syndrome (PCOS) is challenging to diagnose. While the 2003 Rotterdam criteria are widely used for adults, the 2018 international PCOS guideline recommended updated Rotterdam criteria with both hyperandrogenism and oligo-anovulation for adolescents based on evidence-informed expert consensus. This study compared the prevalence of PCOS using updated and original Rotterdam criteria in community-based adolescents and explored long-term body mass index (BMI) trajectories across different diagnostic phenotypes. Methods Overall, 227 postmenarchal adolescent females from the prospective cohort Raine Study undertook comprehensive PCOS assessment at age 14–16 years. Detailed anthropometric measurements were collected from birth until age 22 years. Cross-sectional and longitudinal BMI were analyzed using t tests and generalized estimating equations. Results PCOS was diagnosed in 66 (29.1%) participants using original criteria versus 37 (16.3%) participants using updated Rotterdam criteria. Using updated criteria, participants with PCOS had higher BMI than participants without PCOS from prepubertal. Only the phenotype meeting the updated criteria was significantly associated with higher long-term BMI gain whereas other PCOS phenotypes had similar BMI trajectories to participants without PCOS (p Conclusions The use of the 2018 updated Rotterdam criteria reduces over-diagnosis of PCOS in adolescents and identifies those at the greatest risk of long-term weight gain, a key contributor to disease severity and long-term health implications. The BMI trajectories of females with PCOS on updated criteria diverge prepubertally compared to those without PCOS. This work supports targeting adolescents diagnosed with PCOS on the 2018 updated criteria for early lifestyle interventions to prevent long-term health complications.

Objective People of color and lower socioeconomic groups have higher obesity prevalence, lose less weight compared with Whites and higher socioeconomic groups, and are underrepresented in randomized controlled trials of mindfulness-based interventions. We examined whether mindfulness approaches reduce disparities in weight loss interventions. Methods We analyzed data from a randomized controlled trial of 194 participants with obesity (41% participants of color, 36% without college degree) comparing a 5.5-month mindfulness-based weight loss intervention to an active-control with identical diet-exercise guidelines. We assessed attendance, 18-month attrition, and weight change at 6, 12, and 18 months by race/ethnicity and education level using linear mixed models, adjusting for baseline body mass index, age, and education or race/ethnicity, respectively. Results Participants without versus with a college degree attended fewer sessions and had higher attrition across interventions. Participants of color attended fewer intervention sessions in the mindfulness compared with the control intervention. Overall, participants of color lost significantly less weight at 12 and 18 months compared with Whites. However, during the 6- to 18-month maintenance period, we found an interaction of intervention arm, race/ethnicity, and time (p = .035), indicating that participants of color compared with Whites regained more weight in the control (0.33 kg/mo; p = .005) but not mindfulness intervention (0.06 kg/mo; p = .62). Participants without a college degree had greater initial weight loss in the mindfulness compared to control intervention from 0 to 6 months (-0.46 kg/mo; p = .039). Conclusions Although disparities persist, mindfulness approaches may mitigate some racial/ethnic and socioeconomic differences in weight loss compared with conventional diet-exercise programs. Trial registration Clinicaltrials.gov registration: NCT00960414.

INTRODUCTION Inflammatory bowel disease (IBD) commonly presents during adolescence and may affect health care utilization. This study aimed to assess rates of health maintenance examinations (HMEs) in adolescents with IBD with their primary care physicians (PCPs). METHODS This is a single center, case-control study of adolescents with IBD who received their IBD care and primary care within the same healthcare system. Adolescents diagnosed with IBD between 13 and 17 years of age were matched 1:1 by age, gender, race/ethnicity, and insurance status to healthy controls. Patient demographics, IBD characteristics, and health outcomes were extracted from the medical record. HME rate was defined as having one HME with a PCP during a 12-month period. RESULTS This study included 150 IBD-control matched pairs. HME rates were similar at baseline between cases and controls (83% vs 85%, P = 0.53) but approached significance in year 1 post-diagnosis (77% vs 85%, P = 0.056). In year 2 post-diagnosis, IBD patients had less frequent HME (62% vs 74%, P = 0.0486). Disease severity did not affect HME rates. IBD patients from under-represented minority groups had lower rates than matched controls (46.2% vs 91.7%, P = 0.03). Meningococcal and human papilloma vaccination rates were lower in cases versus controls (79% vs 94%, P = 0.0005 and 60% vs 84%, P

