Epidemiology, risk factors and outcomes of prolonged mechanical ventilation with different cut-points in a PICU

BackgroundA consensus on the definition of prolonged mechanical ventilation (PMV) for children does not exist. There is still lack of published work presenting the epidemiology, risk factors and outcomes at different cut-points for PMV patients. These are important for planning the goals of treatment and counseling of the prognosis for patient families. We aimed to determine the incidence, baseline characteristics, risk factors and outcomes of PMV in pediatric patients at various cut-points (>14, >21 or >30days).MethodsA retrospective cohort study among children <18-years-old who were PMV > 14 days in the PICU of King Chulalongkorn Memorial Hospital was conducted. The primary outcomes were incidence of PMV with various cut-points. We stratified patients into three groups (Group 1; PMV > 14–21, Group 2; >21–30, Group 3; >30 days) for evaluating the baseline characteristics, risk factors, and outcomes of PMV (extubation success, tracheostomy status and death). Factors associated with PMV and deaths were analyzed using univariate and multivariate logistic regression.ResultsFrom January 2018 to August 2022, 1,050 patients were screened. Of these, 114 patients were enrolled. The incidence of PMV > 14, >21 and >30 days were 10.9%, 7.3% and 5.0% respectively. Extubation success was significantly lower in Group 3 than in Groups 1 & 2 (15.4% vs. 62.2% & 56.0%, P < 0.001). Consequently, the tracheostomy rate (63.5% vs. 16.2% & 12.0%, P < 0.001), VAP rate (98.1% vs. 59.5% & 80.0%, P < 0.001), mortality rate by disease (34.6% vs. 5.4% & 20.0%, P = 0.003), median PICU LOS (50.5 vs. 22.0 & 28.0 days, P < 0.001) and median hospital LOS (124.5 vs. 55.0 & 62.0 days, P < 0.001) were also significantly higher for Group 3 compared with Groups 1 & 2. The factor associated with PMV > 30 days was VAP (aOR: 19.53, 95% CI: 2.38–160.34, P = 0.01). Factors associated with non-surviving patients were 3rd degree PEM (aOR: 5.14, 95% CI: 1.57–16.88, P = 0.01), PIM3 score ≥14 (aOR: 6.75, 95% CI: 2.26–20.15, P < 0.001) and muscle relaxant usage (aOR: 5.58, 95% CI: 1.65–18.86, P = 0.01).ConclusionExtubation failure, tracheostomy rate, VAP rate, mortality rate by disease, PICU LOS and hospital LOS were significantly higher for PMV >30 days. Consequently, we suggest that a 30-day duration as a cut-point for PMV in PICUs might be more appropriate

Table1_Epidemiology, risk factors and outcomes of prolonged mechanical ventilation with different cut-points in a PICU.docx

BackgroundA consensus on the definition of prolonged mechanical ventilation (PMV) for children does not exist. There is still lack of published work presenting the epidemiology, risk factors and outcomes at different cut-points for PMV patients. These are important for planning the goals of treatment and counseling of the prognosis for patient families. We aimed to determine the incidence, baseline characteristics, risk factors and outcomes of PMV in pediatric patients at various cut-points (>14, >21 or >30days).MethodsA retrospective cohort study among children  14 days in the PICU of King Chulalongkorn Memorial Hospital was conducted. The primary outcomes were incidence of PMV with various cut-points. We stratified patients into three groups (Group 1; PMV > 14–21, Group 2; >21–30, Group 3; >30 days) for evaluating the baseline characteristics, risk factors, and outcomes of PMV (extubation success, tracheostomy status and death). Factors associated with PMV and deaths were analyzed using univariate and multivariate logistic regression.ResultsFrom January 2018 to August 2022, 1,050 patients were screened. Of these, 114 patients were enrolled. The incidence of PMV > 14, >21 and >30 days were 10.9%, 7.3% and 5.0% respectively. Extubation success was significantly lower in Group 3 than in Groups 1 & 2 (15.4% vs. 62.2% & 56.0%, P  30 days was VAP (aOR: 19.53, 95% CI: 2.38–160.34, P = 0.01). Factors associated with non-surviving patients were 3rd degree PEM (aOR: 5.14, 95% CI: 1.57–16.88, P = 0.01), PIM3 score ≥14 (aOR: 6.75, 95% CI: 2.26–20.15, P ConclusionExtubation failure, tracheostomy rate, VAP rate, mortality rate by disease, PICU LOS and hospital LOS were significantly higher for PMV >30 days. Consequently, we suggest that a 30-day duration as a cut-point for PMV in PICUs might be more appropriate.</p

