Interobserver variability studies in diagnostic imaging: a methodological systematic review.

OBJECTIVES: To review the methodology of interobserver variability studies; including current practice and quality of conducting and reporting studies. METHODS: Interobserver variability studies between January 2019 and January 2020 were included; extracted data comprised of study characteristics, populations, variability measures, key results, and conclusions. Risk of bias was assessed using the COSMIN tool for assessing reliability and measurement error. RESULTS: Seventy-nine full-text studies were included covering various imaging tests and clinical areas. The median number of patients was 47 (IQR:23-88), and observers were 4 (IQR:2-7), with sample size justified in 12 (15%) studies. Most studies used static images (n = 75, 95%), where all observers interpreted images for all patients (n = 67, 85%). Intraclass correlation coefficients (ICC) (n = 41, 52%), Kappa (κ) statistics (n = 31, 39%) and percentage agreement (n = 15, 19%) were most commonly used. Interpretation of variability estimates often did not correspond with study conclusions. The COSMIN risk of bias tool gave a very good/adequate rating for 52 studies (66%) including any studies that used variability measures listed in the tool. For studies using static images, some study design standards were not applicable and did not contribute to the overall rating. CONCLUSIONS: Interobserver variability studies have diverse study designs and methods, the impact of which requires further evaluation. Sample size for patients and observers was often small without justification. Most studies report ICC and κ values, which did not always coincide with the study conclusion. High ratings were assigned to many studies using the COSMIN risk of bias tool, with certain standards scored 'not applicable' when static images were used. ADVANCES IN KNOWLEDGE: The sample size for both patients and observers was often small without justification. For most studies, observers interpreted static images and did not evaluate the process of acquiring the imaging test, meaning it was not possible to assess many COSMIN risk of bias standards for studies with this design. Most studies reported intraclass correlation coefficient and κ statistics; study conclusions often did not correspond with results.

Post-Implant Phosphodiesterase-5 Inhibitors in Patients with Left Ventricular Assist Device: A Systematic Review and Meta-Analysis.

Background: Despite the improvement in left ventricular assist device (LVAD) technology and the advent of third-generation LVADs, hemocompatibility-related events remain a significant issue. Therefore, new pharmacological treatments are necessary to optimize patient management and to further reduce hemocompatibility-related events. The purpose of the present systematic review and meta-analysis was to summarize the existing data regarding the safety and efficacy of post-implant phosphodiesterase-5 inhibitors (PDE-5i) on hemocompatibility-related events. Methods: Among the 258 articles in Pubmed, Scopus, and CENTRAL that were retrieved (1990−2022), 15 studies were included in the qualitative synthesis, and 9 studies were included in the quantitative synthesis. The fixed-effects model was used because it is statistically sound for combining a very small number of studies. The primary endpoint of the study was all-cause mortality, whereas the secondary endpoints were ischemic stroke, pump thrombosis, and gastrointestinal bleeding. Results: Mortality was significantly lower in the PDE-5i group vs. the control group (OR: 0.92 [95% CI: 0.85, 0.98]; p = 0.02). The secondary endpoints ischemic stroke (OR: 0.87 [95% CI: 0.78, 0.98]; p = 0.02) and pump thrombosis (OR: 0.90 [95% CI: 0.82, 0.99]; p = 0.04) were also lower in the PDE-5i group. The incidence of gastrointestinal bleeding was significantly higher in patients with LVAD receiving PDE-5i (OR: 1.26 [95% CI: 1.11, 1.44]; p < 0.01). In the overall analysis, the heterogeneity of outcomes was low, except for pump thrombosis. Conclusions: The use of PDE-5i post-implant was associated with lower mortality and thrombotic events but with a higher risk of gastrointestinal bleeding.

Monofilament suture versus braided suture thread to improve pregnancy outcomes after vaginal cervical cerclage (C-STICH): a pragmatic randomised, controlled, phase 3, superiority trial.

