Routine Conditions Research Articles

The performance of Xpert MTB/RIF and MTBDRplus within a Programmatic setting at TB Laboratory in Rio de Janeiro, Brazil.

Few studies in routine settings have confirmed the high accuracy of the Xpert MTB/RIF assay for detecting rifampicin resistance (RR) and the first-line probe assay (FL-LPA) for detecting both RR and isoniazid resistance (INHR). The performance of Xpert MTB/RIF and MTBDRplus VER 2.0 LPA was evaluated in 180 Mycobacterium tuberculosis samples collected from January 2018 to December 2019 in Rio de Janeiro, Brazil. The results were compared with those from BACTEC MGIT 960 culture and drug susceptibility testing (DST). Whole-genome sequencing was performed on the samples with discordant results. The Xpert MTB/RIF assay showed a sensitivity (Se) of 93.3% and a specificity (Sp) of 97.6%, detecting RR. The performance of FL-LPA to identify RIF and INH resistance was, respectively, (Se) 100% and 83.3% and (Sp) 98.8% and 100%. Among 18 clinical isolates with INHR detected by FL-LPA, mutations in the katG gene were observed in 100% of samples, of which only two (11.1%) had mutations in both katG and inhA genes. Overall, the discordant results were identified in 9 (5%) samples. Among the four Xpert RIF-resistant and DST-sensitive, two harbored mutations in rpoB Leu430Pro. Among the four FL-LPA-sensitive and DST-resistant, one had a mutation in inhA 17G>T. FL-LPA showed high accuracy in detecting RR and INHR. The MTBDRplus test demonstrated excellent performance in detecting RR, and INHR in clinical isolates under routine conditions at a reference laboratory in Rio de Janeiro, Brazil. Incorporating both tests can improve drug-resistant tuberculosis treatment outcomes and monitor the INHR incidence.

Confirmation of the utility of the CA-125 elimination rate (KELIM) as an indicator of the chemosensitivity in advanced-stage ovarian cancer in a "real-life setting".

The modeled CA-125 ELIMination rate constant K (KELIM) has been validated as a marker of response to chemotherapy in >12,000 patients with advanced epithelial ovarian carcinoma (EOC) treated in first-line setting enrolled in >12 clinical trials. Patient KELIM is calculable online https://www.biomarker-kinetics.org/presentation. The objective was to investigate the prognostic value of KELIM in a large real-life national cancer registry with non-selected patients. We investigated 4,025 EOC patients from the Netherlands Cancer Registry treated with neoadjuvant chemotherapy (NACT) ± followed by interval debulking surgery (IDS). Patient KELIM values were calculated in patients with ≥ 3 CA-125 measurements during NACT. KELIM was standardized with a pre-specified cut-off and scored as unfavorable/favorable (<1.0/≥1.0). KELIM's prognostic value regarding radiological response, completeness of IDS, progression-free survival (PFS), and overall survival (OS) was assessed using univariate/multivariate analyses. The data from 1,582 patients treated with heterogeneous chemotherapy regimens and sequences were assessable. KELIM was prognostic for radiological response and the likelihood of complete IDS after NACT (odds ratio=2.59; 95% confidence interval [CI]=2.04-3.29). Moreover, KELIM was independently associated with PFS (hazard ratio [HR]=0.76; 95% CI=0.66-0.87), and OS (HR=0.79; 95% CI=0.69-0.91). Combining KELIM with the completeness of the IDS resulted in 3 prognostic groups (satisfactory, intermediate, and poor) with significant OS differences, namely a good, intermediate, and poor survival respectively. The value of KELIM, as a pragmatic indicator of response to chemotherapy, was maintained in a large real-life population-based cohort, highlighting its applicability in routine conditions.

Deep learning-enabled classification of kidney allograft rejection on whole slide histopathologic images.

Diagnosis of kidney transplant rejection currently relies on manual histopathological assessment, which is subjective and susceptible to inter-observer variability, leading to limited reproducibility. We aim to develop a deep learning system for automated assessment of whole-slide images (WSIs) from kidney allograft biopsies to enable detection and subtyping of rejection and to predict the prognosis of rejection. We collected H&E-stained WSIs of kidney allograft biopsies at 400x magnification from January 2015 to September 2023 at two hospitals. These biopsy specimens were classified as T cell-mediated rejection, antibody-mediated rejection, and other lesions based on the consensus reached by two experienced transplant pathologists. To achieve feature extraction, feature aggregation, and global classification, we employed multi-instance learning and common convolution neural networks (CNNs). The performance of the developed models was evaluated using various metrics, including confusion matrix, receiver operating characteristic curves, the area under the curve (AUC), classification map, heat map, and pathologist-machine confrontations. In total, 906 WSIs from 302 kidney allograft biopsies were included for analysis. The model based on multi-instance learning enables detection and subtyping of rejection, named renal rejection artificial intelligence model (RRAIM), with the overall 3-category AUC of 0.798 in the independent test set, which is superior to that of three transplant pathologists under nearly routine assessment conditions. Moreover, the prognosis models accurately predicted graft loss within 1 year following rejection and treatment response for rejection, achieving AUC of 0.936 and 0.756, respectively. We first developed deep-learning models utilizing multi-instance learning for the detection and subtyping of rejection and prediction of rejection prognosis in kidney allograft biopsies. These models performed well and may be useful in assisting the pathological diagnosis.

