International Variation Research Articles

Large-scale application of ClinGen-InSiGHT APC-specific ACMG/AMP variant classification criteria leads to substantial reduction in VUS

Pathogenic constitutional APC variants underlie familial adenomatous polyposis, the most common hereditary gastrointestinal polyposis syndrome. To improve variant classification and resolve the interpretative challenges of variants of uncertain significance (VUSs), APC-specific variant classification criteria were developed by the ClinGen-InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) based on the criteria of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP). A streamlined algorithm using the APC-specific criteria was developed and applied to assess all APC variants in ClinVar and the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) international reference APC Leiden Open Variation Database (LOVD) variant database, which included a total of 10,228 unique APC variants. Among the ClinVar and LOVD variants with an initial classification of (likely) benign or (likely) pathogenic, 94% and 96% remained in their original categories, respectively. Incontrast, 41% ClinVar and 61% LOVD VUSs were reclassified into clinically meaningful classes, the vast majority as (likely) benign.The total number of VUSs was reduced by 37%. In 24 out of 37 (65%) promising APC variants that remained VUS despite evidence for pathogenicity, a data-mining-driven work-up allowed their reclassification as (likely) pathogenic. These results demonstrated that the application of APC-specific criteria substantially reduced the number of VUSs in ClinVar and LOVD. The study also demonstrated the feasibility of a systematic approach to variant classification in large datasets, which might serve as a generalizable model for other gene- or disease-specific variant interpretation initiatives. It also allowed for the prioritization of VUSs that will benefit from in-depth evidence collection. This subset of APC variants was approved by the VCEP and made publicly available through ClinVar and LOVD for widespread clinical use.

Inter‐hospital variations in the respiratory outcomes of very and extremely pre‐term infants: A cohort study in Japan

AbstractBackgroundHospital‐level and international variations exist in the management strategies of bronchopulmonary dysplasia (BPD). However, studies evaluating hospital‐level variations in the respiratory outcomes of pre‐term infants associated with differing management strategies of BPD are lacking.ObjectiveHerein, we aimed to assess inter‐hospital variations in the respiratory outcomes of BPD in very pre‐term and extremely pre‐term infants.MethodsIn this cohort study, the administrative claims and discharge summary data were extracted from 276 hospitals in Japan between April 2014 and March 2016. This study assessed neonates of a gestational age of 22–31 weeks old, who had been hospitalised for ≥7 days.The primary outcome was a BPD defined using any respiratory support, such as supplemental oxygen, high‐flow nasal cannula, CPAP, or mechanical ventilation at 36 weeks PMA. The median odds ratio (MOR) was calculated using a multilevel logistic regression model, including baseline characteristics, comorbidities, and treatment as covariates, to evaluate the inter‐hospital variation of the outcome.ResultsOf the 8143 neonates from across 132 hospitals, 53.7% were male, with a mean gestational age (standard deviation) of 28.0 (2.5)‐weeks‐old and birthweight of 1086 (386) g. Among these patients, BPD occurred in 2737 (33.6%). The MOR was 2.49, representing the median value of odds ratios when comparing two neonates with identical covariates from hospitals with high and low propensity for the outcomes to occur.ConclusionsOutcome variations in the BPD were observed among hospitals in Japan, even after adjusting for individual factors, including gestational age, birthweight, comorbidities, and treatments. Thus, in Japan, developing strategies is essential to decrease the BPD rates, while minimising inter‐hospital heterogeneity, to improve the healthcare quality for pre‐term neonates.

International Variation in Health Status Benefits in Patients Undergoing Initial Invasive Versus Conservative Management for Chronic Coronary Disease: Insights From the ISCHEMIA Trial