BACKGROUND Diffusion-weighted imaging (DWI) has shown promise to screen for breast cancer without a contrast injection, but image distortion and low spatial resolution limit standard single-shot DWI. Multishot DWI methods address these limitations but introduce shot-to-shot phase variations requiring correction during reconstruction. PURPOSE To investigate the performance of two multishot DWI reconstruction methods, multiplexed sensitivity encoding (MUSE) and shot locally low-rank (shot-LLR), compared to single-shot DWI in the breast. STUDY TYPE Prospective. POPULATION A total of 45 women who consented to have multishot DWI added to a clinically indicated breast MRI. FIELD STRENGTH/SEQUENCES Single-shot DWI reconstructed by parallel imaging, multishot DWI with four or eight shots reconstructed by MUSE and shot-LLR, 3D T2 -weighted imaging, and contrast-enhanced MRI at 3T. ASSESSMENT Three blinded observers scored images for 1) general image quality (perceived signal-to-noise ratio [SNR], ghosting, distortion), 2) lesion features (discernment and morphology), and 3) perceived resolution. Apparent diffusion coefficient (ADC) of the lesion was also measured and compared between methods. STATISTICAL TESTS Image quality features and perceived resolution were assessed with a mixed-effects logistic regression. Agreement among observers was estimated with a Krippendorf's alpha using linear weighting. Lesion feature ratings were visualized using histograms, and correlation coefficients of lesion ADC between different methods were calculated. RESULTS MUSE and shot-LLR images were rated to have significantly better perceived resolution (P

MRI assessment of rectal cancer not only assesses tumor depth and surgical resectability but also extramural disease which affects prognosis. We have observed that nonnodal tumor nodules (tumor deposits; mrTDs) have a distinct MRI appearance compared to lymph node metastases (mrLNMs).We aimed to assess whether mrTDs and mrLNMs have different prognostic implications and compare these to other known prognostic markers.This was a retrospective cohort study of 233 patients undergoing resection for rectal cancer from January 2007 to October 2015. Data were obtained from electronic records and MRIs blindly rereported. Survival was determined using Kaplan-Meier method. Prognostic markers were evaluated using Cox regression and competing risks analysis. Inter-observer agreement for mrTD was measured using Cohen Kappa.On multivariable analysis, baseline mrTD/mrEMVI (extramural venous invasion) status was the only significant MRI factor for adverse survival [hazard ratio (HR) 2.36 (1.54-3.61] for overall survival, 2.37 (1.47-3.80) for disease-free survival (both P0.001), superseding T and N categories. mrLNMs were associated with good prognosis (HR 0.50 (0.31-0.80) P = 0.004 for overall survival, 0.60 (0.40-0.90) P = 0.014 for disease-free survival). On multivariable analysis, mrTDs/mrEMVI were strongly associated with distant recurrence (HR 6.53 (2.52-16.91) P ≤ 0.001) whereas T and N category were not. In a subgroup analysis of posttreatment MRIs in postchemoradiotherapy patients, mrTD/mrEMVI status was again the only significant prognostic factor; furthermore those who showed a good treatment response had a prognosis similar to patients who were negative at baseline. Inter-observer agreement for detection of mrTDs was k0.77 and k0.83.Current MRI staging predicting T and N status does not adequately predict prognosis. Positive mrTD/mrEMVI status has greater prognostic accuracy and would be superior in determining treatment and follow-up protocols. Chemoradiotherapy may be a highly effective treatment strategy in mrTD/mrEMVI positive patients.

The temporal pole (TP) is an associative cortical region required for complex cognitive functions such as social and emotional cognition. However, mapping the TP with functional magnetic resonance imaging is technically challenging and thus understanding its interaction with other key emotional circuitry, such as the amygdala, remains elusive. We exploited the unique advantages of stereo-electroencephalography (sEEG) to assess the responses of the TP and the amygdala during the perception of emotionally salient stimuli of pictures, music and movies. These stimuli consistently elicited high gamma responses (70–140 Hz) in both the TP and the amygdala, accompanied by functional connectivity in the low frequency range (2–12 Hz). Computational analyses suggested that the TP drove this effect in the theta frequency range, modulated by the emotional valence of the stimuli. Notably, cross-frequency analysis indicated the phase of theta oscillations in the TP modulated the amplitude of high gamma activity in the amygdala. These results were reproducible across three types of sensory inputs including naturalistic stimuli. Our results suggest that multimodal emotional stimuli induce a hierarchical influence of the TP over the amygdala.

