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BACKGROUND: The pharmacodynamics of propofol in children have previously been described with the proprietary bispectral index (BIS) as an effect-site marker, and it has been suggested that the rate of onset of propofol might be age dependent, that is, a shorter time to peak effect in younger children. However, these analyses were potentially confounded by co-administered drugs, in particular opioids and benzodiazepines. Thus, the goal of this prospective study was to characterize the influence of age and weight on the onset of hypnotic effects from propofol, reflected by the time to peak of propofol effect-site concentration in the absence of additional drugs. METHODS: A total of 46 healthy children aged 2-12 years presenting for elective surgery were included in our observational cohort study. Solely propofol was administered via a target-controlled infusion pump programmed with the Paedfusor pharmacokinetic model. The BIS and infusion pump data were recorded. The effect of an induction "bolus" was recorded having stopped the pump once a propofol plasma target concentration of 7 µg.mL-1 was achieved. A direct-response and an indirect-response model in the context of nonlinear mixed-effects modeling was used to characterize and compare BIS data in children aged 2-6 years and older children aged 8-12 years. RESULTS: Time to peak of propofol effect-site concentration had a difference (p-value <.01) for age and weight, that is 84 [74, 96] (median [IQR] secs for children aged 2-6 years vs. 99 [91, 113] secs for children aged 8-12 years and 82 [71, 95] secs for weight 11-25 kg vs. 99 [91, 114] secs for weight 30-63 kg). The plasma effect-site equilibration rate constant for propofol had a heterogeneous distribution with a median of 2.36 (IQR: 2.05-2.93; range: 0.83-7.31) per minute but showed a weight-dependent effect in patients with weight below 45 kg. CONCLUSIONS: In children, the age and weight have an influence on time to peak effect of propofol. In the absence of opioids and benzodiazepines, time to peak effect was approximately 20% longer in children aged 8-12 years as compared to younger children. Such clinically relevant age and weight effects are an important consideration in the individualized titration of propofol dosing.
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The most commonly applied way of teaching students to convey the foundations of human anatomy and physiology involves textbooks and lectures. This way of transmitting knowledge causes difficulties for students, especially in the context of three-dimensional imaging of organ structures, and as a consequence translates into difficulties with imagining them. Even despite the rapid uptake of knowledge dissemination provided by online materials, including courses and webinars, there is a clear need for learning programs featuring first-hand immersive experiences tailored to suit individual study paces. In this paper, we present an approach to enhance a classical study program by combining multi-modality data and representing them in a Mixed Reality (MR)-based environment. The advantages of the proposed approach have been proven by the conducted investigation of the relationship between atrial anatomy, its electrophysiological characteristics, and resulting P wave morphology on the electrocardiogram (ECG). Another part of the paper focuses on the role of the sinoatrial node in ECG formation, while the MR-based visualization of combined micro-computed tomography (micro-CT) data with non-invasive CineECG imaging demonstrates the educational application of these advanced technologies for teaching cardiac anatomy and ECG correlations.
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Introduction: The sinus node (SN) is the main pacemaker site of the heart, located in the upper right atrium at the junction of the superior vena cava and right atrium. The precise morphology of the SN in the human heart remains relatively unclear especially the SN microscopical anatomy in the hearts of aged and obese individuals. In this study, the histology of the SN with surrounding right atrial (RA) muscle was analyzed from young non-obese, aged non-obese, aged obese and young obese individuals. The impacts of aging and obesity on fibrosis, apoptosis and cellular hypertrophy were investigated in the SN and RA. Moreover, the impact of obesity on P wave morphology in ECG was also analyzed to determine the speed and conduction of the impulse generated by the SN. Methods: Human SN/RA specimens were dissected from 23 post-mortem hearts (preserved in 4% formaldehyde solution), under Polish local ethical rules. The SN/RA tissue blocks were embedded in paraffin and histologically stained with Masson's Trichrome. High and low-magnification images were taken, and analysis was done for appropriate statistical tests on Prism (GraphPad, USA). 12-lead ECGs from 14 patients under Polish local ethical rules were obtained. The P wave morphologies from lead II, lead III and lead aVF were analyzed. Results: Compared to the surrounding RA, the SN in all four groups has significantly more connective tissue (P ≤ 0.05) (young non-obese individuals, aged non-obese individuals, aged obese individuals and young obese individuals) and significantly smaller nodal cells (P ≤ 0.05) (young non-obese individuals, aged non-obese individuals, aged obese individuals, young obese individuals). In aging, overall, there was a significant increase in fibrosis, apoptosis, and cellular hypertrophy in the SN (P ≤ 0.05) and RA (P ≤ 0.05). Obesity did not further exacerbate fibrosis but caused a further increase in cellular hypertrophy (SN P ≤ 0.05, RA P ≤ 0.05), especially in young obese individuals. However, there was more infiltrating fat within the SN and RA bundles in obesity. Compared to the young non-obese individuals, the young obese individuals showed decreased P wave amplitude and P wave slope in aVF lead. Discussion: Aging and obesity are two risk factors for extensive fibrosis and cellular hypertrophy in SN and RA. Obesity exacerbates the morphological alterations, especially hypertrophy of nodal and atrial myocytes. These morphological alterations might lead to functional alterations and eventually cause cardiovascular diseases, such as SN dysfunction, atrial fibrillation, bradycardia, and heart failure.
