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Objective: The study aimed to prospectively evaluate a new molecular biomarker panel (KRAS, NRAS, BRAF, PIK3CA, and ERBB2) for palliative first-line treatment of colorectal cancer (CRC), including a multidisciplinary treatment approach. The rate of secondary metastasis resections was assessed. Patients and Methods: A total of 40 patients with definitively nonresectable metastatic CRC were enrolled from 10 centers before the interim analysis (June 2019) of the IVOPAK II trial (Interdisciplinary Care with Quality Control in Palliative Treatment of Colorectal Cancer). After determination of 5 molecular biomarkers in the tumor (KRAS, exons 2–4; NRAS, exons 2–4; BRAF V600E; PIK3CA; and ERBB2), patients in the IVOPAK II study received FOLFIRI plus cetuximab for all-RAS/quintuple-wildtype disease and FOLFIRI plus bevacizumab in the case of RAS mutations. The current article presents the early description of the clinical outcome of the interim analysis of IVOPAK II comparing the all-RAS/quintuple-wildtype and RAS-mutations populations, including a multidisciplinary-treated case report of a quintuple-wildtype patient. Results: The quintuple-wildtype population treated with FOLFIRI plus cetuximab in first-line exhibited a significantly higher response rate and enhanced early tumor shrinkage in the interim analysis than the RAS-mutations population, as well as a high rate of secondary metastatic resections. Conclusion: Initial results of this new biomarker panel (quintuple-wildtype) are promising for anti-EGFR therapy with cetuximab plus doublet chemotherapy (FOLFIRI) in first-line treatment of metastatic CRC. These results warrant confirmation with higher case numbers in the IVOPAK II trial.

AIMS Patient satisfaction is paramount to health-related quality of life (HR-QoL) outcomes. High quality, quantitative data from the US describing patients' actual experiences, difficulties, and HR-QoL while on an intermittent self-catheterization (ISC) regimen is very scarce. Our objective was to better understand patient practices with and attitudes towards ISC. METHODS This is a cross-sectional, multi-centered, clinical study of adult men and women performing ISC in the United States. Data collected included demographics, medical history, catheter characteristics, specific self-catheterization habits and two validated HR-QoL questionnaires: The Intermittent Self-Catheterization Questionnaire (ISC-Q) and the Intermittent Catheterization Difficulty Questionnaire (ICDQ). RESULTS Two hundred participants were recruited from six sites; 70.0% were male, 73.5% were Caucasian with a median age was 51.0 years (range 19-90 years). The ISC-Q showed that the vast majority of participants reported ease with ISC (82.0% satisfaction score) had confidence in their ability to perform ISC (91.9% satisfaction score); yet, many felt self-conscious about doing so (58.3% satisfaction score) and had concerns about long-term adverse effects (58.1% satisfaction score). The ICDQ indicated little to no difficulty for most participants with all routine ISC practices. A small minority of participants reported some difficulty with a "blocking sensation" during initiation of catheterization, leg spasticity, and painful catheterization. Multivariate linear regression results are also reported. DISCUSSION/CONCLUSION Participants are confident with ISC and have little overall difficulty, which may be a product of successful education and/or catheter design. urinary tract infections (UTIs) were common (yet variable) and may contribute to the noted long-term ISC concerns. Limitations exist including various selection biases leading to concerns of external validity. Future educational interventions in this population may further improve HR-QoL, optimize UTIs prevention, and diminish concerns with long-term ISC.

The 2020 update of the Canadian Stroke Best Practice Recommendations (CSBPR) for the Secondary Prevention of Stroke includes current evidence-based recommendations and expert opinions intended for use by clinicians across a broad range of settings. They provide guidance for the prevention of ischemic stroke recurrence through the identification and management of modifiable vascular risk factors. Recommendations address triage, diagnostic testing, lifestyle behaviors, vaping, hypertension, hyperlipidemia, diabetes, atrial fibrillation, other cardiac conditions, antiplatelet and anticoagulant therapies, and carotid and vertebral artery disease. This update of the previous 2017 guideline contains several new or revised recommendations. Recommendations regarding triage and initial assessment of acute transient ischemic attack (TIA) and minor stroke have been simplified, and selected aspects of the etiological stroke workup are revised. Updated treatment recommendations based on new evidence have been made for dual antiplatelet therapy for TIA and minor stroke; anticoagulant therapy for atrial fibrillation; embolic strokes of undetermined source; low-density lipoprotein lowering; hypertriglyceridemia; diabetes treatment; and patent foramen ovale management. A new section has been added to provide practical guidance regarding temporary interruption of antithrombotic therapy for surgical procedures. Cancer-associated ischemic stroke is addressed. A section on virtual care delivery of secondary stroke prevention services in included to highlight a shifting paradigm of care delivery made more urgent by the global pandemic. In addition, where appropriate, sex differences as they pertain to treatments have been addressed. The CSBPR include supporting materials such as implementation resources to facilitate the adoption of evidence into practice and performance measures to enable monitoring of uptake and effectiveness of recommendations.

The incidence of airway obstruction in patients with complex CHD other than vascular rings and absent pulmonary valve syndrome is unknown. We reviewed pre-operative CT and clinical data of children with conotruncal abnormalities to assess for airway obstruction. Airway obstruction was common (41% of patients), often moderate to severe, of diverse aetiology, and most commonly associated with a right aortic arch. Patients with airway obstruction showed a trend towards a higher mortality rate. Patients with complex conotruncal abnormalities should be assessed for airway obstruction as it may help predict the need for additional interventions and assist with prognostication.

The objective of the present study is two-fold. First, the elucidation of the biomechanics of penetrating trauma as a result of guardrail intruding into the occupant compartment. Second, the evaluation of the biomechanical efficacy of hybrid tension-compression guardrails to better protect occupants. The nine fatally guardrail penetrating crashes occurred between 2016 and 2019 were analyzed to study the mechanism of injuries. Four car-to-guardrail crash tests were conducted using a hybrid guardrail that integrated the commonly used W-beam with a new design of tension-based end terminal. The test included the impact of a bogey-type platform, small sedan vehicles, and a pick-up truck at highway speeds onto the guardrail. The impact orientation was varied to simulate the frontal and oblique corner crashes with a speed ranging from 90 to 111 kph. The real-world studies showed that the fatal injuries were due to impaling guardrail regardless of vehicular speed and size. The occupants not in the trajectory of the guardrail in the same vehicle sustained minor injuries despite experiencing a similar energy level. In these cases, the crash severity was survivable without the guardrail penetration. The mean pre-impact speed, change in speed, and vehicular acceleration was 117 kph, 20 kph, and 97 m/sec2, respectively. The hybrid guardrail system deflected the vehicle without any penetration into the occupant compartment. The mean peak accelerations in crash tests were below injurious threshold levels. The present research shows that the hybrid guardrail system not only eliminated the intrusion into occupant survival space but also deflected the vehicle.