Background Perforated epithelial appendiceal tumors are uncommon and can give rise to pseudomyxoma peritonei. Pseudomyxoma peritonei is rare, almost always of appendiceal origin, and presents in various ways relevant to abdominal surgeons. Objective The aim of this study was to report the mode of presentation of pseudomyxoma peritonei of appendiceal origin in patients treated in a high-volume UK peritoneal malignancy center. Design A retrospective observational study was conducted. Settings This was a single-center study. Patients Retrospective analysis of a prospective database of consecutive patients undergoing surgery between March 1994 and December 2016 was performed. Main outcome measures Mode of presentation was classified into 7 categories: "histological diagnosis at abdominal surgery for presumed appendicitis," "probable pseudomyxoma peritonei" based on abnormality on cross-sectional imaging (± image-guided biopsy)," "abnormal imaging (other cause suspected) and operative finding of pseudomyxoma peritonei," "diagnostic laparoscopy," "ovarian mass," "new-onset hernia," and "miscellaneous." Results Overall, 1070 patients underwent surgery (female 61%, male 39%); median age was 57. The mode of presentation was abnormality on cross-sectional imaging in 324 of 1070 patients (30.3%), histological diagnosis at emergency surgery for presumed appendicitis in 203 of 1070 patients (19%), and abnormal imaging with eventual pseudomyxoma peritonei diagnosis in 180 of 1070 patients (16.8%); 124 of 651 women (19.2%) presented with an ovarian mass. New-onset hernia was the presenting feature in 9.9%; 83 of 1070 patients (7.7%) were diagnosed at diagnostic laparoscopy, and 32 of 1070 patients (3%) were described as "miscellaneous." Overall, 775 of 1070 patients (72.4%) had complete cytoreductive surgery with 10-year survival of 63.5%. Limitations Results are limited by the retrospective nature of the study, radiological improvements over the study period, and the number of patients who had overlapping features at presentation. Conclusion Perforated appendiceal tumors present in various ways but predominantly at cross-sectional imaging or coincidentally at laparoscopy or laparotomy. All abdominal surgeons will occasionally encounter cases, often unexpectedly, and recognition and referral to a specialized unit results in excellent outcomes in most cases. See Video Abstract at http://links.lww.com/DCR/B256. MODO DE PRESENTACION EN 1070 PACIENTES CON TUMORES EPITELIALES APENDICULARES PERFORADOS, PREDOMINANTEMENTE CON PSEUDOMIXOMA PERITONEAL: Los tumores epiteliales apendiculares perforados son poco frecuentes y pueden dar lugar a Pseudomyxoma peritonei. El pseudomixoma peritoneal es raro, casi siempre de origen apendicular, y se presenta de diversas formas relevantes para los cirujanos abdominales.El objetivo fue informar el modo de presentacion del Pseudomixoma peritoneal de origen apendicular en pacientes tratados en un centro de malignidad peritoneal de alto volumen en el Reino Unido.Se realizo un estudio observacional retrospectivo.Este fue un estudio de centro unico.Analisis retrospectivo de una base de datos prospectiva de pacientes consecutivos sometidos a cirugia entre marzo de 1994 y diciembre de 2016.El modo de presentacion se clasifico en 7 categorias: "diagnostico histologico en la cirugia abdominal por presunta apendicitis", "probable Pseudomixoma peritoneal" basado en la anormalidad en la imagen de corte transversal (biopsia guiada por imagen +/-), "imagen anormal (se sospecha otra causa) y hallazgo quirurgico de Pseudomixoma peritoneal", "laparoscopia diagnostica", "masa ovarica", "hernia de reciente aparicion" y "varios".En total, 1070 pacientes fueron operados (mujeres 61%, hombres 39%); edad media 57. El modo de presentacion fue anormalidad en la imagen transversal en 324/1070 (30.3%), el diagnostico histologico en cirugia de emergencia por presunta apendicitis en 203/1070 (19%), la imagen anormal con eventual diagnostico de Pseudomixoma peritoneal en 180 / 1070 (16.8%), 124/651 (19.2%) las mujeres presentaron una masa ovarica. La hernia de reciente aparicion fue la caracteristica de presentacion en 9.9%, 83/1070 (7.7%) fueron diagnosticados por laparoscopia diagnostica y 32/1070 (3%) "miscelaneos". En general, 775/1070 (72,4%) se sometio a cirugia citorreductora completa con una supervivencia a 10 anos del 63,5%.Una deficiencia es que los resultados estan limitados por la naturaleza retrospectiva del estudio, las mejoras radiologicas a lo largo del periodo de estudio, y varios pacientes tenian caracteristicas superpuestas en la presentacion.Los tumores apendiculares perforados se presentan de varias maneras, pero predominantemente en imagenes transversales o casualmente en laparoscopia o laparotomia. Todos los cirujanos abdominales encontraran ocasionalmente con casos, a menudo inesperados, y el reconocimiento y la derivacion a una unidad especializada da lugar a excelentes resultados en la mayoria de los casos. Consulte Video Resumen en http://links.lww.com/DCR/B256.).