Incidence and factors associated with active tuberculosis among people living with HIV after long-term antiretroviral therapy in Thailand: a competing risk model

Background: Antiretroviral therapy (ART) is known to reduce tuberculosis (TB) incidence among people living with HIV (PLWH). However, studies describing the impact of long-term ART and CD4 count recovery on TB incidence remain scarce due to limited follow up in previous studies. We evaluated TB incidence in a long-term cohort of PLWH on ART in Thailand. Methods: We conducted an analysis of PLWH aged ≥ 18 years who started ART between 1996 and December 2020. Participants were followed up every 6 months for routine HIV care. TB risk factors, body mass index (BMI), physical examination and full differential blood counts were evaluated at each clinic visit, and CD4 cell counts and HIV RNA every 12 months. Participants diagnosed with TB > 3 months after starting ART were classified as incident cases. Time to event models with death as a competing risk, were used to derive the TB cumulative incidence function (CIF) after ART initiation, and assess time-updated factors associated with incident TB using a six month lag. Results: A total of 2,636 PLWH contributing 24,229 person years (PY) of follow-up on ART were analysed. Median age was 32.0 (IQR 27.4–37.6) years; 67.5% were male. Median CD4 cell count at ART initiation was 264 (IQR 167–379) cells/mm3 and median follow-up duration was 7.6 (IQR 1.9–15.7) years. During follow-up, 113 PLWH developed TB. The probability of incident TB was 0.7%, 1.7%, 3.3% and 4.3%, at 1, 2, 5 and 7 years after ART initiation, respectively. TB CIF was highest among participants with CD4 < 50 cells/mm3. The overall crude incidence of TB was 4.66 (95% CI 3.87–5.60) per 1000 PY. Low CD4 count, BMI < 18 kg/m2, and substance use in the previous six months were significantly associated with incident TB. Incidence declined with time on suppressive ART, but remained higher than the Thai general population 7 years after ART initiation (2.2 vs 1.5/1000 PY, respectively). Conclusion: Despite a marked reduction in TB incidence following ART, ongoing TB risk remains high among PLWH, despite long-term suppressive ART. Those with low CD4 cell counts, who are underweight, or currently having substance abuse should be carefully monitored

Incidence and factors associated with active tuberculosis among people living with HIV after long-term antiretroviral therapy in Thailand: a competing risk model

BACKGROUND: Antiretroviral therapy (ART) is known to reduce tuberculosis (TB) incidence among people living with HIV (PLWH). However, studies describing the impact of long-term ART and CD4 count recovery on TB incidence remain scarce due to limited follow up in previous studies. We evaluated TB incidence in a long-term cohort of PLWH on ART in Thailand. METHODS: We conducted an analysis of PLWH aged ≥ 18 years who started ART between 1996 and December 2020. Participants were followed up every 6 months for routine HIV care. TB risk factors, body mass index (BMI), physical examination and full differential blood counts were evaluated at each clinic visit, and CD4 cell counts and HIV RNA every 12 months. Participants diagnosed with TB > 3 months after starting ART were classified as incident cases. Time to event models with death as a competing risk, were used to derive the TB cumulative incidence function (CIF) after ART initiation, and assess time-updated factors associated with incident TB using a six month lag. RESULTS: A total of 2,636 PLWH contributing 24,229 person years (PY) of follow-up on ART were analysed. Median age was 32.0 (IQR 27.4-37.6) years; 67.5% were male. Median CD4 cell count at ART initiation was 264 (IQR 167-379) cells/mm3 and median follow-up duration was 7.6 (IQR 1.9-15.7) years. During follow-up, 113 PLWH developed TB. The probability of incident TB was 0.7%, 1.7%, 3.3% and 4.3%, at 1, 2, 5 and 7 years after ART initiation, respectively. TB CIF was highest among participants with CD4 < 50 cells/mm3. The overall crude incidence of TB was 4.66 (95% CI 3.87-5.60) per 1000 PY. Low CD4 count, BMI < 18 kg/m2, and substance use in the previous six months were significantly associated with incident TB. Incidence declined with time on suppressive ART, but remained higher than the Thai general population 7 years after ART initiation (2.2 vs 1.5/1000 PY, respectively). CONCLUSION: Despite a marked reduction in TB incidence following ART, ongoing TB risk remains high among PLWH, despite long-term suppressive ART. Those with low CD4 cell counts, who are underweight, or currently having substance abuse should be carefully monitored

