Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49\ub74% (95% uncertainty interval [UI] 46\ub74–52\ub70). The TFR decreased from 4\ub77 livebirths (4\ub75–4\ub79) to 2\ub74 livebirths (2\ub72–2\ub75), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83\ub78 million people per year since 1985. The global population increased by 197\ub72% (193\ub73–200\ub78) since 1950, from 2\ub76 billion (2\ub75–2\ub76) to 7\ub76 billion (7\ub74–7\ub79) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2\ub70%; this rate then remained nearly constant until 1970 and then decreased to 1\ub71% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2\ub75% in 1963 to 0\ub77% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2\ub77%. The global average age increased from 26\ub76 years in 1950 to 32\ub71 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59\ub79% to 65\ub73%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1\ub70 livebirths (95% UI 0\ub79–1\ub72) in Cyprus to a high of 7\ub71 livebirths (6\ub78–7\ub74) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0\ub708 livebirths (0\ub707–0\ub709) in South Korea to 2\ub74 livebirths (2\ub72–2\ub76) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0\ub73 livebirths (0\ub73–0\ub74) in Puerto Rico to a high of 3\ub71 livebirths (3\ub70–3\ub72) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2\ub70% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation

Screening genetic variability at the CNR1 gene in both major depression etiology and clinical response to citalopram treatment.

RATIONALE: The endocannabinoid system has been implicated in the pathogenesis of major depression (MD) as well as in the mediation of antidepressant drug effects. OBJECTIVES: To analyze CNR1 gene variants in MD and clinical response to citalopram (selective serotonin re-uptake inhibitors [SSRI]). METHODS: The role of CNR1 gene (rs806368, rs1049353, rs806371, rs806377 and rs1535255) was investigated in 319 outpatients with MD and 150 healthy individuals. A subsample of 155 depressive patients were treated with citalopram and evaluated for response (fourth week) and remission (12th week) by the 21-item Hamilton Depression Rating Scale (HDRS). RESULTS: We observed a higher frequency of rs806371 G carriers in MD patients with both presence of melancholia (p\u2009=\u20090.018) and psychotic symptoms (p\u2009=\u20090.007) than in controls. Haplotype frequency distributions between MD sample and controls showed a significant difference for Block 1 (rs806368-rs1049353-rs806371) (p\u2009=\u20090.008). This haplotype finding was consistent when we compared controls with MD subsample stratified by melancholia (p\u2009=\u20090.0009) and psychotic symptoms (p\u2009=\u20090.014). The TT homozygous of the rs806368 and rs806371 presented more risk of no Remission than the C carriers (p\u2009=\u20090.008 and 0.012, respectively). Haplotype frequency distributions according to Remission status showed a significant difference for Block 1 (p\u2009=\u20090.032). Also, we observed significant effect of time-sex-genotype interaction for the rs806368, showing that the C carrier men presented a better response to antidepressant treatment throughout the follow-up than TT homozygous men and women group (p\u2009=\u20090.026). CONCLUSIONS: These results suggest an effect of CNR1 gene in the etiology of MD and clinical response to citalopram

Prolonged viral shedding in pandemic influenza A(H1N1): Clinical significance and viral load analysis in hospitalized patients