Background Multiple guidelines regarding risk stratification for venous thromboembolism (VTE) incidence following cesarean delivery have been promulgated. Objective To estimate the percentage of cesarean delivery patients for which pharmacologic VTE would be recommended and subsequent incidence of VTE, based on several guidelines. Patients/methods This retrospective cohort study used data from the Nationwide Readmissions Database from October 2015 through December 2017. Diagnosis and procedure codes were used to identify patients undergoing cesarean delivery, incidence of VTE, and risk factors used to stratify risk in the existing guidelines. Time-to-event analysis was used to analyze data, stratified by risk categorization in 2011 American College of Gynecology and Obstetrics (ACOG), 2012 American College of Chest Physician (ACCP), 2015 Royal College of Obstetricians and Gynecologists (RCOG) and 2018 American Society for Hematology (ASH) guidelines. Results/conclusions In a cohort of 1,235,149 cesarean deliveries, VTE incidence was 2.1 per 1,000 deliveries at 330 days following delivery (95% confidence interval: 2.0 - 2.2). Proportions of patients that would be recommended for pharmacologic prophylaxis ranged from 0.2% in 2018 ASH guidelines to 73.4% in 2015 RCOG criteria. Among groups considered at elevated risk for VTE for which pharmacologic prophylaxis would be recommended, VTE incidence varied from 35.2 per 1,000 deliveries based on 2018 ASH criteria to 2.5 per 1,000 in 2015 RCOG criteria. In a large cohort of cesarean deliveries in the United States, application of different risk stratification guidelines identified widely different proportions at risk of VTE following delivery, with implications for being categorized as having elevated risk.

ZusammenfassungDargestellt wird die erfolgreiche Behandlung eines Patienten mit jahrelangem Asthma bronchiale, allergischer Rhinitis, Anaphylaxie und einem Grand-Mal-Anfall mit Mytilus edulis pearl (Miesmuschel). Dabei erfolgte die Mittelbestimmung durch die Empfindungsmethode von Dr. Divya Chhabra. Sowohl die Mittelfindung als auch die Leitsymptome des verordneten Arzneimittels werden erläutert. Durch die Behandlung von 2014 – 2020 konnte die Asthmamedikation reduziert, die Infekthäufigkeit und -schwere konnten erheblich gesenkt und Arbeitsunfähigkeitszeiten konnten vermieden werden. Durch die durchgehende pneumologische Kontrolle können der erfolgreiche Verlauf und die stabile pulmologische Situation gezeigt werden.

Hardcore cartels risk receiving both administrative fines from the cartel authority and civil law claims for damages. There is a legal policy discussion that cartelist should also face criminal law...

AIMS To describe the development and feasibility of a preference elicitation instrument, OABCare, using choice-based adaptive conjoint analysis (ACA) among patients with overactive bladder (OAB). METHODS This was a two-phase study. In Phase 1, an extensive literature review along with patient and provider focus groups yielded the attributes and levels for our OABCare instrument. The hierarchical Bayesian random-effects model generated utilities and mean relative importance scores of treatment attributes. Phase 2 consisted of a cohort study to assess the association between OAB treatment uptake and treatment attributes elicited from OABCare, using generalized linear models. RESULTS Literature review and provider and patient focus groups in Phase 1 yielded themes related to OAB management that were used to develop 11 attributes for the ACA instrument. For Phase 2 of the study, 108 patients were recruited who completed the OABCare instrument. Results showed that the top five attributes with the highest mean utility values were caregiver burden, impaired bladder function, social interaction constraints, treatment side effects, and use of pads. In addition, impaired bladder function (odds ratio [OR] = 1.25, 95% confidence interval [CI] = 1.1, 2.1), disturbed sleep (OR = 1.24, 95% CI = 1.04, 1.47), social interaction constraints (OR = 1.12, 95% CI = 1.05, 1.32), and out-of-pocket costs (OR = 0.79, 95 % CI = 0.61, 0.94) were associated with OAB treatment uptake. CONCLUSIONS Our ACA-based instrument, OABCare, is a feasible and acceptable tool for assessing preferences in OAB patients. Preference assessment can facilitate shared decision-making and may enhance the quality of OAB care. Future work will evaluate the OABCare instrument in different subgroups based on sociodemographic, clinical, and treatment characteristics, and its integration into clinical care settings.

Growing evidence has identified nocturia as a potential manifestation of several cardiovascular disease states. We aimed to determine whether a relationship exists between nocturia and global atherosclerotic cardiovascular disease (ASCVD) risk, defined by the American College of Cardiology/American Heart Association (ACC/AHA) ASCVD risk calculator, using a large nationally-representative study sample from the United States. We explored potential associations between nocturia and ASCVD risk in adults aged 40–79 years with no prior history of overt/known atherosclerotic disease from 7 consecutive cycles of the National Health and Nutrition Examination Survey. Subjects were classified by whether they met the ASCVD high-risk threshold following current ACC/AHA consensus guidelines (10-year major adverse cardiovascular event risk ≥ 20%). Logistic regression analyses were used to explore associations between nocturia (defined as ≥ 2 nocturnal voids) and ASCVD risk. The prevalence of nocturia and high ASCVD risk were 27.0% and 10.9%, respectively. Nocturia, older age, increased body mass index, and diuretic use were associated with high ASCVD risk on univariate logistic regression. After adjusting for age, body mass index, and diuretic use, nocturia remained associated with significantly greater odds of high ASCVD risk in females but not in males. Elicitation of nocturia on clinical history taking may serve to identify high cardiovascular risk in females. Future studies are needed to elucidate mechanisms underlying this association.

Aims Nocturia has been increasingly recognized as a potential manifestation of cardiovascular disease. However, the relationship between nocturia and electrocardiographic (ECG) abnormalities has not been studied. This study aims to characterize the diagnostic utility of nocturia in identifying left ventricular hypertrophy (LVH), left atrial enlargement (LAE), and prolonged QTc on ECG. Methods Retrospective analysis of nocturnal voiding frequency and contemporaneous ECG data from consecutive patients evaluated at a university-based outpatient cardiology clinic. Three sets of three incremental binary multiple logistic regression models controlling for (1) age, (2) sex and race, and (3) body mass index, hypertension, diabetes mellitus, and diuretic utilization were performed to determine whether nocturia was predictive of LVH, LAE, and prolonged QTc. Results Included patients (n = 143, 77.6% nocturia) were predominantly African-American (89.5%), female (74.1%), and obese (61.5%), of whom 44.1%, 41.3%, and 27.3% had LVH, LAE, and prolonged QTc, respectively. Older age, African-American race, obesity, hypertension, diuretic use, LVH, and LAE were significantly associated with nocturia on univariate analysis. No significant differences were observed in the strength of associations between nocturia and LVH, LAE, or QTc prolongation based on age. Nocturia independently predicted LVH in Models I-III (odds ratios [ORs], 2.99-3.20; relative risks [RRs], 1.18 for all, p ≤ .046) and LAE in Models I-III (ORs, 4.24-4.72; RRs, 1.21 for all, p ≤ .015). No significant associations were observed between nocturia and prolonged QTc. Conclusions Nocturia may be a risk marker for underlying structural cardiac abnormalities.

