Centre for Advancing Health Outcomes

Context and Purpose of This Guideline
\nStatement of Remit
\nTo align with its mission to reduce the global burden of raised
\nblood pressure (BP), the International Society of Hypertension
\n(ISH) has developed worldwide practice guidelines for the
\nmanagement of hypertension in adults, aged 18 years and
\nolder.
\nThe ISH Guidelines Committee extracted evidence-based
\ncontent presented in recently published extensively reviewed
\nguidelines and tailored and standards
\nof care in a practical format that is easy-to-use particularly
\nin low, but also in high resource settings – by clinicians, but
\nalso nurses and community health workers, as appropriate.
\nAlthough distinction between low and high resource settings
\noften refers to high (HIC) and low- and middle-income countries (LMIC), it is well established that in HIC there are areas
\nwith low resource settings, and vice versa.
\nHerein optimal care refers to evidence-based standard of
\ncare articulated in recent guidelines1,2 and summarized here,
\nwhereas standards recognize that
\nstandards would not always be possible. Hence essential standards refer to minimum standards of care. To allow specification of essential standards of care for low resource settings,
\nthe Committee was often confronted with the limitation or
\nabsence in clinical evidence, and thus applied expert opinion

BACKGROUND: Overweight and obese persons are at risk of a number of medical conditions which can lead to further morbidity and mortality. The primary objective of this study is to provide an estimate of the incidence of each co-morbidity related to obesity and overweight using a meta-analysis. METHODS: A literature search for the twenty co-morbidities identified in a preliminary search was conducted in Medline and Embase (Jan 2007). Studies meeting the inclusion criteria (prospective cohort studies of sufficient size reporting risk estimate based on the incidence of disease) were extracted. Study-specific unadjusted relative risks (RRs) on the log scale comparing overweight with normal and obese with normal were weighted by the inverse of their corresponding variances to obtain a pooled RR with 95% confidence intervals (CI). RESULTS: A total of 89 relevant studies were identified. The review found evidence for 18 co-morbidities which met the inclusion criteria. The meta-analysis determined statistically significant associations for overweight with the incidence of type II diabetes, all cancers except esophageal (female), pancreatic and prostate cancer, all cardiovascular diseases (except congestive heart failure), asthma, gallbladder disease, osteoarthritis and chronic back pain. We noted the strongest association between overweight defined by body mass index (BMI) and the incidence of type II diabetes in females (RR = 3.92 (95% CI: 3.10-4.97)). Statistically significant associations with obesity were found with the incidence of type II diabetes, all cancers except esophageal and prostate cancer, all cardiovascular diseases, asthma, gallbladder disease, osteoarthritis and chronic back pain. Obesity defined by BMI was also most strongly associated with the incidence of type II diabetes in females (12.41 (9.03-17.06)). CONCLUSION: Both overweight and obesity are associated with the incidence of multiple co-morbidities including type II diabetes, cancer and cardiovascular diseases. Maintenance of a healthy weight could be important in the prevention of the large disease burden in the future. Further studies are needed to explore the biological mechanisms that link overweight and obesity with these co-morbidities.

