Diagnosis of Opioid Use Disorder by Youths Assessed in Acute Care Settings in British Columbia, Canada.

OBJECTIVES: To describe trends in the number of youths diagnosed with opioid use disorder (OUD) and to identify factors associated with OUD diagnosis in acute care settings. STUDY DESIGN: Data from a population-based retrospective cohort study with linkage of 6 health administrative databases for 13 009 youth age 12-24 years identified with OUD between 2001 and 2018 in British Columbia, Canada were used to describe annual diagnoses. Using a multiple logistic regression model, we estimated the association between past-year health care utilization and OUD diagnosis in acute settings, controlling for sociodemographic and OUD-related comorbid conditions. RESULTS: Annual OUD diagnoses quadrupled between 2003 and 2017 (from 326 to 1473). Among the 6579 youth diagnosed with OUD between April 1, 2013 and September 30, 2018, 88.1% had past-year health system contacts. Youth age 12-18 had higher odds of OUD diagnosis in acute care (aOR 2.04; 95% CI 1.78, 2.34). Compared with no health care contact, youth receiving outpatient care only were less likely to be diagnosed with OUD in acute care (aOR 0.69; 95% CI 0.56, 0.84) and those with >1 urgent hospitalization were more likely to be diagnosed with OUD in acute care (aOR 1.87; 95% CI 1.40,2.49). CONCLUSIONS: More than 88% of youth had past-year health system contacts prior to diagnosis. Those age 12-18 years and with urgent hospitalizations in the year prior to diagnosis were more likely to have OUD diagnosed in acute care settings. Establishing an effective evidence-based system for early detection and intervention among youth with OUD must be a priority.

Coffee and pancreatic cancer risk among never-smokers in the UK prospective Million Women Study.

Reported associations between coffee consumption and an increased risk of pancreatic cancer could be due to residual confounding by smoking and/or biased recall of coffee consumption in retrospective studies. Studying associations prospectively in never smokers should minimize these problems, but thus far such studies have included relatively small numbers of cases. In our study, 309,797 never-smoking women self-reported typical daily coffee consumption at a mean age of 59.5 years (SD 5.0 years) and were followed up for a median of 13.7 years (IQR: 12.2-14.9) through record linkage to national health cancer and death registries. During this period, 962 incident cases of pancreatic cancers were registered. Cox regression was used to calculate adjusted relative risks [RRs] of incident pancreatic cancer with 95% confidence intervals [CIs] in relation to coffee consumption at baseline. After adjustment for potential confounding factors, including body mass index and alcohol consumption, RRs of pancreatic cancer in never-smokers who reported usually consuming 1-2, 3-4, and ≥ 5 cups of coffee daily, compared to nondrinkers of coffee, were 1.02 (CI 0.83-1.26), 0.96 (0.76-1.22), and 0.87 (0.64-1.18), respectively (trend p = 0.2). A meta-analysis of results from this cohort and 3 smaller prospective studies found little or no statistically significant association between coffee consumption and pancreatic cancer risk in never smokers (summary RR = 1.00, CI 0.86-1.17 for ≥2 vs. zero cups of coffee per day).

Differences in Prostate Cancer Transcriptomes by Age at Diagnosis: Are Primary Tumors from Older Men Inherently Different?

Older age at diagnosis is consistently associated with worse clinical outcomes in prostate cancer. We sought to characterize gene expression profiles of prostate tumor tissue by age at diagnosis. We conducted a discovery analysis in The Cancer Genome Atlas prostate cancer dataset (n = 320; 29% of men >65 years at diagnosis), using linear regressions of age at diagnosis and mRNA expression and adjusting for TMPRSS2:ERG fusion status and race. This analysis identified 13 age-related candidate genes at FDR < 0.1, six of which were also found in an analysis additionally adjusted for Gleason score. We then validated the 13 age-related genes in a transcriptome study nested in the Health Professionals Follow-up Study and Physicians' Health Study (n = 374; 53% of men >65 years). Gene expression differences by age in the 13 candidate genes were directionally consistent, and age at diagnosis was weakly associated with the 13-gene score. However, the age-related genes were not consistently associated with risk of metastases and prostate cancer-specific death. Collectively, these findings argue against tumor genomic differences as a main explanation for age-related differences in prostate cancer prognosis. PREVENTION RELEVANCE: Older age at diagnosis is consistently associated with worse clinical outcomes in prostate cancer. This study with independent discovery and validation sets and long-term follow-up suggests that prevention of lethal prostate cancer should focus on implementing appropriate screening, staging, and treatment among older men without expecting fundamentally different tumor biology.