In the treatment of de-novo coronary small vessel disease, drug-coated balloons (DCBs) are non-inferior to drug-eluting stents (DESs) regarding clinical outcome up to 12 months, but data beyond 1 year is sparse. We aimed to test the long-term efficacy and safety of DCBs regarding clinical endpoints in an all-comer population undergoing percutaneous coronary intervention.In this prespecified long-term follow-up of a multicentre, randomised, open-label, non-inferiority trial, patients from 14 clinical sites in Germany, Switzerland, and Austria with de-novo lesions in coronary vessels3 mm and an indication for percutaneous coronary intervention were randomly assigned 1:1 to DCB or second-generation DES and followed over 3 years for major adverse cardiac events (ie, cardiac death, non-fatal myocardial infarction, and target-vessel revascularisation [TVR]), all-cause death, probable or definite stent thrombosis, and major bleeding (Bleeding Academic Research Consortium bleeding type 3-5). Analyses were performed on the full analysis set according to the modified intention-to-treat principle. Dual antiplatelet therapy was recommended for 1 month after DCB and 6 months after DES with stable symptoms, but 12 months with acute coronary syndromes. The study is registered with ClinicalTrials.gov, NCT01574534 and is ongoing.Between April 10, 2012, and Feb 1, 2017, of 883 patients assessed, 758 (86%) patients were randomly assigned to the DCB group (n=382) or the DES group (n=376). The Kaplan-Meier estimate of the rate of major adverse cardiac events was 15% in both the DCB and DES groups (hazard ratio [HR] 0·99, 95% CI 0·68-1·45; p=0·95). The two groups were also very similar concerning the single components of adverse cardiac events: cardiac death (Kaplan-Meier estimate 5% vs 4%, HR 1·29, 95% CI 0·63-2·66; p=0·49), non-fatal myocardial infarction (both Kaplan-Meier estimate 6%, HR 0·82, 95% CI 0·45-1·51; p=0·52), and TVR (both Kaplan-Meier estimate 9%, HR 0·95, 95% CI 0·58-1·56; p=0·83). Rates of all-cause death were very similar in DCB versus DES patients (both Kaplan-Meier estimate 8%, HR 1·05, 95% CI 0·62-1·77; p=0·87). Rates of probable or definite stent thrombosis (Kaplan-Meier estimate 1% vs 2%; HR 0·33, 95% CI 0·07-1·64; p=0·18) and major bleeding (Kaplan-Meier estimate 2% vs 4%, HR 0·43, 95% CI 0·17-1·13; p=0·088) were numerically lower in DCB versus DES, however without reaching significance.There is maintained efficacy and safety of DCB versus DES in the treatment of de-novo coronary small vessel disease up to 3 years.Swiss National Science Foundation, Basel Cardiovascular Research Foundation, and B Braun Medical.

PURPOSE: Aging increases oxidative stress, which can have delirious effects on smooth and striated muscle resulting in bladder dysfunction. Consequently, in women aged over 60 years-of-age, urinary incontinence (UI) is a prevalent health problem. Despite the prevalence and consequences, UI continues to be undertreated simply because there are few therapeutic options. METHODS: Here we investigated whether 8-aminoguanine (8-AG), a purine nucleoside phosphorylase (PNPase inhibitor), would restore urethra and external sphincter (EUS) muscle morphology in the aged rat. Aged (>25 months) female Fischer 344 rats were randomized to oral treatment with 8-AG (6 weeks) or placebo, and the urethra and EUS were evaluated by electron microscopy and protein expression (western immunoblotting). RESULTS: Aging was associated with mitochondrial degeneration in smooth and striated muscle cells as compared to young rats. We also observed a significant increase in biomarkers such as PARP, a downstream activator of oxidative/nitrosative stress. Treatment of aged rats with 8-AG normalized all abnormalities to that of a younger state. CONCLUSIONS: 8-AG, a potent inhibitor of PNPase, reverses age-related lower urinary tract morphological and biochemical changes. Our observations support the concept that 8-AG will reverse age-induced lower urinary tract disorders such as UI. These initial findings could have therapeutic implications for the prevention and treatment of age-related UI.

POINTS CLES En 2016, au Canada (a l’exclusion du Quebec), 270 204 personnes ont ete admises a l’hopital pour un trouble cardiaque, un accident vasculaire cerebral (AVC) ou un deficit cognitif d’origine vasculaire; de ce nombre, 107 391 etaient des femmes, 162 813 etaient des hommes

Background Patients with nocturnal polyuria (NP) experience a unique surge in nocturnal diuresis rate during the early hours of sleep. Objective To determine the diagnostic utility of the volume and osmolality of a single early nocturnal urine sample in detecting NP. Design, setting, and participants Analysis of 1 am urine samples obtained from two prospective observational studies at Ghent University Hospital involving participants recruited from a urology ambulatory care unit and those who consulted a continence clinic. Nocturic participants (one or more nocturnal void[s]; n = 176) were stratified based on the presence (n = 87) or absence (n = 89) of NP (>90 ml/h). Outcome measurements and statistical analysis Receiver operating characteristic curves with Youden’s Index were used to determine cutoff values for urine volume and urine osmolality (Uosm). Results and limitations Individuals with NP demonstrated higher 1 am volume (400 [interquartile range 300–515] vs 210 [160–300] ml, area under the curve [AUC] = 0.843, p am volume ≥350 ml or Uosm ≤314 mOsm/kg H2O were 85% sensitive and 75% specific for NP, while criteria of both 1 am volume ≥350 ml and Uosm ≤314 mOsm/kg H2O were 60% sensitive and 92% specific for NP. Comparable AUC values, sensitivities, and specificities were observed in both men and women. Limitations include post hoc design and a relatively small study sample. Conclusions Individuals with NP are more likely than those without NP to produce a higher volume of more dilute urine (ie, “aquaresis”) in the early hours of sleep. Analysis of easily measurable parameters of the first nocturnal void (for which 1 am values serve as a surrogate) in men and women with nocturia can predict a diagnosis of NP with a reasonably high degree of sensitivity and specificity. Patient summary Urologists often try to understand the specific reason why people wake up to urinate at night by asking them to record the amount of urine they make every time they go to the bathroom (also known as a “voiding diary”) during the nighttime as well as the daytime—typically for a total of 1–3 days. In this study, we showed that an analysis of the composition of the urine that people produce when they first wake up to urinate at night might be sufficient to determine whether their symptoms are caused by excessive urine production or something else, and some people might find this urine study easier than keeping a voiding diary.

The proposal "Can we harness the placebo effect to improve care in lower urinary tract dysfunction?" was discussed at the International Consultation on Incontinence-Research Society (ICI-RS) 2019 meeting. The placebo effect can change the treatment outcome whether the treatment is an active treatment or placebo. The total active treatment outcome is a combination of the placebo and the active treatment effect which is seen in placebo-controlled trials. The placebo effect plays an important role in the treatment of lower urinary tract dysfunction in overactive bladder, bladder pain syndrome, and stress urinary incontinence. In clinical practice, a number of factors can be employed to use the placebo effect to maximize its effect on patients receiving an active treatment, such as having the same environment for review such as the same appointment time, same room, and same clinician. Clinicians should also be aware of the nocebo effect which is increased with an overemphasis on side effects or negative outcomes.

