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

Endometriosis-Related Infertility: The Role of the Assisted Reproductive Technologies

The assisted reproductive technologies, particularly in vitro fertilization (IVF), represent the most efficient and successful means of overcoming infertility associated with endometriosis. Although older studies suggest that IVF outcomes are compromised in endometriosis patients, more contemporary reports show no differences compared to controls. The exception may be evidence of poorer outcomes and diminished ovarian response in women with advanced disease, particularly those with significant ovarian involvement or prior ovarian surgery. Prolonged pre-IVF cycle suppressive medical therapy, particularly gonadotropin releasing hormone agonists, appears to improve success rates in a subset of endometriosis patients. However, as of yet, there is no diagnostic marker to specifically identify those who would most benefit from this approach. Pre-IVF cycle surgical resection of nonovarian disease has not been consistently shown to improve outcomes with the possible exception of resection of deeply invasive disease, although the data is limited. Precycle resection of ovarian endometriomas does not have benefit and should only be performed for gynecologic indications. Indeed, there is a large body of evidence to suggest that this procedure may have a deleterious impact on ovarian reserve and response. A dearth of appropriately designed trials makes development of definitive treatment paradigms challenging

GnRH agonists in the treatment of symptomatic endometriosis: a reviewEssential Points

The development of highly potent gonadotropin-releasing hormone agonists (GnRHa) allowed for a significant addition to options for the medical management of symptomatic endometriosis. Pituitary GnRH receptor down-regulation leads to a hypogonadotropic and secondary hypoestrogenic state resulting in lesion regression and symptom improvement. There may be an additional effect of these agents on the inflammatory processes associated with endometriosis as well. This is a review of critical milestones in the clinical application of these agents.Most initial trials of various GnRHa employed danazol as a control and demonstrated general equivalence in reducing symptoms and extent of lesions but without hyperandrogenic side effects and adverse metabolic changes induced by the latter. Short-acting GnRHa is administered intranasally or subcutaneously. Longer-acting preparations are administered intramuscularly or as subcutaneous implants. GnRHa also decrease symptom recurrence rates after surgical management. The hypoestrogenic side effects, including bone mineral density loss and vasomotor symptoms, have limited the duration of use of these agents alone to six months. The use of an appropriate add-back allows for the mitigation of side effects while maintaining efficacy and allowing extension of use for up to 12 months. There is a limited amount of data regarding the use of GnRHa in adolescents out of concern for the effect on developing bone. These agents should be used with caution in this group. The lack of dose flexibility, need for parental administration, and side effect profiles represent drawbacks to GnRHa use. The development of oral GnRH antagonists with short half-lives, variable dosing, and decreased side effects represents an exciting alternative

Nucleic acid detection using non-radioactive labelling methods.

Nucleic acid probe-based assays are now widely used in genetic research, human identification, forensics and in a broad spectrum of clinical assays in the fields of microbiology, haematology/oncology and virology. Labelled probes are used in a variety of assay formats including dot-blots, Southern blots (DNA target), Northern blots (RNA target), Western blots (protein target), in situ hybridization, plaque or colony screening and immobilized arrays on silicon or glass surfaces. Traditionally, the probes used in these assays have a radioactive 32phosphorous label that has a short shelf-life, is dangerous, has high disposal costs and, when labelled to high specific-activity, may be unstable. Extensive efforts to develop alternative labelling techniques have resulted in colorimetric, chemiluminescent and fluorescent assay formats. This review summarizes the properties desired in a probe, describes the advantages and disadvantages of the different non-radioactive labelling strategies, and illustrates examples of probe-based assays in which detection is facilitated by imaging samples using a general purpose fluorescence scanner

Reductions in endometriosis-associated pain among women treated with elagolix are consistent across a range of baseline characteristics reflective of real-world patients

Abstract Background Elagolix is an oral, gonadotropin-releasing hormone (GnRH) receptor antagonist, that significantly reduces dysmenorrhea and non-menstrual pelvic pain (NMPP) in women with moderate to severe endometriosis-associated pain. Methods Data were pooled from two 6-month, placebo-controlled, phase 3 studies (Elaris Endometriosis [EM]-I and II) in which 2 doses of elagolix were evaluated (150 mg once daily and 200 mg twice daily). Pooled data from > 1600 women, aged 18–49, were used to evaluate the efficacy of elagolix and health-related quality of life (HRQoL) in prespecified subgroups of women with various baseline characteristics. Results Of the 1686 women treated, 1285 (76.2%) completed the studies. The percentages of women with clinically meaningful reductions in dysmenorrhea and NMPP were generally consistent by subgroup. Significant treatment by subgroup interaction was demonstrated for dysmenorrhea response in baseline analgesic use (p < 0.01) and previous history of pregnancy (p < 0.05) subgroups, and for NMPP response in the baseline NMPP score (p < 0.05) and history of pregnancy (p < 0.05) subgroups. Patient-reported reduction in pain at month 3 was significant across all subgroups taking elagolix 200 mg BID, and significant across most subgroups with elagolix 150 mg QD. Women across subgroups experienced improvement within each domain of the Endometriosis Health Profile-30 (EHP-30), although significant treatment by subgroup interactions were observed in several categories. Conclusions Elagolix was effective in reducing dysmenorrhea and NMPP, and improving HRQoL, compared with placebo across numerous subgroups of women with various baseline characteristics, covering a broad segment of the endometriosis disease and patient types. Clinical trial registration: ClinicalTrials.gov: https://www.clinicaltrials.gov/ct2/show/NCT01620528 ; https://www.clinicaltrials.gov/ct2/show/NCT01931670

Real-World Characterization of Women with Diagnosed Endometriosis Initiating Therapy with Elagolix Using a US Claims Database.

