Non-invasive ventilation in obesity hypoventilation syndrome without severe obstructive sleep apnoea

Background Non-invasive ventilation (NIV) is an effective form of treatment in patients with obesity hypoventilation syndrome (OHS) who have concomitant severe obstructive sleep apnoea (OSA). However, there is a paucity of evidence on the efficacy of NIV in patients with OHS without severe OSA. We performed a multicentre randomised clinical trial to determine the comparative efficacy of NIV versus lifestyle modification (control group) using daytime arterial carbon dioxide tension (PaCO2) as the main outcome measure. Methods Between May 2009 and December 2014 we sequentially screened patients with OHS without severe OSA. Participants were randomised to NIV versus lifestyle modification and were followed for 2 months. Arterial blood gas parameters, clinical symptoms, health-related quality of life assessments, polysomnography, spirometry, 6-min walk distance test, blood pressure measurements and healthcare resource utilisation were evaluated. Statistical analysis was performed using intention-to-treat analysis. Results A total of 365 patients were screened of whom 58 were excluded. Severe OSA was present in 221 and the remaining 86 patients without severe OSA were randomised. NIV led to a significantly larger improvement in PaCO2 of -6 (95% CI -7.7 to -4.2) mm Hg versus -2.8 (95% CI -4.3 to -1.3) mm Hg, (p<0.001) and serum bicarbonate of -3.4 (95% CI -4.5 to -2.3) versus -1 (95% CI -1.7 to -0.2 95% CI) mmol/L (p<0.001). PaCO2 change adjusted for NIV compliance did not further improve the inter-group statistical significance. Sleepiness, some health-related quality of life assessments and polysomnographic parameters improved significantly more with NIV than with lifestyle modification. Additionally, there was a tendency towards lower healthcare resource utilisation in the NIV group. Conclusions NIV is more effective than lifestyle modification in improving daytime PaCO2, sleepiness and polysomnographic parameters. Long-term prospective studies are necessary to determine whether NIV reduces healthcare resource utilisation, cardiovascular events and mortality

Acrylamide and Glycidamide Hemoglobin Adducts and Epithelial Ovarian Cancer: A Nested Case-Control Study in Nonsmoking Postmenopausal Women from the EPIC Cohort

Background: Acrylamide was classified as “probably carcinogenic to humans (group 2A)” by the International Agency for Research on Cancer. Epithelial ovarian cancer (EOC) is the fourth cause of cancer mortality in women. Five epidemiological studies have evaluated the association between EOC risk and dietary acrylamide intake assessed using food frequency questionnaires, and one nested case–control study evaluated hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) and EOC risk; the results of these studies were inconsistent. Methods: A nested case–control study in nonsmoking postmenopausal women (334 cases, 417 controls) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Unconditional logistic regression models were used to estimate ORs and 95% confidence intervals (CI) for the association between HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA and EOC and invasive serous EOC risk. Results: No overall associations were observed between biomarkers of acrylamide exposure analyzed in quintiles and EOC risk; however, positive associations were observed between some middle quintiles of HbGA and HbAA+HbGA. Elevated but nonstatistically significant ORs for serous EOC were observed for HbGA and HbAA+HbGA (ORQ5vsQ1, 1.91; 95% CI, 0.96–3.81 and ORQ5vsQ1, 1.90; 95% CI, 0.94–3.83, respectively); however, no linear dose–response trends were observed. Conclusion: This EPIC nested case–control study failed to observe a clear association between biomarkers of acrylamide exposure and the risk of EOC or invasive serous EOC. Impact: It is unlikely that dietary acrylamide exposure increases ovarian cancer risk; however, additional studies with larger sample size should be performed to exclude any possible association with EOC risk