KEY POINTS In 2016, 270 204 people in Canada (excluding Quebec) were admitted to hospital for heart conditions, stroke and vascular cognitive impairment, including 107 391 women and 162 813 men, of whom 91 524 died.[1][1] This equates to 1 out of every 3 deaths in Canada and outpaces other diseases

Aim Compare the circadian trajectory of diuresis between nocturnal polyuria (NP) patients with versus without identifiable contributory comorbidities. Methods Retrospective analysis of frequency-volume charts from male patients with clinically-significant nocturia (>= 2 nocturnal voids) and NP (defined by nocturnal urine production [NUP] >= 90 mL/hour or nocturnal polyuria index [NPi] >= 0.33). Patients with NP and chronic kidney disease, congestive heart failure, and/or undertreated obstructive sleep apnea (OSA) were deemed to have secondary NP. Nocturnal polyuria syndrome (NPS) was defined as NP without edema, loop diuretic use, or the aforementioned conditions. Patients with diabetes insipidus or OSA with appropriate continuous positive airway pressure utilization were excluded. The timing and volumes of nocturnal voids were used to derive "early" and "late" nocturnal diuresis rates (mL/hour of urine produced before and after the first nocturnal awakening, respectively). The likelihood of an early peak nocturnal diuresis rate (ie, early >late nocturnal diuresis rate) was compared between patients with NPS versus secondary NP using both a crude and adjusted odds ratio. Results The likelihood of an early peak nocturnal diuresis rate in patients with NPS compared with secondary NP was 2.58 (1.05-6.31) at NUP >= 90 mL/hour and 1.96 (0.87-4.42) at NPi >= 0.33 on crude analysis, and 2.44 (0.96-6.24) and 1.93 (0.83-4.48) after adjustment, respectively. Conclusions A peak early nocturnal diuresis rate was significantly more likely in patients with NPS at NUP >= 90 mL/hour, with similar odds ratios at NPi >= 0.33 and following adjustment. Delineating nocturic patients by NP subgroup may facilitate more individualized management. Patient Summary Many people have to wake up to urinate because they produce too much urine at night-a condition known as "nocturnal polyuria." Nocturnal polyuria might be caused by drinking too much fluid, other behavioral factors, or conditions that make your body hold on to too much fluid, like heart disease, kidney disease, and sleep apnea. In cases of nocturnal polyuria where no clear cause can be identified, it is thought that patients may suffer from a deficiency in nighttime vasopressin, a hormone that plays a key role in how much urine you produce. In this study, we compared the pattern of nighttime urine production in patients with different causes of nocturnal polyuria, which may lead to more personalized treatment options for patients with this condition.

Background Radial (RA) instead of femoral access (FA) for coronary interventions has become a European Society of Cardiology Class-IA guideline recommendation. But when the decision on the access site is left to the discretion of the operator, differences in adverse event rates mitigate. Methods We compared the 30-day outcome for RA and FA in all patients recruited for the observational German Austrian ABSORB Registry (GABI-R) in regard to all-cause mortality, stroke, myocardial infarction (MI), TIMI major bleedings (TMB) and quality of life (QoL). All patients were treated with a bioresorbable vascular scaffold. Access site was left to the discretion of the operator. Results In total, 3137 patients included by 92 centers received percutaneous coronary interventions (PCI) for acute MI in 51.5% and non-acute settings in 48.5%. RA was performed in 47.8% and had a higher median radiation exposure (3896 vs. 3082 cGycm2, p Conclusions In this contemporary GABI-R cohort, in which access site was left to the discretion of the operator, both access routes were safe and equal concerning QoL ( ClinicalTrials.gov ; NCT02066623 ).

Glucocorticoid (GC)-induced osteoporosis and subsequent bone fragility are preceded by death and dysfunction at the cellular level. In particular, short-term glucocorticoid excess suppresses osteocyte remodeling of the surrounding bone mineral, causes apoptosis of osteoblasts and osteocytes, and disrupts homeostatic bone remodeling. Preventing apoptosis and preserving osteocyte morphology and function could be effective means of preventing bone loss during glucocorticoid excess. We hypothesized that osteocrin, which preserves osteocyte viability and morphology in other models where osteocyte defects exist, could prevent osteocyte death and dysfunction in a GC excess model. We used a liver-targeted adeno-associated virus (AAV8) to induce osteocrin overexpression in mice one week prior to implantation with prednisolone or placebo pellets. After 28 days, tissues were collected for micro-CT and histological analysis. GC excess caused the expected reduction in cortical bone thickness and osteocyte canalicular length in control AAV8-treated mice, and these effects were blunted in mice overexpressing osteocrin. However, GC-induced changes in cortical porosity, trabecular bone mass, and gene expression were not prevented by osteocrin. While the mechanism of osteocrin’s effects on osteocyte morphology warrants further investigation, this study does not support a role for this model of osteocrin supplementation to combat the full skeletal effects of GC excess.

To determine the cut-off value for the 75-g glucose challenge test administered in early pregnancy to screen for gestational diabetes mellitus and abnormal carbohydrate metabolism in pregnancy.A prospective study involving 1500 antenatal patients attending a community hospital. Patients were screened with the 75-g 1-h glucose challenge test in early pregnancy and subsequently tested with the 75-g 2-h glucose tolerance test to diagnose gestational diabetes mellitus. Statistical methods were employed to determine the optimal plasma glucose cut-off value for a positive result in early pregnancy.A glucose challenge test value of 6.0 mmol/L (108 mg/dl) or more was selected as the preferred cut-off level for further testing with a sensitivity of 83.5% (95% confidence interval [CI] 77.0%-88.9%) and specificity of 49.2% (95% CI 46.5%-52.0%).An early pregnancy glucose challenge test reading of 6.0 mmol/L (108 mg/dl) or more is effective in screening for gestational diabetes mellitus; a value of 10.0 mmol/L (180 mg/dl) or more is effective for finding pre-pregnancy abnormalities of carbohydrate metabolism. The false-positive glucose challenge test diagnoses gestational hyperglycemia, the treatment of which will improve perinatal outcome. Further testing based on risk factors will exclude a false-negative glucose challenge test. A combination of universal early pregnancy screening and selective risk-factor testing is recommended to detect the full range of abnormalities of carbohydrate metabolism encountered in pregnancy.

Background: Opening schools and keeping children safe from SARS-CoV-2 infections at the same time is urgently needed to protect children from direct and indirect consequences of the COVID-19 pandemic. To achieve this goal, a safe, efficient, and cost-effective SARS-CoV-2 testing system for schools in addition to standard hygiene measures is necessary.Methods: We implemented the screening WICOVIR concept for schools in the southeast of Germany, which is based on gargling at home, pooling of samples in schools, and assessment of SARS-CoV-2 by pool rRT-PCR, performed decentralized in numerous participating laboratories. Depooling was performed if pools were positive, and results were transmitted with software specifically developed for the project within a day. Here, we report the results after the first 13 weeks in the project.Findings: We developed and implemented the proof-of-concept test system within a pilot phase of 7 weeks based on almost 17,000 participants. After 6 weeks in the main phase of the project, we performed >100,000 tests in total, analyzed in 7,896 pools, identifying 19 cases in >100 participating schools. On average, positive children showed an individual CT value of 31 when identified in the pools. Up to 30 samples were pooled (mean 13) in general, based on school classes and attached school staff. All three participating laboratories detected positive samples reliably with their previously established rRT-PCR standard protocols. When self-administered antigen tests were performed concomitantly in positive cases, only one of these eight tests was positive, and when antigen tests performed after positive pool rRT-PCR results were already known were included, 3 out of 11 truly positive tests were also identified by antigen testing. After 3 weeks of repetitive WICOVIR testing twice weekly, the detection rate of positive children in that cohort decreased significantly from 0.042 to 0.012 (p = 0.008).Interpretation: Repeated gargle pool rRT-PCR testing can be implemented quickly in schools. It is an effective, valid, and well-received test system for schools, superior to antigen tests in sensitivity, acceptance, and costs.