CONTEXT: Gene expression analysis has identified several breast cancer subtypes, including basal-like, human epidermal growth factor receptor-2 positive/estrogen receptor negative (HER2+/ER-), luminal A, and luminal B. OBJECTIVES: To determine population-based distributions and clinical associations for breast cancer subtypes. DESIGN, SETTING, AND PARTICIPANTS: Immunohistochemical surrogates for each subtype were applied to 496 incident cases of invasive breast cancer from the Carolina Breast Cancer Study (ascertained between May 1993 and December 1996), a population-based, case-control study that oversampled premenopausal and African American women. Subtype definitions were as follows: luminal A (ER+ and/or progesterone receptor positive [PR+], HER2-), luminal B (ER+ and/or PR+, HER2+), basal-like (ER-, PR-, HER2-, cytokeratin 5/6 positive, and/or HER1+), HER2+/ER- (ER-, PR-, and HER2+), and unclassified (negative for all 5 markers). MAIN OUTCOME MEASURES: We examined the prevalence of breast cancer subtypes within racial and menopausal subsets and determined their associations with tumor size, axillary nodal status, mitotic index, nuclear pleomorphism, combined grade, p53 mutation status, and breast cancer-specific survival. RESULTS: The basal-like breast cancer subtype was more prevalent among premenopausal African American women (39%) compared with postmenopausal African American women (14%) and non-African American women (16%) of any age (P<.001), whereas the luminal A subtype was less prevalent (36% vs 59% and 54%, respectively). The HER2+/ER- subtype did not vary with race or menopausal status (6%-9%). Compared with luminal A, basal-like tumors had more TP53 mutations (44% vs 15%, P<.001), higher mitotic index (odds ratio [OR], 11.0; 95% confidence interval [CI], 5.6-21.7), more marked nuclear pleomorphism (OR, 9.7; 95% CI, 5.3-18.0), and higher combined grade (OR, 8.3; 95% CI, 4.4-15.6). Breast cancer-specific survival differed by subtype (P<.001), with shortest survival among HER2+/ER- and basal-like subtypes. CONCLUSIONS: Basal-like breast tumors occurred at a higher prevalence among premenopausal African American patients compared with postmenopausal African American and non-African American patients in this population-based study. A higher prevalence of basal-like breast tumors and a lower prevalence of luminal A tumors could contribute to the poor prognosis of young African American women with breast cancer.

Large-scale societies in which strangers regularly engage in mutually beneficial transactions are puzzling. The evolutionary mechanisms associated with kinship and reciprocity, which underpin much of primate sociality, do not readily extend to large unrelated groups. Theory suggests that the evolution of such societies may have required norms and institutions that sustain fairness in ephemeral exchanges. If that is true, then engagement in larger-scale institutions, such as markets and world religions, should be associated with greater fairness, and larger communities should punish unfairness more. Using three behavioral experiments administered across 15 diverse populations, we show that market integration (measured as the percentage of purchased calories) positively covaries with fairness while community size positively covaries with punishment. Participation in a world religion is associated with fairness, although not across all measures. These results suggest that modern prosociality is not solely the product of an innate psychology, but also reflects norms and institutions that have emerged over the course of human history.

Document reviewers: Hind Beheiry (Sudan), Irina Chazova (Russia), Albertino Damasceno (Mozambique), Anna Dominiczak (UK), Anastase Dzudie (Cameroon), Stephen Harrap (Australia), Hiroshi Itoh (Japan), Tazeen Jafar (Singapore), Marc Jaffe (USA), Patricio Jaramillo-Lopez (Colombia), Kazuomi Kario (Japan), Giuseppe Mancia (Italy), Ana Mocumbi (Mozambique), Sanjeevi N.Narasingan (India), Elijah Ogola (Kenya), Srinath Reddy (India), Ernesto Schiffrin (Canada), Ann Soenarta (Indonesia), Rhian Touyz (UK), Yudah Turana (Indonesia), Michael Weber (USA), Paul Whelton (USA), Xin Hua Zhang, (Australia), Yuqing Zhang (China).

BACKGROUND: Percutaneous aortic valve replacement represents an endovascular alternative to conventional open heart surgery without the need for sternotomy, aortotomy, or cardiopulmonary bypass. METHODS AND RESULTS: Transcatheter implantation of a balloon-expandable stent valve using a femoral arterial approach was attempted in 50 symptomatic patients with severe aortic stenosis in whom there was a consensus that the risks of conventional open heart surgery were very high. Valve implantation was successful in 86% of patients. Intraprocedural mortality was 2%. Discharge home occurred at a median of 5 days (interquartile range, 4 to 13). Mortality at 30 days was 12% in patients in whom the logistic European System for Cardiac Operative Risk Evaluation risk score was 28%. With experience, procedural success increased from 76% in the first 25 patients to 96% in the second 25 (P=0.10), and 30-day mortality fell from 16% to 8% (P=0.67). Successful valve replacement was associated with an increase in echocardiographic valve area from 0.6+/-0.2 to 1.7+/-0.4 cm2. Mild paravalvular regurgitation was common but was well tolerated. After valve insertion, there was a significant improvement in left ventricular ejection fraction (P<0.0001), mitral regurgitation (P=0.01), and functional class (P<0.0001). Improvement was maintained at 1 year. Structural valve deterioration was not observed with a median follow-up of 359 days. CONCLUSIONS: Percutaneous valve replacement may be an alternative to conventional open heart surgery in selected high-risk patients with severe symptomatic aortic stenosis.