High test-retest reliability of the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire completed by primary care patients in routine care.

The Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) is a three-item screening measure of unhealthy alcohol use that is widely used in healthcare settings. Evidence shows high test-retest reliability of the AUDIT-C in research samples, but most studies had limited external validity and used small samples that could not be used to evaluate reliability across demographic subgroups and/or screening modalities. This study evaluates the test-retest reliability of the AUDIT-C completed in routine care in a large primary care sample, including across demographic subgroups defined by age, sex, race, ethnicity, and screening modality (i.e., completed in-clinic or online). We used electronic health record (EHR) data from Kaiser Permanente Washington. The sample included 18,491 adult primary care patients who completed two AUDIT-C screens 1-21 days apart as part of routine care in 2021. Test-retest reliability was evaluated for AUDIT-C total scores (0-12) and for a binary measure indicating unhealthy alcohol use (scores ≥3 women, ≥4 men). Using previously established cutoffs, we interpreted reliability coefficients >0.75 as indicating "excellent" reliability. AUDIT-C screens completed in routine care and documented in EHRs had excellent test-retest reliability for total scores (ICC = 0.87, 95% CI: 0.87-0.87) and the binary indicator of unhealthy alcohol use (κ = 0.79, 95% CI: 0.78-0.80). Reliability coefficients were good to excellent across all demographic groups and for in-clinic and online modalities. Higher reliability was seen when both screens were completed through online patient portals (ICC = 0.93, 95% CI: 0.93-0.93) versus in-clinic (ICC = 0.81, 95% CI: 0.79-0.82) or when one screen was completed using each modality (ICC = 0.83, 95% CI: 0.82-0.83). Lower reliability was seen in American Indian/Alaska Native (ICC = 0.82, 95% CI: 0.75-0.87) and multiracial individuals (ICC = 0.82, 95% 0.80-0.84). In real-world routine care conditions, AUDIT-C screens have excellent test-retest reliability across demographic subgroups and modalities (online and in-clinic). Future research should examine why reliability varies slightly across modalities and demographic subgroups.

Development and Pilot Implementation of Neotree, a Digital Quality Improvement Tool Designed to Improve Newborn Care and Survival in 3 Hospitals in Malawi and Zimbabwe: Cost Analysis Study.

Two-thirds of the 2.4 million newborn deaths that occurred in 2020 within the first 28 days of life might have been avoided by implementing existing low-cost evidence-based interventions for all sick and small newborns. An open-source digital quality improvement tool (Neotree) combining data capture with education and clinical decision support is a promising solution for this implementation gap. We present results from a cost analysis of a pilot implementation of Neotree in 3 hospitals in Malawi and Zimbabwe. We combined activity-based costing and expenditure approaches to estimate the development and implementation cost of a Neotree pilot in 1 hospital in Malawi, Kamuzu Central Hospital (KCH), and 2 hospitals in Zimbabwe, Sally Mugabe Central Hospital (SMCH) and Chinhoyi Provincial Hospital (CPH). We estimated the costs from a provider perspective over 12 months. Data were collected through expenditure reports, monthly staff time-use surveys, and project staff interviews. Sensitivity and scenario analyses were conducted to assess the impact of uncertainties on the results or estimate potential costs at scale. A pilot time-motion survey was conducted at KCH and a comparable hospital where Neotree was not implemented. Total cost of pilot implementation of Neotree at KCH, SMCH, and CPH was US $37,748, US $52,331, and US $41,764, respectively. Average monthly cost per admitted child was US $15, US $15, and US $58, respectively. Staff costs were the main cost component (average 73% of total costs, ranging from 63% to 79%). The results from the sensitivity analysis showed that uncertainty around the number of admissions had a significant impact on the costs in all hospitals. In Malawi, replacing monthly web hosting with a server also had a significant impact on the costs. Under routine (nonresearch) conditions and at scale, total costs are estimated to fall substantially, up to 76%, reducing cost per admitted child to as low as US $5 in KCH, US $4 in SMCH, and US $14 in CPH. Median time to admit a baby was 27 (IQR 20-40) minutes using Neotree (n=250) compared to 26 (IQR 21-30) minutes using paper-based systems (n=34), and the median time to discharge a baby was 9 (IQR 7-13) minutes for Neotree (n=246) compared to 3 (IQR 2-4) minutes for paper-based systems (n=50). Neotree is a time- and cost-efficient tool, comparable with the results from limited similar mHealth decision-support tools in low- and middle-income countries. Implementation costs of Neotree varied substantially between the hospitals, mainly due to hospital size. The implementation costs could be substantially reduced at scale due to economies of scale because of integration to the health systems and reductions in cost items such as staff and overhead. More studies assessing the impact and cost-effectiveness of large-scale mHealth decision-support tools are needed.