Objective Pyelonephritis is the most common nonobstetric cause for hospitalization during pregnancy. The maternal and obstetric complications associated with antepartum pyelonephritis are well described. However, it is not clear whether these risks extend into the postpartum period. The primary objective of this study was to describe the morbidity associated with postpartum pyelonephritis, by comparing the morbidity associated with pyelonephritis in the postpartum period to morbidity seen during pregnancy or delivery. Methods A retrospective cohort study was performed using the Nationwide Readmissions Database (NRD), an all-payor sample of discharges from approximately 60% of U.S. hospitalizations. Discharges between October 2015 and December 2018 were included. Maternity-associated hospitalizations, diagnosis of pyelonephritis, comorbid conditions, and incidence of severe maternal morbidity were identified using International Classification of Disease-10th Revision (ICD-10) diagnosis and procedure codes. Bivariate statistics, weighted to account for the complex survey methods in the NRD, were used to evaluate the association between antepartum, delivery, and postpartum hospital stays associated with pyelonephritis and maternal morbidity. Weighted regression models were used to evaluate the association between admission timing and maternal outcomes. Results A total of 32,850 pyelonephritis admissions were identified, corresponding to a national estimate of 61,837 admissions. Of these, 1,465 (2.4%) were postpartum, 55,056 (89.0%) were antepartum, and 5,317 (8.6%) involved a delivery stay. Rates of severe maternal morbidity were higher in the postpartum group than the antepartum or delivery hospitalization groups (59.5 vs. 12.9 and 15.8%, respectively, p Conclusion Though relatively uncommon, postpartum hospitalizations for pyelonephritis are associated with higher rates of severe maternal morbidity, driven by differential rates of sepsis, than are antepartum or delivery-associated hospitalizations.

Since identified in December 2019, COVID-19 has remained a pandemic across the globe. Although primarily a respiratory illness, the impact of COVID-19 on other end organs has been increasingly identified. The effect of COVID-19 on the liver has yet to be completely understood. We describe a case of COVID-19 leading to end-stage cholangiopathy and deceased donor liver transplantation (LT). A 64-year-old man with no underlying respiratory or liver disease presented with acute respiratory distress secondary to COVID-19 pneumonia requiring intubation. Several months after resolution of his respiratory symptoms, he developed transaminitis, worsening jaundice, abdominal pain and dark-coloured urine. Hepatic function remained severely impaired warranting LT 259 days following his initial COVID-19 diagnosis. Explant pathology demonstrated diffuse hepatic injury, onion skinning of the bile ducts and bile duct loss in scattered portal tracts. As more patients develop COVID-19-related complications, we suggest LT as an option for COVID-19-related end-stage liver disease.

Blinding mitigates several sources of bias which, if left unchecked, can quantitively affect study outcomes. Blinding remains under-utilized, particularly in non-pharmaceutical clinical trials, but is often highly feasible through simple measures. Although blinding is generally viewed as an effective method by which to eliminate bias, blinding does also pose some inherent limitations, and it behooves clinicians and researchers to be aware of such caveats. This article will review general principles for blinding in clinical trials, including examples of useful blinding techniques for both pharmaceutical and non-pharmaceutical trials, while also highlighting the limitations and potential consequences of blinding. Appropriate reporting on blinding in trial protocols and manuscripts, as well as future directions for blinding research, will also be discussed.

Background Coronavirus disease 2019 (COVID-19) continues to stress the health care system. Neutralizing monoclonal antibodies (mAbs) were effective in reducing COVID-19–related hospitalizations and emergency department (ED) visits in their respective clinical trials. However, these results have yet to be reproduced in a practical setting following implementation of current US Food and Drug Administration (FDA) guidance. Methods This retrospective cohort study included outpatients with confirmed COVID-19 infection, who had mild/moderate symptoms for 10 days or less, and who were deemed high-risk for severe COVID-19 under FDA’s Emergency Use Authorization for mAbs. Patients who received either bamlanivimab or casirivimab/imdevimab from 18 November 2020 through 5 January 2021 were included (n = 200). This was compared against a control cohort of randomly selected high-risk COVID-19 outpatients who declined or were not referred for mAb treatment during the same period (n = 200). The primary outcome was a composite of 29-day COVID-19–related hospitalizations and/or ED visits. Prespecified secondary outcomes included the individual components of the primary endpoint, 29-day all-cause mortality, and serious adverse drug events. Results Patients treated with mAbs were significantly less likely to be hospitalized or visit the ED compared with patients not treated with mAb (13.5% vs 40.5%; odds ratio, 0.23 [95% confidence interval, .14–.38]; P Conclusions Among high-risk COVID-19 outpatients with mild/moderate symptoms, early administration of mAbs can potentially reduce the strain on the health care system during the current pandemic.

Aims Multiple sclerosis (MS) is characterized by demyelinated white matter plaque throughout the central nervous system. Plaque involvement in regions that regulate micturition may be associated with urinary symptom severity in patients with MS. The aim of this prospective study is to investigate the relationship between cerebral plaque volume (PV), location, and urinary symptoms in women with MS. Methods We conducted a case-control pilot study of women with MS undergoing routine yearly brain MRI. Women were administered the American Urologic Association-Symptom Index (AUA-SI) and divided into two groups: severe urinary symptoms (AUA-SI ≥20) and mild symptoms (AUA-SI ≤7). PV and location in the brain were determined using a validated automated white matter lesion segmentation algorithm. Results This study of 36 women found that the median total PV did not differ between groups. Women with severe urinary symptoms had larger median PV in the left frontal lobe (LFL) and right limbic lobe (RLL) compared with women with mild urinary symptoms. Within the RLL, women with severe symptoms had a larger median PV in the right cingulate gyrus (RCG). There was a moderate correlation between LFL lesion volume and RLL lesion volume with the AUA emptying subscore; however, these regions did not correlate with the storage subscore. Conclusions This preliminary study found urinary symptom severity in women with MS is associated with PV in the RCG and LFL, and not total cerebral PV. These findings may explain why disease burden alone is not a predictor of severity or type of voiding dysfunction in patients with MS.

Aims: The Stent for Life initiative aims at the reduction of mortality in patients with ST-elevation myocardial infarction by enhancing timely access to primary percutaneous coronary intervention. To assess the associated health and socioeconomic impact, the Stent for Life economic project was launched and applied to four model regions: Romania, Portugal, the Basque Country in Spain, and the Kemerovo region in the Russian Federation. Methods and results: The Stent for Life economic model is based on a decision tree that incorporates primary percutaneous coronary intervention rates and mortality. Healthcare costs and indirect costs caused by loss of productivity were estimated. A baseline scenario simulating the status quo was compared to the Stent for Life scenario which integrated changes initiated by the Stent for Life programme. In the four model regions, primary percutaneous coronary intervention numbers rose substantially between 29–303%, while ST-elevation myocardial infarction mortality was reduced between 3–10%. Healthcare costs increased by 8% to 70%. Indirect cost savings ranged from 2–7%. Net societal costs were reduced in all model regions by 2–4%. Conclusion: The joint effort of the Stent for Life initiative and their local partners successfully saves lives. Moreover, the increase in healthcare costs was outweighed by indirect cost savings, leading to a net cost reduction in all four model regions. These findings demonstrate that systematic investments to improve the access of ST-elevation myocardial infarction patients to guideline-coherent therapy is beneficial, not only for the individual, but also for the society at large.