Comparison of piperacillin plasma concentrations in a prospective randomised trial of extended infusion versus intermittent bolus of piperacillin/tazobactam in paediatric patients

Objectives: To be effective, piperacillin/tazobactam (PTZ) unbound plasma levels need to be above the minimum inhibitory concentration (MIC) at least 50% of the time between dosing intervals (50% fT>MIC). This study aimed to compare the plasma piperacillin concentrations at the mid-dosing intervals (Cmid, 50% fT) and the proportion of patients achieving 50% fT>MIC between extended infusion (EI) and intermittent bolus (IB) methods in children. Methods: A prospective, randomised trial of EI versus IB of PTZ was conducted in children aged 1 month to 18 years. The PTZ dose was 100 mg/kg intravenously every 8 h. Patients were randomly assigned to receive EI (4-h infusion) or IB (30-min infusion). The primary outcome that was measured was plasma piperacillin Cmid. Results: Ninety patients with a median age (IQR) of 48 months (16–127) were enrolled. The most common indication for PTZ use was pneumonia (32.2%). Geometric mean (95% CI) plasma piperacillin Cmid of EI versus IB was 51.9 mg/L (40.6–66.6) versus 6.0 mg/L (4.2–8.6) (P 4xMIC (72.7% versus 30.0%; P = 0.06). Conclusions: PTZ administration with EI resulted in a higher Cmid compared with IB. In settings with increased piperacillin MICs, this approach should be implemented, particularly during the empirical treatment period

Immunogenicity and Reactogenicity of mRNA BNT162b2 COVID-19 Vaccine among Thai Adolescents with Chronic Diseases

Adolescents with underlying diseases are at risk of severe COVID-19. The immune response of BNT162b2 may be poor among immunocompromised adolescents. We aim to describe immunogenicity of mRNA BNT162b2 among adolescents who are immunocompromised or have chronic diseases. We recruited adolescents 12&ndash;18 years of age; group A impaired-immunity (post-transplantation, cancer, on immunosuppressive drugs) and group B chronic diseases. A two-dose regimen of BNT162b2 was given. Immunogenicity was determined by surrogate virus neutralization test (sVNT) and IgG against receptor-binding domain (RBD). From August to October 2021, 312 adolescents, with a median age (IQR) of 15 years (13.7&ndash;16.5), were enrolled (group A 100, group B 212). The geometric means (GMs) of sVNT (% inhibition) against Delta strain and anti-RBD IgG (BAU/mL) after the 2nd dose among group A were: post-transplantation recipients 52.9 (95% CI 37.7&ndash;74.2) and 233.6 (95% CI 79&ndash;690.6); adolescents with cancer 62.3 (95% CI 29.2&ndash;133.1) and 214.9(95% CI 34.2&ndash;1348.6); and adolescents with other immunosuppressive conditions 66.7 (95% CI 52.4&ndash;84.8) and 849.8 (95% CI 393.4&ndash;1835.8). In group B were: adolescents living with HIV 98 (95% CI 97.3&ndash;98.8) and 3240.3 (95% CI 2699&ndash;3890.2), and adolescents with other chronic disease 98.6 (95% CI 98.3&ndash;98.9) and 3818.5 (95% CI 3490.4&ndash;4177.4). At day 90, immunity declined; among impaired-immunity participants were 43.9 (95% CI 30.8&ndash;62.4) and 178.7 (95% CI 91.2&ndash;350.1) and adolescents with chronic diseases were 90.6 (95% CI 88.4&ndash;92.8) and 1037.1 (95% CI 933.3&ndash;1152.5). In conclusion, adolescents with impaired immunity had a poor response to 2-doses of BNT162b2, additional dose should be considered. Adolescents with chronic diseases had excellent response but immunity waned after 3 m, booster dose may be required