BACKGROUND: Miscarriage in the second trimester and preterm birth are significant global problems. Vaginal cervical cerclage is performed to prevent pregnancy loss and preterm birth. We aimed to determine the effectiveness of a monofilament suture thread compared with braided suture thread on pregnancy loss rates in women undergoing a cervical cerclage. METHODS: C-STICH was a pragmatic, randomised, controlled, superiority trial done at 75 obstetric units in the UK. Women with a singleton pregnancy who received a vaginal cervical cerclage due to a history of pregnancy loss or premature birth, or if indicated by ultrasound, were centrally randomised (1:1) using minimisation to receive a monofilament suture or braided suture thread for their cervical cerclage. Women and outcome assessors were masked to allocation as far as possible. The primary outcome was pregnancy loss, defined as miscarriage, stillbirth, or neonatal death in the first week of life, analysed in the intention-to-treat population (ie, all women who were randomly assigned). Safety was also assessed in the intention-to-treat population. The trial was registered with ISRCTN, ISRCTN15373349. FINDINGS: Between Aug 21, 2015, and Jan 28, 2021, 2049 women were randomly assigned to receive a monofilament suture (n=1025) or braided suture (n=1024). The primary outcome was ascertained in 1003 women in the monofilament suture group and 993 women in the braided suture group. Pregnancy loss occurred in 80 (8·0%) of 1003 women in the monofilament suture group and 75 (7·6%) of 993 women in the braided suture group (adjusted risk ratio 1·05 [95% CI 0·79 to 1·40]; adjusted risk difference 0·002 [95% CI -0·02 to 0·03]). INTERPRETATION: Monofilament suture did not reduce rate of pregnancy loss when compared with a braided suture. Clinicians should use the results of this trial to facilitate discussions around the choice of suture thread to optimise outcomes. FUNDING: National Institute of Health Research Health Technology Assessment Programme.

COVID-19 Infection among Elite Football Players: A Nationwide Prospective Cohort Study.

Little is known about the risk of COVID-19 infection among footballers. We aimed to investigate the incidence and characteristics of COVID-19 infection among footballers. In total, 480 football players of Super League Greece and 420 staff members participated in a prospective cohort study, which took place from May 2020 to May 2021. Nasopharyngeal swabs were collected from footballers and staff members weekly. All samples (n = 43,975) collected were tested using the reverse transcriptase polymerase chain reaction (RT-PCR) test for the detection of "SARS-CoV-2". In total, 190 positive cases (130 among professional football players and 60 among staff) were recorded. Out of the 190 cases that turned positive, 64 (34%) cases were considered as symptomatic, and 126 (66%) cases were asymptomatic. The incidence rate of a positive test result for footballers was 0.57% (confidence interval (CI) 0.48−0.68%) and for staff members it was 0.27% (CI 0.20%, 0.34%), respectively. Footballers recorded a twofold increased risk of COVID-19 infection in comparison to staff members (relative risk = 2.16; 95% CI = 1.59−2.93; p-value < 0.001). No significant transmission events were observed during the follow-up period. We found a low incidence of COVID-19 infection among professional footballers over a long follow-up period. Furthermore, the implementation of a weekly diagnostic testing (RT-PCR) was critical to break the transmission chain of COVID-19, especially among asymptomatic football players and staff members.

Coexisting Morbidity Burden in Hospitalized Elderly Patients with New-Onset Heart Failure vs Acutely Decompensated Chronic Heart Failure.

Coexisting morbidities (CM) are common in patients with heart failure (HF). This study evaluated the CM burden and its clinical significance in elderly hospitalized patients with new-onset (De-novo) HF (n = 84) and acutely decompensated chronic HF (ADCHF) (n = 122). All had HF symptoms associated with: (a) LVEF <50%, or, (b) left ventricular ejection fraction (LVEF) ≥50% and NT-proBNP ≥300 pg/mL. The primary endpoint was the composite of all-cause death/HF rehospitalization at 6 months. Age was similar between patients with new-onset HF and ADCHF [82 (12.5) vs 80 (11) years, respectively; P = .549]. The CM burden was high in both groups. However, the number of CM [3 (2) vs 4 (1.75)] and the prevalence of multimorbidity [CM ≥2; 65 (77.4%) vs 108 (88.5%)] were lower in new-onset HF (P = .016 and P = .035, respectively). The survival probability without the primary endpoint was higher in new-onset HF than in ADCHF (P = .001) driven by less rehospitalizations (P = .001). In the total study population significant primary endpoint predictors were red blood cell distribution width (RDW), urea, and coronary artery disease (CAD) prevalence (AUC of the model =.7685), whereas significant death predictors were RDW, urea, and the number of CM (AUC = .7859), all higher in ADCHF. Thus, the higher CM burden in ADCHF than in new-onset HF most likely contributed to the worse outcome.

Red blood cell distribution width in elderly hospitalized patients with cardiovascular disease.