BACKGROUND: The ISCHEMIA trial (International Study of Comparative Health Effectiveness with Medical and Invasive Approaches) demonstrated greater health status benefits with an initial invasive strategy, as compared with a conservative one, for patients with chronic coronary disease and moderate or severe ischemia. Whether these benefits vary globally is important to understand to support global adoption of the results. METHODS: We analyzed participants’ disease-specific health status using the validated 7-item Seattle Angina Questionnaire (SAQ: >5-point differences are clinically important) at baseline and over 1-year follow-up across 37 countries in 6 international regions. The average effect of initial invasive versus conservative strategies on 1-year SAQ scores was estimated using Bayesian proportional odds regression and compared across regions. RESULTS: Considerable regional variation in baseline health status was observed among 4617 participants (mean age=64.4±9.5 years, 24% women), with the mean SAQ summary scores of 67.4±19.5 in Eastern Europe participants (17% of the total), 71.4±15.4 in Asia-Pacific (18%), 74.9±16.7 in Central and South America (10%), 75.5±19.5 in Western Europe (26%), and 78.6±19.2 in North America (28%). One-year improvements in SAQ scores were greater in regions with lower baseline scores with initial invasive management (17.7±20.9 in Eastern Europe and 11.4±19.3 in North America), but similar in the conservative arm. Adjusting for baseline SAQ scores, similar health status benefits of an initial invasive strategy on 1-year SAQ scores were observed (ranging from 2.38 points [95% CI, 0.04–4.50] in North America to 4.66 points [95% CI, 2.46–6.94] in Eastern Europe), with an 88.3% probability that the difference in benefit across regions was <5 points. CONCLUSIONS: In patients with chronic coronary disease and moderate or severe ischemia, initial invasive management was associated with a consistent health status benefit across regions, with modest regional variability, supporting the international generalizability of health status benefits from invasive management of chronic coronary disease. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01471522

737. ETHNIC, GENDER AND TUMOR-SPECIFIC ASSESSMENT OF BODY COMPOSITION IS CRITICAL FOR CLINICAL RELEVANCE IN PATIENTS UNDERGOING THERAPY FOR ESOPHAGEAL

Abstract Background Growing evidence has supported a role for body composition in predicting survival in patients undergoing esophagectomy. A contemporary meta-analysis of published data (n=44 studies) conducted for this study confirmed an association between reduced muscle mass at diagnosis and worse overall survival (HR 1.72, 95%CI 1.49-1.97). Variation in methods of assessing and defining parameters of body composition remain however an important barrier to the wider adoption in routine clinical practice. This is particularly pertinent in esophageal cancer due to known sex, biological and geographical difference in tumor subtypes. This study seeks to define baseline variation in body composition parameters and to report their association with 90-day and overall survival in a large international cohort of patients undergoing esophagectomy for cancer. Methods Patients who underwent esophagectomy in fourteen high-volume centers between January 2007 to December 2019 were eligible for inclusion. Survival data were included up until June 2022. Skeletal muscle, visceral and subcutaneous adipose tissues within CT images, acquired at the time of diagnosis, were analyzed in accordance with a standardized protocol. Results 1716 patients were recruited to this study from three global regions: North America (n=386;22.5%), Europe (n=940;54.8%) and Asia (n=390;22.7%). Patients were predominantly male (79.5%) and adenocarcinoma was the most common histological subtype (66.6%). Wide variation of skeletal muscle (17.1-83.5cm2), visceral adiposity (0.2-170.1cm2) and subcutaneous adiposity (0.2-216.8cm2) was observed at presentation. Characteristics significantly associated with levels of muscle and adiposity were global region, sex, age, and histological subtype (P<0.001) (Figure 1). Compared to adenocarcinoma, squamous cell carcinoma was associated with significantly lower levels of muscle and adiposity, a finding that was independent of global region, sex, and age using a multivariable linear regression model (p<.0001). Median follow-up was 71.3 (95%CI 69.1-73.5) months with a median overall survival of 60.9 (95%CI 53.0-68.9) months. Reduced skeletal muscle and an excess of total adiposity at the time of diagnosis was associated with worse 90-day mortality and long-term survival. An interactive online survival prediction tool was developed to provide personalized survival estimates based on relevant predictors including skeletal muscle, total adiposity at diagnosis and other tumor and patient specific variables. Conclusions This is the first and largest study to adopt standardized methods to define international variation in parameters of body composition in esophageal cancer patients. Findings corroborate the potential role of body composition as a method of prognostication in esophageal cancer and presents a on-line tool for convenient integration into clinical practice.

A New Approach for Understanding International Hospital Bed Numbers and Application to Local Area Bed Demand and Capacity Planning.