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The impact of hydroxyurea (HU) on the ovarian reserve of female patients with sickle cell disease (SCD) remains poorly elucidated. Only direct histological analysis of ovarian follicle density can effectively evaluate HU's effect on ovarian reserve. By analyzing digitized slides of ovarian tissue from girls and young women with SCD who underwent ovarian tissue cryopreservation (OTC) before hematological stem cell transplantation (HSCT), we meticulously counted follicles and categorized them based on their growth stage. We then calculated the densities of different follicle types and assessed their correlation with patient characteristics, clinical manifestations, and treatments extracted from medical records. Seventy-six SCD patients participated in the study, with a median age at OTC of 10.2 years (interquartile range [IQR] 7.5, 14.6), and 50 (65.8%) were prepubertal. Of these, 35 patients (46.1%) had received HU, with a median daily dosage of 23.0 mg/kg (IQR 20.0, 25.0) and median exposure time of 44 months (IQR 24.0, 54.0). Primordial follicle density was comparable between the HU and non-HU groups (5.8 follicles/mm2 [IQR 1.0, 13.3] versus 4.2 follicles/mm2 [IQR 1.1, 14.4], respectively; P = .95). However, in the HU group, after adjusting for age, the density of growing follicles was marginally lower compared to the non-HU group (P = .09). Notably, other parameters such as vaso-occlusive crisis did not affect follicular density. In conclusion, exposure to hydroxyurea did not demonstrate a reduction in ovarian reserve in girls/women with SCD. Therefore, fertility preservation measures before initiating HU treatment do not seem necessary.
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Importance: Preoperative skin antisepsis is an established procedure to prevent surgical site infections (SSIs). The choice of antiseptic agent, povidone iodine or chlorhexidine gluconate, remains debated. Objective: To determine whether povidone iodine in alcohol is noninferior to chlorhexidine gluconate in alcohol to prevent SSIs after cardiac or abdominal surgery. Design, Setting, and Participants: Multicenter, cluster-randomized, investigator-masked, crossover, noninferiority trial; 4403 patients undergoing cardiac or abdominal surgery in 3 tertiary care hospitals in Switzerland between September 2018 and March 2020 were assessed and 3360 patients were enrolled (cardiac, n = 2187 [65%]; abdominal, n = 1173 [35%]). The last follow-up was on July 1, 2020. Interventions: Over 18 consecutive months, study sites were randomly assigned each month to either use povidone iodine or chlorhexidine gluconate, each formulated in alcohol. Disinfectants and skin application processes were standardized and followed published protocols. Main Outcomes and Measures: Primary outcome was SSI within 30 days after abdominal surgery and within 1 year after cardiac surgery, using definitions from the US Centers for Disease Control and Prevention's National Healthcare Safety Network. A noninferiority margin of 2.5% was used. Secondary outcomes included SSIs stratified by depth of infection and type of surgery. Results: A total of 1598 patients (26 cluster periods) were randomly assigned to receive povidone iodine vs 1762 patients (26 cluster periods) to chlorhexidine gluconate. Mean (SD) age of patients was 65.0 years (39.0-79.0) in the povidone iodine group and 65.0 years (41.0-78.0) in the chlorhexidine gluconate group. Patients were 32.7% and 33.9% female in the povidone iodine and chlorhexidine gluconate groups, respectively. SSIs were identified in 80 patients (5.1%) in the povidone iodine group vs 97 (5.5%) in the chlorhexidine gluconate group, a difference of 0.4% (95% CI, -1.1% to 2.0%) with the lower limit of the CI not exceeding the predefined noninferiority margin of -2.5%; results were similar when corrected for clustering. The unadjusted relative risk for povidone iodine vs chlorhexidine gluconate was 0.92 (95% CI, 0.69-1.23). Nonsignificant differences were observed following stratification by type of surgical procedure. In cardiac surgery, SSIs were present in 4.2% of patients with povidone iodine vs 3.3% with chlorhexidine gluconate (relative risk, 1.26 [95% CI, 0.82-1.94]); in abdominal surgery, SSIs were present in 6.8% with povidone iodine vs 9.9% with chlorhexidine gluconate (relative risk, 0.69 [95% CI, 0.46-1.02]). Conclusions and Relevance: Povidone iodine in alcohol as preoperative skin antisepsis was noninferior to chlorhexidine gluconate in alcohol in preventing SSIs after cardiac or abdominal surgery. Trial Registration: ClinicalTrials.gov Identifier: NCT03685604.