BACKGROUND: Red blood cell distribution width (RDW) is elevated in patients with cardiovascular disease (CVD). AIM: To determine RDW values and impact of CV and non-CV coexisting morbidities in elderly patients hospitalized with chronic CVD. METHODS: This prospective study included 204 consecutive elderly patients (age 77.5 [7.41] years, female 94 [46%], left ventricular ejection fraction 53.00% [37.50, 55.00]) hospitalized with chronic CVD at the Cardiology Department of Larissa University General Hospital (Larissa, Greece) from January 2019 to April 2019. Elderly patients were selected due to the high prevalence of coexisting morbidities in this patient population. Hospitalized patients with acute CVD (acute coronary syndromes, new-onset heart failure [HF], and acute pericarditis/myocarditis), primary isolated valvular heart disease, sepsis, and those with a history of blood transfusions or cancer were excluded. The evaluation of the patients within 24 h from admission included clinical examination, laboratory blood tests, and echocardiography. RESULTS: The most common cardiac morbidities were hypertension and coronary artery disease, with acutely decompensated chronic heart failure (ADCHF) and atrial fibrillation (AF) also frequently being present. The most common non-cardiac morbidities were anemia and chronic kidney disease followed by diabetes mellitus, chronic obstructive pulmonary disease, and sleep apnea. RDW was significantly elevated 15.48 (2.15); 121 (59.3%) of patients had RDW > 14.5% which represents the upper limit of normal in our institution. Factors associated with RDW in stepwise regression analysis were ADCHF (coefficient: 1.406; 95% confidence interval [CI]: 0.830-1.981; P < 0.001), AF (1.192; 0.673 to 1.711; P < 0.001), and anemia (0.806; 0.256 to 1.355; P = 0.004). ADCHF was the most significant factor associated with RDW. RDW was on average 1.41 higher for patients with than without ADCHF, 1.19 higher for patients with than without AF, and 0.81 higher for patients with than without anemia. When patients were grouped based on the presence or absence of anemia, ADCHF and AF, heart rate was not increased in those with anemia but was significantly increased in those with ADCHF or AF. CONCLUSION: RDW was elevated in elderly hospitalized patients with chronic CVD. Factors associated with RDW were anemia and CV factors associated with elevated heart rate (ADCHF, AF), suggesting sympathetic overactivity.

C-STICH: Cerclage Suture Type for an Insufficient Cervix and its effect on Health outcomes-a multicentre randomised controlled trial.

BACKGROUND: Preterm birth is associated with significant mortality and morbidity for mothers and babies. Women are identified as high risk for preterm birth based on either previous medical/pregnancy history or on ultrasound assessment of the cervix. Women identified as high risk can be offered a cervical cerclage (a purse string stitch) around the cervix (neck of the womb) to reduce the risk of preterm birth. In women who have a cervical cerclage, the procedure can be performed using either a monofilament (single-stranded) or braided (woven) suture material. Both suture materials are routinely used for cervical cerclage and there is uncertainty as to which is superior. METHODS: A multicentre, open, randomised controlled superiority trial of 2050 women presenting at obstetric units, deemed to be at risk of preterm birth and already scheduled to have a cervical cerclage as part of their standard care. Inclusion criteria include singleton pregnancies and an indication for cervical cerclage for either a history of three or more previous mid-trimester losses or premature births (≤ 28 weeks), insertion of cervical sutures in previous pregnancies, a history of mid trimester loss or premature birth with a (current) shortened (≤ 25 mm) cervix, or women whom clinicians deem to be at risk of preterm birth either by history or the results of an ultrasound scan. Exclusion criteria include women who have taken part in C-STICH previously, are aged less than 18 years old at the time of presentation, require a rescue cerclage, and are unwilling or unable to give informed consent and in whom a cerclage will be placed by any route other than vaginally (e.g. via an abdominal route). Following informed consent, women are randomised on a 1:1 basis to either monofilament or braided suture, by minimisation. The primary outcome is pregnancy loss (miscarriage and perinatal mortality, including any stillbirth or neonatal death in the first week of life), and secondary outcomes include the core outcome set for preterm birth trials. DISCUSSION: Optimising established interventions to prevent preterm birth is important in reducing perinatal mortality rates. TRIAL REGISTRATION: ISRCTN 15373349 . Registered before recruitment on 03 December 2014 prior to first recruit.