Peer Reviewed

BACKGROUND: Asthma is associated with enormous healthcare expenditures that include both direct and indirect costs. It is also associated with the loss of future potential earnings related to both morbidity and mortality. The objective of the study is to determine the burden of disease costs associated with asthma. METHODS: We performed a systematic search of MEDLINE, EMBASE, CINAHL, CDSR, OHE-HEED, and Web of Science Databases between 1966 and 2008. RESULTS: Sixty-eight studies met the inclusion criteria. Hospitalization and medications were found to be the most important cost driver of direct costs. Work and school loss accounted for the greatest percentage of indirect costs. The cost of asthma was correlated with comorbidities, age, and disease severity. CONCLUSION: Despite the availability of effective preventive therapy, costs associated with asthma are increasing. Strategies including education of patients and physicians, and regular follow-up are required to reduce the economic burden of asthma.

BACKGROUND: The effects of less-tight versus tight control of hypertension on pregnancy complications are unclear. METHODS: We performed an open, international, multicenter trial involving women at 14 weeks 0 days to 33 weeks 6 days of gestation who had nonproteinuric preexisting or gestational hypertension, office diastolic blood pressure of 90 to 105 mm Hg (or 85 to 105 mm Hg if the woman was taking antihypertensive medications), and a live fetus. Women were randomly assigned to less-tight control (target diastolic blood pressure, 100 mm Hg) or tight control (target diastolic blood pressure, 85 mm Hg). The composite primary outcome was pregnancy loss or high-level neonatal care for more than 48 hours during the first 28 postnatal days. The secondary outcome was serious maternal complications occurring up to 6 weeks post partum or until hospital discharge, whichever was later. RESULTS: Included in the analysis were 987 women; 74.6% had preexisting hypertension. The primary-outcome rates were similar among 493 women assigned to less-tight control and 488 women assigned to tight control (31.4% and 30.7%, respectively; adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.77 to 1.35), as were the rates of serious maternal complications (3.7% and 2.0%, respectively; adjusted odds ratio, 1.74; 95% CI, 0.79 to 3.84), despite a mean diastolic blood pressure that was higher in the less-tight-control group by 4.6 mm Hg (95% CI, 3.7 to 5.4). Severe hypertension (≥160/110 mm Hg) developed in 40.6% of the women in the less-tight-control group and 27.5% of the women in the tight-control group (P<0.001). CONCLUSIONS: We found no significant between-group differences in the risk of pregnancy loss, high-level neonatal care, or overall maternal complications, although less-tight control was associated with a significantly higher frequency of severe maternal hypertension. (Funded by the Canadian Institutes of Health Research; CHIPS Current Controlled Trials number, ISRCTN71416914; ClinicalTrials.gov number, NCT01192412.).

BACKGROUND: Transcatheter aortic valve implantation is an alternative to open heart surgery in patients with aortic stenosis. However, long-term data on a programmatic approach to aortic valve implantation remain sparse. METHODS AND RESULTS: Transcatheter aortic valve implantation was performed in 168 patients (median age, 84 years) in the setting of severe aortic stenosis and high surgical risk. Access was transarterial (n=113) or, in the presence of small iliofemoral artery diameter, transapical (n=55). The overall success rate was 94.1% in this early experience. Intraprocedural mortality was 1.2%. Operative (30-day) mortality was 11.3%, lower in the transarterial group than the transapical group (8.0% versus 18.2%; P=0.07). Overall mortality fell from 14.3% in the initial half to 8.3% in the second half of the experience, from 12.3% to 3.6% (P=0.16) in transarterial patients and from 25% to 11.1% (P=0.30) in transapical patients. Functional class improved over the 1-year postprocedure period (P<0.001). Survival at 1 year was 74%. The bulk of late readmission and mortality was not procedure or valve related but rather was due to comorbidities. Paravalvular regurgitation was common but generally mild and remained stable at late follow-up. At a maximum of >3 years and a median of 221 days, structural valve failure was not observed. CONCLUSIONS: Transcatheter aortic valve implantation can result in early and sustained functional improvement in high-risk aortic stenosis patients. Late outcome is determined primarily by comorbidities unrelated to aortic valve disease.