PURPOSE To study the effectiveness of the Patient Preferences for Prostate Cancer Care (PreProCare) intervention in improving the primary outcome of satisfaction with care and secondary outcomes of satisfaction with decision, decision regret, and treatment choice among patients with localized prostate cancer. METHODS In this multicenter randomized controlled study, we randomly assigned patients with localized prostate cancer to the PreProCare intervention or usual care. Outcomes were satisfaction with care, satisfaction with decision, decision regret, and treatment choice. Assessments were performed at baseline and at 3, 6, 12, and 24 months, and were analyzed using repeated measures. We compared treatment choice across intervention groups by prostate cancer risk categories. RESULTS Between January 2014 and March 2015, 743 patients with localized prostate cancer were recruited and randomly assigned to receive PreProCare (n = 372) or usual care (n = 371). For the general satisfaction subscale, improvement at 24 months from baseline was significantly different between groups ( P < .001). For the intervention group, mean scores at 24 months improved by 0.44 (SE, 0.06; P < .001) from baseline. This improvement was 0.5 standard deviation, which was clinically significant. The proportion reporting satisfaction with decision and no regret increased over time and was higher for the intervention group, compared with the usual care group at 24 months ( P < .05). Among low-risk patients, a higher proportion of the intervention group was receiving active surveillance, compared with the usual care group ( P < .001). CONCLUSION Our patient-centered PreProCare intervention improved satisfaction with care, satisfaction with decision, reduced regrets, and aligned treatment choice with risk category. The majority of our participants had a high income, with implications for generalizability. Additional studies can evaluate the effectiveness of PreProCare as a mechanism for improving clinical and patient-reported outcomes in different settings.

INTRODUCTION: The terminology for nocturia and nocturnal lower urinary tract function is reviewed and updated in a clinically and practically-based consensus report.METHODS: This report has been created by a Working Group under the auspices and guidelines of the International Continence Society (ICS) Standardisation Steering Committee (SSC). All relevant definitions were updated on the basis of research over the last 16 years since the publication of the first nocturia standardization document in 2002. An extensive process of 16 rounds of internal and external reviews was involved to examine each definition exhaustively, with decision-making by collective opinion (consensus).RESULTS: A clinically-based terminology report for nocturia and nocturnal lower urinary tract function, encompassing five key definitions divided into signs and symptoms has been developed. Clarity and user-friendliness have been key aims to make it interpretable by healthcare professionals and allied healthcare practitioners involved in the care of individuals with nocturnal lower urinary tract function.CONCLUSION: A consensus-based terminology report for nocturia and nocturnal lower urinary tract function has been produced to aid clinical practice and research.

Myiasis is defined as an infestation of the organs or tissues of live vertebrates (humans or animals) by dipterous larvae, commonly referred to as maggots. Wound myiasis is a common presentation in the emergency department. The presence of wild maggots and larvae in wounds is concerning for subsequent myiasis-induced infections and complications. Proper extraction of wild maggots and larvae is required to avoid complications that may occur with wound myiasis. Surgical debridement is often utilized to extract wild maggots and larvae, but can be painful and time-consuming. There is limited literature available on alternative approaches for removal of wild maggots and larvae. We present a case of lower extremity wound myiasis that had wild maggots and larvae successfully removed with no complications using ether. This procedure is a novel, noninvasive, and pain-free way to extract wild maggots and larvae from wound myiasis.

In 2010, we published our stroke prevention clinic's performance as compared to Canadian stroke prevention guidelines. We now compare our clinic's adherence with guidelines to our previous results, following the implementation of an electronic documentation form.All new patients referred to our clinic (McGill University Health Center) for recent transient ischemic attack (TIA) or ischemic stroke between 2014 and 2017 were included. We compared adherence to guidelines to our previous report (N=408 patients for period 2008-2010) regarding vascular risk management and treatment.Three hundred and ninety-two patients were included, of which 36% had a TIA and 64% had an ischemic stroke, with a mean age of 70 years and 43% female. Although the more recent cohort has shown a higher proportion of cardioembolic stroke compared to previous (19.1% vs. 14.7%) following new guidelines regarding prolonged cardiac monitoring, increased popularity in CT angiography has not translated into greater proportion of large-artery stroke subtype (26.3% vs. 26.2%). Blood pressure (BP) targets were achieved in 83% compared with 70% in our previous report (plt;0.01). Attainment of low-density lipoprotein cholesterol target was also improved in our recent study (66% vs. 46%, plt;0.01). No significant difference was found in the consistency of antithrombotic use (97.7% vs. 99.8%, p=0.08). However, there was a decline in smoking cessation (35% vs. 73%, p=0.02). Overall, optimal therapy status was better attained in the present cohort compared to the previous one (52% vs. 22%, plt;0.01). The male sex was associated with better attainment of optimal therapy status (odds ratio, 1.61; 95% confidence interval, 1.04-2.51). The number of follow-up visits and the length of follow-up were not associated with attainment of stroke prevention targets.Our study shows improvement in attainment of therapeutic goals as recommended by Canadian stroke prevention guidelines, possibly attributed in part to the implementation of electronic medical recording in our clinic. Areas for improvement include smoking cessation counseling and diabetes screening.En 2010, nous avons rendu publics les résultats de notre clinique de prévention des AVC en ce qui regarde les lignes directrices canadiennes de prévention des AVC. Suite à la mise en place d’un formulaire d’information électronique, nous voulons maintenant comparer l’adhésion actuelle de notre clinique à ces lignes directrices à celle mesurée en 2010.Tous les nouveaux patients adressés à notre clinique (Centre universitaire de santé McGill) pour des cas récents d’ischémie cérébrale transitoire (ICT) ou d’AVC ischémique survenus entre 2014 et 2017 ont été inclus dans cette étude. Nous avons ainsi comparé l’adhésion actuelle aux lignes directrices évoquées ci-haut à celle du précédent rapport (N = 408 patients pour la période allant de 2008 à 2010), et ce, en ce qui concerne la prise en charge du risque vasculaire et les traitements nécessaires.Au total, 392 patients ont été inclus; de ce nombre, 36 % d’entre eux avaient été victimes d’ICT tandis que 64 % avaient été victimes d’un AVC ischémique. Leur âge moyen était de 70 ans et 43 % d’entre eux étaient de sexe féminin. Bien que la cohorte la plus récente, à la suite de l’introduction de nouvelles lignes directrices portant sur la surveillance cardiaque prolongée, ait donné à voir une proportion plus élevée d’AVC d’origine cardio-embolique comparativement à la précédente (19,1 % par opposition à 14,7 %), la popularité croissante de l’angiographie par tomodensitométrie ne s’est pas traduite par une proportion plus grande de sous-types d’AVC affectant de grandes artères (26,3 % de 2014 à 2017 par opposition à 26,2 % de 2008 à 2010). Les valeurs cibles fixées en matière de pression artérielle ont été atteintes dans 83 % des cas comparativement à 70 % des cas dans notre rapport précédent (p0,01). L’atteinte de la valeur cible en ce qui concerne le taux de LDL-cholestérol (lipoprotéines de faible intensité) a également été améliorée dans notre plus récent rapport (66 % par opposition à 46 %; p0,01). Ajoutons aussi qu’aucune différence notable n’a été observée quant à une utilisation constante d’anti-thrombotiques (97,7 % par opposition à 99,8 %; p = 0,08). Fait à souligner, un déclin dans l’abandon du tabagisme a été noté (35 % par opposition à 73%; p = 0,02). Dans l’ensemble, les conditions d’une guérison optimale (optimal therapy status) ont été davantage atteintes dans la cohorte la plus récente comparativement à celle de 2008 à 2010 (52 % par opposition à 22 %; p0,01). Le fait d’être de sexe masculin a été associé à de meilleures conditions de guérison optimale (rapport des cotes: 1,61; IC 95 %, 1,04 – 2,51). Enfin, mentionnons que le nombre de consultations de suivi et la durée des suivis n’ont pas été associés à l’atteinte de valeurs cibles en matière de prévention des AVC.Notre étude montre une série d’améliorations dans l’atteinte des objectifs thérapeutiques recommandés par les lignes directrices canadiennes de prévention des AVC. Cela pourrait être en partie attribuable à la mise en place de dossiers médicaux informatisés au sein de notre clinique. Parmi les aspects qui méritent une amélioration, citons l’établissement d’un programme de counseling en ce qui regarde l’abandon du tabagisme et le dépistage du diabète.