Objective Lifestyle is the first-line treatment for women with polycystic ovary syndrome (PCOS). This study examines the physical activity (PA) levels and sedentary behaviours of women with and without PCOS, and their alignment with the PCOS PA guideline. Methods This cross-sectional study on women (aged 22-27 years) in the Australian Longitudinal Study on Women's Health was conducted in 2019 using data collected in 2017. Self-reported PA levels and total daily sitting time (ST) of women with (n = 7051) and without (n = 796) self-reported PCOS were presented, stratified by body mass index (BMI) and a combined overweight/obese group. Results 71.0% and 56.7% of the entire study cohort achieved PA levels recommended for weight maintenance and weight loss, respectively. Overall, PA levels were lower and ST was higher in women with than without PCOS. In each BMI category, similar proportions of women with and without PCOS met the PA guidelines but became lower as BMI category increased. Fewer overweight/obese group women with than without PCOS aligned with recommendations for weight maintenance (58.7% vs 65.7%, P = .003) or weight loss (45.1% vs 50.3%, P = .032). ST ≥8 h/d was observed in two-thirds of women with and without self-reported PCOS similarly before and after stratifying by BMI. Conclusion High sedentary behaviour was extremely prevalent. Although the majority of women met PA recommendations for weight maintenance, only one in two overweight/obese women met PA recommendation for weight loss. Overweight/obese women with PCOS were more likely to participate in insufficient PA and require increased support to achieve sustainable healthy lifestyle.

Issue addressed Lifestyle modification plays a key role in weight management and chronic disease prevention in polycystic ovary syndrome (PCOS). Women with PCOS experience challenges in adopting and maintaining healthy lifestyle behaviours, which may be related to health literacy. The aims of this study were to explore the health literacy needs of women with PCOS in lifestyle and weight management to inform research and practice. Methods Ten women with PCOS participated in focus groups and semi-structured telephone interviews on lifestyle and weight management in PCOS. Results For functional health literacy, women with PCOS are highly motivated for lifestyle and weight management due to the long-term consequences of PCOS. For interactive health literacy, barriers included delayed diagnosis and poor communication. Women with PCOS were resourceful in accessing a wide range of weight management services but some experience barriers such as costs or the feelings of embarrassment associated with accessing relevant services. For critical health literacy, no facilitators and barriers could be identified for the domain of participation in making decisions for health. Conclusions Women with PCOS experience facilitators and barriers in functional and interactive health literacy in lifestyle and weight management. SO WHAT?: Future interventions should seek to further understand and address these gaps in health literacy by increasing weight management skills through behaviour change techniques, improving health professional-patient communication through tools such as question prompt lists, enhancing peer support by increasing distributed health literacy in PCOS support groups and by providing opportunities for co-design of interventions.

The US Department of Agriculture (USDA) Supplemental Nutrition Assistance Program (SNAP) is the cornerstone of the US nutrition safety net. Each month, SNAP provides assistance to 40 million low-income Americans—nearly half of them children. A number of changes could strengthen the public health impacts of SNAP. This review first presents a framework describing the mechanisms through which SNAP policy can influence public health, particularly by affecting the food security, the diet quality, and, subsequently, the health of SNAP participants. We then discusspolicy opportunities with the greatest potential to strengthen the public health impacts of SNAP, organized into three areas: ( a) food production and distribution, ( b) benefit allocation, and ( c) eligibility and enrollment. For each section, we describe current policy and limitations of the status quo, suggest evidence-based opportunities for policy change to improve public health, and identify important areas for future research.