Sleep-independent circadian rhythm of aldosterone secretion in healthy young adults

ObjectiveA diurnal variation in urine output has been described in humans, whereby it is lowest at night. Fluid balance hormones such as vasopressin and aldosterone as well as urine output have a diurnal variation. Although the diurnal variation of vasopressin results in part from a circadian rhythm, the variation in aldosterone has until recently been reported to be due to the sleep/wake cycle. The present study used a specialized protocol to explore whether aldosterone has an underlying circadian rhythm. MethodsTen healthy participants (average age 23.1) were enrolled in the 57.3-hour protocol that included an 8-hour baseline sleep episode, 40 hours in constant routine conditions (wakefulness, food and fluid intake, posture, and dim light), and a 9.3-hour recovery sleep. Blood samples for aldosterone were taken every 4 hours. Cosinor analysis was performed on the constant routine data to test the effect of the sleep/wake cycle on overall aldosterone secretion. ResultsThere was a significant circadian rhythm during the 40-hour constant routine, independent of sleep, with aldosterone higher at the end of the biological night and lower at the end of the biological day. When analyzing data from the entire 57.3-hour protocol and controlling for this circadian rhythm, aldosterone concentration was significantly higher during the recovery night following the 40-hour sleep deprivation compared to the night spent awake. ConclusionWe found a significant endogenous circadian rhythm in the secretion of aldosterone, independent of sleep. In addition, as shown previously, there was a significant effect of the sleep/wake cycle on aldosterone secretion.

Implementation of guidelines on prevention of coercion and violence (PreVCo) in psychiatry: a multicentre randomised controlled trial

Interventions to prevent the use of coercion in psychiatric hospitals have been summarized in the 2018 German Association for Psychiatry, Psychotherapy, and Psychosomatic's comprehensive guidelines. Twelve recommendations for implementation of these guideline on psychiatric wards have been deducted and their feasibility has been tested in a pilot study, using external implementation consultants as facilitators. The objective of the PreVCo study was to test their effect in a randomised clinical trial. Fifty-four psychiatric wards in Germany treating voluntary and involuntary patients were randomly allocated to either an intervention or to a waiting list condition. The intervention consisted of the implementation of three out of 12 suggested recommendations as selected by the ward teams, supported by external study workers. As the primary outcome measure, the number of coercive measures used per bed and month in the final 3 months of the intervention period was determined. Secondary outcomes were the cumulative duration of coercive measures used per bed and months and assaults per bed and month. Achieved guideline adherence was measured by a fidelity scale developed for this purpose during a pilot study for the PreVCo Rating Tool. After a 3-month baseline collection period under routine conditions, randomisation was done after matching wards pairwise according to frequency of coercive measures used and scores on the PreVCo Rating Tool at baseline. The duration of the intervention period was 12 months; control wards received only an initial workshop presentation of the study and completed their PreVCo ratings. We used the Wilcoxon signed rank test and the paired t-test and conducted sensitivity analyses for different periods of observation. Neither the number of coercive measures used per month and bed nor their cumulative duration nor the number of assaults per bed and months differed significantly between the 27 intervention wards and the 27 control wards in the final 3 months of the intervention period. The median number of coercive measures used decreased by 45% (median 0.96 (IQR 1.34)-0.53 (IQR 0.59) from baseline until the end of the intervention period on the intervention wards and by 28% (median 0.98 (IQR 1.71)-0.71 (IQR 1.08) on waiting list wards. The PreVCo Rating Tool showed a significant improvement in intervention wards compared to control wards, indicating a successful implementation. The study demonstrated that guideline adherence could be significantly improved by the intervention. However, there was no evidence for an effect on the frequency or duration of coercive measures used. Spill-over effects and the impact of the COVID-19 pandemic on in-patient care might have limited the effect of the intervention. Further research from robust randomised controlled trials are necessary to identify effective interventions to reduce the use of coercion in psychiatric hospitals. The study was funded by the German Innovationsfonds beim Gemeinsamen Bundesausschuss (project no. 01VSF19037). The funder had no role in study design or data collection.

