Safety of Atrovent® CFC-free inhaler:respiratory events reported from an observational cohort study in England

ObjectivesThe aim of the study was to identify any unexpected clinical events associated with starting the new CFC‐free formulation of Atrovent® MDI in general practice in England.MethodsAn active surveillance cohort study was conducted with a focus on selected clinical events, including respiratory symptoms, in past users of Atrovent® CFC MDI (‘switchers’) and Atrovent® naïve users. Incidence density rate ratios (with 99% confidence intervals) for events occurring in the first 3 months of exposure (risk period‐ID1‐3) compared to 3 months prior to starting treatment (reference period‐IDR) were calculated.ResultsThe cohort consisted of 13 211 patients (median age 70 years, 50.1% female; 63.5% prior users of Atrovent® CFC MDI (‘switchers’)). Common respiratory events occurred at higher rates after starting treatment than before for switchers, for example lower respiratory tract infection (LRTI) [ID1/IDR = 1.45 (99% CI: 1.17, 1.81)] and worsening asthma [ID1/IDR = 1.58 (99% CI: 1.00, 2.51)]. Of these events only LRTI was significant for Atrovent® naïve patients [ID1/IDR = 1.42 (99% CI: 1.04, 1.95)].ConclusionsThe results of this study suggest effect modification of risk as a result of prior Atrovent® CFC MDI use. Overall, Atrovent® CFC‐free MDI appeared to be reasonably well tolerated in the immediate postmarketing period and the safety profile appeared similar to that of the CFC formulation

In Situ Hybridization for Molecular Detection of Human Papilloma Viral 6 / 11 DNA in Adenoctomized Tissues from A group of Iraqi Pediatric Patients

هنالك أكثر من 200 من الأنماط الجينية لفايروس الورمي الحليمي البشري والتي تم التعرف عليها من خلال  الترابط مابين الانماط الجينية ذات الاختطار الواطئ للفايروس الحليمي البشري مع مجموعة متنوعة من الأورام الفموية والبلعوم والبلعوم الأنفي وكذلك الأورام الحليمية غير الخبيثة  وتضخم الغدة. هدفت هذه الدراسة  من نوع الاستقصائية- السيطرة إلى تحديد الحمض النووي للفيروس الورمي الحليمي البشري 6/11 في انسجة الغدد البلعومية الأنفية واللوزتين لمجموعة من المرضى الذين يخضعون لاستئصال اللوزتين. تم الحصول على 60عينة من أنسجة اللوزتين الأنفية البلعومية من الأطفال الذين يعانون من تضخم اللوزتين الغدي, تضمنت 40 من أنسجة اللوزتين الأنفية البلعومية للمرضى الذين يعانون من تضخم غدي ، و 20 عينة نسجية من الأطفال  بعد عمليات التشذيب للانسجة الأنفية السفلية بدون  تغييرات مرضية ملحوظة (كمجموعة  سيطرة). تم اجراء الكشف الجزيئي عن الحامض النووي للفيروس الورمي الحليمي البشري نمط 6\11 باستخدام تقنية التهجين الموضعي ذات الحساسية العالية في عينات الأنسجة الضخمة الغدية ز تم العثور على 8 من أصل 40 تحتوي على نتائج إيجابية للحمض النووي للفيروس الحليمي البشري 6\11 حيث شكلت 20 ٪ من إجمالي الأنسجة الغدية البلعومية الأنفية.بينما لاتوجد أي اشارة موجبة للحامض النووي للفايروس الحليمي البشري نمط 6\11 في مجموعة السيطرة. أظهر التحليل الإحصائي للنتائج في هذا البحث اختلافًا كبيرًا مقارنةً  مابين مجموعتي المرضى والسيطرة عند مستوى احتمالية اقل او يساوي 5%. يمكن أن يلعب فيروس الورم الحليمي البشري ذات الاختطار الواطئ في تلك الأنسجة الغدية المتضخمة دورًا في التسبب في الأمراض و / أو يشكل عامل  لانتشار العدوى الفيروسية للانسجة الاخرىAmong more than 200 different human papilloma viral genotypes, the association of low oncogenic risk-HPV genotypes have been recognized with a variety of oral, oropharyngeal, nasopharyngeal benign tumors as well as non-neoplastic polyposis and papillomas and adenoid hypertrophy. This prospective case- control study aims to determine the rate of DNA detection of HPV genotype 6/11 in nasopharyngeal adeno- tonsillar tissues from a group of patients subjected to adenoctomy for adenoid hypertrophy . A total number of nasopharyngeal adeno-tonsillar tissue specimens from pediatric patients with adenoid hypertrophy were enrolled; 40 nasopharyngeal adeno-tonsillar tissues from patients with adenoid hypertrophy, and 20 normal nasal tissue specimens were obtained from pediatric patients following trimming operations of their inferior nasal turbinates' with unremarkable pathological changes (as an apparently healthy control group). The molecular detection methods for HPV detection were performed by using DNA probes via a recent version of chromogenic in situ hybridization specified for low- risk HPV genotypes.  Among total adenoid hypertrophied tissue specimens group, 8 out of 40 were found to contain positive results for DNA of HPV 6 / 11 genotype, constituting 20% of the total screened nasopharyngeal adenotonsillar tissues. No positive– CISH reactions were detected in the control nasal tissues. The statistical analysis of results in this research showed significant difference when compared to the control apparently healthy tissues.   The significant rate of low- oncogenic HPV genotypes detection in those adenoid hypertrophied tissues could play, in part, a role in their pathogenesis and / or constituting a herald focus for the spread of such important virally transmitted infection