Background Polycystic ovary syndrome (PCOS) is a prevalent women’s health condition with reproductive, metabolic, and psychological manifestations. Weight loss can improve these symptoms and is a key goal; however, many women find this difficult to achieve. Acupuncture is a Chinese medical treatment that involves insertion of very fine metal needles into specific areas of the body and has been shown to be efficacious for weight loss in non-PCOS populations. However, few studies have been conducted in women with PCOS. A variant of acupuncture, auricular electro-acupuncture (AEA), may have beneficial effects on sympathetic tone, which is associated with insulin resistance, obesity and PCOS. Methods This prospective three-arm open label parallel randomised controlled trial will assess feasibility and acceptability of acupuncture and/or AEA for weight loss in women with PCOS. We will enrol 39 women from the community aged between 18 and 45 years, with physician diagnosis of PCOS according to the Rotterdam criteria: body mass index (BMI) between 25 and 40 kg/m2. Women will be randomly allocated to receive one of three treatments for 12 weeks duration: body electro-acupuncture + lifestyle interventions, AEA + lifestyle interventions, or lifestyle interventions alone. The lifestyle intervention in this study is telephone-based health coaching (between 4 and 13 phone calls, depending on individual need), provided by the Get Healthy Service. Primary outcomes of the study are feasibility and acceptability of trial methods as determined by recruitment and retention rates, adherence, acceptability, credibility, and safety. Secondary outcomes include anthropometric (body weight, BMI, waist and hip circumference), metabolic (glucose tolerance and insulin sensitivity obtained from a 2-h 75 g oral glucose tolerance test with area under the curve insulin calculated using the trapezoid rule), reproductive (androgen levels, menstrual cyclicity, clinical hyperandrogenism using the Ferriman-Gallwey scoring system), autonomic (heart rate variability, blood pressure), lifestyle (physical activity levels, diet quality, weight self-efficacy), quality of life, and psychological (depression and anxiety symptoms, internal health locus of control). Discussion This study addresses the feasibility and acceptability of novel interventions to treat overweight/obesity in PCOS. Study findings have the potential to generate a new understanding of the role of acupuncture and auricular acupuncture in weight management. Trial registration Australian New Zealand Clinical Trial Registry, 8/6/18 ACTRN12618000975291

Purpose To perform a systematic review of the randomized controlled trials (RCTs) evaluating the efficacy of platelet-rich plasma (PRP) to augment anterior cruciate ligament (ACL) reconstruction. Methods Two independent reviewers screened the MEDLINE, The Cochrane Library, and EMBASE databases using Preferred Reporting for Systematic Reviews and Meta-Analyses guidelines for applicable RCTs evaluating the efficacy of PRP in ACL reconstruction. A meta-analysis was performed on the papers involving bone–patellar tendon–bone (BPTB) grafting. Results Thirteen RCTs fulfilled the inclusion criteria involving 765 patients. There was no clinical improvement (Tegner, Lysholm, Knee Injury and Osteoarthritis Outcome Score, or International Knee Documentation Committee scores) in any of the 7 studies evaluating PRP alongside the hamstring tendon autograft ACL reconstructions versus the control. Two studies evaluating PRP for hamstring tendon autograft demonstrated significantly improved magnetic resonance imaging findings. Two studies analyzed the use of PRP with allograft ACL reconstruction showed no clinical, biochemical, or radiologic improvements in postoperative follow-up. No functional improvements were found when PRP was used alongside BPTB in 4 studies. There was no significant difference in visual analog scale score in the BPTB group (1.1 vs 1.5, P = .18), or tibial filling defects (P = .30). Conclusions This study found that the current level I evidence does not support the use of PRP to improve graft healing, improve donor-site morbidity, reduce postoperative pain levels, or improve functional outcomes following ACL reconstruction. Level of Evidence Level I; systematic review of level I evidence