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BACKGROUND: Congenital syphilis disproportionately affects individuals impacted by adverse social determinants of health. Understanding these determinants may help facilitate holistic care. METHODS: We performed a retrospective review of mother-infant dyads with potential congenital syphilis in a Missouri hospital system. Cases were classified per Centers for Disease Control and Prevention clinical scenarios. Information was collected regarding demographics, prenatal care, substance use, and other social factors. Dyads with confirmed/highly probable or possible congenital syphilis ("congenital syphilis outcomes") were compared to those with less likely/unlikely congenital syphilis ("non-congenital syphilis outcomes") using descriptive statistics. RESULTS: We identified 131 dyads with infant dates of birth from 12/2015-6/2022: 74 (56%) with congenital syphilis outcomes and 56 (43%) with non-congenital syphilis outcomes. Most mothers were Black/African American (n = 84, 65%) and lived in areas with high Social Vulnerability Indices. Many had inadequate prenatal care (n = 61, 47%) and/or substance use histories (n = 55, 42%). Significant associations with congenital syphilis outcomes included limited prenatal care (OR 3.01, 95% CI 1.38-6.56), no prenatal care (OR 16.08, 95% CI 1.96-132.11), substance use (OR 3.42, 95% CI 1.61-7.25), housing instability (OR 3.42, 95% CI 1.39-8.38), and justice system interactions (OR 2.29, 95% CI 1.00-5.24). Substance use correlated with prenatal care adequacy (p < 0.001). 30% of infants with congenital syphilis outcomes were taken into protective custody. CONCLUSIONS: Adverse social determinants of health are common in dyads impacted by congenital syphilis. Health systems should consider interdisciplinary programming to improve testing and linkage to care. Future studies should evaluate social support for congenital syphilis prevention and management.
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Ivermectin has been used since the 1980s as an anthelmintic and antiectoparasite agent worldwide. Currently, the only available oral formulation is tablets designed for adult patients. A patient-friendly orodispersible tablet formulation designed for pediatric use (CHILD-IVITAB) has been developed and is entering early phase clinical trials. To inform the pediatric program of CHILD-IVITAB, 16 healthy adults were enrolled in a phase I, single-center, open-label, randomized, 2-period, crossover, single-dose trial which aimed to compare palatability, tolerability, and bioavailability and pharmacokinetics of CHILD-IVITAB and their variability against the marketed ivermectin tablets (STROMECTOL) at a single dose of 12 mg in a fasting state. Palatability with CHILD-IVITAB was considerably enhanced as compared to STROMECTOL. Both ivermectin formulations were well tolerated and safe. Relative bioavailability of CHILD-IVITAB compared to STROMECTOL was estimated as the ratios of geometric means for Cmax, AUC 0-∞, and AUC0-last, which were 1.52 [90% CI: 1.13-2.04], 1.27 [0.99-1.62], and 1.29 [1.00-1.66], respectively. Maximum drug concentrations occurred earlier with the CHILD-IVITAB formulation, with a median Tmax at 3.0 h [range 2.0-4.0 h] versus 4.0 h [range 2.0-5.0 h] with STROMECTOL (P = .004). With CHILD-IVITAB, variability in exposure was cut in half (coefficient of variation: 37% vs 70%) compared to STROMECTOL. Consistent with a more controlled absorption process, CHILD-IVITAB was associated with reduced variability in drug exposure as compared to STROMECTOL. Together with a favorable palatability and tolerability profile, these findings motivate for further clinical studies to evaluate benefits of such a patient-friendly ODT formulation in pediatric patients with a parasitic disease, including infants and young children <15 kg.
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OBJECTIVES: In trials of acute severe infections or inflammations frequent administration of non-randomised treatment (ie, intercurrent event) in response to clinical events is expected. These events may affect the interpretation of trial findings. Swissped-RECOVERY was set up as one of the first randomised controlled trials worldwide, investigating the comparative effectiveness of anti-inflammatory treatment with intravenous methylprednisolone or intravenous immunoglobulins in children and adolescents with Paediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2 (PIMS-TS). We present one approach towards improving the interpretation of non-randomised treatment in a randomised controlled trial. DESIGN: This is a pre-planned ancillary analysis of the Swissped-RECOVERY trial, a randomised multicentre open-label two-arm trial. SETTING: 10 Swiss paediatric hospitals (secondary and tertiary care) participated. PARTICIPANTS: Paediatric patients hospitalised with PIMS-TS. INTERVENTIONS: All patient-first intercurrent events, if applicable, were presented to an independent adjudication committee consisting of four international paediatric COVID-19 experts to provide independent clinical adjudication to a set of standardised questions relating to whether additional non-randomised treatments were clinically indicated and disease classification at the time of the intercurrent event. RESULTS: Of 41 treatments in 75 participants (24/41 (59%) and 17/41 (41%) in the intravenous methylprednisolone and immunoglobulin arms of the trial, respectively), two-thirds were considered indicated. The most common treatment (oral glucocorticoids, 14/41, 35%) was mostly considered not indicated (11/14, 79%), although in line with local guidelines. Intercurrent events among patients with Shock-like PIMS-TS at baseline were mostly considered indicated. A significant proportion of patients with undifferentiated PIMS-TS at baseline were not attributed to the same group at the time of the intercurrent event (6/12 unchanged, 4/12 Kawasaki disease-like, 2/12 Shock-like). CONCLUSION: The masked adjudication of intercurrent events contributes to the interpretation of results in open-label trials and should be incorporated in the future. TRIAL REGISTRATION NUMBERS: SNCTP000004720 and NCT04826588.