BACKGROUND In the Northern Hemisphere, influenza season typically starts in December and lasts through March. Pregnant people are at increased risk for influenza-related morbidity and mortality. Potentially, new viral strains or reduced provider suspicion leading to delayed diagnosis of late-season influenza could result in an increased risk of severe infection. OBJECTIVE This study aimed to assess the incidence and morbidity associated with late-season influenza in pregnancy, compared with influenza in other seasons. STUDY DESIGN This was a retrospective cohort study using the 2007–2018 National Inpatient Sample. Pregnant patients with discharge diagnosis codes consistent with influenza infection were compared on the basis of hospital admission quarter (quarter 1: October to December; quarter 2: January to March; quarter 3: April to June; quarter 4: July to September), with quarter 3 defined as “late-season.” The primary outcome was the severe maternal morbidity composite defined by the Centers for Disease Control and Prevention. The secondary outcomes included sepsis, shock, acute renal failure, acute heart failure, temporary tracheostomy, and invasive mechanical ventilation. Associations between outcomes and quarter of infection were adjusted for age, hospitalization type (antepartum, delivery, or postpartum), and comorbid conditions using relative risk regression, weighted to reflect the National Inpatient Sample design. RESULTS Of 7355 hospitalizations, corresponding to a weighted national estimate of 36,042, 2266 (30.8%) occurred in quarter 1, 4051 (55.0%) in quarter 2, 633 (8.6%) in quarter 3, and 405 (5.5%) in quarter 4. A nonsignificant trend toward higher rates of severe maternal morbidity was seen in the “late-season” compared with other quarters (13.9% [quarter 3] vs 10.5% [quarter 1] vs 12.1% [quarter 2] vs 13.6% [quarter 4]; P=.07). Moreover, sepsis was more common in patients with late-season influenza (8.0% [quarter 3] vs 4.8% [quarter 1] vs 5.8% [quarter 2] vs 5.9% [quarter 4]; P=.03). In the adjusted analyses, patients with late-season influenza had a 1.34 (95% confidence interval, 1.01–1.78) higher risk of severe maternal morbidity and 1.57 (95% confidence interval, 1.06–2.32) higher risk of sepsis than patients with influenza in quarter 1. CONCLUSION Influenza infection between April and June, that is, late-season influenza, is associated with a higher risk of severe maternal morbidity and sepsis in pregnant patients. Obstetrical providers must continue to have awareness and suspicion for influenza infection during these months.

BackgroundRecently developed software utilizing artificial intelligence for fast detection and triage of stroke cases has the potential to accelerate stroke care and improve patient outcomes. We performed this analysis to evaluate the performance and time-to-notification of one such software - RAPID LVO.MethodsWe created a database of 151 consecutive acute stroke patients for whom CT scans were processed by the RAPID LVO software over a period of eight months. The LVO notification and time to notification of the software were collected, alongside patient information and the CTA findings.ResultsRAPID LVO achieved a sensitivity of 63.6% and specificity of 85.8% for large vessel occlusion, with an average time to notification of 32.53 minutes.ConclusionsRAPID LVO has low sensitivity, moderate specificity and high time-to-notification performance. Our study data demonstrated in particular low overall sensitivity (63%) for distal occlusions (M2-3). The disparity between the observed performance and the performance reported in RAPID LVO’s FDA clearance demonstrates the importance of independent, multi-center evaluation. The gap between the performance in this study compared to published records of RAPID AI may be due to differences in imaging hardware, software implementation, connectivity or clinical definitions.

There is extensive literature supporting the efficacy of botulinum toxin (BoNT-A) for the treatment of post-stroke spasticity, however, there remain gaps in the routine management of patients with post-stroke spasticity. A panel of 21 Italian experts was selected to participate in this web-based survey Delphi process to provide guidance that can support clinicians in the decision-making process. There was a broad consensus among physicians that BoNT-A intervention should be administered as soon as the spasticity interferes with the patients’ clinical condition. Patients monitoring is needed over time, a follow-up of 4–6 weeks is considered necessary. Furthermore, physicians agreed that treatment should be offered irrespective of the duration of the spasticity. The Delphi consensus also stressed the importance of patient-centered goals in order to satisfy the clinical needs of the patient regardless of time of onset or duration of spasticity. The findings arising from this Delphi process provide insights into the unmet needs in managing post-stroke spasticity from the clinician’s perspective and provides guidance for physicians for the utilization of BoNT-A for the treatment of post-stroke spasticity in daily practice.

Background: Stroke is one of the leading causes of mortality worldwide. During the last decade, there have been several improvements in stroke-related care such as raising public awareness for early presentation, lifestyle modification, thrombolytic therapy and endovascular therapy. We aimed to evaluate the potential changes in global stroke-related mortality following these innovations. Methods: We completed a systematic review of all population-based cohort studies published during the last two decades (2000-2020). We retained all studies which reported age-adjusted and sex-specific stroke-related mortality. We grouped the countries into: developed countries with predominant White population* (Canada, United States of America, Western Europe, Australia, New Zealand), Eastern Europe, Latin America, and Asia. For each of the region, we compared the median stroke-related mortality during the decade 2010 to the stroke-related mortality of the 2000 decade. Results: Of 210 articles screened, there were eight studies that reported population-based age-standardized and sex-specific stroke-related mortality in 47 countries. We presented the international secular variations in sex-specific stroke-related mortality in Figure 1. We noted significant temporal decreases in age-standardized stroke-related mortality for both men and women in all regions except for Eastern European women and Asian men. Globally, the stroke-related mortality decreased from 40.0 to 31.7 and from 31.6 to 22.8 per 100,000 for men and women, respectively The reductions of stroke-related deaths approximated 22% and 29%, for men and women, respectively. Conclusion: Despite its temporal decrease in most regions, the lack of reduction in stroke-related mortality of Eastern European women and Asian men are noteworthy. Future research is needed to decrease the stroke-related mortality in these high-risk populations. *: As defined by the International Monetary Fund

