Nevin Manimala

Hum Reprod. 2023 Aug 8:dead154. doi: 10.1093/humrep/dead154. Online ahead of print.

ABSTRACT

STUDY QUESTION: In children affected by rhabdoid tumors (RT), are there clinical, therapeutic, and/or (epi-)genetic differences between those conceived following ART compared to those conceived without ART?

SUMMARY ANSWER: We detected a significantly elevated female predominance, and a lower median age at diagnosis, of children with RT conceived following ART (RT_ART) as compared to other children with RT.

WHAT IS KNOWN ALREADY: Anecdotal evidence suggests an association of ART with RT.

STUDY DESIGN, SIZE, DURATION: This was a multi-institutional retrospective survey. Children with RT conceived by ART were identified in our EU-RHAB database (n = 11/311 children diagnosed between January 2010 and January 2018) and outside the EU-RHAB database (n = 3) from nine different countries. A population-representative German EU-RHAB control cohort of children with RTs conceived without ART (n = 211) (EU-RHAB control cohort) during the same time period was used as a control cohort for clinical, therapeutic, and survival analyses. The median follow-up time was 11.5 months (range 0-120 months) for children with RT_ART and 18.5 months (range 0-153 months) for the EU-RHAB control cohort.

PARTICIPANTS/MATERIALS, SETTING, METHODS: We analyzed 14 children with RT_ART diagnosed from January 2010 to January 2018. We examined tumors and matching blood samples for SMARCB1 mutations and copy number alterations using FISH, multiplex ligation-dependent probe amplification, and DNA sequencing. DNA methylation profiling of tumor and/or blood samples was performed using DNA methylation arrays and compared to respective control cohorts of similar age (n = 53 tumors of children with RT conceived without ART, and n = 38 blood samples of children with no tumor born small for gestational age).

MAIN RESULTS AND THE ROLE OF CHANCE: The median age at diagnosis of 14 individuals with RT_ART was 9 months (range 0-66 months), significantly lower than the median age of patients with RT (n = 211) in the EU-RHAB control cohort (16 months (range 0-253), P = 0.03). A significant female predominance was observed in the RT_ART cohort (M:F ratio: 2:12 versus 116:95 in EU-RHAB control cohort, P = 0.004). Eight of 14 RT_ART patients were diagnosed with atypical teratoid rhabdoid tumor, three with extracranial, extrarenal malignant rhabdoid tumor, one with rhabdoid tumor of the kidney and two with synchronous tumors. The location of primary tumors did not differ significantly in the EU-RHAB control cohort (P = 0.27). Six of 14 RT_ART patients presented with metastases at diagnosis. Metastatic stage was not significantly different from that within the EU-RHAB control cohort (6/14 vs 88/211, P = 1). The incidence of pathogenic germline variants was five of the 12 tested RT_ART patients and, thus, not significantly different from the EU-RHAB control cohort (5/12 versus 36/183 tested, P = 0.35). The 5-year overall survival (OS) and event free survival (EFS) rates of RT_ART patients were 42.9 ± 13.2% and 21.4 ± 11%, respectively, and thus comparable to the EU-RHAB control cohort (OS 41.1 ± 3.5% and EFS 32.1 ± 3.3). We did not find other clinical, therapeutic, outcome factors distinguishing patients with RT_ART from children with RTs conceived without ART (EU-RHAB control cohort). DNA methylation analyses of 10 tumors (atypical teratoid RT = 6, extracranial, extrarenal malignant RT = 4) and six blood samples from RT_ART patients showed neither evidence of a general DNA methylation difference nor underlying imprinting defects, respectively, when compared to a control group (n = 53 RT samples of patients without ART, P = 0.51, n = 38 blood samples of patients born small for gestational age, P = 0.1205).

LIMITATIONS, REASONS FOR CAUTION: RTs are very rare malignancies and our results are based on a small number of children with RT_ART.

WIDER IMPLICATIONS OF THE FINDINGS: This cohort of patients with RT_ART demonstrated a marked female predominance, and a rather low median age at diagnosis even for RTs. Other clinical, treatment, outcome, and molecular factors did not differ from those conceived without ART (EU-RHAB control cohort) or reported in other series, and there was no evidence for imprinting defects. Long-term survival is achievable even in cases with pathogenic germline variants, metastatic disease at diagnosis, or relapse. The female preponderance among RT_ART patients is not yet understood and needs to be evaluated, ideally in larger international series.

