Estimating incidence and attributable length of stay of healthcare-associated infections—Modeling the Swiss point-prevalence survey

Objectives: In 2017, a point-prevalence survey was conducted with 12,931 patients in 96 hospitals across Switzerland as part of the national strategy to prevent healthcare-associated infections (HAIs). We present novel statistical methods to assess incidence proportions of HAI and attributable length-of-stay (LOS) in point-prevalence surveys. Methods: Follow-up data were collected for a subsample of patients and were used to impute follow-up data for all remaining patients. We used weights to correct length bias in logistic regression and multistate analyses. Methods were also tested in simulation studies. Results: The estimated incidence proportion of HAIs during hospital stay and not present at admission was 2.3% (95% confidence intervals [CI], 2.1–2.6), the most common type being lower respiratory tract infections (0.8%; 95% CI, 0.6–1.0). Incidence proportion was highest in patients with a rapidly fatal McCabe score (7.8%; 95% CI, 5.7–10.4). The attributable LOS for all HAI was 6.4 days (95% CI, 5.6–7.3) and highest for surgical site infections (7.1 days, 95% CI, 5.2–9.0). It was longest in the age group of 18–44 years (9.0 days; 95% CI, 5.4–12.6). Risk-factor analysis revealed that McCabe score had no effect on the discharge hazard after infection (hazard ratio [HR], 1.21; 95% CI, 0.89–1.63). Instead, it only influenced the infection hazard (HR, 1.84; 95% CI, 1.39–2.43) and the discharge hazard prior to infection (HR, 0.73; 95% CI, 0.66–0.82). Conclusions: In point-prevalence surveys with limited follow-up data, imputation and weighting can be used to estimate incidence proportions and attributable LOS that would otherwise require complete follow-up data.

Role of Secondary Attack Rate in The Surge of COVID 19 Cases: A Comparative Retrospective Cohort Study between First Wave and Second Wave of COVID 19

India had the worst conditions during the second wave, and yet, the cause of the enormous spike in COVID-19 cases in a short time span remains unexplained. We aimed to decipher the cause of the enormous spike in COVID-19 cases in the second wave in India. A comparative retrospective cohort study was conducted between the first wave and the second wave. An individual primary case was interviewed using the "COVID-19 transmission questionaries sheet" to trace the total number of primary cases and age-wise unrestricted social interaction and secondary cases. Between January-2021 and May-2021, 1587 unrestricted social interactions were traced with 437 primary cases for the second wave. While for the first wave, 436 unrestricted social interactions were traced with 112 primary cases between January-2020 and December-2020. In the second wave, 36.8% of primary cases developed 334 secondary cases, while 25.0% of primary cases developed 82 secondary cases in the first wave. The secondary attack rate rose 2.5-fold in the age group >50years, and rose ~86% in the age group <10years, while it remained stable in the age group 10-50years. The overall 58% increment in secondary attack rate in the second wave indicates changes in the pattern of unrestricted social interaction amongst household members. This was further supported by the incidence proportion rate that surprisingly rose to ~39% in households of two- and three members in the second wave, while it was negligible in the first wave. Changes in the pattern of unrestricted social interaction among household members and a high affinity of the delta variant virus for infecting people in the age groups of <10 years and >50 years escalated the secondary attack rate and incidence proportion rate that led to the unprecedented surge of COVID-19 cases in the second wave.

Unrestricted Social Interaction: Underappreciated Cause of COVID 19 Surge

India had the worst conditions during the second wave, and yet, its cause for the enormous spike of COVID-19 cases in short time span remains unexplained. We retrospectively studied the comparative secondary attack rate, incidence proportion rate and extent of unrestricted social interactions’ contribution between the first and second wave of COVID-19 to decipher what caused the second wave's enormous spike in COVID-19 cases. We found that the unrestricted social interaction accounted equally, i.e., >42% of all COVID-19 cases in the both waves. Overall secondary attack rate rose 58% in the second wave's, among which, we find increment of 2.5-fold and 88% for the age group <10 years and >50years, respectively, while it remains stable in the age group 10-50years. We find significantly higher incidence proportion rate, ~39%, in household size of two- and three members in the second wave while it was significant in household size of four or more members in the first wave. We anticipated that changes in the pattern of unrestricted social interaction amongst household members escalated the secondary attack rate and higher incidence proportion rate even in two members family size could lead to the unprecedented surge of COVID-19 cases in the second wave.