Background: Stroke is one of the leading causes of mortality worldwide. We aimed to evaluate the international variations in stroke-related mortality in men and women. Methods: We completed a systematic review of all population-based cohort studies published during the decade 2010-2020. We retained only studies which reported age-adjusted and sex-specific stroke-related all-cause mortality (per 100 000 population). We computed the median sex-specific stroke-related mortality for each of the following group of countries: developed countries (as defined by the International Monetary Fund) with predominantly white population (Canada, United States of America, Western Europe, Australia, New Zealand), Eastern Europe, Latin America, Asia and Africa. We compared stroke-related mortality between women and men and between regions. Results: Of the 210 articles screened, there were seven studies which reported population-based age-standardized and sex-specific stroke-related mortality in 57 countries. We presented the most recent age-adjusted and sex-specific stroke-related mortality medians (and 25 th and 75 th percentiles) in Figure 1. Globally, we observed a significantly lower stroke-related mortality rate in women compared to men (23.6 and 30.8, respectively) (p-value = 0.007). Age-adjusted stroke-related mortality was the highest for both sexes in Eastern Europe, followed by the African rates. Age-adjusted stroke-related mortality was the lowest for both men and women (p Conclusions: There were marked international variations in the age-adjusted stroke-related mortality for both men and women. The high stroke-related mortality in Eastern Europe and Africa should motivate further improvement in stroke care in these regions. Finally, future research is needed to understand and decrease the sex-related difference in stroke-related mortality.

PurposeTo determine the contributions of proprioceptive and visual feedbacks for postural control at 6 months following ACLR, and to determine their associations with knee laxity, isokinetic tests and clinical scores.Study designLevel IV, Case series.MethodsFifty volunteers who received ACLR between May 2015 and January 2017 were prospectively enrolled, and at 6 months following ACLR, postural stability was assessed. Somatosensory ratios (somatic proprioception), and visual ratios (visual compensation), were calculated to evaluate the use of sensory inputs for postural control. Univariable regression analyses were performed to determine associations of somatosensory and visual ratios with knee laxity, isokinetic tests and clinical scores.ResultsAt 6 months following ACLR, the somatosensory ratio did not change, while the visual ratio decreased significantly from 5.73 ± 4.13 to 3.07 ± 1.96 (p = 0.002), indicating greater reliance on visual cues to maintain balance. Univariable analyses revealed that the somatosensory ratio was significantly lower for patients who performed aquatic therapy (β = -0.50;p = 0.045), but was not associated with knee laxity, muscle strength or clinical scores. An increased visual ratio was associated with patients who received hamstrings tendon autografts (β = 1.32;p = 0.049), but was not associated with knee laxity, muscle strength or clinical scores.ConclusionAt 6 months following ACLR, visual ratios decreased significantly, while somatosensory ratios did not change. This may suggest that there is little or no improvement in neuromuscular proprioception and therefore greater reliance on visual cues to maintain balance. The clinical relevance of this study is that posturography can provide useful information to help research following ACLR and to predict successful return to play.

Objective To assess the effectiveness of pelvic floor muscle training (PFMT) plus electromyographic biofeedback or PFMT alone for stress or mixed urinary incontinence in women. Design Parallel group randomised controlled trial. Setting 23 community and secondary care centres providing continence care in Scotland and England. Participants 600 women aged 18 and older, newly presenting with stress or mixed urinary incontinence between February 2014 and July 2016: 300 were randomised to PFMT plus electromyographic biofeedback and 300 to PFMT alone. Interventions Participants in both groups were offered six appointments with a continence therapist over 16 weeks. Participants in the biofeedback PFMT group received supervised PFMT and a home PFMT programme, incorporating electromyographic biofeedback during clinic appointments and at home. The PFMT group received supervised PFMT and a home PFMT programme. PFMT programmes were progressed over the appointments. Main outcome measures The primary outcome was self-reported severity of urinary incontinence (International Consultation on Incontinence Questionnaire-urinary incontinence short form (ICIQ-UI SF), range 0 to 21, higher scores indicating greater severity) at 24 months. Secondary outcomes were cure or improvement, other pelvic floor symptoms, condition specific quality of life, women’s perception of improvement, pelvic floor muscle function, uptake of other urinary incontinence treatment, PFMT self-efficacy, adherence, intervention costs, and quality adjusted life years. Results Mean ICIQ-UI SF scores at 24 months were 8.2 (SD 5.1, n=225) in the biofeedback PFMT group and 8.5 (SD 4.9, n=235) in the PFMT group (mean difference −0.09, 95% confidence interval −0.92 to 0.75, P=0.84). Biofeedback PFMT had similar costs (mean difference £121 ($154; €133), −£409 to £651, P=0.64) and quality adjusted life years (−0.04, −0.12 to 0.04, P=0.28) to PFMT. 48 participants reported an adverse event: for 23 this was related or possibly related to the interventions. Conclusions At 24 months no evidence was found of any important difference in severity of urinary incontinence between PFMT plus electromyographic biofeedback and PFMT alone groups. Routine use of electromyographic biofeedback with PFMT should not be recommended. Other ways of maximising the effects of PFMT should be investigated. Trial registration ISRCTN57756448.

This narrative review synthesizes current evidence on the medical management of nocturnal polyuria, including antidiuretic replacement therapy as well as other emerging modalities, with particular emphasis on areas of active investigation and future research directions. Relative to earlier formulations, the pharmacological profiles of novel desmopressin acetate nasal spray and orally disintegrating tablet formulations appear favorable in optimizing the balance between efficacy and safety. Additionally, several highly selective small-molecule arginine vasopressin 2 receptor agonists are under active development, while appropriately timed short-acting diuretics, pharmacotherapy for hypertension, nonsteroidal anti-inflammatory drugs, and sex hormone replacement therapy are also a focal point of extensive ongoing nocturnal polyuria research. Emerging laboratory technologies now make feasible a sub-stratification of nocturnal polyuria patients into substrate-based phenotypes for individualized treatment. An increasingly refined understanding of the pathogenesis of nocturnal polyuria, and arginine vasopressin dysregulation in particular, has also introduced new opportunities for point-of-care testing in patients with nocturnal polyuria.

Introduction The diagnosis or exclusion of obstructive stable coronary artery disease (SCAD) in clinical practice is challenging and therefore clinical guidelines provide recommendations on the use of non-invasive and invasive testing. For Germany, data obtained from the OECD and health insurances indicate a potential non-adherence to guideline-recommended diagnostic pathways. However, there is a lack of prospective and reliable evidence for appropriate use of invasive coronary angiography (CA) in Germany. Objective To provide evidence on the nature and extent of guideline non-adherence in patients undergoing CA with presumed obstructive SCAD in Germany and, to evaluate the clinical and economic consequences of potential deviations in guideline adherence. Methods ENLIGHT-KHK is a multicentre, prospective observational study recruiting 1500 patients being admitted for CA with presumed obstructive SCAD and exclusion of acute myocardial infarction (DRKS00015638). The primary outcome measure is the adherence to clinical guidelines in the decision-making process for use of CA. Therefore, the patients' diagnostic pathways and adherence to German and European guidelines will be assessed using clinical data, health-claims data, and a patient questionnaire. The primary safety outcome is a composite of myocardial infarction, stroke and all-cause death. Secondary outcome measures are periprocedural complications and costs. Using a decision-analytic model, the clinical and economic impact of observed guideline adherence in clinical practice will be assessed. Potential barriers and facilitators of guideline-adherent decision-making will be evaluated via semi-structured interviews. Conclusions ENLIGHT-KHK will give insights into the appropriateness of invasive CA in Germany and enable the development of concepts to improve guideline-adherence in the German health-care setting.

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