Effectivness and Safety of Orelabrutinib in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Retrospective, Real-World Study in China

Introduction: Orelabrutinib is a second-generation Bruton tyrosine kinase inhibitor (BTKi) with high kinase selectivity. Clinical studies have demonstrated that orelabrutinib achieved a high complete response rate of 26.3% in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), showing promising efficacy and acceptable safety profile. However, the real-world data of Orelabrutinib are not available. This study aimed to evaluate the effectiveness and safety of orelabrutinib-containing regimens for the treatment of patients (pts) with CLL/SLL in a real-world setting. Methods: This was a retrospective, multi-center, real-world study conducted. Pts (aged 18 years or older) with CLL/SLL who received at least 3 months of orelabrutinib-containing regimens between December 2020 and March 2023 were analyzed. Efficacy was evaluated by hematologic response rate (HRR), defined as the proportion of pts who met at least 1 of the following hematologic response criteria: hemoglobin response (pts having a recovery of hemoglobin value or ≥50% increase from baseline), platelet response (pts having a recovery of platelet count or ≥50% increase from baseline), or lymphocyte response (pts having a recovery of lymphocyte count or ≥50% reduction from baseline). Safety was assessed by adverse events (AEs) as per NCI-CTCAE 5.0. Results: 24 pts with CLL/SLL (12 males; 22 CLL) were included, with a median age of 62.5 years (range: 38-82). Most pts had an Eastern Cooperative Oncology Group score of 0-1 (17/24, 70.8%) and Rai stage III or IV disease (16/18, 88.9%). 7 pts with hypertension, of which 2 with very high-risk hypertension. 3 pts have previously received other BTKi. A total of 9 pts(37.5%) performed del(17p), TP53, or IGHV testing. Among them, pts received orelabrutinib 100 mg (2/24,) or 150 mg (22/24,) once daily. As of the cut-off date (July 13, 2023), the median follow-up was 10.67 (range, 2.73-25.77) months. 18 pts (16 CLL, 2 SLL) with abnormal hemoglobin value, platelet count, or lymphocyte count at baseline were evaluable for hematologic response. Hematologic response was achieved in 11 (61.1%) of 18 evaluable pts. Pts aged &amp;lt;65 years had a higher HRR versus pts aged ≥65 years (87.5% vs. 40.0%, p=0.040). HRR was 56.3% in CLL versus 100.0% in SLL pts, and 60.0% in pts with hypertension versus 61.5% without hypertension . Four of 11 responders had a hematologic response in at least two criteria (CLL, n=3; SLL, n=1), of which 3 pts had a hemoglobin response (Figure 1). The most commonly reported AEs included hemoglobin decreased (16.7%) and platelet count decreased (16.7%). Grade ≥3 AEs were white blood cell count decreased (4.2%), platelet count decreased (4.2%), and lymphocyte count decreased (4.2%). No pts experienced severe AEs. No cardiovascular AEs were reported during treatment in 7 pts with hypertension at baseline. Conclusions: This real-world study assessed the preliminary characteristics and clinical outcome of patients receiving orelabrutinib-containing regimens under routine clinical practice conditions in China. The orelabrutinib-containing regimens in this study furnished beneficial evidence for the treatment of CLL/SLL and is essential for determining the best treatment option, future data with a larger sample and longer follow-up will be updated.

Implementation of a piritramide based patient-controlled analgesia (PCA) as a standard of care for pain control in late abortion induction: A prospective cohort study from a patient perspective

ObjectiveTo assess whether the implementation of patient-controlled analgesia (PCA) with piritramide using an automatic pump system under routine conditions is effective to reduce pain in late abortion inductions Study designProspective observational cohort study SettingPatients requiring medically indicated abortion induction from 14 weeks of pregnancy onwards between July 2019 and July 2020 at the department of Obstetrics and Prenatal Medicine of the Bonn University Hospital in Germany. MethodsEvaluation of pain management after implementation of a PCA system compared with previous nurse-controlled tramadol-based standard under routine conditions. Patients answered a validated pain questionnaire and requirement of rescue analgesics was assessed. Pain intensity and satisfaction were measured on a ten-point numeric rating scale. Main Outcome Measure Maximal pain intensity ResultsForty patients were included. Patients using Piritramide-PCA complained of higher pain sores than those in the standard group (6.90 (± 2.34) vs. 4.83 (± 2.87), (p < 0.05)). In both groups the level of satisfaction with the analgesia received was comparable (8.00 (± 2.45) vs 7.67 (± 2.62), (p = 0.7)). Patients in the PCA group suffered more nausea (63.2 % vs 30 % respectively, OR 4.0, 95 % CI 1.05–15.20, p < 0.05) and expressed more the desire for more analgesic support compared to the control group (OR 5.7 (1–33.25), p = 0.05). ConclusionWomen with abortion induction after 14 weeks of gestation suffer from relevant severe pain, which requires adequate therapy. However, addition of PCA does not seem to bring any advantage in patients undergoing this procedure.