In this paper, we define the Association of Standardized Patient Educators (ASPE) Standards of Best Practice (SOBP) for those working with human role players who interact with learners in a wide range of experiential learning and assessment contexts. These human role players are variously described by such terms as standardized/simulated patients or simulated participants (SP or SPs). ASPE is a global organization whose mission is to share advances in SP-based pedagogy, assessment, research, and scholarship as well as support the professional development of its members. The SOBP are intended to be used in conjunction with the International Nursing Association for Clinical Simulation and Learning (INACSL) Standards of Best Practice: Simulation SM , which address broader simulation practices. We begin by providing a rationale for the creation of the ASPE SOBP, noting that with the increasing use of simulation in healthcare training, it is incumbent on ASPE to establish SOBP that ensure the growth, integrity, and safe application of SP-based educational endeavors. We then describe the three and a half year process through which these standards were developed by a consensus of international experts in the field. Key terms used throughout the document are defined. Five underlying values inform the SOBP: safety, quality, professionalism, accountability, and collaboration. Finally, we describe five domains of best practice: safe work environment; case development; SP training for role portrayal, feedback, and completion of assessment instruments; program management; and professional development. Each domain is divided into principles with accompanying key practices that provide clear and practical guidelines for achieving desired outcomes and creating simulations that are safe for all stakeholders. Failure to follow the ASPE SOBP could compromise the safety of participants and the effectiveness of a simulation session. Care has been taken to make these guidelines precise yet flexible enough to address the diversity of varying contexts of SP practice. As a living document, these SOBP will be reviewed and modified periodically under the direction of the ASPE Standards of Practice Committee as SP methodology grows and adapts to evolving simulation practices.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

BACKGROUND: Previous reports of variations in outcomes among neonatal intensive care units (NICUs) examined only specific subpopulations of interest (eg, very low birth weight [VLBW] infants <1500 g of birth weight [BW]). OBJECTIVES: We report on current practice and outcomes variations in a population-based national study of Canadian NICUs from January 8, 1996 to October 31, 1997. METHOD: Information on 20 488 admissions to 17 tertiary level NICUs across Canada was prospectively collected by trained abstractors using a standard manual of operations and definitions. Data were verified and analyzed in concert with a steering committee comprising experienced researchers and neonatologists. Patient information included demographic information, antenatal history, mode of delivery, problems at delivery, status of infant and problems at birth, illness severity (Clinical Risk Index for Babies, Score for Neonatal Acute Physiology, Score for Neonatal Acute Physiology-Version II), therapeutic intensity (Neonatal Therapeutic Intensity Scoring System [NTISS]), selected NICU practices and procedures, use of technology and resources, and selected patient outcomes. Patients were tracked until death or discharge home. RESULTS: The mean number of annual admissions to an NICU was 657, with 26% outborn infants. Fifty-three percent were <2500 g BW, 20% were <1500 g BW (VLBW), and 65% were preterm (<38 weeks' gestational age [GA]). Only 2% of mothers received no prenatal care. Antenatal steroids were given to 58%, but there was wide variation in use (23%-76%). Congenital anomalies were present in 14%, and 4% were small for GA (less than the third percentile). Admission illness severity was lowest among infants 33 to 37 weeks of GA and correlated with risk of death. Ninety-six percent of patients survived until discharge, but fewer survived at lower GA. No infant <22 weeks' GA survived. Seven percent of infants had at least 1 episode of infection, but 75% received antibiotics in the NICU. Forty-three percent received respiratory support, and 14% received surfactant. Nitric oxide was given to 150 term infants and to 102 preterm infants. Selected outcomes of VLBW infants were: survival rate (87%); chronic lung disease (26%); >/=stage 3 retinopathy of prematurity (ROP; 11%); >/=grade 3 intraventricular hemorrhage (IVH; 10%); nosocomial infection (22%); necrotizing enterocolitis (NEC; 7%). Sixty-nine percent of VLBW infants survived without major morbidity (>/=grade 3 IVH, chronic lung disease, NEC, >/=grade 3 ROP). The mean duration of NICU stay was 19 days. Forty-seven percent of infants were discharged from the hospital, and 43% were retrotransferred to a community facility before discharge home. Significant variation in practices and outcomes were observed in all aspects of NICU care. CONCLUSION: This study provides population-based information about NICU outcomes. Significant variation in NICU practices and outcomes was observed despite Canada's universal health insurance system. This national database provides valuable information for planning research, allocating resources, designing health and public policy, and serving as a basis for longitudinal studies of NICU care in Canada.