The clinical significance of prolonged viral shedding (PVS) and viral load (VL) dynamics has not been sufficiently assessed in hospitalized patients with pandemic 2009 influenza A(H1N1). We performed a prospective study of adults with confirmed influenza A(H1N1) virus infection admitted to our hospital from 20 September 2009 to 31 December 2009. Consecutive nasopharyngeal swabs were collected every 2 days during the first week after diagnosis, and then every week or until viral detection was negative. Relative VL was measured on the basis of haemagglutinin and RNaseP gene analysis. PVS was defined as positive detection of influenza A(H1N1) virus by real-time RT-PCR at day 7 after diagnosis. We studied 64 patients: 16 (25%) presented PVS. The factors associated with PVS were admission to the intensive-care unit (69% vs. 33%, p0.02), purulent expectoration (75% vs. 44%, p0.04), higher dosage of oseltamivir (62.5% vs. 27%, p0.016), corticosteroid treatment (50% vs. 21%, p0.05), mechanical ventilation (MV) (50% vs. 12.5%, p0.004), and longer stay (34 vs. 7 median days, p0.003). Multivariate analysis revealed the factors independently associated with PVS to be immunosuppression (OR 5.15; 95% CI 1.2-22.2; p0.03) and the need for MV (OR 11.7; 95% CI 2.5-54.4; p0.002). VL at diagnosis correlated negatively with age and septic shock. VL dynamics of patients with acute respiratory distress syndrome and/or mortality were very different from those of other patients. PVS was detected in 25% of hospitalized patients with pandemic 2009 influenza A(H1N1) and was strongly associated with immunosuppression and the need for MV. Diagnostic VL and viral clearance varied with the clinical course. \ua9 2010 The Authors. Clinical Microbiology and Infection \ua9 2010 European Society of Clinical Microbiology and Infectious Diseases

TPH1, MAOA, serotonin receptor 2A and 2C genes in citalopram response: possible effect in melancholic and psychotic depression.

BACKGROUND: Serotonergic genes have been widely investigated regarding antidepressant response in major depressive disorder (MDD) but results are still not univocal. METHODS: 159 MDD patients treated with citalopram were genotyped and evaluated by the 21-item Hamilton Depression Rating Scale at the beginning and every 4 weeks during the 12-week follow-up. Four serotonin-related genetic variants were tested for association with treatment outcome: tryptophane hydroxylase 1 (TPH1) rs1800532, monoamine oxidase A \ub5VNTR, serotonin 2A receptor rs6311 and serotonin 2C receptor rs6318. The effect of these polymorphisms was tested both in the whole sample and in depressive subtypes with usually higher clinical severity: psychotic and melancholic MDD. RESULTS: No effect on response, remission and symptom improvement was found for the four polymorphisms. However, rs1800532 was found to affect the outcome depending on the MDD subtype: the A allele predicted worse response both in MDD with psychotic (F\u2086,\u2083\u2087\u2088 = 2.90; p = 0.009) and melancholic (F\u2086,\u2083\u2088\u2081 = 2.86; p = 0.0097) features. CONCLUSIONS: The A allele at TPH1 rs1800532 may be associated with citalopram efficacy only in melancholic and psychotic MDD. These results suggest the usefulness of investigating the effect of genetic variants in conjunction with specific clinical features

Karu-INIA, nuevo cultivar de papa para Chile

Karu-INIA is a new potato ( Solanum tuberosum L.) cultivar, created from a cross between the cultivars Yagana-INIA x Fanfare by the Potato Breeding Program of the National Agricultural Research Institue (INIA), at the Remehue Regional Research Center, Osorno, Chile, in 1989. It is a semi-erect plant, with vigorous growth, a medium to large size, long oval-shaped tuber, red skin and clear yellow flesh. It is a high yielding cultivar and adapts well to the majority of the potato production areas and crop seasons in Chile. It is preferred for fresh consumption, although it has fairly good frying quality, similar to Yagana-INIA.Karu-INIA es un nuevo cultivar de papa ( Solanum tuberosum L.) creado a partir del cruzamiento Yagana-INIA x Fanfare, por el Programa de Mejoramiento Gen\ue9tico de la Papa del Instituto de Investigaciones Agropecuarias (INIA), en el Centro Regional de Investigaci\uf3n Remehue, Osorno, el a\uf1o 1989. Es una planta semi erecta, de buen vigor, con tub\ue9rculos de tama\uf1o medio a grande, uniformes, de forma oval alargada, piel roja y pulpa amarilla clara. Posee altos rendimientos y se adapta bien a la mayor\ueda de las zonas y \ue9pocas de cultivo de la papa en Chile. Su uso preferente es para consumo fresco, aunque produce una fritura de calidad altamente aceptable, similar a Yagana-INIA

