Prevalence of iatrogenic CNS inflammation at a tertiary neuroimmunology clinic.

BACKGROUND: Various vaccines, tumor-necrosis-factor-alpha inhibitors (TNFAIs), immune-checkpoint inhibitors (ICIs), and other immunomodulators have been linked to inflammatory CNS events. The prevalence of iatrogenic events in the neuroimmunology clinic is unknown. OBJECTIVE: To evaluate the prevalence and clinical characteristics of iatrogenic CNS inflammation in a tertiary neuroimmunology clinic. METHODS: We analyzed 422 consecutive patients seen over five years at a tertiary neuroimmunology clinic who were systematically screened for exposure to vaccines, TNFAIs, ICIs, or other immunomodulators. In patients with suspected iatrogenic events, the Naranjo Adverse Drug Reaction Probability Scale was used to score the probability of iatrogenicity. RESULTS: In total, 27 potential iatrogenic events were observed, accounting for 6.4% of all new referrals. The average Naranjo score was 5.78 +/- 1.65 with 74% of the cases scored as probable and 26% scored as possible. The clinical phenotypes included MS relapses (37%); autoimmune encephalitis (30%); NMOSD attacks (15%); transverse myelitis (11%); optic neuritis (4%); and MOGAD attacks (4%). A monophasic course was observed in 44% of cases while 41% had a relapsing course. All patients stopped or interrupted treatment with the offending agent. In addition, 41% of the iatrogenic events were fully responsive to corticosteroids; 22% were partially responsive; and 15% resolved spontaneously. The most common potential triggers were vaccines (37%) followed by TNFAIs (33%) then ICIs (26%). A significantly higher number of probable iatrogenic events were observed among the ICI and vaccine groups compared to a higher number of possible events among the TNFAI group. The latter group also had a significantly longer interval since exposure. The ICI group was more likely to present with monophasic autoimmune encephalitis. CONCLUSION: Iatrogenic CNS inflammation is rare and typically involves steroid-responsive monophasic events. A subset of iatrogenic events can unmask or worsen relapsing disorders. The probability of iatrogenicity was higher in vaccine and ICI-related events compared to TNFAI-related events.

Investigating service delivery and perinatal outcomes during the low prevalence first year of COVID-19 in a multiethnic Australian population: a cohort study.

OBJECTIVE: Investigate the impact of the COVID-19 pandemic on perinatal outcomes in an Australian high migrant and low COVID-19 prevalent population to identify if COVID-19 driven health service changes and societal influences impact obstetric and perinatal outcomes. DESIGN: Retrospective cohort study with pre COVID-19 period 1 January 2018-31 January 2020, and first year of global COVID-19 period 1 February 2020-31 January 2021. Multivariate logistic regression analysis was conducted adjusting for confounders including age, area-level socioeconomic status, gestation, parity, ethnicity and body mass index. SETTING: Obstetric population attending three public hospitals including a major tertiary referral centre in Western Sydney, Australia. PARTICIPANTS: Women who delivered with singleton pregnancies over 20 weeks gestation. Ethnically diverse women, 66% overseas born. There were 34 103 births in the district that met inclusion criteria: before COVID-19 n=23 722, during COVID-19 n=10 381. MAIN OUTCOME MEASURES: Induction of labour, caesarean section delivery, iatrogenic and spontaneous preterm birth, small for gestational age (SGA), composite neonatal adverse outcome and full breastfeeding at hospital discharge. RESULTS: During the first year of COVID-19, there was no change for induction of labour (adjusted OR, aOR 0.97; 95% CI 0.92 to 1.02, p=0.26) and a 25% increase in caesarean section births (aOR 1.25; 95% CI 1.19 to 1.32, p<0.001). During the COVID-19 period, we found no change in iatrogenic preterm births (aOR 0.94; 95% CI 0.80 to 1.09) but a 15% reduction in spontaneous preterm birth (aOR 0.85; 95% CI 0.75 to 0.97, p=0.02) and a 10% reduction in SGA infants at birth (aOR 0.90; 95% CI 0.82 to 0.99, p=0.02). Composite adverse neonatal outcomes were marginally higher (aOR 1.08; 95% CI 1.00 to 1.15, p=0.04) and full breastfeeding rates at hospital discharge reduced by 15% (aOR 0.85; 95% CI 0.80 to 0.90, p<0.001). CONCLUSION: Despite a low prevalence of COVID-19, both positive and adverse obstetric outcomes were observed that may be related to changes in service delivery and interaction with healthcare providers. Further research is suggested to understand the drivers for these changes.

Association between COVID-19 lockdown measures and the incidence of iatrogenic versus spontaneous very preterm births in the Netherlands: a retrospective study.