BACKGROUND Aneurysm recurrence after coiling has been associated with aneurysm growth, (re)hemorrhage, and a greater need for follow-up. The second-generation HydroCoil Embolic System (HES; MicroVention, Inc) consists of a platinum core with integrated hydrogel and was developed to reduce recurrence through enhancing packing density and healing within the aneurysm. OBJECTIVE To compare recurrence between the second-generation HES and bare platinum coil (BPC) in the new-generation Hydrogel Endovascular Aneurysm Treatment Trial (HEAT). METHODS HEAT is a randomized, controlled trial that enrolled subjects with ruptured or unruptured 3- to 14-mm intracranial aneurysms amenable to coiling. The primary endpoint was aneurysm recurrence using the Raymond-Roy scale. Secondary endpoints included minor and major recurrence, packing density, adverse events related to the procedure and/or device, mortality, initial complete occlusion, aneurysm retreatment, hemorrhage from target aneurysm during follow-up, aneurysm occlusion stability, and clinical outcome at final follow-up. RESULTS A total of 600 patients were randomized (HES, n = 297 and BPC, n = 303), including 28% with ruptured aneurysms. Recurrence occurred in 11 (4.4%) subjects in the HES arm and 44 (15.4%) subjects in the BPC arm (P = .002). While the initial occlusion rate was higher with BPC, the packing density and both major and minor recurrence rates were in favor of HES. Secondary endpoints including adverse events, retreatment, hemorrhage, mortality, and clinical outcome did not differ between arms. CONCLUSION Coiling of small-to-medium aneurysms with second-generation HES resulted in less recurrence when compared to BPC, without increased harm. These data further support the use of the second-generation HES for the embolization of intracranial aneurysms. VIDEO ABSTRACT

Background Women of childbearing age are vulnerable to weight gain. This scoping review examines the extent and range of research undertaken to evaluate behavioral interventions to support women of childbearing age to prevent and treat overweight and obesity. Methods Eight electronic databases were searched for randomized controlled trials (RCT) or systematic reviews of RCTs until 31st January 2018. Eligible studies included women of childbearing age (aged 15–44 years), evaluated interventions promoting behavior change related to diet or physical activity to achieve weight gain prevention, weight loss or maintenance and reported weight-related outcomes. Results Ninety studies met the inclusion criteria (87 RCTs, 3 systematic reviews). Included studies were published from 1998 to 2018. The studies primarily focused on preventing excessive gestational weight gain (n = 46 RCTs, n = 2 systematic reviews), preventing postpartum weight retention (n = 18 RCTs) or a combination of the two (n = 14 RCTs, n = 1 systematic review). The RCTs predominantly evaluated interventions that aimed to change both diet and physical activity behaviors (n = 84) and were delivered in-person (n = 85). Conclusions This scoping review identified an increasing volume of research over time undertaken to support women of childbearing age to prevent and treat overweight and obesity. It highlights, however, that little research is being undertaken to support the young adult female population unrelated to pregnancy or preconception.

Although no nebulized, dual mechanism, long-acting bronchodilator is currently marketed, with the approval of once-daily long-acting muscarinic antagonist (LAMA) revefenacinefenacin, it is theoretically possible to deliver a LAMA and long-acting beta2-agonist via standard jet nebulizer. The primary and secondary objectives of our study were to characterize the safety profile of revefenacin administered sequentially before or in combination with formoterol, via standard jet nebulizer in patients with moderate to very severe chronic obstructive pulmonary disease (COPD). In this randomized, double-blind, 42-day trial (NCT03573817), patients received revenacin 175 µg (n=63) or placebo (n=59), followed by formoterol 20 µg in the morning and formoterol alone in the evening formoterol 21 days via standard jet nebulizer (sequential administration). For another 21 days, revefenacin/placebo and formoterol, were administered as mixed solutions via single nebulization in the morning (combined administration), and formoterol alone in the evening. The adverse events’ (AEs) incidence was higher in the placebo + formoterol arms (11%–12%) than in the revefenacin + formoterol arms (5%–8%). The most common AEs were worsening/exacerbation of COPD, cough, and dizziness. There were no serious AEs or deaths reported in any arm. The least squares mean in trough forced expiratory volume in 1 second (FEV(1)) versus baseline was higher in the revefenacin + formoterol arms (116–157 mL) than in the placebo + formoterol arms (35–53 mL). Revefenacin had a safety profile similar to formoterol alone when delivered sequentially or combined. Trough FEV(1) was similar when revefenacin was delivered sequentially or combined with formoterol, with revefenacin providing an additional 81–104 mL improvements over formoterol alone.