Three models/methods are given to understand the extreme international variation in available and occupied hospital bed numbers. These models/methods all rely on readily available data. In the first, occupied beds (rather than available beds) are used to measure the expressed demand for hospital beds. The expressed occupied bed demand for three countries was in the order Australia > England > USA. Next, the age-standardized mortality rate (ASMR) has dual functions. Less developed countries/regions have low access to healthcare, which results in high ASMR, or a negative slope between ASMR versus available/occupied beds. In the more developed countries, high ASMR can also be used to measure the 'need' for healthcare (including occupied beds), a positive slope among various social (wealth/lifestyle) groups, which will include Indigenous peoples. In England, a 100-unit increase in ASMR (European Standard population) leads to a 15.3-30.7 (feasible range) unit increase in occupied beds per 1000 deaths. Higher ASMR shows why the Australian states of the Northern Territory and Tasmania have an intrinsic higher bed demand. The USA has a high relative ASMR (for a developed/wealthy country) because healthcare is not universal in the widest sense. Lastly, a method for benchmarking the whole hospital's average bed occupancy which enables them to run at optimum efficiency and safety. English hospitals operate at highly disruptive and unsafe levels of bed occupancy, manifesting as high 'turn-away'. Turn-away implies bed unavailability for the next arriving patient. In the case of occupied beds, the slope of the relationship between occupied beds per 1000 deaths and deaths per 1000 population shows a power law function. Scatter around the trend line arising from year-to-year fluctuations in occupied beds per 1000 deaths, ASMR, deaths per 1000 population, changes in the number of persons hidden in the elective, outpatient and diagnostic waiting lists, and local area variation in births affecting maternity, neonatal, and pediatric bed demand. Additional variation will arise from differences in the level of local funding for social care, especially elderly care. The problems associated with crafting effective bed planning are illustrated using the English NHS as an example.

An Analysis of Computed Tomography Diagnostic Reference Levels in India Compared to Other Countries.

Computed Tomography (CT) is vital for diagnosing and monitoring medical conditions. However, increased usage raises concerns about patient radiation exposure. Diagnostic Reference Levels (DRLs) aim to minimize radiation doses in CT imaging. This study examines CT DRLs in India compared to other countries to identify optimization opportunities. A literature review was conducted to gather data from published studies, guidelines, and regulatory authorities. Findings show significant international variations in CT DRLs, with differences up to 50%. In India, DRLs also vary significantly across states. For head CT exams, Indian DRLs are generally 20-30% lower than international standards (27-47 mGy vs. 60 mGy). Conversely, for abdominal CT scans, Indian DRLs are 10-15% higher (12-16 mGy vs. 13 mGy). Factors influencing DRL variations include equipment differences, imaging protocols, patient demographics, and regulatory conditions. Dose-optimization techniques like automatic exposure control and iterative reconstruction can reduce radiation exposure by 25-60% while maintaining image quality. Comparative data highlight best practices, such as the United Kingdom's 30% reduction in CT doses from 1984 to 1995 via DRL implementation. This study suggests that adopting similar practices in India could reduce radiation doses by 20-40% for common CT procedures, promoting responsible CT usage and minimizing patient exposure.

An International Registry Study of Early-Stage NSCLC treatment variations (LUCAEUROPE) in Europe and the USA highlighting variations

ObjectiveHarmonized European NSCLC incidence, treatment approach, and survival based on national tumor registries are unclear. Summary background dataSurgery has the potential to cure NSCLC and significantly prolong survival. This large-scale international study aimed to investigate treatment variations in Europe and the USA, as well as the determinants for its utilization. MethodsThe retrospective cohort study analyzed data from six European national population-based cancer registries (Belgium, Denmark, Estonia, Germany, the Netherlands, and Slovenia) and the US SEER database from 2010–2015. ResultsThe study computed cancer incidence, survival, and age-standardized proportions of the use of various therapies. Multivariable logistic regression models were used to assess associations between resection and demographic and clinical parameters. A total of 428,107 records were analyzed. Among all countries, Estonia had the highest surgical resection rate (79.3 %) and the lowest radiation rate (7.3 %) for stage I patients. The Netherlands had the highest rate of radiotherapy across all years of investigation and the lowest surgery rate between 2012 and 2015. The primary treatment for early-stage NSCLC showed significant international variation, with the USA having a decrease in surgical rates from 67.6 % to 59.5 %. Resection was less frequently performed as tumor stage increased, patients aged, other lung cancer besides adenocarcinoma was present, and when the tumor site overlapped multiple lobes. ConclusionsResection rates have declined in some studied European countries and the USA and resection rates vary substantially among countries. Interpretation of current scientific lung cancer evidence and international guidelines results in wide variations in patient treatment.