BACKGROUND: Every year in Ontario, the records of over 42 million prescriptions dispensed to persons eligible for Ontario Drug Benefit (ODB) benefits are transmitted to a central database. The ODB database is the second largest database of medications in Canada, containing records on almost half of all medications dispensed in Ontario. There is no information about the reliability of the coding on the ODB drug claims database and, therefore, the objective of this study was to estimate the reliability of coding of the Drug Identification Number, and the date, quantity and duration of the dispensation on claims sent to the ODB. METHODS: To meet this objective, approximately 100 randomly selected prescriptions dispensed from each of 50 pharmacies in southern Ontario between July 1, 1998 and December 31, 1999 were audited. For each claim, the written information on the prescription was compared with the electronic information submitted to the ODB database. Logistic regression was used to test the association between coding errors and the location, owner affiliation, and productivity of each pharmacy (defined as the annual volume of dispensations divided by the annual number of hours worked by all pharmacists and pharmacy assistants). RESULTS: Of the 183 pharmacies owners invited to participate, consent to abstract information was obtained in 50, yielding a participation rate of 27%. Of the 5155 dispensed prescriptions, 37 errors were found, yielding an overall error rate of 0.7% (95% CI 0.5% to 0.9%). None of the characteristics of pharmacies that were examined (location, owner affiliation, productivity) was associated with coding errors. CONCLUSIONS: Pharmacists almost always dispense the medication that is prescribed and this information is reliably transmitted to the ODB drug claims database. This means that any conclusions drawn by researchers using these data are not likely to be compromised by low coding reliability.

BACKGROUND: The 5-level version of the EQ-5D (EQ-5D-5L) was recently developed. A number of preference-based scoring systems are being developed for several countries around the world. OBJECTIVE: To develop a value set for the EQ-5D-5L based on societal preferences in Canada. METHODS: We used age, sex, and education quota sampling from the general population from 4 cities across Canada. Composite time trade-off (cTTO) and traditional time trade-off (tTTO) were used as the main elicitation technique. A total of 86 EQ-5D-5L health states grouped into 10 blocks were valued using cTTO, whereas a subset of 18 severe states was also valued using tTTO. Participants meeting predefined inconsistency criteria were excluded from the analyses. For the value set development, we used tTTO and positive cTTO values, while censoring negative and zero cTTO values at zero. Models with the main effects presented using linear terms combined with various additional terms were estimated. The preferred model was selected based primarily on logically ordered coefficients, and secondly model fit. RESULTS: Of the 1209 participants who completed the interview, 136 met criteria that excluded them from the primary analyses. The demographics and socioeconomic status of the remaining 1073 participants were similar to the Canadian general population. The preferred model has 5 linear terms for the main effects, a term for level 4 or 5 for each dimension, and a term for the squared total number of level 4 or 5 beyond the first. For this preferred model, the health utilities ranged from -0.148 for the worst (55555) to 0.949 for the best (11111) EQ-5D-5L states. CONCLUSIONS: This is the first TTO-based value set of the EQ-5D-5L for Canada. It can be used to support the health utility estimation in economic evaluations for reimbursement decision making in Canada.