Background Guidelines for physical activity and exercise during pregnancy recommend that all women without contraindications engage in regular physical activity to improve both their own health and the health of their baby. Many women are uncertain how to safely engage in physical activity and exercise during this life stage and are increasingly using mobile apps to access health-related information. However, the extent to which apps that provide physical activity and exercise advice align with current evidence-based pregnancy recommendations is unclear. Objective This study aims to conduct a systematic search and content analysis of apps that promote physical activity and exercise in pregnancy to examine the alignment of the content with current evidence-based recommendations; delivery, format, and features of physical activity and exercise instruction; and credentials of the app developers. Methods Systematic searches were conducted in the Australian App Store and Google Play Store in October 2020. Apps were identified using combinations of search terms relevant to pregnancy and exercise or physical activity and screened for inclusion (with a primary focus on physical activity and exercise during pregnancy, free to download or did not require immediate paid subscription, and an average user rating of ≥4 out of 5). Apps were then independently reviewed using an author-designed extraction tool. Results Overall, 27 apps were included in this review (Google Play Store: 16/27, 59%, and App Store: 11/27, 41%). Two-thirds of the apps provided some information relating to the frequency, intensity, time, and type principles of exercise; only 11% (3/27) provided this information in line with current evidence-based guidelines. Approximately one-third of the apps provided information about contraindications to exercise during pregnancy and referenced the supporting evidence. None of the apps actively engaged in screening for potential contraindications. Only 15% (4/27) of the apps collected information about the user’s current exercise behaviors, 11% (3/27) allowed users to personalize features relating to their exercise preferences, and a little more than one-third provided information about developer credentials. Conclusions Few exercise apps designed for pregnancy aligned with current evidence-based physical activity guidelines. None of the apps screened users for contraindications to physical activity and exercise during pregnancy, and most lacked appropriate personalization features to account for an individual’s characteristics. Few involved qualified experts during the development of the app. There is a need to improve the quality of apps that promote exercise in pregnancy to ensure that women are appropriately supported to engage in exercise and the potential risk of injury, complications, and adverse pregnancy outcomes for both mother and child is minimized. This could be done by providing expert guidance that aligns with current recommendations, introducing screening measures and features that enable personalization and tailoring to individual users, or by developing a recognized system for regulating apps.

Regenerative medicine is a promising new area of research that offers potential to treat diseased and injured tissue. In particular, the development of new biomaterial-based approaches shows promise for the treatment of challenging bone and cartilage injuries. Recent trends have focused on the development of biofunctional materials that have bioactive properties and are capable of supporting and promoting new tissue formation during the tissue repair process. This article discusses current biomaterial-based approaches for bone and cartilage repair and highlights emerging material functionalization methodologies including surface modification, growth factor delivery, cell-seeding strategies and gene therapy.

To assess psychological features in young women with and without PCOS.Observational, cross-sectional pilot study in young women aged 18-25 with (n = 24) or without (n = 22) PCOS (age: 22.41 +/- 0.39 vs. 21.95 +/- 0.47 years, p = 0.46; BMI: 29.17 +/- 1.54 vs. 22.05 +/- 0.83 kg/m(2), p = 0.0003). The main outcome measures were quality of life, anxiety, depression, risk perception and fears on future health.Women with PCOS demonstrated worsened quality of life (p = 0.033) and greater anxiety (p = 0.01) and depression (p = 0.023) than women without PCOS related to BMI status. Women with PCOS were more likely to perceive themselves as at risk of obesity (p = 0.012) and infertility (p0.0001), and perceived greater importance in reducing future risk of prediabetes (p = 0.027), gestational diabetes (p = 0.039), type 2 diabetes (p = 0.01), heart disease (p = 0.005), obesity (p = 0.0007) and infertility (p = 0.023) than women without PCOS. Women with PCOS were more likely to have fears about future health related to weight gain (p = 0.045), loss of femininity (p = 0.035), loss of sexuality (p = 0.003) and infertility (p = 0.019) than women without PCOS.Worsened quality of life, anxiety and depression in young women with PCOS is related to BMI. Risk perception is appropriately high in PCOS, yet perceived risks of future metabolic complications are less common than those related to weight gain and infertility.