Subject(s)
COVID-19/complications , Immunoglobulins, Intravenous , Methylprednisolone , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Humans , Methylprednisolone/therapeutic use , Methylprednisolone/administration & dosage , Systemic Inflammatory Response Syndrome/drug therapy , Child , Switzerland , Immunoglobulins, Intravenous/therapeutic use , Immunoglobulins, Intravenous/administration & dosage , Adolescent , Hospitals, Pediatric , COVID-19 Drug Treatment , Female , Male , Anti-Inflammatory Agents/therapeutic use , Child, Preschool , Treatment OutcomeABSTRACT
Understanding pharmacokinetics (PK) in children is a prerequisite to determine optimal pediatric dosing. As plasma sampling in children is challenging, alternative PK sampling strategies are needed. In this case study we evaluated the suitability of saliva as alternative PK matrix to simplify studies in infants, investigating metamizole, an analgesic used off-label in infants. Six plasma and 6 saliva PK sample collections were scheduled after a single intravenous dose of 10 mg/kg metamizole. Plasma/saliva pharmacometric (PMX) modeling of the active metabolites 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA) was performed. Various reduced plasma sampling scenarios were evaluated by PMX simulations. Saliva and plasma samples from 25 children were included (age range, 5-70 months; weight range, 8.7-24.8 kg). Distribution of metamizole metabolites between plasma and saliva was without delay. Estimated mean (individual range) saliva/plasma fractions of 4-MAA and 4-AA were 0.32 (0.05-0.57) and 0.57 (0.25-0.70), respectively. Residual variability of 4-MAA (4-AA) in saliva was 47% (28%) versus 17% (11%) in plasma. A simplified sampling scenario with up to 6 saliva samples combined with 1 plasma sample was associated with similar PK parameter estimates as the full plasma sampling scenario. This case study with metamizole shows increased PK variability in saliva compared to plasma, compromising its suitability as single matrix for PK studies in infants. Nonetheless, rich saliva sampling can reduce the number of plasma samples required for PK characterization, thereby facilitating the conduct of PK studies to optimize dosing in pediatric patients.
Subject(s)
Dipyrone , Models, Biological , Saliva , Humans , Saliva/metabolism , Saliva/chemistry , Infant , Male , Dipyrone/pharmacokinetics , Dipyrone/administration & dosage , Child, Preschool , Female , Child , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Ampyrone/pharmacokinetics , Ampyrone/administration & dosageABSTRACT
Background: Posterior cruciate ligament (PCL) injuries to the knee are uncommon, and ideal surgical management of these injuries is unclear. Current surgical techniques include PCL reconstruction with remnant debridement, remnant-preserving techniques, and primary PCL repair. Augmentation of PCL repairs and reconstructions has been proposed to protect repairs or grafts in the postoperative period. Purpose: To describe PCL repair with the hamstring autograft augmentation technique and examine our preliminary midterm outcomes from a sequential cohort of patients. Study Design: Case series; Level of evidence, 4. Methods: The authors identified patients at their institution who underwent remnant-preserving primary PCL repair with hamstring autograft augmentation for both isolated tears and tears associated with multiligament knee injury (MLKI). Patient-reported outcomes were evaluated at a minimum 2-year follow-up using the International Knee Documentation Committee (IKDC) subjective knee form, the 12-item Short Form Survey, and a custom return-to-play questionnaire. Patient-reported outcomes data were summarized, and the predictors of outcomes from the descriptive data and clinical measures were further examined. Results: A total of 23 patients with a mean follow-up of 5.3 years met the inclusion criteria. Of these patients, 87% were associated with MLKI. The mean IKDC score was 87.7. Approximately 83% of patients were able to successfully return to their sport or occupation. Among 19 athletes, only 2 reported being unable to return to their preinjury level of sport because of limitations from their PCL surgery. Patient-reported outcome scores and return to sport or occupation did not have a statistically significant association with age, sex, body mass index, time from injury to surgery, or follow-up time. Conclusion: Outcomes of our cohort with remnant-preserving primary PCL repairs with hamstring autograft augmentation demonstrated comparable clinical outcomes to previously published PCL data. The advantages of remnant preservation, primary repair, and augmentation with an independent hamstring autograft reconstruction are combined within this technique.
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Data on COVID-19 vaccine acceptability among parents of children with multisystem inflammatory syndrome (MIS-C) are limited. In this cohort of children with MIS-C, enrolled in the Swissped RECOVERY trial (NCT04826588), comparing intravenous immunoglobulins or methylprednisolone, who, in accordance with Swiss guidelines, were recommended for SARS-CoV-2 vaccination, 65% (73/112) of parents reported being vaccinated against SARS-CoV-2 before the MIS-C, while 70% were vaccinated after the MIS-C episode of their child. None of the children were vaccinated before the occurrence of the MIS-C, and only 9% (5/56) received the COVID-19 vaccine after the MIS-C. The predominant barriers to COVID-19 vaccination were concerns over potential side effects and insufficient support from their doctors. This emphasizes the crucial role of health care providers in promoting COVID-19 vaccination among children.