P–592 Safety and effectiveness of follitropin alfa biosimilar to originator follitropin alfa in real-world clinical practice: A Multinational Comparative, Prospective Cohort Study

Study question Are safety and effectiveness of Ovaleap® (follitropin alfa), and Gonal-f®, comparable in one treatment cycle of ART in routine clinical practice? Summary answer Safety in terms of incidence proportions of OHSS and OHSS severity, as well as pregnancy and live birth rates, were similar between Ovaleap® and Gonal-f®. What is known already Ovaleap® (Theramex), a r-hFSH, is a biosimilar medicinal product to Gonal-f® (Merck). As a biosimilar, it went through a rigorous series of physio-chemical, in vitro, in vivo tests and confirmatory Phase I and III studies, to demonstrate similarity/equivalence in quality, safety and efficacy to the reference medicinal product, per the European Medicines Agency (EMA) guidelines. Ovaleap® was approved by the EMA in 2013 for use at the same dose and for the same therapeutic indications as Gonal-f®. Further outcome data from a broader patient population on safety and live birth outcomes provides clinically important insights on newly introduced FSH medicines. Study design, size, duration SOFIA (Safety of Ovaleap® Follitropin alfa in Infertile women undergoing superovulation for Assisted reproductive technologies) was a multi-national, comparative, non-interventional, prospective cohort study. The study was performed at 56 centers specializing in ART from six European countries, (Belgium, France, Germany, Italy, Spain, and the United Kingdom) from January 2017 to September 2019 and comprised of 817 infertile women undergoing controlled ovarian hyperstimulation in one treatment cycle for ART Participants/materials, setting, methods The study population comprised of infertile women undergoing controlled ovarian hyperstimulation for ART, who were administered Ovaleap® or Gonal-f® and were naïve to any FSH containing products. Eligible patients were enrolled at a ratio of approximately 1:1, both within and between countries. They were followed up to 30 days after the last FSH dose administration. Women who had a confirmed clinical pregnancy were followed until the end of the pregnancy or until delivery. Main results and the role of chance A total of 408 and 409 women who were administered Ovaleap® or Gonal-f®, respectively, were eligible for analysis. A total of 382 patients (94%) in the Ovaleap® and 390 patients (95%) in the Gonal-f® cohort completed FSH treatment (up to oocyte maturation triggering), respectively. The two cohorts were generally similar with regard to demographic and baseline characteristics. The incidence proportion of OHSS was 5.1% (95% CI: 3.4, 7.7) in the Ovaleap® and 3.2% (95% CI: 1.9, 5.4) in the Gonal-f® cohort. This difference in OHSS incidence proportion between the two cohorts was not statistically significant neither before (p = 0.159) nor after univariate adjustment for each potential confounder (p &gt; 0.05). The incidence proportion of OHSS severity grades was similar in the two treatment groups (3.4% versus 2.0% for Grade I, 1.2% versus 1.0% Grade II, and 0.5% versus 0.2% Grade III, in the Ovaleap® and Gonal-f® cohorts, respectively) and without a significant statistical difference (p = 0.865, for each grade). Among patients who had embryo transfer, clinical pregnancy rates were 33% and 31%, live birth rates 27% and 26% in the Ovaleap® and Gonal-f® cohorts, respectively. Limitations, reasons for caution Since treatment was non-randomised, the study may have been susceptible to selection bias. This was addressed at both the design stage, by balancing recruitment to a 1:1 ratio for Ovaleap® and Gonal-f® treatments, and also at the analysis stage in which, a univariate analysis was performed. Wider implications of the findings: Findings from this first large European prospective comparative real-world SOFIA study demonstrated that effectiveness (pregnancy and delivery rates) and safety (risk and severity of OHSS), were similar between Ovaleap®and Gonal-f® treatments. Ovaleap, a biosimilar r-hFSH is therefore a suitable option for follicular stimulation in routine clinical practice. Trial registration number EUPAS17328