Postimplant Phosphodiesterase Type 5 Inhibitors Use Is Associated With Lower Rates of Thrombotic Events After Left Ventricular Assist Device Implantation.

Background Left ventricular assist device (LVAD) thrombosis is clinically devastating and impacts the cost effectiveness of LVAD therapy for advanced heart failure. Anticoagulation and antiplatelet therapies represent the standard of care to mitigate LVAD thrombosis. Phosphodiesterase type 5 inhibitors (PDE-5is) exhibit hemodynamic, antiplatelet, and antithrombotic effects. Using a national registry, we examined the relationship of PDE-5i use on thrombotic events in patients with continuous-flow LVADs. Methods and Results We obtained data from 13 772 patients with continuous flow LVADs participating in a national registry. Patients implanted with primary LVADs from 2012 to 2017 were included in the analysis. The primary end point was a composite of LVAD thrombosis and ischemic stroke. Patients were analyzed according to any use of PDE-5i after LVAD implantation (PDE-5i group) versus no use after LVAD implantation (no PDE-5i group). The primary end point was significantly lower in the PDE-5i group compared with the no PDE-5i group (hazard ratio [HR], 0.84; 95% CI, 0.77-0.91; P<0.001) at 48 months. The components of the primary end point (LVAD thrombosis: HR, 0.82; 95% CI, 0.74-0.90; P<0.001; and ischemic stroke: HR, 0.85; 95% CI, 0.75-0.97; P=0.019), as well as the secondary end point all-cause mortality (HR, 0.86; 95% CI, 0.79-0.93; P<0.001) were lower in the PDE-5i group versus the no PDE-5i at 48 months post LVAD. The favorable results observed with postimplant PDE-5i use were consistent with both axial and centrifugal flow devices. Conclusions The postimplant use of PDE-5i was associated with fewer thrombotic events and improved survival in LVAD patients. A randomized clinical trial is warranted to confirm these findings.

MRI versus laparoscopy to diagnose the main causes of chronic pelvic pain in women: a test-accuracy study and economic evaluation.

BACKGROUND: Chronic pelvic pain (CPP) symptoms in women are variable and non-specific; establishing a differential diagnosis can be hard. A diagnostic laparoscopy is often performed, although a prior magnetic resonance imaging (MRI) scan may beneficial. OBJECTIVES: To estimate the accuracy and added value of MRI in making diagnoses of (1) idiopathic CPP and (2) the main gynaecological causes of CPP. To quantify the impact MRI can have on decision-making with respect to triaging for therapeutic laparoscopy and to conduct an economic evaluation. DESIGN: Comparative test-accuracy study with cost-effectiveness modelling. SETTING: Twenty-six UK-based hospitals. PARTICIPANTS: A total of 291 women with CPP. METHODS: Pre-index information concerning the patient's medical history, previous pelvic examinations and ultrasound scans was collected. Women reported symptoms and quality of life at baseline and 6 months. MRI scans and diagnostic laparoscopy (undertaken and interpreted blind to each other) were the index tests. For each potential cause of CPP, gynaecologists indicated their level of certainty that the condition was causing the pelvic pain. The analysis considered both diagnostic laparoscopy as a reference standard for observing structural gynaecological causes and consensus from a two-stage expert independent panel for ascertaining the cause of CPP. The stage 1 consensus was based on pre-index, laparoscopy and follow-up data; for stage 2, the MRI scan report was also provided. The primary analysis involved calculations of sensitivity and specificity for the presence or absence of each structural gynaecological cause of pain. A decision-analytic model was developed, with a 6-month time horizon. Two strategies, laparoscopy or MRI, were considered and populated with study data. RESULTS: Using reference standards of laparoscopic and expert panel diagnoses, MRI scans had high specificity but poor sensitivity for observing deep-infiltrating endometriosis, endometrioma, adhesions and ovarian cysts. MRI scans correctly identified 56% [95% confidence interval (CI) 48% to 64%] of women judged to have idiopathic CPP, but missed 46% (95% CI 37% to 55%) of those considered to have a gynaecological structural cause of CPP. MRI added significant value, over and above the pre-index information, in identifying deep-infiltrating endometriosis (p = 0.006) and endometrioma (p = 0.02) as the cause of pain, but not for other gynaecological structural causes or for identifying idiopathic CPP (p = 0.08). Laparoscopy was significantly more accurate than MRI in diagnosing idiopathic CPP (p < 0.0001), superficial peritoneal endometriosis (p < 0.0001), deep-infiltrating endometriosis (p < 0.0001) and endometrioma of the ovary (p = 0.02) as the cause of pelvic pain. The accuracy of laparoscopy appeared to be able to rule in these diagnoses. Using MRI to identify women who require therapeutic laparoscopy would lead to 369 women in a cohort of 1000 receiving laparoscopy unnecessarily, and 136 women who required laparoscopy not receiving it. The economic analysis highlighted the importance of the time horizon, the prevalence of CPP and the cut-off values to inform the sensitivity and specificity of MRI and laparoscopy on the model results. MRI was not found to be a cost-effective diagnostic approach in any scenario. CONCLUSIONS: MRI was dominated by laparoscopy in differential diagnosis of women presenting to gynaecology clinics with CPP. It did not add value to information already gained from history, examination and ultrasound about idiopathic CPP and various gynaecological conditions. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13028601. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 40. See the NIHR Journals Library website for further project information.