Educational inequalities in deaths of despair in 14 OECD countries: a cross-sectional observational study

BackgroundDeaths of despair are a key contributor to stagnating life expectancy in the USA, especially among those without a university-level education, but these findings have not been compared internationally.MethodsMortality and...

Outpatient parenteral antimicrobial therapy (OPAT) across the world: a comparative analysis-what lessons can we learn?

This paper presents a comparative analysis of Outpatient Parenteral Antimicrobial Therapy (OPAT) structures and delivery options across different countries. OPAT, a cost-effective alternative to inpatient care for patients requiring IV antimicrobial therapy, has demonstrated multiple benefits such as patient satisfaction, economic cost savings, and reduced hospital-acquired infections. Despite these advantages, there is considerable international variation in OPAT use and implementation. By examining the OPAT structures of multiple countries, we aim to identify areas of variation and explore opportunities for expansion and improvement of OPAT services.

1190 Clinical Features and Outcomes from the Acute PresentatiOn of coLorectaL Cancer – an internatiOnal Snapshot (APOLLO) – an International Prospective Audit

Abstract Aim The APOLLO study aimed to describe the international variation in the presentation, management and outcomes of patients presenting acutely with colorectal cancer. Method APOLLO was an international prospective, multicentre cohort study delivered through the EuroSurg student and trainee-led collaborative network. Adult patients presenting acutely with colorectal cancers were included. The primary outcome was 90-day mortality. Country-level variation was analysed using funnel plots. Results 1414 patients (216 centres, 39 countries) were enrolled (median age 70 years; 645 females [45.6%]; ASA Grade I-II: 689 [48.7%]). Common presentations were bowel obstruction (n=774, 54.7%), gastrointestinal haemorrhage (n=297, 21.0%),bowel perforation (n=161, 11.4%). Overall, 56.9% of patients presented with a new diagnosis of cancer (n=804), 13.9% presented while awaiting elective surgery (n=196), and 9.3% while undergoing neoadjuvant therapy (n=132). Most cases were managed with curative intent (n=805, 56.9%). Of the 1022 patients undergoing surgery, 813 underwent surgical resection (79.5%), 582 underwent stoma formation (56.9%), and 498 (48.7%) underwent primary anastomosis. Only 57 patients underwent colonic metallic stenting (4.0%). Overall, 90-day mortality was 19.4%; 90-day surgical mortality was 13.9% and 90-day non-operative mortality was 33.7%. There was significant variation in overall mortality, but not surgical mortality, between countries after case-mix adjustment. Conclusions Emergency colorectal cancer presentations carry significant mortality with and without surgery. Many acute presentations are in patients with known colorectal cancer awaiting treatment. Operative mortality is similar globally, but overall mortality varies between countries. Further work is needed to guide individualised decision making on who benefits from acute surgery with curative-intent.

International variation in injury burden and comparative outcomes: How injury looks like in different parts of the world

Injury is reported as one of the leading causes of morbidity and mortality globally. However, its burden stays under-reported in low- and middle-income countries, which prevents understanding of the true distribution and impact of injury worldwide. This dearth of data not only includes the burden of trauma-associated mortality but also involves the identification of long-term patient-reported outcomes after injury. High-income countries have shown that the development of trauma registries can achieve proper data collection, the findings from which can ultimately decrease trauma-associated morbidity and mortality. Expanding such an initiative to low-resource settings with high injury proportions can aid in understanding the long-term outcomes of post-trauma patients, identifying the factors that continue to contribute to its injury burden, and developing strategies catered to reducing it.Here, we discuss the variation in the global injury burden and go a step beyond mortality to highlight the importance of capturing long-term patient-reported outcomes post-trauma. We describe the process of developing trauma registries in high-income countries and extrapolate the findings from this experience to set up similar registries in resource-limited settings. Lastly, we demonstrate the feasibility and initial impact of using its data on identifying predictors of in-hospital mortality and determining long-term patient-reported outcomes in the context of low-resource settings. Through these findings, we share the outlook of an evolved trauma care system in both high- and low-income regions with reduced morbidity and mortality globally.