Survival analysis for AdVerse events with VarYing follow-up times (SAVVY)—estimation of adverse event risks

Background The SAVVY project aims to improve the analyses of adverse events (AEs), whether prespecified or emerging, in clinical trials through the use of survival techniques appropriately dealing with varying follow-up times and competing events (CEs). Although statistical methodologies have advanced, in AE analyses, often the incidence proportion, the incidence density, or a non-parametric Kaplan-Meier estimator are used, which ignore either censoring or CEs. In an empirical study including randomized clinical trials from several sponsor organizations, these potential sources of bias are investigated. The main purpose is to compare the estimators that are typically used to quantify AE risk within trial arms to the non-parametric Aalen-Johansen estimator as the gold-standard for estimating cumulative AE probabilities. A follow-up paper will consider consequences when comparing safety between treatment groups. Methods Estimators are compared with descriptive statistics, graphical displays, and a more formal assessment using a random effects meta-analysis. The influence of different factors on the size of deviations from the gold-standard is investigated in a meta-regression. Comparisons are conducted at the maximum follow-up time and at earlier evaluation times. CEs definition does not only include death before AE but also end of follow-up for AEs due to events related to the disease course or safety of the treatment. Results Ten sponsor organizations provided 17 clinical trials including 186 types of investigated AEs. The one minus Kaplan-Meier estimator was on average about 1.2-fold larger than the Aalen-Johansen estimator and the probability transform of the incidence density ignoring CEs was even 2-fold larger. The average bias using the incidence proportion was less than 5%. Assuming constant hazards using incidence densities was hardly an issue provided that CEs were accounted for. The meta-regression showed that the bias depended mainly on the amount of censoring and on the amount of CEs. Conclusions The choice of the estimator of the cumulative AE probability and the definition of CEs are crucial. We recommend using the Aalen-Johansen estimator with an appropriate definition of CEs whenever the risk for AEs is to be quantified and to change the guidelines accordingly.