Objectives In the first wave of the COVID-19 pandemic, social isolation, school/child care closures and employment instability have created unprecedented conditions for families raising children at home. This study describes the mental health impacts of the COVID-19 pandemic on families with children in Canada. Design, setting and participants This descriptive study used a nationally representative, cross-sectional survey of adults living in Canada (n=3000) to examine the mental health impacts of the COVID-19 pandemic. Outcomes among parents with children &lt;18 years old living at home (n=618) were compared with the rest of the sample. Data were collected via an online survey between 14 May to 29 May 2020. Outcome measures Participants reported on changes to their mental health since the onset of the pandemic and sources of stress, emotional responses, substance use patterns and suicidality/self-harm. Additionally, parents identified changes in their interactions with their children, impacts on their children’s mental health and sources of support accessed. Results 44.3% of parents with children &lt;18 years living at home reported worse mental health as a result of the COVID-19 pandemic compared with 35.6% of respondents without children &lt;18 living at home, χ 2 (1, n=3000)=16.2, p&lt;0.001. More parents compared with the rest of the sample reported increased alcohol consumption (27.7% vs 16.1%, χ 2 (1, n=3000)=43.8, p&lt;0.001), suicidal thoughts/feelings (8.3% vs 5.2%, χ 2 (1, n=3000)=8.0, p=0.005) and stress about being safe from physical/emotional domestic violence (11.5% vs 7.9%, χ 2 (1, n=3000)=8.1, p=0.005). 24.8% (95% CI 21.4 to 28.4) of parents reported their children’s mental health had worsened since the pandemic. Parents also reported more frequent negative as well as positive interactions with their children due to the pandemic (eg, more conflicts, 22.2% (95% CI 19.0 to 25.7); increased feelings of closeness, 49.7% (95% CI 45.7 to 53.7)). Conclusions This study identifies that families with children &lt;18 at home have experienced deteriorated mental health due to the pandemic. Population-level responses are required to adequately respond to families’ diverse needs and mitigate the potential for widening health and social inequities for parents and children.

OBJECTIVES/HYPOTHESIS: To determine the evidence for different etiologies of sudden sensorineural hearing loss (SSNHL) identified by clinical diagnostic tests in the adult population. STUDY DESIGN: Systematic literature review. METHODS: Review of MEDLINE (1950-October 2009), EMBASE (1980-October 2009), and EBM Review databases in addition to manual reference search of identified papers. Randomized controlled trials, prospective cohort studies, and retrospective reviews of consecutive patients in which a clear definition of SSNHL was stated and data from consecutive patients were reported with respect to etiology of hearing loss. Three researchers independently extracted data regarding patient demographic information, diagnostic tests employed, and the identified presumed etiologies. Discrepancies were resolved by mutual consensus. RESULTS: : Twenty-three articles met the inclusion criteria. The first group of papers searched for different etiologies among patients with SSNHL. Multiple etiologies were identified, including viral infection, vascular impairment, autoimmune disease, inner ear pathology, and central nervous system anomalies. The diagnosis for the majority of patients remained idiopathic. The second group of papers evaluated SSNHL patients with specific diagnostic tests such as autoimmune markers, hemostatic parameters, and diagnostic imaging. CONCLUSIONS: The suspected etiologies for patients suffering sudden sensorineural hearing loss included idiopathic (71.0%), infectious disease (12.8%), otologic disease (4.7%), trauma (4.2%), vascular or hematologic (2.8%), neoplastic (2.3%), and other causes (2.2%). Establishment of a direct causal link between SSNHL and these etiologies remains elusive. Diagnostic imaging is a useful method for identification of temporal bone or intracranial pathology that can present with SSNHL as a primary symptom.