Update of EULAR recommendations for the treatment of systemic sclerosis

The aim was to update the 2009 European League against Rheumatism (EULAR) recommendations for the treatment of systemic sclerosis (SSc), with attention to new therapeutic questions. Update of the previous treatment recommendations was performed according to EULAR standard operating procedures. The task force consisted of 32 SSc clinical experts from Europe and the USA, 2 patients nominated by the pan-European patient association for SSc (Federation of European Scleroderma Associations (FESCA)), a clinical epidemiologist and 2 research fellows. All centres from the EULAR Scleroderma Trials and Research group were invited to submit and select clinical questions concerning SSc treatment using a Delphi approach. Accordingly, 46 clinical questions addressing 26 different interventions were selected for systematic literature review. The new recommendations were based on the available evidence and developed in a consensus meeting with clinical experts and patients. The procedure resulted in 16 recommendations being developed (instead of 14 in 2009) that address treatment of several SSc-related organ complications: Raynaud's phenomenon (RP), digital ulcers (DUs), pulmonary arterial hypertension (PAH), skin and lung disease, scleroderma renal crisis and gastrointestinal involvement. Compared with the 2009 recommendations, the 2016 recommendations include phosphodiesterase type 5 (PDE-5) inhibitors for the treatment of SSc-related RP and DUs, riociguat, new aspects for endothelin receptor antagonists, prostacyclin analogues and PDE-5 inhibitors for SSc-related PAH. New recommendations regarding the use of fluoxetine for SSc-related RP and haematopoietic stem cell transplantation for selected patients with rapidly progressive SSc were also added. In addition, several comments regarding other treatments addressed in clinical questions and suggestions for the SSc research agenda were formulated. These updated data-derived and consensus-derived recommendations will help rheumatologists to manage patients with SSc in an evidence-based way. These recommendations also give directions for future clinical research in SSc

Spending on health and HIV/AIDS: domestic health spending and development assistance in 188 countries, 1995\u20132015

Background: Comparable estimates of health spending are crucial for the assessment of health systems and to optimally deploy health resources. The methods used to track health spending continue to evolve, but little is known about the distribution of spending across diseases. We developed improved estimates of health spending by source, including development assistance for health, and, for the first time, estimated HIV/AIDS spending on prevention and treatment and by source of funding, for 188 countries. Methods: We collected published data on domestic health spending, from 1995 to 2015, from a diverse set of international agencies. We tracked development assistance for health from 1990 to 2017. We also extracted 5385 datapoints about HIV/AIDS spending, between 2000 and 2015, from online databases, country reports, and proposals submitted to multilateral organisations. We used spatiotemporal Gaussian process regression to generate complete and comparable estimates for health and HIV/AIDS spending. We report most estimates in 2017 purchasing-power parity-adjusted dollars and adjust all estimates for the effect of inflation. Findings: Between 1995 and 2015, global health spending per capita grew at an annualised rate of 3\ub71% (95% uncertainty interval [UI] 3\ub71 to 3\ub72), with growth being largest in upper-middle-income countries (5\ub74% per capita [UI 5\ub73\u20135\ub75]) and lower-middle-income countries (4\ub72% per capita [4\ub72\u20134\ub73]). In 2015, 9\ub77 trillion (9\ub77 trillion to 9\ub78 trillion) was spent on health worldwide. High-income countries spent 6\ub75 trillion (6\ub74 trillion to 6\ub75 trillion) or 66\ub73% (66\ub70 to 66\ub75) of the total in 2015, whereas low-income countries spent 70\ub73 billion (69\ub73 billion to 71\ub73 billion) or 0\ub77% (0\ub77 to 0\ub77). Between 1990 and 2017, development assistance for health increased by 394\ub77% (29\ub79 billion), with an estimated 37\ub74 billion of development assistance being disbursed for health in 2017, of which 9\ub71 billion (24\ub72%) targeted HIV/AIDS. Between 2000 and 2015, 562\ub76 billion (531\ub71 billion to 621\ub79 billion) was spent on HIV/AIDS worldwide. Governments financed 57\ub76% (52\ub70 to 60\ub78) of that total. Global HIV/AIDS spending peaked at 49\ub77 billion (46\ub72\u201354\ub77) in 2013, decreasing to 48\ub79 billion (45\ub72 billion to 54\ub72 billion) in 2015. That year, low-income and lower-middle-income countries represented 74\ub76% of all HIV/AIDS disability-adjusted life-years, but just 36\ub76% (34\ub74 to 38\ub77) of total HIV/AIDS spending. In 2015, 9\ub73 billion (8\ub75 billion to 10\ub74 billion) or 19\ub70% (17\ub76 to 20\ub76) of HIV/AIDS financing was spent on prevention, and 27\ub73 billion (24\ub75 billion to 31\ub71 billion) or 55\ub78% (53\ub73 to 57\ub79) was dedicated to care and treatment. Interpretation: From 1995 to 2015, total health spending increased worldwide, with the fastest per capita growth in middle-income countries. While these national disparities are relatively well known, low-income countries spent less per person on health and HIV/AIDS than did high-income and middle-income countries. Furthermore, declines in development assistance for health continue, including for HIV/AIDS. Additional cuts to development assistance could hasten this decline, and risk slowing progress towards global and national goals. Funding: The Bill & Melinda Gates Foundation