BACKGROUND: The COVID-19 pandemic led to regional or nationwide lockdowns as part of risk mitigation measurements in many countries worldwide. Recent studies suggest an unexpected and unprecedented decrease in preterm births during the initial COVID-19 lockdowns in the first half of 2020. The objective of the current study was to assess the effects of the two months of the initial national COVID-19 lockdown period on the incidence of very and extremely preterm birth in the Netherlands, stratified by either spontaneous or iatrogenic onset of delivery, in both singleton and multiple pregnancies. METHODS: Retrospective cohort study using data from all 10 perinatal centers in the Netherlands on very and extremely preterm births during the initial COVID-19 lockdown from March 15 to May 15, 2020. Incidences of very and extremely preterm birth were calculated using an estimate of the total number of births in the Netherlands in this period. As reference, we used data from the corresponding calendar period in 2015-2018 from the national perinatal registry (Perined). We differentiated between spontaneous versus iatrogenic onset of delivery and between singleton versus multiple pregnancies. RESULTS: The incidence of total preterm birth < 32 weeks in singleton pregnancies was 6.1‰ in the study period in 2020 versus 6.5‰ in the corresponding period in 2015-2018. The decrease in preterm births in singletons was solely due to a significant decrease in iatrogenic preterm births, both < 32 weeks (OR 0.71; 95%CI 0.53 to 0.95) and < 28 weeks (OR 0.53; 95%CI 0.29 to 0.97). For multiple pregnancies, an increase in preterm births < 28 weeks was observed (OR 2.43; 95%CI 1.35 to 4.39). CONCLUSION: This study shows a decrease in iatrogenic preterm births during the initial COVID-19-related lockdown in the Netherlands in singletons. Future studies should focus on the mechanism of action of lockdown measures and reduction of preterm birth and the effects of perinatal outcome.

The impact of mitigation measures on perinatal outcomes during the first nine months of the COVID-19 pandemic: A systematic review with meta-analysis.

Worldwide reports have produced conflicting data on perinatal outcomes during the COVID-19 pandemic. This systematic review and meta-analysis addressed the effect of mitigation measures against COVID-19 on preterm birth, stillbirth, low birth weight, and NICU admission during the first nine months of the pandemic. A search was performed using MEDLINE, Embase and SCOPUS for manuscripts published up until 24th May 2021. Studies that reported perinatal outcomes (preterm birth, stillbirth, low birth weight, NICU admission) during the COVID-19 pandemic with a pre-pandemic control period were included. Risk of bias assessment was performed using ROBINS-I tool. RevMan5 was used to perform meta-analysis with random-effects models. A score of the stringency of mitigation measures was calculated from the Oxford COVID-19 Government Response Tracker. Thirty-eight studies of moderate to serious risk of bias were included, with varied methodology, analysis and regional mitigation measures, using stringency index scores. There was no overall effect on preterm birth at less than 37 weeks (OR 0.96, 95% CI 0.92-1.00). However, there was a reduction in preterm birth at less than 37 weeks (OR 0.89, 95% CI 0.81-0.98) and 34 weeks (OR 0.56, 95% CI 0.37-0.83) for iatrogenic births and in singleton pregnancies. There was also a significant reduction in preterm births at less than 34 weeks in studies with above median stringency index scores (OR 0.71, 95% CI 0.58-0.88). There was no effect on risk of stillbirth (OR 1.04, 95% CI 0.90-1.19) or birth weight. NICU admission rates were significantly reduced in studies with above median stringency index scores (OR 0.87, 95% CI 0.78-0.97). The reduction in preterm births in regions with high mitigation measures against SARS-CoV-2 infection is likely driven by a reduction in iatrogenic births. Variability in study design and cohort characteristics need to be considered for future studies to allow further investigation of population level health measures of perinatal outcomes.

Prevalence, risk factors, treatment and outcome of multidrug resistance Candida auris infections in Coronavirus disease (COVID-19) patients: A systematic review.

BACKGROUND: Candida auris is an emerging multidrug-resistant pathogen in intensive care settings (ICU). During the coronavirus disease 19 (COVID-19) pandemic, ICU admissions were overwhelmed, possibly contributing to the C. auris outbreak in COVID-19 patients. OBJECTIVES: The present systematic review addresses the prevalence, underlying diseases, iatrogenic risk factors, treatment and outcome of C. auris infections in COVID-19 patients. METHODS: MEDLINE, Scopus, Embase, Web of Science and LitCovid databases were systematically searched with appropriate keywords from 1 January 2020 to 31 December 2021. RESULTS: A total of 97 cases of C. auris were identified in COVID-19 patients. The pooled prevalence of C. auris infections (encompassing candidemia and non-candidemia cases) in COVID-19 patients was 14%. The major underlying diseases were diabetes mellitus (42.7%), hypertension (32.9%) and obesity (14.6%), followed by the iatrogenic risk factors such as a central venous catheter (76.8%%), intensive care unit (ICU) stay (75.6%) and broad-spectrum antibiotic usage (74.3%). There were no significant differences in underlying disease and iatrogenic risk factors among C. auris non-candidemia/colonisation and C. auris candidemia cases. The mortality rate of the total cohort is 44.4%, whereas, in C. auris candidemia patients, the mortality was 64.7%. CONCLUSION: This study shows that the prevalence of C. auris infections remains unchanged in the COVID-19 pandemic. Hospital-acquired risk factors may contribute to the clinical illness. Proper infection control practices and hospital surveillance may stop future hospital outbreaks during the pandemic.