Usual medical treatments or levonorgestrel-IUS for women with heavy menstrual bleeding: long-term randomised pragmatic trial in primary care.

BACKGROUND: Heavy menstrual bleeding (HMB) is a common, chronic problem affecting women and health services. However, long-term evidence on treatment in primary care is lacking. AIM: To assess the effectiveness of commencing the levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical treatments for women presenting with HMB in general practice. DESIGN AND SETTING: A pragmatic, multicentre, parallel, open-label, long term, randomised controlled trial in 63 primary care practices across the English Midlands. METHOD: In total, 571 women aged 25-50 years, with HMB were randomised to LNG-IUS or usual medical treatment (tranexamic/mefenamic acid, combined oestrogen-progestogen, or progesterone alone). The primary outcome was the patient reported Menorrhagia Multi-Attribute Scale (MMAS, measuring effect of HMB on practical difficulties, social life, psychological and physical health, and work and family life; scores from 0 to 100). Secondary outcomes included surgical intervention (endometrial ablation/hysterectomy), general quality of life, sexual activity, and safety. RESULTS: At 5 years post-randomisation, 424 (74%) women provided data. While the difference between LNG-IUS and usual treatment groups was not significant (3.9 points; 95% confidence interval = -0.6 to 8.3; P = 0.09), MMAS scores improved significantly in both groups from baseline (mean increase, 44.9 and 43.4 points, respectively; P<0.001 for both comparisons). Rates of surgical intervention were low in both groups (surgery-free survival was 80% and 77%; hazard ratio 0.90; 95% CI = 0.62 to 1.31; P = 0.6). There was no difference in generic quality of life, sexual activity scores, or serious adverse events. CONCLUSION: Large improvements in symptom relief across both groups show treatment for HMB can be successfully initiated with long-term benefit and with only modest need for surgery.

Hysteroscopic local anesthetic intrauterine cornual block in office endometrial ablation: a randomized controlled trial.

OBJECTIVE: To evaluate the efficacy of a hysteroscopic local anesthetic intrauterine cornual block (ICOB) on pain experienced during office endometrial ablation (EA) in addition to a traditional direct local anesthetic cervical block (DCB). DESIGN: Prospective, randomized, double-blind, placebo-controlled trial. SETTING: University teaching hospital. PATIENT(S): Women with heavy menstrual bleeding scheduled for an office endometrial ablation. INTERVENTION(S): Before office EA, DCB plus hysteroscopic ICOB just medial to each tubal ostium using local anesthetic mixture made up of 1 mL 3% mepivacaine plus 1 mL 0.5% bupivacaine versus control group receiving DBC plus ICOB with 2 mL of placebo (saline). PRIMARY OUTCOME: pain reported during procedure via visual analogue scale (VAS) from 0 to 10; secondary outcomes: postoperative pain, rescue analgesic requirement, and duration of hospital stay. RESULT(S): Most characteristics were similar across groups. The mean VAS score during the procedure was statistically significantly lower by 1.44 (95% confidence interval, -2.65 to -0.21) in the active group compared with the placebo group. There were no statistically significant differences between the two groups in the postprocedural mean VAS scores, rescue analgesic requirement, or duration of hospital stay. CONCLUSION(S): Used in addition to DCB, ICOB reduces the pain experienced during office EA compared with DCB alone. CLINICAL TRIAL REGISTRATION NUMBER: NCT01808898.