Subject(s)
COVID-19 Vaccines , COVID-19 , Child , Humans , COVID-19/prevention & control , COVID-19/complications , Parents , SARS-CoV-2 , Systemic Inflammatory Response Syndrome , Clinical Trials as Topic , Cohort StudiesABSTRACT
BACKGROUND: In pediatric rheumatic diseases (PRD), adalimumab is dosed using fixed weight-based bands irrespective of methotrexate co-treatment, disease activity (DA) or other factors that might influence adalimumab pharmacokinetics (PK). In rheumatoid arthritis (RA) adalimumab exposure between 2-8 mg/L is associated with clinical response. PRD data on adalimumab is scarce. Therefore, this study aimed to analyze adalimumab PK and its variability in PRD treated with/without methotrexate. METHODS: A two-center prospective study in PRD patients aged 2-18 years treated with adalimumab and methotrexate (GA-M) or adalimumab alone (GA) for ≥ 12 weeks was performed. Adalimumab concentrations were collected 1-9 (maximum concentration; Cmax), and 10-14 days (minimum concentration; Cmin) during ≥ 12 weeks following adalimumab start. Concentrations were analyzed with enzyme-linked immunosorbent assay (lower limit of quantification: 0.5 mg/L). Log-normalized Cmin were compared between GA-M and GA using a standard t-test. RESULTS: Twenty-eight patients (14 per group), diagnosed with juvenile idiopathic arthritis (71.4%), non-infectious uveitis (25%) or chronic recurrent multifocal osteomyelitis (3.6%) completed the study. GA-M included more females (71.4%; GA 35.7%, p = 0.13). At first study visit, children in GA-M had a slightly longer exposure to adalimumab (17.8 months [IQR 9.6, 21.6]) compared to GA (15.8 months [IQR 8.5, 30.8], p = 0.8). Adalimumab dosing was similar between both groups (median dose 40 mg every 14 days) and observed DA was low. Children in GA-M had a 27% higher median overall exposure compared to GA, although median Cmin adalimumab values were statistically not different (p = 0.3). Cmin values ≥ 8 mg/L (upper limit RA) were more frequently observed in GA-M versus GA (79% versus 64%). Overall, a wide range of Cmin values was observed in PRD (0.5 to 26 mg/L). CONCLUSION: This study revealed a high heterogeneity in adalimumab exposure in PRD. Adalimumab exposure tended to be higher with methotrexate co-treatment compared to adalimumab monotherapy although differences were not statistically significant. Most children showed adalimumab exposure exceeding those reported for RA with clinical response, particularly with methotrexate co-treatment. This highlights the need of further investigations to establish model-based personalized treatment strategies in PRD to avoid under- and overexposure. TRIAL REGISTRATION: NCT04042792 , registered 02.08.2019.
Subject(s)
Antirheumatic Agents , Arthritis, Rheumatoid , Female , Humans , Child , Adalimumab/adverse effects , Methotrexate/adverse effects , Antirheumatic Agents/adverse effects , Prospective Studies , Antibodies, Monoclonal, Humanized/therapeutic use , Treatment Outcome , Drug Therapy, Combination , Arthritis, Rheumatoid/drug therapyABSTRACT
OBJECTIVE: To compare clinical outcomes over time of inpatients with healthcare-associated coronavirus disease 2019 (HA-COVID-19) versus community-acquired COVID-19 (CA-COVID-19). DESIGN: We conducted a multicenter, prospective observational cohort study of inpatients with COVID-19. SETTING: The study was conducted across 16 acute-care hospitals in Switzerland. PARTICIPANTS AND METHODS: We compared HA-COVID-19 cases, defined as patients with a positive severe acute respiratory coronavirus virus 2 (SARS-CoV-2) test > 5 days after hospital admission, with hospitalized CA-COVID-19 cases, defined as those who tested positive within 5 days of admission. The composite primary outcome was patient transfer to an intensive care unit (ICU) or an intermediate care unit (IMCU) and/or all-cause in-hospital mortality. We used cause-specific Cox regression and Fine-Gray regression to model the time to the composite clinical outcome, adjusting for confounders and accounting for the competing event of discharge from hospital. We compared our results to those from a conventional approach using an adjusted logistic regression model where time-varying effects and competitive risk were ignored. RESULTS: Between February 19, 2020, and December 31, 2020, we included 1,337 HA-COVID-19 cases and 9,068 CA-COVID-19 cases. HA-COVID-19 patients were significantly older: median, 80 (interquartile range [IQR], 71-87) versus median 70 (IQR, 57-80) (P < .001). A greater proportion of HA-COVID-19 patients had a Charlson comorbidity index ≥ 5 (79% vs 55%; P < .001) than did CA-COVID-19 patients. In time-varying analyses, between day 0 and 8, HA-COVID-19 cases had a decreased risk of death or ICU or IMCU transfer compared to CA-COVID-19 cases (cause-specific hazard ratio [csHR], 0.43; 95% confidence interval [CI], 0.33-0.56). In contrast, from day 8 to 30, HA-COVID-19 cases had an increased risk of death or ICU or IMCU transfer (csHR, 1.49; 95% CI, 1.20-1.85), with no significant effect on the rate of discharge (csHR, 0.83; 95% CI, 0.61-1.14). In the conventional logistic regression model, HA-COVID-19 was protective against transfer to an ICU or IMCU and/or all-cause in-hospital mortality (adjusted odds ratio [aOR], 0.79, 95% CI, 0.67-0.93). CONCLUSIONS: The risk of adverse clinical outcomes for HA-COVID-19 cases increased substantially over time in hospital and exceeded that for CA-COVID-19. Using approaches that do not account for time-varying effects or competing events may not fully capture the true risk of HA-COVID-19 compared to CA-COVID-19.