Real-world experience with CLAIRYG® 50 mg/mL (intravenous immunoglobulin) in children under 12 years with primary immunodeficiency or immmune thrombocytopenia: a post-approval safety study.

This study presents the results of a real-life, multicenter, prospective, post-approval safety evaluation of Clairyg® 50 mg/mL, a 5% intravenous immunoglobulin (IVIg) liquid, in 59 children (aged < 12 years) with primary immunodeficiency diseases (PID) (n = 32) or immune thrombocytopenia (ITP) (n = 27) in France. The primary objective of the study was to assess the safety and tolerability of Clairyg®, recording all serious and non-serious adverse events (AEs), whether related (rAEs) or not related to the product. Secondary objectives aimed at evaluating the administration of Clairyg® under routine conditions and the available efficacy data to better document the benefit/risk ratio in this pediatric population. An exploratory objective was added to evaluate the potential factors associated with the occurrence of rAEs. Patients received Clairyg® according to the approved dosage under normal conditions of prescriptions over a median follow-up period of 11.8 months. A total of 549 infusions (PID: n = 464 and ITP: n = 85), were administered, of which 58.8% were preceded by premedication. The most frequent rAEs were headache, vomiting, and pyrexia in both indications. Most of them were considered non-serious and mild or moderate in intensity. A severe single rAE was observed (aseptic meningitis) in a 4-year-old girl presenting with chronic ITP. The exploratory multivariate analysis of potential co-factors showed that the occurrence of rAEs is significantly linked to high IVIg doses and possibly to female gender. The annualized rate of serious bacterial infections was 0.11 for patients with PID. For patients with ITP, 74.1% experienced at least one bleeding episode during the follow-up, mostly a cutaneous one, and none had gastrointestinal, genitourinary, or central nervous system bleeding. Clairyg® was well tolerated and allowed for control of serious bacterial infection in PID and serious bleeding in ITP, which are the main complications in these respective pediatric disorders. No new safety signal was detected in children less than 12 years-old in real-life conditions of use.

Impact of Severe Weather on Operations of a Radiation Oncology Department

In 2022, two major storms in Western New York brought blizzard conditions and historic snowfall amounts to the region. Beyond the immediate impact to life and property, these weather events resulted in disruptions to cancer care as a result of hazardous travel conditions, and facility closures as a result of regional travel bans. We sought to understand the impact of these disruptive incidents on departmental operations to develop better contingency plans for future occurrences. The radiation treatment machine schedules for a large academic center in Western New York, as well as a neighboring affiliated satellite clinic were queried for daily treatment adherence rates from November 1, 2022 through February 4, 2023. We classified "severe weather days" based on travel advisories issued by the National Weather Service or from local county officials. Out of a total of 68 working days during the study period, 15 days were classified as having severe weather. We compared the percentage of scheduled patients treated (adherence rates) on severe weather days compared with days without severe weather. Statistical analysis was performed using a two-tailed Z-test for proportions. Under routine operating conditions, out of a total of 7045 scheduled treatment visits, we found a mean daily treatment adherence rate of 93.57%. On severe weather days, out of a total of 2093 scheduled treatments, we found a mean daily treatment adherence rate of 77.83%. Out of these 15 days, the satellite clinic closed for a total of 3 days, while the academic center closed for 1 day. Excluding the dates of facility closure, overall treatment adherence rate was 84.76% on severe weather days (Risk Ratio: 0.91). We found that the difference in treatment adherence rates between regular and severe weather days was statistically significant (p<0.001), even when excluding dates of facility closure. This study demonstrates a significant reduction in treatment adherence rates around severe winter storms, even when excluding dates of facility closure. We suggest that preparation for such incidents be a part of facility contingency planning. Weekend openings can be considered for closures ≥ 2 days, or sustained adherence rates of 85% or less for 3 or more days.