Outcomes of hospital-acquired SARS-CoV-2 infection in the Canadian first wave epicentre: a retrospective cohort study.

BACKGROUND: During the first wave of the COVID-19 pandemic, a substantial number of Quebec hospitals were hit by hospital-acquired (HA) SARS-CoV-2 infections. Our objective was to assess whether mortality is higher in HA cases than in non-hospital-acquired (NHA) cases and determine the prevalence of HA-SARS-CoV-2 infection in our hospital. METHODS: This retrospective single-centre cohort study included all adults (≥ 18 yr) who had COVID-19, admitted to Hôpital Maisonneuve-Rosemont (Montréal, Canada) from Mar. 1 to June 30, 2020. We collected data on demographic characteristics, comorbidities, treatment, admission to the intensive care unit (ICU) and mechanical ventilation requirements from electronic health records. We adjudicated hospital acquisition based on the timing of symptom onset, and polymerase chain reaction testing for and exposures to SARS-CoV-2. To evaluate the association between HA-SARS-CoV-2 infection and in-hospital mortality, we computed a multivariable logistic regression analysis including known risk factors for death in patients with COVID-19 as covariates. RESULTS: Among 697 patients with SARS-CoV-2 infection, 253 (36.3%) were classified as HA. The mortality rate was higher in the HA group than in the NHA group (38.2% v. 26.4%, p = 0.001), while the rates of ICU admission (8.3% v. 19.1%, p = 0.001) and requirement for mechanical ventilation (3.6% v. 13.0%, p = 0.001) were lower. Multivariable logistic regression analysis showed that HA-SARS-CoV-2 infection in patients younger than 75 years is an independent risk factor for death (odds ratio 2.78, 95% confidence interval 1.44-5.38). INTERPRETATION: Our results show that HA-SARS-CoV-2 infection in younger patients was associated with higher mortality. Future studies need to evaluate relevant patient-centred long-term outcomes in this population.

Mortality and evolution between community and hospital-acquired COVID-AKI.

BACKGROUND: Acute kidney injury (AKI) is associated with poor outcomes in COVID patients. Differences between hospital-acquired (HA-AKI) and community-acquired AKI (CA-AKI) are not well established. METHODS: Prospective, observational cohort study. We included 877 patients hospitalized with COVID diagnosis at two third-level hospitals in Mexico. Primary outcome was all-cause mortality at 28 days compared between COVID patients with CA-AKI and HA-AKI. Secondary outcomes included the need for KRT, and risk factors associated with the development of CA-AKI and HA-AKI. RESULTS: A total of 377 patients (33.7%) developed AKI. CA-AKI occurred in 202 patients (59.9%) and HA-AKI occurred in 135 (40.1%). Patients with CA-AKI had more significant comorbidities, including diabetes (52.4% vs 38.5%), hypertension (58.4% vs 39.2%), CKD (30.1% vs 14.8%), and COPD (5.9% vs 1.4%), than those with HA-AKI. Patients' survival without AKI was 87.1%, with CA-AKI it was 75.4%, and with HA-AKI it was 69.6%, log-rank test p < 0.001. Only age > 60 years (OR 1.12, 95% CI 1.06-1.18, p <0.001), COVID severity (OR 1.09, 95% CI 1.03-1.16, p = 0.002), the need in mechanical lung ventilation (OR 1.67, 95% CI 1.56-1.78, p <0.001), and HA-AKI stage 3 (OR 1.16, 95% CI 1.05-1.29, p = 0.003) had a significant increase in mortality. The presence of CKD (OR 1.48, 95% CI 1.391.56, p < 0.001), serum lymphocytes < 1000 µL (OR 1.03, 95% CI 1.00-1.07, p = 0.03), the need in mechanical lung ventilation (OR 1.06, 95% CI 1.02-1.11, p = 0.003), and CA-AKI stage 3 (OR 1.37, 95% CI 1.29-1.46, p < 0.001) were the only variables associated with a KRT start. CONCLUSIONS: We found that COVID patients who are complicated by CA-AKI have more comorbidities and worse biochemical parameters at the time of hospitalization than HA-AKI patients, but despite these differences, their probability of dying is similar.