Subject(s)
COVID-19 , Humans , COVID-19/epidemiology , Prospective Studies , SARS-CoV-2 , Inpatients , Retrospective Studies , Intensive Care Units , Hospital MortalityABSTRACT
Background: Previous findings from the Swissped RECOVERY trial showed that patients with Pediatric Inflammatory Multisystem Syndrome-Temporally Associated with SARS-CoV-2 (PIMS-TS) who were randomly assigned to intravenous immunoglobulins or methylprednisolone have a comparable length of hospital stay. Here, we report the 6-month follow-up outcomes of cardiac pathologies and normalisation of clinical or laboratory signs of inflammation from this study population. Methods: This pre-planned follow-up of patients with PIMS-TS included the Swissped RECOVERY Trial reports on the 6-month outcomes of the cohort after randomisation, with a focus on cardiac, haematological, and biochemical findings. The trial was an investigator-initiated randomised multicentre open-label two-arm trial in children and adolescents hospitalised with PIMS-TS at ten hospitals in Switzerland. Cardiological assessments and laboratory analyses were prospectively collected in the intention-to-treat analysis on pre-defined intervals after hospital discharge. Differences between randomised arms were investigated using Chi-square test for categorical and Wilcoxon test for continuous variables. The trial is registered with the Swiss National Clinical Trials Portal (SNCTP000004720) and ClinicalTrials.gov (NCT04826588). Findings: Between May 21, 2021 and April 15, 2022, 75 patients with a median age of 9.1 years (IQR 6.2-12.2) were included in the intention-to-treat population (37 in the methylprednisolone group and 38 in the intravenous immunoglobulin group). During follow-up, the incidence of abnormal left ventricular systolic function, coronary artery aneurysms (CAA), and other signs of inflammation were comparable in both groups. However, we detected cardiac abnormalities with low incidence and a mild degree grade of pathology. CAAs were observed in 2/38 children (5.3%) in the IVIG group and 1/37 children (2.7%) in the methylprednisolone group at 6-month follow-up (difference proportion 0.75; 95% confidence interval (CI) -0.05 to 1.0; p = 0.39). Interpretation: Methylprednisolone alone may be an acceptable first-line treatment as left ventricular systolic dysfunction and clinical/laboratory evidence for inflammation quickly resolved in all children. However, our findings need further confirmation through larger studies as our sample size is likely to be of insufficient power to address rare clinically relevant adverse outcomes. Funding: NOMIS, Vontobel, and Gaydoul Foundation.
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Objective: To evaluate the effects of handshake antimicrobial stewardship on medicine floors at a large tertiary care hospital. Design: Retrospective observational study. Setting: 1,278-bed academic hospital. Patients: Adults admitted to non-ICU medicine services. Interventions: A handshake stewardship team consisting of an infectious diseases (ID) physician and pharmacist reviewed charts of patients receiving antimicrobials on medicine floors without a formal ID consult. Recommendations were communicated in-person to providers and acceptance rates were examined with descriptive statistics. Additional data regarding program perception among providers were obtained via surveys. Antibiotic usage trends were extracted from National Healthcare Safety Network Antimicrobial Use option data and evaluated using an interrupted time-series analysis pre- and post-intervention. Results: The overall acceptance rate of interventions was 80%, the majority being recommendations either to discontinue (37%) or de-escalate therapy (28%). Medical residents and hospitalists rated the intervention favorably with 90% reporting recommendations were helpful all or most of the time. There was a statistically significant decrease in vancomycin (78 vs 70 DOT/1,000 d present (DP), p = 0.002) and meropenem (24 vs 17 DOT/1,000 DP, p = 0.007) usage and a statistically significant increase in amoxicillin-clavulanate usage (11 vs 15 DOT/1,000 DP, p < 0.001). Overall antibiotic usage remained unchanged by the intervention, though pre-intervention there was a nonsignificant overall increasing trend while post-intervention there was a nonsignificant decreasing trend in overall usage. There was no change in in-hospital mortality. Conclusion: The addition of handshake stewardship with adult medicine services was favorably viewed by participants and led to shifts in antibiotic usage.