Polycystic Ovary Syndrome (PCOS) is a complex condition with mechanisms likely to involve the interaction between genetics and lifestyle. Familial clustering of PCOS symptoms is well documented, providing evidence for a genetic contribution to the condition. This overview aims firstly to systematically summarise the current literature surrounding genetics and PCOS, and secondly, to assess the methodological quality of current systematic reviews and identify limitations. Four databases were searched to identify candidate gene systematic reviews, and quality was assessed with the AMSTAR tool. Genome-wide association studies (GWAS) were identified by a semi structured literature search. Of the candidate gene systematic reviews, 17 were of high to moderate quality and four were of low quality. A total of 19 gene loci have been associated with risk of PCOS in GWAS, and 11 of these have been replicated across two different ancestries. Gene loci were located in the neuroendocrine, metabolic, and reproductive pathways. Overall, the gene loci with the most robust findings were THADA, FSHR, INS-VNTR, and DENND1A, that now require validation. This overview also identified limitations of the current literature and important methodological considerations for future genetic studies. Much work remains to identify causal variants and functional relevance of genes associated with PCOS.

Background: Mechanisms previously described for traumatic shoulder injuries in rugby may not adequately describe all the mechanisms that result in shoulder dislocations. Purpose: To investigate the mechanism of shoulder dislocation events in professional rugby players through use of systematic video analysis. Study Design: Case series; Level of evidence, 4. Methods: In our series, 39 cases of shoulder dislocations from games played in top professional leagues and international matches across a 2-year period were available for video analysis. All cases were independently assessed by 2 analysts to identify the sequence of events occurring during shoulder dislocation. This included injury circumstance such as contact with another player or the ground, game scenario, injury timing, and the movements and force vectors involved in the dislocation mechanism. Results: We identified 4 distinct injury mechanisms. The previously described mechanisms “try scorer,”“tackler,” and “direct impact” were identified in 67% of cases. We describe a new injury mechanism occurring in the “poach position,” accounting for 18% of all shoulder dislocations studied. The remaining 15% could not be categorized. Shoulder dislocations occurred to a ball carrier in 15% of cases (n = 6) and a non–ball carrier in 85% of cases (n = 33). The injury most commonly occurred during a tackle (49%; n = 19) followed by ruck/maul (26%; n = 10). Time of injury showed that 36% (n = 14) of cases occurred in the last quarter of the game. Conclusion: Shoulder dislocations have now been shown to occur predominantly as a result of 1 of 4 distinct mechanisms, most frequently in the second half of the game. A new mechanism for shoulder dislocation has been described in this series, termed the poach position.

Purpose Long-term outcomes reveal equivalent biochemical outcomes with low-dose-rate (LDR) brachytherapy (BT) compared with radical prostatectomy and external-beam radiotherapy for the management of prostate cancer. Iodine-125, the most commonly used isotope, may be associated with long-term urinary consequences. Cesium-131 (131Cs) has a higher dose rate and shorter dose delivery time, predicting a shorter duration of urinary morbidity. We report our institution's high-volume experience and the most mature data to date on outcomes with 131Cs prostate BT. Methods and Materials 571 men (median age: 65.38 years) with low (55%)-, intermediate (36%)-, and high-risk disease (9%) received monobrachytherapy, dual-modality, or trimodality using 131Cs at a single institution. Risk groups were defined according to the National Comprehensive Cancer Network definition. Median prescription dose for definitive LDR-BT and LDR-BT boost was 115 Gy and 70 Gy, respectively. Median initial PSA was 6.1 ng/mL (IQR: 4.6–8.7). Results Median followup time was 5 years. 5/7-year overall survival for low-, intermediate-, and high-risk patients was 96.9%/96/9%, 92.8%/89.7%, and 95.8%/87.1%, respectively (p = 0.02). 5/7-year freedom from biochemical failure for low-, intermediate-, and high-risk patients was 98.5%/96.3%, 94.1%/86.4%, and 93.2%/74.5%, respectively (p Conclusions 131Cs is a viable alternative isotope for prostate brachytherapy for organ-confined disease. Long-term biochemical control and survival outcomes are excellent and on par with those attained with the use of 125I or 103Pd. This report therefore supports the continued use of 131Cs as an effective and comparable alternative isotope.