Temporal Analysis of the Incidence, Mortality and Disability-Adjusted Life Years of Benign Gallbladder and Biliary Diseases in High-Income Nations, 1990-2019.

The aim of this observational study was to analyze trends in the incidence, mortality, and disability-adjusted life years (DALYs) of benign gallbladder and biliary diseases across high-income countries between 1990 and 2019. Benign gallbladder and biliary diseases place a substantial burden on healthcare systems in high-income countries. Accurate characterization of the disease burden may help optimize healthcare policy and resource distribution. Age-standardized incidence rates (ASIRs), age-standardized mortality rates (ASMRs), and DALYs data for gallbladder and biliary diseases in males and females were extracted from the 2019 Global Burden of Disease (GBD) study. A mortality-incidence index (MII) was also calculated. Joinpoint regression analysis was performed. The median ASIRs across the European Union 15+ countries in 2019 were 758/100,000 for females and 282/100,000 for males. Between 1990 and 2019 the median percentage change in ASIR was +2.49% for females and +1.07% for males. The median ASMRs in 2019 were 1.22/100,000 for females and 1.49/100,000 for males with a median percentage change over the observation period of -21.93% and -23.01%, respectively. In 2019, the median DALYs was 65/100,000 for females and 37/100,000 among males, with comparable percentage decreases over the observation period of -21.27% and -19.23%, respectively. International variation in lifestyle factors, diagnostic and management strategies likely account for national and sex disparities. This study highlights the importance of ongoing clinical efforts to optimize treatment pathways for gallbladder and biliary diseases, particularly in the provision of emergency surgical services and efforts to address population risk factors.

International trends in shoulder replacement: a meta-analysis from 11 public joint registers.

International variation exists in the types of shoulder replacement used for treatment of specific diseases. Implant choice continues to evolve without high-quality evidence. Our aim was to evaluate trends in incidence rates of shoulder replacement and assess any recent changes in practice between countries by using registry data. Patient characteristics, indication and year of surgery, type of replacement, and collection methods of patient-reported outcomes (PROMs) was extracted from 11 public joint registries. Meta-analyses examined use of reverse total shoulder replacement (RTSR) for osteoarthritis, cuff tear arthropathy, and acute fracture; use of anatomical total shoulder replacement (TSR) for osteoarthritis; and use of humeral hemiarthroplasty for fracture. The annual growth rate of shoulder replacements performed is 6-15% (2011-2019). The use of RTSR has almost doubled (93%). RTSR is now universally performed for cuff tear arthropathy (97.3%, 95% confidence interval [CI] 96.0-98.1). Its use for avascular necrosis, trauma, and inflammatory arthropathy is increasing. The use of RTSR was similar (43.1%, CI 30.0-57.2) versus TSR (44.7%, CI 31.1-59.1) for osteoarthritis. The types of PROMs used, collection time points, and response rates lack standardization. COVID-19 had a varying inter-registry impact on incidence rates. The incidence of shoulder replacements has grown. Use of RTSR has increased for all disease indications despite limited high-quality evidence driving this change in indications outside of cuff arthropathy. Consequently, less variation is observed in international practice. Existing differences now relate to use of newer implant types and methodology of PROMs collection, which prevents international comparison and outcome analysis.

Limited consensus on the diagnosis and treatment of lymphedema after head and neck cancer: results from an International Delphi study

Purpose To explore current practice variation and degree of consensus among international clinical experts regarding the diagnosis, classification, measurement, and treatment of head and neck lymphedema (HNL) after head and neck cancer treatment. Materials and Methods We conducted an online Delphi study. Eligible participants were clinical researchers who had (co)authored at least one publication on HNL and healthcare professionals who had treated at least five patients with HNL the last two years. The first round was to collect views about current best practices. The second and third rounds delved deeper into these topics using statements with 7-point adjective rating scales. Results An expert panel of seventeen participants (7 clinicians, 8 researchers, and 2 others) from 8 countries completed all rounds. Regarding diagnosis, there was limited consensus on most subjects, with palpation being most endorsed. No consensus was reached on the need to use standardized classification systems. As a treatment method, complex decongestive therapy (CDT) was the most commonly used in practice and investigated in the literature. However, no consensus was reached on the importance of aspects of CDT. Conclusions There is substantial intra- and international practice variation in the management of HNL. This calls for more robust evidence and guidelines.