Evaluation of remote radiologist-interpreted point-of-care ultrasound for suspected dengue patients in a primary health care facility in Colombia

BackgroundEarly identification of plasma leakage may guide treatment decisions in dengue patients. This study evaluated the value of point-of-care ultrasound (POCUS) to detect plasma leakage and predict hospitalization or referral to a higher level of care in suspected dengue patients under routine conditions at a primary care facility in Colombia.MethodsWe conducted a cohort study between April 2019 and March 2020 in a primary care hospital in Cali, Colombia. We prospectively included and followed 178 patients who were at least 2 years old with fever of less than 10 days and clinician-suspected dengue. A trained general practitioner performed a standardized POCUS protocol. Images were quality-rated and overread by an expert radiologist, and her results and those of the general practitioner were compared using the Kappa index. Logistic regression was used to identify factors associated with plasma leakage at enrollment and explore its prognostic value regarding hospital admission or referral to a higher level of care.ResultsHalf (49.6%) POCUS images were of suitable quality to be interpreted. The proportion of plasma leakage reported by the radiologist was 85.1% (95% CI: 78.6–90.2%) and 47.2% by the study physician (Kappa = 0.25, 95% CI: 0.15–0.35). The most frequent ultrasound findings were ascites (hepatorenal 87.2%, splenorenal 64%, or pelvic 21.8%) and gallbladder wall thickening (10.5%). Plasma leakage was higher in subjects with thrombocytopenia (aOR = 4, 95% CI: 1.3–12.1) and lower in patients 30–59 years old (aOR = 0.1, 95% CI: 0.0–0.4) than in those 18 years old or younger. POCUS evidence of plasma leakage (aOR = 8.2, 95% CI: 2.2–29.9), thrombocytopenia (aOR = 6.3, 95% CI: 2.4–16.0) and pulse pressure (aOR = 1.1, 95% CI: 1.07–1.2) were associated with hospital admission or referral to a higher level of care.ConclusionsUltrasound is useful to detect plasma leakage in primary care and, challenges remain to guarantee high-quality images and diagnostic accuracy, for which a standardized dengue POCUS protocol and training program is needed.Graphical

Malaria vaccine coverage estimation using age-eligible populations and service user denominators in Kenya

BackgroundThe World Health Organization approved the RTS,S/AS01 malaria vaccine for wider rollout, and Kenya participated in a phased pilot implementation from 2019 to understand its impact under routine conditions. Vaccine delivery requires coverage measures at national and sub-national levels to evaluate progress over time. This study aimed to estimate the coverage of the RTS,S/AS01 vaccine during the first 36 months of the Kenyan pilot implementation.MethodsMonthly dose-specific immunization data for 23 sub-counties were obtained from routine health information systems at the facility level for 2019–2022. Coverage of each RTS,S/AS01 dose was determined using reported doses as a numerator and service-based (Penta 1 and Measles) or population (projected infant populations from WorldPop) as denominators. Descriptive statistics of vaccine delivery, dropout rates and coverage estimates were computed across the 36-month implementation period.ResultsOver 36 months, 818,648 RTSS/AS01 doses were administered. Facilities managed by the Ministry of Health and faith-based organizations accounted for over 88% of all vaccines delivered. Overall, service-based malaria vaccine coverage was 96%, 87%, 78%, and 39% for doses 1–4 respectively. Using a population-derived denominator for age-eligible children, vaccine coverage was 78%, 68%, 57%, and 24% for doses 1–4, respectively. Of the children that received measles dose 1 vaccines delivered at 9 months (coverage: 95%), 82% received RTSS/AS01 dose 3, only 66% of children who received measles dose 2 at 18 months (coverage: 59%) also received dose 4.ConclusionThe implementation programme successfully maintained high levels of coverage for the first three doses of RTSS/AS01 among children defined as EPI service users up to 9 months of age but had much lower coverage within the community with up to 1 in 5 children not receiving the vaccine. Consistent with vaccines delivered over the age of 1 year, coverage of the fourth malaria dose was low. Vaccine uptake, service access and dropout rates for malaria vaccines require constant monitoring and intervention to ensure maximum protection is conferred.

Microplastic Abundance in Rainbow Trout Life Cycle: Step by Step

In recent years, with the encouragement of national and international authorities, researchers on plastic levels in aquaculture have begun to assess consumer health risks as well as ecological monitoring. Based on this guidance, the aim of this study is to determine the microplastic load of rainbow trout raised under routine breeding conditions without an external treatment in all developmental stages from egg to +1 year of age. Sperm, egg, fertilized egg, eyed egg, alevin or such fry, and swimming fry on growing stock (1-year-old) stages of cultured fish and commercial feeds were used for the following stages: 300–500 µm, 500–800 µm, 800–1200 µm, 1 mm, 2 mm, 3 mm, 4 mm, and 5 mm. The samples were collected to determine the presence of microplastic (MP) and at which stage of this life cycle the MP has entered into the system intensively. The obtained findings showed that the total amount of MP determined in the stages without feed intake was 14 pieces, and this value increased by 557% (total of 92-piece MP) in fish that started external feeding. While no significant difference was found between the MP amounts in different feed groups, the dominant microplastic color in the feed groups was black and blue, and the polymer type was polyethylene. This general modelling, in which MP concentrations are determined in all life cycles from egg to adult in a cultured fish species, including in the given feeds, will encourage further research. Current findings have shown that any outsourced input used during growing periods can cause MP contamination to the end of fish production, processing, and storage.