BACKGROUND: Chronic neuropathic pain affects 1%-2% of the adult population and is often refractory to standard pharmacologic treatment. Patients with chronic pain have reported using smoked cannabis to relieve pain, improve sleep and improve mood. METHODS: Adults with post-traumatic or postsurgical neuropathic pain were randomly assigned to receive cannabis at four potencies (0%, 2.5%, 6% and 9.4% tetrahydrocannabinol) over four 14-day periods in a crossover trial. Participants inhaled a single 25-mg dose through a pipe three times daily for the first five days in each cycle, followed by a nine-day washout period. Daily average pain intensity was measured using an 11-point numeric rating scale. We recorded effects on mood, sleep and quality of life, as well as adverse events. RESULTS: We recruited 23 participants (mean age 45.4 [standard deviation 12.3] years, 12 women [52%]), of whom 21 completed the trial. The average daily pain intensity, measured on the 11-point numeric rating scale, was lower on the prespecified primary contrast of 9.4% v. 0% tetrahydrocannabinol (5.4 v. 6.1, respectively; difference = 0.7, 95% confidence interval [CI] 0.02-1.4). Preparations with intermediate potency yielded intermediate but nonsignificant degrees of relief. Participants receiving 9.4% tetrahydrocannabinol reported improved ability to fall asleep (easier, p = 0.001; faster, p < 0.001; more drowsy, p = 0.003) and improved quality of sleep (less wakefulness, p = 0.01) relative to 0% tetrahydrocannabinol. We found no differences in mood or quality of life. The most common drug-related adverse events during the period when participants received 9.4% tetrahydrocannabinol were headache, dry eyes, burning sensation in areas of neuropathic pain, dizziness, numbness and cough. CONCLUSION: A single inhalation of 25 mg of 9.4% tetrahydrocannabinol herbal cannabis three times daily for five days reduced the intensity of pain, improved sleep and was well tolerated. Further long-term safety and efficacy studies are indicated. (International Standard Randomised Controlled Trial Register no. ISRCTN68314063).

IMPORTANCE: Surgical site infection (SSI) complicates 2-5% of surgeries in the United States. Severity of SSI ranges from superficial skin infection to life-threatening conditions such as severe sepsis, and SSIs are responsible for increased morbidity, mortality, and economic burden associated with surgery. Staphylococcus aureus (S. aureus) is a commonly-isolated organism for SSI, and methicillin-resistant S. aureus SSI incidence is increasing globally. OBJECTIVE: The objective of this systematic review was to characterize risk factors for SSI within observational studies describing incidence of SSI in a real-world setting. EVIDENCE REVIEW: An initial search identified 328 titles published in 2002-2012; 57 were identified as relevant for data extraction. Extracted information included study design and methodology, reported cumulative incidence and post-surgical time until onset of SSI, and odds ratios and associated variability for all factors considered in univariate and/or multivariable analyses. FINDINGS: Median SSI incidence was 3.7%, ranging from 0.1% to 50.4%. Incidence of overall SSI and S. aureus SSI were both highest in tumor-related and transplant surgeries. Median time until SSI onset was 17.0 days, with longer time-to-onset for orthopedic and transplant surgeries. Risk factors consistently identified as associated with SSI included co-morbidities, advanced age, risk indices, patient frailty, and surgery complexity. Thirteen studies considered diabetes as a risk factor in multivariable analysis; 85% found a significant association with SSI, with odds ratios ranging from 1.5-24.3. Longer surgeries were associated with increased SSI risk, with a median odds ratio of 2.3 across 11 studies reporting significant results. CONCLUSIONS AND RELEVANCE: In a broad review of published literature, risk factors for SSI were characterized as describing reduced fitness, patient frailty, surgery duration, and complexity. Recognition of risk factors frequently associated with SSI allows for identification of such patients with the greatest need for optimal preventive measures to be identified and pre-treatment prior to surgery.

Morphological evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer is gaining momentum as evidence strengthens the clinical relevance of this immunological biomarker. TILs in the post-neoadjuvant residual disease setting are acquiring increasing importance as a stratifying marker in clinical trials, considering the raising interest on immunotherapeutic strategies after neoadjuvant chemotherapy. TILs in ductal carcinoma in situ, with or without invasive carcinoma, represent an emerging area of clinical breast cancer research. The aim of this report is to update pathologists, clinicians and researchers on TIL assessment in both the post-neoadjuvant residual disease and the ductal carcinoma in situ settings. The International Immuno-Oncology Working Group proposes a method for assessing TILs in these settings, based on the previously published International Guidelines on TIL Assessment in Breast Cancer. In this regard, these recommendations represent a consensus guidance for pathologists, aimed to achieve the highest possible consistency among future studies.