PurposeElagolix is an oral gonadotropin-releasing hormone antagonist approved in the United States for the management of moderate to severe pain associated with endometriosis. We performed a real-world evaluation of the demographic and clinical characteristics of women diagnosed with endometriosis who were initiating elagolix therapy in the United States.Patients and methodsThis retrospective cohort database analysis included women 18-49 years of age with ≥1 pharmacy claim for elagolix between August 2018 and December 2019 from the Copyright © 2020 Truven Health Analytics LLC. All Rights Reserved. Women had continuous medical and pharmacy health plan enrollment during the baseline period (year immediately preceding the index date [date of earliest elagolix claim]) and had ≥1 medical claim with endometriosis (International Classification of Diseases [ICD]-9/10 code [617.x and N80.x]) on or before the index date. Baseline demographics, comorbidities, ICD code-based endometriosis anatomic site, endometriosis-related treatments, and pain symptoms were summarized descriptively.ResultsThe study included 2083 patients with mean age at baseline of 33.2 ± 8.1 years. Comorbidities most commonly recorded were non-cancer, non-endometriosis pain (59.5%), including arthritis/joint pain (43.7%) and back/neck pain (31.7%), and mental disorder (40.7%), including anxiety (32.7%). The majority of endometriosis diagnosis codes recorded referred to unspecified location (52.3%) and pelvic peritoneum (23.0%); 61.0% of patients received a medical endometriosis-related treatment in the baseline period, with the most common treatments being contraceptives (various routes of administration, 40.2%) and progestins (31.7%). Additionally, 35.4% of the patients received an endometriosis-related surgery during baseline, with the most common being laparoscopy (33.2% of all patients). Opioids were used during the baseline period by 57.3% of the patients. For pain symptoms, 71.5%, 30.4%, and 19.3% of the patients had claims for pelvic pain, dysmenorrhea, and dyspareunia, respectively.ConclusionEndometriosis therapies were used by a significant proportion of patients with endometriosis in the year immediately preceding elagolix initiation

Endometriosis-Related Pain Reduction During Bleeding and Nonbleeding Days in Women Treated with Elagolix.

ObjectiveIn this post hoc analysis, we evaluated the impact of elagolix on dysmenorrhea and nonmenstrual pelvic pain across menstrual period (bleeding days) and nonmenstrual (nonbleeding) days.MethodsData from two randomized, 6-month, placebo-controlled trials (Elaris Endometriosis (EM)-I and EM-II) of elagolix (150 mg once daily (QD) and 200 mg twice daily (BID)) in premenopausal women with moderate to severe endometriosis-associated pain (N = 1686) were pooled. Women recorded the presence of menstrual period and severity of dysmenorrhea or nonmenstrual pelvic pain in a daily electronic diary.ResultsAt baseline, women in the placebo group and both elagolix treatment groups reported moderate or severe dysmenorrhea, on average, 81% of their menstrual period days and moderate/severe nonmenstrual pelvic pain, on average, 56% of their nonmenstrual (nonbleeding) days. Compared with placebo at month 6, elagolix-treated women had a significantly lower mean (standard deviation (SD)) percentage of menstrual period days with moderate or severe dysmenorrhea (elagolix 150 mg QD = 52.4 (38.9), p = 0.002; elagolix 200 mg BID = 38.5 (43.6), p &lt; 0.001, placebo = 61.3 (33.7)) and a significantly lower mean (SD) percentage of nonmenstrual (nonbleeding) days with moderate or severe nonmenstrual pelvic pain (elagolix 150 mg QD = 31.1 (35.8), p &lt; 0.001; elagolix 200 mg BID = 19.7 (29.9), p &lt; 0.001; placebo = 35.6 (33.9)).ConclusionFollowing 6 months of elagolix treatment, women who still menstruated had a lower proportion of menstrual period days with moderate or severe dysmenorrhea compared with placebo, demonstrating pain reduction despite continued menses. Additionally, pain did not shift from dysmenorrhea to nonmenstrual pelvic pain, as the percentage of days with moderate or severe nonmenstrual pelvic pain was also reduced for elagolix-treated women compared with placebo.Trial registrationThe Elaris EM-I study is registered with the US National Library of Medicine, www.ClinicalTrials.gov, NCT01620528. The Elaris EM-II study is registered with the US National Library of Medicine, www.ClinicalTrials.gov, NCT01931670. Both studies are registered with the EU Clinical Trial Register, www.clinicaltrialsregister.ed, 2011-004295-11