Dynamical Measurement of Team Resilience

Resilient teams overcome sudden, dynamic changes by enacting rapid, adaptive responses that maintain system effectiveness. We analyzed two experiments on human-autonomy teams (HATs) operating a simulated remotely piloted aircraft system (RPAS) and correlated dynamical measures of resilience with measures of team performance. Across both experiments, HATs experienced automation and autonomy failures, using a Wizard of Oz paradigm. Team performance was measured in multiple ways, using a mission-level performance score, a target processing efficiency score, a failure overcome score, and a ground truth resilience score. Novel dynamical systems metrics of resilience measured the timing of system reorganization in response to failures across RPAS layers, including vehicle, controls, communications layers, and the system overall. Time to achieve extreme values of reorganization and novelty of reorganization were consistently correlated with target processing efficiency and ground truth resilience across both studies. Correlations with mission-level performance and the overcome score were apparent but less consistent. Across both studies, teams displayed greater system reorganization during failures compared to routine task conditions. The second experiment revealed differential effects of team training focused on coordination coaching and trust calibration. These results inform the measurement and training of resilience in HATs using objective, real-time resilience analysis.

Is the automated Elecsys tacrolimus assay on the Roche cobas e 602 analyzer an acceptable replacement for a liquid chromatography-tandem mass spectrometry-based assay?

This study evaluated the suitability and accuracy of the automated Roche Elecsys tacrolimus electrochemiluminescence immunoassay (ECLIA) by comparing it with a current laboratory-developed test by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The tacrolimus ECLIA was evaluated for precision, linearity, interference, and postextraction stability. Accuracy was compared with LC-MS/MS. The tacrolimus ECLIA assay is precise, exhibits a measuring range of 0.75 to 30 ng/mL, and is tolerant of significant interferences (plasma indices: hemolysis <2306, icterus <55, lipemia <1427, and biotin <1200 ng/mL). Comparison with LC-MS/MS revealed a 26% proportional bias in patient samples evaluated for tacrolimus concentration (y = 1.26x + 0.08; r2 = 0.97; Sy/x = 0.94; n = 43) and an absolute mean (SD) bias of 2.2 (1.7) ng/mL. Postextraction studies confirmed that samples were stable for up to 30 minutes under routine laboratory conditions. The 2 major challenges for implementation of the tacrolimus ECLIA assay are the postextraction sample stability and the significant proportional bias observed compared with the LC-MS/MS reference method. The 30-minute window for analysis of extracted samples is a practical challenge to the routine workflow of the core laboratory. In addition, disagreement between the immunoassay and LC-MS/MS methods can lead to discordant clinical interpretations and ultimately affect patient care.

Investigations of aged metal seals for transport package safety assessment

Abstract. Acceptable limits for activity release from transport casks for high-level radioactive material specified in the IAEA regulations must be kept by the integrity of cask body and the cask sealing system. BAM – the German competent authority for mechanical, thermal and containment assessment of packages liable for approval – verifies the activity release compliance with the regulatory limits. One of the fundamental aspects in assessment is the specification of conservative package design leakage rates. To ensure the required package tightness for both storage and transport of the cask before and after storage, usually metal seals of the HELICOFLEX® type are used. Due to long-term use, the seal behaviour is influenced by temperature and time. The mechanical and thermal loadings associated with the routine, normal and accident conditions of transport specified in the regulations can have a significant effect on the leak tightness of the sealing system. Whereas the safety for application of new, non-aged HELICOFLEX® seals is verified sufficiently, there are still technical data gaps concerning the efficiency of aged HELICOFLEX® seals. BAM performed experiments to learn more about the sealing efficiency of aged HELICOFLEX® seals with aluminium and silver outer jackets. The seals were compressed in test flanges, and for artificial ageing the complete flange systems were stored in an oven for several months at a high temperature. During the compression and decompression tests after the ageing, load-deformation characteristics of the seals and leakage rates were measured. With these tests a load situation was simulated, which can occur in the regulatory drop test of the cask: under high-impact loads the bolted lid can lift a little for a short moment, allowing a little movement of the seal so that the contact area can change before compressing again. The poster presentation will show details about test conditions and first results.

COMBI-r: A Prospective, Non-Interventional Study of Dabrafenib Plus Trametinib in Unselected Patients with Unresectable or Metastatic BRAF V600-Mutant Melanoma.