STUDY FUNDING/COMPETING INTEREST(S): M.C.F. is supported by the ‘Deutsche Kinderkrebsstiftung’ DKS 2020.10, by the ‘Deutsche Forschungsgemeinschaft’ DFG FR 1516/4-1 and by the Deutsche Krebshilfe 70113981. R.S. received grant support by Deutsche Krebshilfe 70114040 and for infrastructure by the KinderKrebsInitiative Buchholz/Holm-Seppensen. P.D.J. is supported by the Else-Kroener-Fresenius Stiftung and receives a Max-Eder scholarship from the Deutsche Krebshilfe. M.H. is supported by DFG (HA 3060/8-1) and IZKF Münster (Ha3/017/20). BB is supported by the ‘Deutsche Kinderkrebsstiftung’ DKS 2020.05. We declare no competing interests.

TRIAL REGISTRATION NUMBER: N/A.

PMID:37553222 | DOI:10.1093/humrep/dead154

Respir Care. 2023 Aug 8:respcare.11037. doi: 10.4187/respcare.11037. Online ahead of print.

ABSTRACT

BACKGROUND: Progressive resistance inspiratory muscle training is the principle of inspiratory air-flow resistance loading training to restore diaphragm function, increase alveolar compliance, and further improve respiratory function. However, there is a lack of research on the effectiveness of progressive resistance inspiratory training in post-lobectomy rehabilitation and the accurate assessment of lung volumes.

METHODS: In this study, 79 subjects diagnosed with lung cancer and undergoing thoracoscopic lobectomy were retrospectively analyzed. The subjects were divided into a control group (n = 40) and an observation group (n =39) according to the different training modalities. The control group received conventional respiratory training. The observation group received progressive resistance inspiratory muscle training based on conventional breathing training. The primary outcome indicators were the following: lung function and lung volume. The secondary outcome indicators were the following: the number of postoperative hospital days, duration of drain retention, and incidence of postoperative pulmonary complications.

RESULTS: Baseline data on age, sex, body mass index, smoking history, education level, underlying disease, type of pathology, lung cancer stages, surgical site, preoperative lung volume, and preoperative lung function were not statistically different between the 2 groups (P > .05). The subjects in the observation group had median (interquartile range [IQR]) lung volumes at 1 month after surgery (3.22 [3.12-3.37] L vs 3.14 [2.95-3.24] L; P = .031), median (IQR) FEV₁ (2.11 [1.96-2.21] L vs 2.01 [1.81-2.12] L; P = .031), and mean ± SD peak expiratory flow (5.07 ± 0.62 L/s vs 4.66 ± 0.64 L/s; P = .005) were higher than those in the control group. The median (IQR) postoperative hospital stays (5 [4-5] d vs 5 [4-6] d; P = .030) and the median (IQR) chest drain retention times were shorter in the observation group versus the control group (74 [72-96] h vs 96 [84-96] h; P = .02). There was no significant difference in the incidence of postoperative atelectasis (5.1% vs 10.0%; P = .41) and pneumonia (7.7% vs 12.5%; P = .48).

CONCLUSIONS: Progressive resistance inspiratory muscle training was effective in improving lung volume and lung function, and in reducing the length of hospital stay and chest drain closure time after lobectomy.

PMID:37553214 | DOI:10.4187/respcare.11037

Respir Care. 2023 Aug 8:respcare.10932. doi: 10.4187/respcare.10932. Online ahead of print.

ABSTRACT

BACKGROUND: It is unclear if high-frequency chest-wall compression (HFCWC) has a role to assist with secretion clearance in patients on mechanical ventilation. The effect of HFCWC on the delivery of mechanical ventilation is unknown. This study describes the effect of HFCWC on mechanical ventilation delivery and flow bias in an orally intubated and mechanically ventilated bench model.

METHODS: An orally intubated mannequin was mechanically ventilated in 5 commonly used modes of ventilation at settings that reflect current practice. HFCWC was applied via a randomized combination of oscillation frequencies and pressure settings. Mechanical ventilator flow, flow bias, and breathing frequency were measured before and during the application of HFCWC.

RESULTS: HFCWC led to 3- to 7-fold increases in ventilator-delivered breathing frequency during synchronized intermittent mandatory ventilation, bi-level (with pressure support), bi-level-assist, and pressure-regulated volume control modes of ventilation. Only in the bi-level mode without pressure support was the ventilator breathing frequency unaffected by HFCWC. During HFCWC, peak inspiratory flow to peak expiratory flow ratios toward an expiratory flow bias, particularly at higher HFCWC pressures, only in pressure-regulated volume control and synchronized intermittent mandatory ventilation modes were peak inspiratory flow to peak expiratory flow ratios of <0.9 generated that would facilitate secretion clearance.