Review on the influence of process parameters in incremental sheet forming

Incremental sheet forming (ISF) is a relatively new flexible forming process. ISF has excellent adaptability to conventional milling machines and requires minimum use of complex tooling, dies and forming press, which makes the process cost-effective and easy to automate for various applications. In the past two decades, extensive research on ISF has resulted in significant advances being made in fundamental understanding and development of new processing and tooling solutions. However, ISF has yet to be fully implemented to mainstream high-value manufacturing industries due to a number of technical challenges, all of which are directly related to ISF process parameters. This paper aims to provide a detailed review of the current state-of-the-art of ISF processes in terms of its technological capabilities and specific limitations with discussions on the ISF process parameters and their effects on ISF processes. Particular attention is given to the ISF process parameters on the formability, deformation and failure mechanics, springback and accuracy and surface roughness. This leads to a number of recommendations that are considered essential for future research effort

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<00001), age 70 years or older versus younger than 70 years (230 [165-322], p<00001), American Society of Anesthesiologists grades 3-5 versus grades 1-2 (235 [157-353], p<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

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

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Genome Wide Analysis of Drug-Induced Torsades de Pointes: Lack of Common Variants with Large Effect Sizes

Marked prolongation of the QT interval on the electrocardiogram associated with the polymorphic ventricular tachycardia Torsades de Pointes is a serious adverse event during treatment with antiarrhythmic drugs and other culprit medications, and is a common cause for drug relabeling and withdrawal. Although clinical risk factors have been identified, the syndrome remains unpredictable in an individual patient. Here we used genome-wide association analysis to search for common predisposing genetic variants. Cases of drug-induced Torsades de Pointes (diTdP), treatment tolerant controls, and general population controls were ascertained across multiple sites using common definitions, and genotyped on the Illumina 610k or 1M-Duo BeadChips. Principal Components Analysis was used to select 216 Northwestern European diTdP cases and 771 ancestry-matched controls, including treatment-tolerant and general population subjects. With these sample sizes, there is 80% power to detect a variant at genome-wide significance with minor allele frequency of 10% and conferring an odds ratio of ≥2.7. Tests of association were carried out for each single nucleotide polymorphism (SNP) by logistic regression adjusting for gender and population structure. No SNP reached genome wide-significance; the variant with the lowest P value was rs2276314, a non-synonymous coding variant in C18orf21 (p  =  3×10(-7), odds ratio = 2, 95% confidence intervals: 1.5-2.6). The haplotype formed by rs2276314 and a second SNP, rs767531, was significantly more frequent in controls than cases (p  =  3×10(-9)). Expanding the number of controls and a gene-based analysis did not yield significant associations. This study argues that common genomic variants do not contribute importantly to risk for drug-induced Torsades de Pointes across multiple drugs