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BACKGROUND: In Switzerland, the national surgical site infection (SSI) surveillance program showed a modest decrease in SSI rates for different procedures over the last decade. The study aimed to determine whether a multimodal, targeted intervention program in addition to existing SSI surveillance is associated with decreased SSI rates in the participating hospitals. METHODS: Prospective multicenter pre- and postintervention study conducted in eight Swiss acute care hospitals between 2013 and 2020. All consecutive patients > 18 years undergoing cardiac, colon, or hip/knee replacement surgery were included. The follow-up period was 30 days and one year for implant-related surgery. Patients with at least one follow-up were included. The intervention was to optimize three elements of preoperative management: (i) hair removal; (ii) skin disinfection; and (iii) perioperative antimicrobial prophylaxis. We compared SSI incidence rates (main outcome measure) pre- and postintervention (three years each) adjusted for potential confounders. Poisson generalized linear mixed models fitted to quarter-yearly confirmed SSIs and adjusted for baseline differences between hospitals and procedures. Adherence was routinely monitored through on-site visits. RESULTS: A total of 10 151 patients were included, with a similar median age pre- and postintervention (69.6 and IQR 60.9, 76.8 years, vs 69.5 and IQR 60.4, 76.8 years, respectively; P = 0.55) and similar proportions of females (44.8% vs. 46.1%, respectively; P = 0.227). Preintervention, 309 SSIs occurred in 5 489 patients (5.6%), compared to 226 infections in 4 662 cases (4.8%, P = 0.09) postintervention. The adjusted incidence rate ratio (aIRR) for overall SSI after intervention implementation was 0.81 (95% CI, 0.68 to 0.96, P = 0.02). For cardiac surgery (n = 2 927), the aIRR of SSI was 0.48 (95% CI, 0.32 to 0.72, P < 0.001). For hip/knee replacement surgery (n = 4 522), the aIRR was 0.88 (95% CI, 0.52 to 1.48, P = 0.63), and for colon surgery (n = 2 702), the aIRR was 0.92 (95% CI, 0.75 to 1.14, P = 0.49). CONCLUSIONS: The SSI intervention bundle was associated with a statistically significant decrease in SSI cases. A significant association was observed for cardiac surgery. Adding a specific intervention program can add value compared to routine surveillance only. Further prevention modules might be necessary for colon and orthopedic surgery.
Subject(s)
Hospitals , Surgical Wound Infection , Female , Humans , Incidence , Prospective Studies , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Surgical Wound Infection/drug therapy , Switzerland/epidemiology , Adult , Aged , Middle AgedABSTRACT
OBJECTIVE: We aimed to evaluate the association between post-appendectomy SSI rates and the two most commonly used regimens for perioperative antimicrobial prophylaxis in Swiss children. METHODS: We conducted a retrospective cohort study, analysing data from the Swiss national SSI surveillance database with a study period from 2014 to 2018. All hospitals undertaking paediatric appendectomies in Switzerland participate in the surveillance. We compared the cumulative incidence and odds of post-appendectomy SSI within 30 days of surgery in children ≤ 16 years of age undergoing appendectomy for uncomplicated appendicitis and receiving perioperative antimicrobial prophylaxis with cefuroxime plus metronidazole or with amoxicillin/clavulanic acid using multivariable adjusted logistic regression and propensity-score matching. RESULTS: A total of 6207 cases were recorded in the study time frame. Overall SSI cumulative incidence was 1.9% (n = 119). 4256 children (54.9% male, median (IQR) age 12 [10, 14] years) received either cefuroxime plus metronidazole (n = 2348, 53.8% male) or amoxicillin/clavulanic acid (n = 1491, 57.0% male). SSI cumulative incidence was 1.1% (25/2348) among children receiving cefuroxime plus metronidazole and 2.8% (42/1491, p < 0.001) when receiving amoxicillin/clavulanic acid. The administration of cefuroxime plus metronidazole was associated with statistically significantly lower SSI odds compared to amoxicillin/clavulanic acid (aOR 0.35, 95%CI [0.20, 0.61], p < 0.001), and this was confirmed upon propensity-score matching. CONCLUSION: We found lower odds of post-appendectomy SSI in children receiving cefuroxime plus metronidazole compared to amoxicillin/clavulanic acid. Treating amoxicillin/clavulanic acid as the baseline, only 55 children need to receive cefuroxime plus metronidazole perioperative prophylaxis to avert one SSI. Existing guidelines recommending amoxicillin/clavulanic acid may need to be revised. Trial registration ISRCTN47727811, registered retrospectively.