Diuretic prescriptions in the first year of haemodialysis: international practice patterns and associations with outcomes.

The use of diuretics in patients on haemodialysis (HD) is thought to maintain diuresis. However, this assumption and the optimal dose are based on little scientific evidence, and associations with clinical outcomes are unclear. We reported international variations in diuretic use and loop diuretic dose across 27759 HD patients with dialysis vintage <1year in the Dialysis Outcomes and Practice Patterns Study phases 2-5 (2002-2015), a prospective cohort study. Doses of torsemide (4:1) and bumetanide (80:1) were converted to oral furosemide-equivalent doses. Adjusted Cox, logistic and linear regressions were used to investigate the association of diuretic use and dose with outcomes. Diuretic utilization varied widely by country at vintage <3months, ranging from >80% in Germany and Sweden to <35% in the USA, at a median dose ranging from 400-500mg/day in Germany and Sweden to <100mg/day in Japan and the USA. Neither diuretic use nor higher doses were associated with a lower risk of all-cause mortality, a higher risk of hospitalization for fracture or elevated parathyroid hormone levels, but the prescription of higher doses (>200mg/day) was associated with a higher risk of all-cause hospitalization. Substantial international differences exist in diuretic prescriptions, with use and doses much higher in some European countries than the USA. The prescription and higher doses of loop diuretics was not associated with improved outcomes.

Opioid Use Prior to Adult Spine Deformity Correction Surgery is Associated With Worse Pre- and Postoperative Back Pain and Prolonged Opioid Demands.

Prospective multicenter database post-hoc analysis. Opioids are frequently prescribed for painful spinal conditions to provide pain relief and to allow for functional improvement, both before and after spine surgery. Amidst a current opioid epidemic, it is important for providers to understand the impact of opioid use and its relationship with patient-reported outcomes. The purpose of this study was to evaluate pre-/postoperative opioid consumption surrounding ASD and assess patient-reported pain outcomes in older patients undergoing surgery for spinal deformity. Patients ≥60 years of age from 12 international centers undergoing spinal fusion of at least 5 levels and a minimum 2-year follow-up were included. Patient-reported outcome scores were collected using the Numeric Rating Scale for back and leg pain (NRS-B; NRS-L) at baseline and at 2 years following surgery. Opioid use, defined based on a specific question on case report forms and question 11 from the SRS-22r questionnaire, was assessed at baseline and at 2-year follow-up. Of the 219 patients who met inclusion criteria, 179 (81.7%) had 2-year data on opioid use. The percentages of patients reporting opioid use at baseline (n = 75, 34.2%) and 2 years after surgery (n = 55, 30.7%) were similar (P = .23). However, at last follow-up 39% of baseline opioid users (Opi) were no longer taking opioids, while 14% of initial non-users (No-Opi) reported opioid use. Regional pre- and postoperative opioid use was 5.8% and 7.7% in the Asian population, 58.3% and 53.1% in the European, and 50.5% and 40.2% in North American patients, respectively. Baseline opioid users reported more preoperative back pain than the No-Opi group (7.0 vs 5.7, P = .001), while NRS-Leg pain scores were comparable (4.8 vs 4, P = .159). Similarly, at last follow-up, patients in the Opi group had greater NRS-B scores than Non-Opi patients (3.2 vs 2.3, P = .012), but no differences in NRS-Leg pain scores (2.2 vs 2.4, P = .632) were observed. In this study, almost one-third of surgical ASD patients were consuming opioids both pre- and postoperatively world-wide. There were marked international variations, with patients from Asia having a much lower usage rate, suggesting a cultural influence. Despite both opioid users and nonusers benefitting from surgery, preoperative opioid use was strongly associated with significantly more back pain at baseline that persisted at 2-year follow up, as well as persistent postoperative opioid needs.

Understanding clozapine-related blood dyscrasias. Developments, genetics, ethnicity and disparity: it's a CIN.