Combined BRAF/MEK-inhibition constitutes a relevant treatment option for BRAF-mutated advanced melanoma. The prospective, non-interventional COMBI-r study assessed the effectiveness and tolerability of the BRAF-inhibitor dabrafenib combined with the MEK-inhibitor trametinib in patients with advanced melanoma under routine clinical conditions. Progression-free survival (PFS) was the primary objective, and secondary objectives included overall survival (OS), disease control rate, duration of therapy, and the frequency and severity of adverse events. This study enrolled 472 patients at 55 German sites. The median PFS was 8.3 months (95%CI 7.1-9.3) and the median OS was 18.3 months (14.9-21.3), both tending to be longer in pre-treated patients. In the 147 patients with CNS metastases, PFS was similar in those requiring corticosteroids (probably representing symptomatic patients, 5.6 months (3.9-7.2)) compared with those not requiring corticosteroids (5.9 months (4.8-6.9)); however, OS was shorter in patients with brain metastases who received corticosteroids (7.8 (6.3-11.6)) compared to those who did not (11.9 months (9.6-19.5)). The integrated subjective assessment of tumor growth dynamics proved helpful to predict outcome: investigators' upfront categorization correlated well with time-to-event outcomes. Taken together, COMBI-r mirrored PFS outcomes from other prospective, observational studies and confirmed efficacy and safety findings from the pivotal phase III COMBI-d/-v and COMBI-mb trials.

Understanding the organisational influences on the quality of and access to primary care in English prisons: a qualitative interview study.

Primary care for routine healthcare conditions is delivered to thousands of people in the English prison estate every day but the prison environment presents unique challenges to the provision of high-quality health care. Little research has focused on the organisational factors that affect quality of and access to prison health care. To understand key influences on the quality of primary care in prisons. This was a qualitative interview study across the North of England from 2019 to 2021. Interviews were undertaken with 43 participants: 21 prison leavers and 22 prison healthcare professionals. Reflexive thematic analysis was undertaken. The overarching organisational issue influencing quality and access was that of chronic understaffing coupled with a workforce in flux and dependence on locum staff. This applied across different prisons, roles, and grades of staff, and was vocally discussed by both patient and staff participants. Intricately related to understaffing (and fuelled by it) was the propensity for a reactive and sometimes crisis-led service to develop that was characterised by continual firefighting. A persistent problem exacerbated by the above issues was unreliable communication about healthcare matters within some prisons, creating frustration. Positive commentary focused on the characteristics and actions of individual healthcare professionals. This study highlights understaffing and its consequences as the most significant threat to the quality of and access to prison primary care. Strategies to address health care affecting prison populations urgently need to consider staffing. This issue should receive high-profile and mainstream attention to address health inequalities.

Long-Term Observation of Patients With Cancer - an Entity-Independent Registry for Healthcare and Translational Research at the University Medicine Dresden (Cancer-Reg-VT).

Translational research is important, especially in medicine where decisions affect people's lives. Clinical registries and the studies embedded in them allow the depiction of actual care practice under routine conditions. Translating the findings of health services research back into clinical research through prospective cohort studies has the potential to drive medical innovations faster, more effectively and, above all, in a more targeted manner. These must therefore be a central component of cutting-edge oncological research. The aim of the registry is the establishment of clinical cohorts and the provision of a comprehensive, high-quality data set for oncological diseases. The registry will prospectively record all patients treated for cancer at Dresden University Hospital (UKD). In addition to the data from the hospital information systems (ORBIS, TDS, GEPADO, etc.), monitoring of health-related quality of life (HRQOL) is to be carried out at regular intervals at the beginning and during the course of treatment. In addition, individual linkage with data from clinical cancer registries and health insurance companies (including AOK PLUS) is planned for a period of five years before and after inclusion. All these data will be merged in a registry database. The selection of variables and measurement time points is closely based on the guidelines for colorectal carcinoma of the international initiative ICHOM (International Consortium for Health Outcomes Measurement). The study management software (STeVe) separates personal identification characteristics (IDAT) and medical data (MDAT) at an early stage. The independent trust centre of the TU Dresden (Treuhandstelle) ensures that no personal data enter the registry database. It is thereby also ensured that the data owners involved (UKD, biobank, health insurance company, cancer registry, patient) only receive the personal data they need for allocation. The MOSAIC software tools recommended by the TMF (Technologie- und Methodenplattform für die vernetzte medizinische Forschung e.V.) are used to manage the pseudonyms. With the registry, previously missing evidence on the effectiveness, safety and costs of diagnostic and therapeutic measures can be made, taking into account long-term and patient-reported outcomes of routine care. The data potentially allow for the identification of barriers to and facilitators of innovative promising cancer diagnostics and therapies. They also enable generation of scientifically relevant hypotheses in the field of translational and outcomes research.