Subject(s)
Metronidazole , Surgical Wound Infection , Child , Male , Humans , Female , Surgical Wound Infection/epidemiology , Surgical Wound Infection/prevention & control , Metronidazole/therapeutic use , Cefuroxime/therapeutic use , Appendectomy/adverse effects , Retrospective Studies , Switzerland/epidemiology , Amoxicillin-Potassium Clavulanate Combination/therapeutic useABSTRACT
Objective: To determine the relationship between severe acute respiratory syndrome coronavirus 2 infection, hospital-acquired infections (HAIs), and mortality. Design: Retrospective cohort. Setting: Three St. Louis, MO hospitals. Patients: Adults admitted ≥48 hours from January 1, 2017 to August 31, 2020. Methods: Hospital-acquired infections were defined as those occurring ≥48 hours after admission and were based on positive urine, respiratory, and blood cultures. Poisson interrupted time series compared mortality trajectory before (beginning January 1, 2017) and during the first 6 months of the pandemic. Multivariable logistic regression models were fitted to identify risk factors for mortality in patients with an HAI before and during the pandemic. A time-to-event analysis considered time to death and discharge by fitting Cox proportional hazards models. Results: Among 6,447 admissions with subsequent HAIs, patients were predominantly White (67.9%), with more females (50.9% vs 46.1%, P = .02), having slightly lower body mass index (28 vs 29, P = .001), and more having private insurance (50.6% vs 45.7%, P = .01) in the pre-pandemic period. In the pre-pandemic era, there were 1,000 (17.6%) patient deaths, whereas there were 160 deaths (21.3%, P = .01) during the pandemic. A total of 53 (42.1%) coronavirus disease 2019 (COVID-19) patients died having an HAI. Age and comorbidities increased the risk of death in patients with COVID-19 and an HAI. During the pandemic, Black patients with an HAI and COVID-19 were more likely to die than White patients with an HAI and COVID-19. Conclusions: In three Midwestern hospitals, patients with concurrent HAIs and COVID-19 were more likely to die if they were Black, elderly, and had certain chronic comorbidities.
ABSTRACT
OBJECTIVE: To compare intravenous (IV) amoxicillin/clavulanic acid (A/CA) to IV cefuroxime plus metronidazole (C + M) for preventing surgical site infections (SSI) in colorectal surgery. BACKGROUND: Given their spectra that include most Enterobacterales and anaerobes, C + M is commonly recommended as prophylaxis of SSI in colorectal surgery. A/CA offers good coverage of Enterobacterales and anaerobes as well, but, in contrast to C + M, it also includes Enterococcus faecalis which is also isolated from patients with SSI and could trigger anastomotic leakage. METHODS: Data from a Swiss SSI surveillance program were used to compare SSI rates after class II (clean contaminated) colorectal surgery between patients who received C + M and those who received A/CA. We employed multivariable logistic regression to adjust for potential confounders, along with propensity score matching to adjust for group imbalance. RESULTS: From 2009 to 2018, 27,922 patients from 127 hospitals were included. SSI was diagnosed in 3132 (11.2%): 278/1835 (15.1%) in those who received A/CA and 2854/26,087 (10.9%) in those who received C + M (p < 0.001). The crude OR for SSI in the A/CA group as compared to C + M was 1.45 [CI 95% 1.21-1.75]. The adjusted OR was 1.49 [1.24-1.78]. This finding persisted in a 1:1 propensity score matched cohort of 1835 patients pairs with an OR of 1.60 [1.28-2.00]. Other factors independently associated with SSI were an ASA score > 2, a longer duration of operation, and a reoperation for a non-infectious complication. Protective factors were female sex, older age, antibiotic prophylaxis received 60 to 30 min before surgery, elective operation, and endoscopic approach. CONCLUSIONS: Despite its activity against enterococci, A/CA was less effective than C + M for preventing SSI, suggesting that it should not be a first choice antibiotic prophylaxis for colorectal surgery.
Subject(s)
Anti-Infective Agents , Colorectal Surgery , Gammaproteobacteria , Humans , Female , Male , Metronidazole/therapeutic use , Surgical Wound Infection/prevention & control , Cefuroxime/therapeutic use , Colorectal Surgery/adverse effects , Amoxicillin-Potassium Clavulanate Combination/therapeutic useABSTRACT
OBJECTIVES: Aminoglycosides and ß-lactams have been recommended for treatment of sepsis/septic shock despite a lack of mortality benefit. Previous studies have examined resistance emergence for the same bacterial isolate using old dosing regimens and during a narrow follow-up window. We hypothesised that combination regimens employing aminoglycosides will decrease the cumulative incidence of infections due to multidrug-resistant (MDR) Gram-negative bacilli (GNB) compared with ß-lactams alone. METHODS: All adult patients admitted to Barnes Jewish Hospital between 2010 and 2017 with a diagnosis of sepsis/septic shock were included in this retrospective cohort study. Patients were divided into two treatment groups, with and without aminoglycosides. Patient demographics, severity of presentation, administered antibiotics, follow-up cultures with susceptibility results for a period of 4-60 days, and mortality were extracted. After propensity score matching, a Fine-Gray subdistribution proportional hazards model summarised the estimated incidence of subsequent infections with MDR-GNB in the presence of all-cause death as a competing risk. RESULTS: A total of 10 212 septic patients were included, with 1996 (19.5%) treated with at least two antimicrobials including one aminoglycoside. After propensity score matching, the cumulative incidence of MDR-GNB infections between 4-60 days was lower in the combination group (incidence at 60 days 0.073, 95% CI 0.062-0.085) versus patients not receiving aminoglycosides (0.116, 95% CI 0.102-0.130). Patients aged ≤65 years and with haematological malignancies had a larger treatment effect in subgroup analyses. CONCLUSION: Addition of aminoglycosides to ß-lactams may protect against subsequent infections due to MDR-GNB in patients with sepsis/septic shock.