Clozapine remains the gold standard intervention for treatment-resistant schizophrenia; however, it remains underused, especially for some minority groups. A significant impediment is concern about propensity to neutropenia. The aim of this article is to provide an update on current knowledge relating to: the pattern and incidence of severe blood dyscrasias; the effectiveness of current monitoring regimes in reducing harm; the mechanisms of and the distinctions between clozapine-induced neutropenia and agranulocytosis; benign ethnic neutropenia; and changes to the monitoring thresholds in the USA and other international variations. These all have implications for the practical use of clozapine; specifically, how barriers to initiating, maintaining and restarting clozapine can be understood and in many cases overcome, especially for patients from minority groups, potentially with simpler approaches than the use of lithium or G-CSF.

Pitfalls, patience and patients: developing a physiotherapy-led balance clinic.

Balance dysfunction and vestibular conditions are major problems requiring significant resources. There is significant national and international variation in management pathways for such patients. This paper outlines a collaborative project run by the ENT department and two vestibular rehabilitation trained physiotherapists to establish a clinic to manage patients referred to ENT with vestibular and/or balance complaints. As part of a six-month pilot, two physiotherapy-led balance clinics were provided per week. A total of 159 new patients were seen, with only 15 needing ENT consultant input. This led to the successful creation of substantive posts; the clinic has seen 698 patients in its first two years. Patient outcomes and experience have been positive, and accompanied by reduced waiting and in-service times. The authors discuss some of the pitfalls, challenges and opportunities of developing this type of clinic.

International Variations in Surgical Quality of Care in Men With Prostate Cancer: Results From the TrueNTH Global Registry.

Functional problems such as incontinence and sexual dysfunction after radical prostatectomy (RP) are important outcomes to evaluate surgical quality in prostate cancer (PC) care. Differences in survival after RP between countries are known, but differences in functional outcomes after RP between providers from different countries are not well described. Data from a multinational database of patients with PC (nonmetastatic, treated by RP) who answered the EPIC-26 questionnaire at baseline (before RP, T0) and 1 year after RP (T1) were used, linking survey data to clinical information. Casemix-adjusted incontinence and sexual function scores (T1) were calculated for each country and provider on the basis of regression models and then compared using minimally important differences (MIDs). A total of 21,922 patients treated by 151 providers from 10 countries were included. For the EPIC-26 incontinence domain, the median adjusted T1 score of countries was 76, with one country performing more than one MID (for incontinence: 6) worse than the median. Eighteen percent of the variance (R2) of incontinence scores was explained by the country of the providers. The median adjusted T1 score of sexual function was 33 with no country performing perceivably worse than the median (more than one MID worse), and 34% (R2) of the variance of the providers' scores could be explained by country. To our knowledge, this is the first comparison of functional outcomes 1 year after surgical treatment of patients with PC between different countries. Country is a relevant predictor for providers' incontinence and sexual function scores. Although the results are limited because of small samples from some countries, they should be used to enhance cross-country initiatives on quality improvement in PC care.

Dissecting the surgeon's personality: cross-cultural comparisons in Western Europe.

The surgeon's personality contributes to variation in surgical decision-making. Previous work on surgeon personality has largely been reserved to Anglo-Saxon studies, with limited international comparisons. In this work we built upon recent work on gastrointestinal surgeon personality and aimed to detect international variations. Gastrointestinal surgeons from the UK and the Netherlands were invited to participate in validated personality assessments (44-item, 60-item Big Five Inventory; BFI). These encompass personality using five domains (open-mindedness, conscientiousness, extraversion, agreeableness and negative emotionality) with three subtraits each. Mean differences in domain factors were calculated between surgeon and nonsurgeon populations from normative data using independent-samples t-tests, adjusted for multiple testing. The items from the 44-item and 60-item BFI were compared between UK and Dutch surgeons and classified accordingly: identical (n = 16), analogous (n = 3), comparable (n = 12). UK (n = 78, 61.5% male) and Dutch (n = 280, 65% male) gastrointestinal surgeons had marked differences in the domains of open-mindedness, extraversion and agreeableness compared with national normative datasets. Moreover, although surgeons had similar levels of emotional stability, country of work influenced differences in specific BFI items. For example, Netherlands-based surgeons scored highly on questions related to sociability and organization versus UK-based surgeons who scored highly on creative imagination (p < 0.0001). In a first cross-cultural setting, we identified country-specific personality differences in gastrointestinal surgeon cohorts across domain and facet levels. Given the variation between Dutch and UK surgeons, understanding country-specific data could be useful in guiding personality research in healthcare. Furthermore, we advocate that future work adopts consensus usage of the five factor model.