European trends in cervical cancer mortality in relation to national screening programs, 1985-2014.

BACKGROUND: Cervical cancer is the fourth leading oncological cause of death in women. Variable trends in cervical cancer mortality have been observed across Europe, despite the widespread adoption of screening programs. This variability has previously been attributed to heterogeneity in the quality of screening programs. METHODS: Age-standardized cervical cancer death rates for European countries between 1985 and 2014 were analyzed using Joinpoint regression. Countries were dichotomized based on year of implementation and population invitational coverage of national population-based cervical cancer screening programs. National cervical cancer mortality trends during the study period were compared based on this classification. RESULTS: Decreasing trends in mortality were observed in all European countries with the specific exceptions of Bulgaria, Greece and Latvia. The highest rates of cervical cancer mortality throughout the study period were in Romania (16.0-14.9/100,000) and the lowest rates in Italy (1.4-1.2/100,000). The greatest percentage decline in mortality was observed in the United Kingdom and the greatest absolute reduction in mortality was seen in Hungary. European countries which implemented a national population-based cervical cancer screening program prior to 2009 demonstrated greater improvements in cervical cancer mortality outcomes compared to those that did not (p = 0.016). CONCLUSION: Cervical cancer mortality is improving in most European countries; however, substantial variation remains. Trends in mortality were associated with the time of implementation of national population-based cervical screening programs.

A systematic analysis of UK cancer research funding by gender of primary investigator.

OBJECTIVES: To categorically describe cancer research funding in the UK by gender of primary investigator (PIs). DESIGN: Systematic analysis of all open-access data. METHODS: Data about public and philanthropic cancer research funding awarded to UK institutions between 2000 and 2013 were obtained from several sources. Fold differences were used to compare total investment, award number, mean and median award value between male and female PIs. Mann-Whitney U tests were performed to determine statistically significant associations between PI gender and median grant value. RESULTS: Of the studies included in our analysis, 2890 (69%) grants with a total value of £1.82 billion (78%) were awarded to male PIs compared with 1296 (31%) grants with a total value of £512 million (22%) awarded to female PIs. Male PIs received 1.3 times the median award value of their female counterparts (P<0.001). These apparent absolute and relative differences largely persisted regardless of subanalyses. CONCLUSIONS: We demonstrate substantial differences in cancer research investment awarded by gender. Female PIs clearly and consistently receive less funding than their male counterparts in terms of total investment, the number of funded awards, mean funding awarded and median funding awarded.

Systemic Therapy in Metastatic or Unresectable Well-Differentiated/Dedifferentiated Liposarcoma.

Liposarcoma is one of the most common subtypes of soft-tissue sarcoma and consists of three main subtypes, of which well-differentiated liposarcoma and dedifferentiated liposarcoma account for 40-45%. The current mainstay of systemic treatment for patients with metastatic or unresectable disease remains doxorubicin with or without ifosfamide in the first-line setting. Recently, eribulin and trabectedin have been approved by the US Food and Drug Administration for recurrent liposarcomas and progress in molecular characterization of these tumors has opened up new and potential novel treatment targets. This review will focus on the evidence base for current treatment strategies and will also discuss potential future options.

Unemployment and HIV mortality in the countries of the Organisation for Economic Co-operation and Development: 1981-2009.