Iatrogenic immune-mediated neuropathies: diagnostic, epidemiological and mechanistic uncertainties for causality and implications for clinical practice.

Acute and chronic immune-mediated neuropathies have been widely reported with medical intervention. Although causal relationship may be uncertain in many cases, a variety of drugs, several vaccination types, surgical procedures and bone marrow transplants have been reported as possible cause or trigger of a putative immune-mediated response resulting in acute and chronic neuropathies. We conducted a systematic review of the literature from 1966 to 2020 on reported cases of possible iatrogenic immune-mediated neuropathies. We determined in each case the likelihood of causality based on frequency of the association, focusing primarily on clinical presentation and disease course as well as available ancillary investigations (electrophysiology, blood and cerebrospinal fluid and neuropathology). The response to immunotherapy and issue of re-exposure were also evaluated. We also considered hypothesised mechanisms of onset of immune-mediated neuropathy in the specific iatrogenic context. We believe that a likely causal relationship exists for only few drugs, mainly antitumour necrosis factor alpha agents and immune checkpoint inhibitors, but remains largely unsubstantiated for most other suggested iatrogenic causes. Unfortunately, given the lack of an accurate diagnostic biomarker for most immune-mediated neuropathies, clinical assessment will often override ancillary investigations, resulting in lower levels of certainty that may continue to cast serious doubts on reliability of their diagnosis. Consequently, future reports of suspected cases should collect and exhaustively assess all relevant data. At the current time, besides lack of evidence for causality, the practical implications on management of suspected cases is extremely limited and therapeutic decisions appear likely no different to those made in non-iatrogenic cases.

Learning During Crisis: The Impact of COVID-19 on Hospital-Acquired Pressure Injury Incidence.

ABSTRACT: The impact of COVID-19, on the health and safety of patients, staff, and healthcare organizations, has yet to be fully uncovered. Patient adverse events, such as hospital-acquired pressure injuries (HAPIs), have been problematic for decades. The introduction of a pandemic to an environment that is potentially at-risk for adverse events may result in unintended patient safety and quality concerns. We use the learning health system framework to motivate our understanding of the impact of the COVID-19 pandemic on the incidence of HAPIs within our health system. Using a retrospective, observational design, we used descriptive statistics to evaluate trends in HAPI from March to July 2020. Hospital-acquired pressure injury numbers have fluctuated from a steady increase from March-May 2020, hitting a peak high of 90 cases in the month of May. However, the trend in the total all stage HAPIs began to decline in June 2020, with a low of 51 in July, the lowest number since March 2020. Patients evaluated in this study did not have a longitudinal increase in HAPIs from March-July 2020 during the COVID-19 pandemic, despite similarities in illness severity between the two time points. Our experience has demonstrated the ability of our organizational leaders to learn quickly during crisis.

Managing central venous access during a health care crisis.

OBJECTIVE: During the COVID-19 pandemic, central venous access line teams were implemented at many hospitals throughout the world to provide access for critically ill patients. The objective of this study was to describe the structure, practice patterns, and outcomes of these vascular access teams during the COVID-19 pandemic. METHODS: We conducted a cross-sectional, self-reported study of central venous access line teams in hospitals afflicted with the COVID-19 pandemic. To participate in the study, hospitals were required to meet one of the following criteria: development of a formal plan for a central venous access line team during the pandemic; implementation of a central venous access line team during the pandemic; placement of central venous access by a designated practice group during the pandemic as part of routine clinical practice; or management of an iatrogenic complication related to central venous access in a patient with COVID-19. RESULTS: Participants from 60 hospitals in 13 countries contributed data to the study. Central venous line teams were most commonly composed of vascular surgery and general surgery attending physicians and trainees. Twenty sites had 2657 lines placed by their central venous access line team or designated practice group. During that time, there were 11 (0.4%) iatrogenic complications associated with central venous access procedures performed by the line team or group at those 20 sites. Triple lumen catheters, Cordis (Santa Clara, Calif) catheters, and nontunneled hemodialysis catheters were the most common types of central venous lines placed by the teams. Eight (14%) sites reported experience in placing central venous lines in prone, ventilated patients with COVID-19. A dedicated line cart was used by 35 (59%) of the hospitals. Less than 50% (24 [41%]) of the participating sites reported managing thrombosed central lines in COVID-19 patients. Twenty-three of the sites managed 48 iatrogenic complications in patients with COVID-19 (including complications caused by providers outside of the line team or designated practice group). CONCLUSIONS: Implementation of a dedicated central venous access line team during a pandemic or other health care crisis is a way by which physicians trained in central venous access can contribute their expertise to a stressed health care system. A line team composed of physicians with vascular skill sets provides relief to resource-constrained intensive care unit, ward, and emergency medicine teams with a low rate of iatrogenic complications relative to historical reports. We recommend that a plan for central venous access line team implementation be in place for future health care crises.