The Global Burden of Cancer 2013

Importance - Cancer is among the leading causes of death worldwide. Current estimates of cancer burden in individual countries and regions are necessary to inform local cancer control strategies. Objective - To estimate mortality, incidence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 28 cancers in 188 countries by sex from 1990 to 2013. Evidence Review - The general methodology of the Global Burden of Disease (GBD) 2013 study was used. Cancer registries were the source for cancer incidence data as well as mortality incidence (MI) ratios. Sources for cause of death data include vital registration system data, verbal autopsy studies, and other sources. The MI ratios were used to transform incidence data to mortality estimates and cause of death estimates to incidence estimates. Cancer prevalence was estimated using MI ratios as surrogates for survival data; YLDs were calculated by multiplying prevalence estimates with disability weights, which were derived from population-based surveys; YLLs were computed by multiplying the number of estimated cancer deaths at each age with a reference life expectancy; and DALYs were calculated as the sum of YLDs and YLLs. Findings - In 2013 there were 14.9 million incident cancer cases, 8.2 million deaths, and 196.3 million DALYs. Prostate cancer was the leading cause for cancer incidence (1.4 million) for men and breast cancer for women (1.8 million). Tracheal, bronchus, and lung (TBL) cancer was the leading cause for cancer death in men and women, with 1.6 million deaths. For men, TBL cancer was the leading cause of DALYs (24.9 million). For women, breast cancer was the leading cause of DALYs (13.1 million). Age-standardized incidence rates (ASIRs) per 100 000 and age-standardized death rates (ASDRs) per 100 000 for both sexes in 2013 were higher in developing vs developed countries for stomach cancer (ASIR, 17 vs 14; ASDR, 15 vs 11), liver cancer (ASIR, 15 vs 7; ASDR, 16 vs 7), esophageal cancer (ASIR, 9 vs 4; ASDR, 9 vs 4), cervical cancer (ASIR, 8 vs 5; ASDR, 4 vs 2), lip and oral cavity cancer (ASIR, 7 vs 6; ASDR, 2 vs 2), and nasopharyngeal cancer (ASIR, 1.5 vs 0.4; ASDR, 1.2 vs 0.3). Between 1990 and 2013, ASIRs for all cancers combined (except nonmelanoma skin cancer and Kaposi sarcoma) increased by more than 10% in 113 countries and decreased by more than 10% in 12 of 188 countries. Conclusions and relevance - Cancer poses a major threat to public health worldwide, and incidence rates have increased in most countries since 1990. The trend is a particular threat to developing nations with health systems that are ill-equipped to deal with complex and expensive cancer treatments. The annual update on the Global Burden of Cancer will provide all stakeholders with timely estimates to guide policy efforts in cancer prevention, screening, treatment, and palliation