AB0156 INCIDENCE OF CERVICAL SPINE INVOLVEMENT IN RHEUMATOID ARTHRITIS, RESULTS FROM A SINGLE CENTRE OBSERVATIONAL STUDY

Background:Rheumatoid arthritis (RA) manifests as a chronic, symmetrical articular disease; any synovial joint may be involved and the cervical spine is another possible affected site [1,2]. Although the cervical spine involvement is a very severe complication of RA, the exact incidence of cervical spine abnormalities in RA is not fully elucidated yet.Objectives:In this work, we aimed at evaluating the incidence of a cervical spine involvement and associated clinical characteristics in patients with RA in a single centre observational study.Methods:In this study, we performed a retrospective analysis of prospectively followed-up patients with RA attending our Rheumatologic Clinic, University of L’Aquila, L’Aquila, Italy, between January 2010 and December 2020. Patients who met the diagnostic criteria of 1987 ACR and/or ACR/EULAR 2010 criteria were assessed. Each patient was investigated for cervical spine involvement occurrence, particularly the atlas-axis cervical involvement. Instrumental imaging evaluation of the cervical spine was performed in all patients with clinical suspicion of involvement, by both MRI and CT examinations. MRI examinations were performed on a 1.5 Tesla scanner, acquiring T1, T2, and STIR sequences on sagittal, coronal and axial planes. CT examinations were performed on a multidetector 320-row CT scanner (Aquilion One,Toshiba) acquired with a thin collimation; soft tissue or bone algorithms were applied for image data reconstruction and analysis.Incident cases of cervical spine involvement were reported as incidence proportion and incidence rate per 1000 person-years at risk.Results:In this evaluation, 347 consecutive patients, (mostly female 87.6%, mean age of 66.1 ± 11.3 years) attending our Rheumatologic Clinic, were studied. The incidence proportion of cervical spine involvement was 2.0% [0.6 – 3.4%], occurring in 7 out of 347 patients, and identified by both MRI and CT scan. Considering over 1623 person-years, an incidence rate of 4.0 × 1000 [3.0 – 5.0] person-years was also estimated. All our patients with cervical spine involvement were characterised by female gender, rheumatoid factor, ACPA, fulfilment of ACR 1987 classificative criteria, and poorly controlled disease activity. Smoking habit and extra-articular manifestations were also frequently reported. Glucocorticoids, methotrexate, and infliximab were mainly administered in these patients. This therapeutic strategy resulted in a complete resolution of the inflammatory synovitis in all but one patient. The latter developed a cervical spinal instability resulting in neurological progression and required a subsequent surgical management.Conclusion:The cervical spine involvement is an uncommon but serious manifestation of RA, since possibly causing severe neurologic damage. A poorly controlled inflammatory process would be an important risk factor for developing a cervical spine involvement in RA, thus, a proper management is required, from an early accurate recognition to a timely therapeutic strategy. MRI could provide a useful clinical tool to early evaluate the cervical spine involvement in RA. Finally, considering the low incidence, further studies are needed to fully estimate the exact incidence of this manifestation, mostly in poorly symptomatic patients.References:[1]Shlobin NA, Dahdaleh NS. Cervical spine manifestations of rheumatoid arthritis: a review. Neurosurg Rev. 2020 Oct 10. Neurosurg Rev. 2020 Oct 10. doi: 10.1007/s10143-020-01412-1.[2]Kothe, R.Rheumatoid instability in the cervical spine: Diagnostic and therapeutic strategies. Orthopade. 2018 Jun;47(6):489-495.Disclosure of Interests:None declared

Impact of the first COVID-19 shutdown on patient volumes and surgical procedures of a Level I trauma center

Purpose In Dec 2019, COVID-19 was first recognized and led to a worldwide pandemic. The German government implemented a shutdown in Mar 2020, affecting outpatient and hospital care. The aim of the present article was to evaluate the impact of the COVID-19 shutdown on patient volumes and surgical procedures of a Level I trauma center in Germany. Methods All emergency patients were recorded retrospectively during the shutdown and compared to a calendar-matched control period (CTRL). Total emergency patient contacts including trauma mechanisms, injury patterns and operation numbers were recorded including absolute numbers, incidence proportions and risk ratios. Results During the shutdown period, we observed a decrease of emergency patient cases (417) compared to CTRL (575), a decrease of elective cases (42 vs. 13) and of the total number of operations (397 vs. 325). Incidence proportions of emergency operations increased from 8.2 to 12.2% (shutdown) and elective surgical cases decreased (11.1 vs. 4.3%). As we observed a decrease for most trauma mechanisms and injury patterns, we found an increasing incidence proportion for severe open fractures. Household-related injuries were reported with an increasing incidence proportion from 26.8 to 47.5% (shutdown). We found an increasing tendency of trauma and injuries related to psychological disorders. Conclusion This analysis shows a decrease of total patient numbers in an emergency department of a Level I trauma center and a decrease of the total number of operations during the shutdown period. Concurrently, we observed an increase of severe open fractures and emergency operations. Furthermore, trauma mechanism changed with less traffic, work and sports-related accidents.