An epidemiological model for prediction of endometrial cancer risk in Europe

Endometrial cancer (EC) is the fourth most frequent cancer in women in Europe, and as its incidence is increasing, prevention strategies gain further pertinence. Risk prediction models can be a useful tool for identifying women likely to benefit from targeted prevention measures. On the basis of data from 201,811 women (mostly aged 30–65 years) including 855 incident EC cases from eight countries in the European Prospective Investigation into Cancer and Nutrition cohort, a model to predict EC was developed. A step-wise model selection process was used to select confirmed predictive epidemiologic risk factors. Piece-wise constant hazard rates in 5-year age-intervals were estimated in a cause-specific competing risks model, five-fold-cross-validation was applied for internal validation. Risk factors included in the risk prediction model were body-mass index (BMI), menopausal status, age at menarche and at menopause, oral contraceptive use, overall and by different BMI categories and overall duration of use, parity, age at first full-term pregnancy, duration of menopausal hormone therapy and smoking status (specific for pre, peri- and post-menopausal women). These variables improved the discriminating capacity to predict risk over 5 years from 71 % for a model based on age alone to 77 % (overall C statistic), and the model was well-calibrated (ratio of expected to observed cases = 0.99). Our model could be used for the identification of women at increased risk of EC in Western Europe. To achieve an EC-risk model with general validity, a large-scale cohort-consortium approach would be needed to assess and adjust for population variation

Circulating Osteopontin and Prediction of Hepatocellular Carcinoma Development in a Large European Population

We previously identified osteopontin (OPN) as a promising marker for the early detection of hepatocellular carcinoma (HCC). In this study, we investigated the association between pre-diagnostic circulating OPN levels and HCC incidence in a large population-based cohort. A nested-case control study was conducted within the EPIC cohort. During a mean follow-up of 4.8 years, 100 HCC cases were identified. Each case was matched to two controls and OPN levels were measured in baseline plasma samples. Viral hepatitis, liver function and alpha-fetoprotein (AFP) tests were also conducted. Conditional logistic regression models were used to calculate multivariable odds ratio (OR) and 95% confidence intervals (95%CI) for OPN levels in relation to HCC. Receiver operating characteristics curves were constructed to determine the discriminatory accuracy of OPN alone or in combination with other liver biomarkers in the prediction of HCC. OPN levels were positively associated with HCC risk (per 10% increment, ORmultivariable=1.30; 95%CI:1.14-1.48). The association was stronger among cases diagnosed within two years of follow-up. Adding liver function tests to OPN improved the discriminatory performance for subjects who developed HCC (AUC=0.86). For cases diagnosed within two years, the combination of OPN and AFP was best able to predict HCC risk (AUC=0.88). The best predictive model for HCC in this low-risk population is OPN in combination with liver function tests. Within two years of diagnosis, the combination of OPN and AFP best predicted HCC development, suggesting that measuring OPN and AFP could identify high-risk groups independently of a liver disease diagnosis

The comparative responsiveness of Hospital Universitario Princesa Index and other composite indices for assessing rheumatoid arthritis activity

Objective To evaluate the responsiveness in terms of correlation of the Hospital Universitario La Princesa Index (HUPI) comparatively to the traditional composite indices used to assess disease activity in rheumatoid arthritis (RA), and to compare the performance of HUPI-based response criteria with that of the EULAR response criteria. Methods Secondary data analysis from the following studies: ACT-RAY (clinical trial), PROAR (early RA cohort) and EMECAR (pre-biologic era long term RA cohort). Responsiveness was evaluated by: 1) comparing change from baseline (Delta) of HUPI with Delta in other scores by calculating correlation coefficients; 2) calculating standardised effect sizes. The accuracy of response by HUPI and by EULAR criteria was analyzed using linear regressions in which the dependent variable was change in global assessment by physician (Delta GDA-Phy). Results Delta HUPI correlation with change in all other indices ranged from 0.387 to 0.791); HUPI's standardized effect size was larger than those from the other indices in each database used. In ACT-RAY, depending on visit, between 65 and 80% of patients were equally classified by HUPI and EULAR response criteria. However, HUPI criteria were slightly more stringent, with higher percentage of patients classified as non-responder, especially at early visits. HUPI response criteria showed a slightly higher accuracy than EULAR response criteria when using Delta GDA-Phy as gold standard. Conclusion HUPI shows good responsiveness in terms of correlation in each studied scenario (clinical trial, early RA cohort, and established RA cohort). Response criteria by HUPI seem more stringent than EULAR''s

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 (740%) had emergency surgery and 280 (248%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (261%) patients. 30-day mortality was 238% (268 of 1128). Pulmonary complications occurred in 577 (512%) of 1128 patients; 30-day mortality in these patients was 380% (219 of 577), accounting for 817% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 175 [95% CI 128-240], p&lt;00001), age 70 years or older versus younger than 70 years (230 [165-322], p&lt;00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p&lt;00001), malignant versus benign or obstetric diagnosis (155 [101-239], p=0046), emergency versus elective surgery (167 [106-263], p=0026), and major versus minor surgery (152 [101-231], p=0047). 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

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

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