OBJECTIVES: To determine an association between unemployment rates and human immunodeficiency virus (HIV) mortality in the Organisation for Economic Co-operation and Development (OECD). DESIGN: Multivariate regression analysis. PARTICIPANTS: OECD member states. SETTING: OECD. MAIN OUTCOME MEASURES: World Health Organization HIV mortality. RESULTS: Between 1981 and 2009, a 1% increase in unemployment was associated with an increase in HIV mortality in the OECD (coefficient for men 0.711, 0.334-1.089, p = 0.0003; coefficient for women 0.166, 0.071-0.260, p = 0.0007). Time lag analysis showed a significant increase in HIV mortality for up to two years after rises in unemployment: p = 0.0008 for men and p = 0.0030 for women in year 1, p = 0.0067 for men and p = 0.0403 for women in year 2. CONCLUSIONS: Rises in unemployment are associated with increased HIV mortality. Economic fiscal policy may impact upon population health. Policy discussions should take into consideration potential health outcomes.

Effects of health and social care spending constraints on mortality in England: a time trend analysis.

OBJECTIVE: Since 2010, England has experienced relative constraints in public expenditure on healthcare (PEH) and social care (PES). We sought to determine whether these constraints have affected mortality rates. METHODS: We collected data on health and social care resources and finances for England from 2001 to 2014. Time trend analyses were conducted to compare the actual mortality rates in 2011-2014 with the counterfactual rates expected based on trends before spending constraints. Fixed-effects regression analyses were conducted using annual data on PES and PEH with mortality as the outcome, with further adjustments for macroeconomic factors and resources. Analyses were stratified by age group, place of death and lower-tier local authority (n=325). Mortality rates to 2020 were projected based on recent trends. RESULTS: Spending constraints between 2010 and 2014 were associated with an estimated 45 368 (95% CI 34 530 to 56 206) higher than expected number of deaths compared with pre-2010 trends. Deaths in those aged ≥60 and in care homes accounted for the majority. PES was more strongly linked with care home and home mortality than PEH, with each £10 per capita decline in real PES associated with an increase of 5.10 (3.65-6.54) (p<0.001) care home deaths per 100 000. These associations persisted in lag analyses and after adjustment for macroeconomic factors. Furthermore, we found that changes in real PES per capita may be linked to mortality mostly via changes in nurse numbers. Projections to 2020 based on 2009-2014 trend was cumulatively linked to an estimated 152 141 (95% CI 134 597 and 169 685) additional deaths. CONCLUSIONS: Spending constraints, especially PES, are associated with a substantial mortality gap. We suggest that spending should be targeted on improving care delivered in care homes and at home; and maintaining or increasing nurse numbers.

Investments in cancer research awarded to UK institutions and the global burden of cancer 2000-2013: a systematic analysis.

OBJECTIVES: To systematically categorise cancer research investment awarded to United Kingdom (UK) institutions in the period 2000-2013 and to estimate research investment relative to disease burden as measured by mortality, disability-adjusted life years (DALYs) and years lived with disability (YLDs). DESIGN: Systematic analysis of all open-access data. SETTING AND PARTICIPANTS: Public and philanthropic funding to all UK cancer research institutions, 2000-2013. MAIN OUTCOME MEASURES: Number and financial value of cancer research investments reported in 2013 UK pounds (UK£). Mortality, DALYs and YLDs data were acquired from the Global Burden of Disease Study. A compound metric was adapted to estimate research investment relative to disease burden as measured by mortality, DALYs and YLDs. RESULTS: We identified 4299 funded studies with a total research investment of £2.4 billion. The highest fundings by anatomical sites were haematological, breast, prostate, colorectal and ovarian cancers. Relative to disease burden as determined by a compound metric combining mortality, DALYs and YLDs, gender-specific cancers were found to be highest funded-the five sites that received the most funding were prostate, ovarian, breast, mesothelioma and testicular cancer; the least well-funded sites were liver, thyroid, lung, upper gastrointestinal (GI) and bladder. Preclinical science accounted for 66.2% of award numbers and 62.2% of all funding. The top five areas of primary research focus by funding were pathogenesis, drug therapy, diagnostic, screening and monitoring, women's health and immunology. The largest individual funder was the Medical Research Council. In combination, the five lowest funded site-specific cancers relative to disease burden account for 47.9%, 44.3% and 20.4% of worldwide cancer mortality, DALYs and YLDs. CONCLUSIONS: Research funding for cancer is not allocated according to relative disease burden. These findings are in line with earlier published studies. Funding agencies and industry should openly document their research investments to improve better targeting of research investment.