Adverse events associated with administration of vasopressor medications through a peripheral intravenous catheter: a systematic review and meta-analysis

Background It is unclear whether vasopressors can be safely administered through a peripheral intravenous (PIV). Systematic review and meta-analysis methodology was used to examine the incidence of local anatomic adverse events associated with PIV vasopressor administration in patients of any age cared for in any acute care environment. Methods MEDLINE, EMBASE, CINAHL, the Cochrane Central Register of controlled trials, and the Database of Abstracts of Reviews of Effects were searched without restriction from inception to October 2019. References of included studies and related reviews, as well as relevant conference proceedings were also searched. Studies were included if they were: (1) cohort, quasi-experimental, or randomized controlled trial study design; (2) conducted in humans of any age or clinical setting; and (3) reported on local anatomic adverse events associated with PIV vasopressor administration. Risk of bias was assessed using the Revised Cochrane risk-of-bias tool for randomized trials or the Joanna Briggs Institute checklist for prevalence studies where appropriate. Incidence estimates were pooled using random effects meta-analysis. Subgroup analyses were used to explore sources of heterogeneity. Results Twenty-three studies were included in the systematic review, of which 16 and 7 described adults and children, respectively. Meta-analysis from 11 adult studies including 16,055 patients demonstrated a pooled incidence proportion of adverse events associated with PIV vasopressor administration as 1.8% (95% CI 0.1–4.8%, I2 = 93.7%). In children, meta-analysis from four studies and 388 patients demonstrated a pooled incidence proportion of adverse events as 3.3% (95% CI 0.0–10.1%, I2 = 82.4%). Subgroup analyses did not detect any statistically significant effects associated with stratification based on differences in clinical location, risk of bias or design between studies, PIV location and size, or vasopressor type or duration. Most studies had high or some concern for risk of bias. Conclusion The incidence of adverse events associated with PIV vasopressor administration is low. Additional research is required to examine the effects of PIV location and size, vasopressor type and dose, and patient characteristics on the safety of PIV vasopressor administration.

Safety of Ovaleap® (Follitropin Alfa) in Infertile Women Undergoing Superovulation for Assisted Reproductive Technologies: A Multinational Comparative, Prospective Cohort Study

BackgroundOvaleap® (follitropin alfa), a recombinant human follicle stimulating hormone, is a biosimilar medicinal product to Gonal-f® and is used for ovarian stimulation. The main objective of this study was to assess the safety and effectiveness of Ovaleap® compared to Gonal-f® in one treatment cycle in routine clinical practice.MethodsSafety of Ovaleap® Follitropin alfa in Infertile women undergoing superovulation for Assisted reproductive technologies (SOFIA) was a prospective cohort study conducted in six European countries. Eligible patients were infertile women undergoing superovulation for assisted reproductive technology, who were administered Ovaleap® or Gonal-f® for ovarian stimulation and were naïve to follicle stimulating hormone treatment. The recruitment ratio was 1:1. The primary endpoint was incidence proportion of ovarian hyperstimulation syndrome (OHSS) and the secondary endpoint was OHSS severity (Grades I, II, III). The effect of risk factors or potential confounders on the odds ratio for OHSS incidence as well as treatment effect on OHSS incidence was explored using univariate logistic regression. Pregnancy and live birth rates were also assessed.ResultsA total of 408 women who were administered Ovaleap® and 409 women who were administered Gonal-f® were eligible for analysis. The incidence proportion of OHSS was 5.1% (95% CI: 3.4, 7.7) in the Ovaleap® cohort and 3.2% (95% CI: 1.9, 5.4) in the Gonal-f® cohort. This difference in OHSS incidence proportion between the two cohorts was not statistically significant neither before (p = 0.159) nor after univariate adjustment for each potential confounder (p &gt; 0.05). The incidence proportion of OHSS severity grades was similar in the two treatment groups (3.4% versus 2.0% for Grade I, 1.2% versus 1.0% for Grade II, and 0.5% versus 0.2% for Grade III, in the Ovaleap® and Gonal-f® cohorts, respectively), without a significant statistical difference (p = 0.865, for each grade). Among patients who had embryo transfer, clinical pregnancy rates were 33% and 31% and live birth rates were 27% and 26%, in the two cohorts, respectively.ConclusionsFindings from the SOFIA study indicate that the incidence proportions of OHSS and OHSS severity, as well as pregnancy and live birth rates, are similar between Ovaleap® and Gonal-f® treatments and corroborate the safety and effectiveness of Ovaleap® as a biosimilar to Gonal-f®.