The impact of team familiarity and surgical experience on operative efficiency: a retrospective analysis.

OBJECTIVES: The independent impact of individual surgical experience and team familiarity on surgical performance has been widely studied; however, the interplay of these factors and their relative, quantified, contributions to performance is poorly understood. We determined the impact of team familiarity and surgeon, and cumulative team experience on operative efficiency in total knee replacement. DESIGN: Retrospective analysis of all total knee replacements conducted at the host institution in 1996-2009. Multivariate generalised-estimating-equation regression models were used to adjust for patient risk and clustering. SETTING: Tertiary care academic hospital. PARTICIPANTS: All patients undergoing TKR at the host institution in 1996-2009. MAIN OUTCOME MEASURE: Operative efficiency. RESULTS: A total of 4276 total knee replacements were completed by 1163 different surgical teams. The median experience level was 17.6 years for consultant surgeons and 3.7 years for trainee surgeons. After patient-risk adjustment, consultant surgical experience (p < 0.0001), trainee surgical experience (p < 0.05), cumulative team operative experience (p < 0.0001) and team familiarity (p < 0.0001) were associated with significant reductions in operative time. Surgical experience and team familiarity demonstrated concave and linear relationships with operative time, respectively. For a consultant surgeon, the expected reduction in operative time after 25 years in practice was 51 min, compared to a 21-min reduction over the span of 40 collaborations with the same team members. CONCLUSIONS: Surgical experience and team familiarity display important and distinct relationships with operative time in total knee replacement. Appreciation of this interplay may serve to guide implementation and allocation of procedure-specific quality improvement strategies in surgery.

Unmasking the surgeons: the evidence base behind the use of facemasks in surgery.

The use of surgical facemasks is ubiquitous in surgical practice. Facemasks have long been thought to confer protection to the patient from wound infection and contamination from the operating surgeon and other members of the surgical staff. More recently, protection of the theatre staff from patient-derived blood/bodily fluid splashes has also been offered as a reason for their continued use. In light of current NHS budget constraints and cost-cutting strategies, we examined the evidence base behind the use of surgical facemasks. Examination of the literature revealed much of the published work on the matter to be quite dated and often studies had poorly elucidated methodologies. As a result, we recommend caution in extrapolating their findings to contemporary surgical practice. However, overall there is a lack of substantial evidence to support claims that facemasks protect either patient or surgeon from infectious contamination. More rigorous contemporary research is needed to make a definitive comment on the effectiveness of surgical facemasks.

Unemployment, public-sector health care expenditure and HIV mortality: An analysis of 74 countries, 1981-2009.

BACKGROUND: The global economic downturn has been associated with increased unemployment and reduced public-sector expenditure on health care (PSEH). We determined the association between unemployment, PSEH and HIV mortality. METHODS: Data were obtained from the World Bank and the World Health Organisation (1981-2009). Multivariate regression analysis was implemented, controlling for country-specific demographics and infrastructure. Time-lag analyses and robustness-checks were performed. FINDINGS: Data were available for 74 countries (unemployment analysis) and 75 countries (PSEH analysis), equating to 2.19 billion and 2.22 billion people, respectively, as of 2009. A 1% increase in unemployment was associated with a significant increase in HIV mortality (men: 0.1861, 95% CI: 0.0977 to 0.2744, P = 0.0000, women: 0.0383, 95% CI: 0.0108 to 0.0657, P = 0.0064). A 1% increase in PSEH was associated with a significant decrease in HIV mortality (men: -0.5015, 95% CI: -0.7432 to -0.2598, P = 0.0001; women: -0.1562, 95% CI: -0.2404 to -0.0720, P = 0.0003). Time-lag analysis showed that significant changes in HIV mortality continued for up to 5 years following variations in both unemployment and PSEH. INTERPRETATION: Unemployment increases were associated with significant HIV mortality increases. PSEH increases were associated with reduced HIV mortality. The facilitation of access-to-care for the unemployed and policy interventions which aim to protect PSEH could contribute to improved HIV outcomes.