CONCLUSIONS: HFCWC led to 3- to 7-fold increases in ventilator breathing frequency delivered by mechanical ventilation except in the bi-level mode. The bi-level mode may be the optimal mode to use HFCWC to minimize disruption to the delivered ventilator breathing frequency. The peak inspiratory flow to peak expiratory flow ratios < 0.9, the optimal flow bias for secretion clearance, was only achieved in the pressure-regulated volume control and synchronized intermittent mandatory ventilation modes. However, the findings in this bench model with a fixed low compliance may not be generalizable to the patient in the ICU, and we recommend further investigation into the effects of HFCWC in the patient in the ICU.

PMID:37553213 | DOI:10.4187/respcare.10932

Arch Dis Child. 2023 Aug 8:archdischild-2023-325992. doi: 10.1136/archdischild-2023-325992. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the need for routine urine studies in children with febrile neutropenia with cancer.

DESIGN: A prospective, observational study was conducted in two hospitals between November 2019 and October 2021.

PATIENTS: We recruited 205 patients in total.

MAIN OUTCOME MEASURES: The primary outcome was presence of positive urine culture (UC). Urinary tract infection (UTI) was defined as urinary signs/symptoms and positive UC with or without pyuria. A descriptive analysis of data is provided.We conducted a prospective study of paediatric patients with cancer with urinary continence. Data were analysed using descriptive statistics. The diagnostic performance of urinalysis was calculated using positive UC as the gold standard.

RESULTS: Positive UC was found in 7 of the 205 patients (3.4%; 95% CI 1.4% to 6.9%), 2 presenting urinary symptoms. UTI prevalence was 1.0% (95% CI 0.1% to 3.5%). A 23.8% prevalence of positive UC was found in patients with urinary symptoms and/or history of urinary tract disease (95% CI 8.2% to 47.2%) as compared with 1.1% of those without symptoms or history (95% CI 0.1% to 3.9%) (p<0.001). The sensitivity, specificity, negative predictive value, and area under the curve for urinalysis were 16.7% (95% CI 3.0% to 56.4%), 98.4% (95% CI 95.3% to 99.4%), 97.3% (95% CI 93.9% to 98.9%), and 0.65 (95% CI 0.51 to 0.79), respectively.

CONCLUSIONS: UTI is an infrequent cause of infection in these patients. Urinalysis is indicated only in children with febrile neutropenia with urinary signs/symptoms and in asymptomatic patients with a history of urinary tract disease or unknown history. When urine is collected, UC should be requested regardless of the result of the urinalysis.

PMID:37553208 | DOI:10.1136/archdischild-2023-325992

Arch Dis Child. 2023 Aug 8:archdischild-2023-325607. doi: 10.1136/archdischild-2023-325607. Online ahead of print.

ABSTRACT

OBJECTIVE: Diagnosing tuberculous meningitis (TBM) in children is challenging due to the low sensitivity with time delay of bacterial culture techniques and the lack of brain imaging facilities in many low- and middle-income settings. This study aims to establish and test a scoring system consisting of clinical manifestations on history and examination for diagnosing TBM in children.

DESIGN: A retrospective study was conducted using a diagnostic multivariable prediction model.

PARTICIPANTS: 167 children diagnosed with meningitis (tuberculous, bacterial, viral and others) aged 3 months to 18 years who were hospitalised from July 2011 until November 2021 in a national tertiary hospital in Indonesia.

RESULTS: Eight out of the 10 statistically significant clinical characteristics were used to develop a predictive model. These resulted in good discrimination and calibration variables, which divided into systemic features with a cut-off score of ≥3 (sensitivity 78.8%; specificity 86.6%; the area under the curve (AUC) value 0.89 (95% CI 0.85 to 0.95; p<0.001)) and neurological features with a cut-off score of ≥2 (sensitivity 61.2%; specificity 75.2%; the AUC value 0.73 (95% CI 0.66 to 0.81; p<0.001)). Combined together, this scoring system predicted the diagnosis of TBM with a sensitivity, specificity and positive predictive value of 47.1%, 95.1% and 90.9%, respectively.

CONCLUSION: The clinical scoring system consisting of systemic and neurological features can be used to predict the diagnosis of TBM in children with limited resource setting. The scoring system should be assessed in a prospective cohort.

PMID:37553207 | DOI:10.1136/archdischild-2023-325607

BMJ Open. 2023 Aug 8;13(8):e073602. doi: 10.1136/bmjopen-2023-073602.

ABSTRACT

BACKGROUND: Globally, prostate cancer is the most common cancer among men. It is the second most common cause of cancer-related deaths in men. Symptoms may be non-specific and may not present until the cancer has progressed. Raising awareness, knowing risk factors and symptoms and seeking early medical attention is critical for prevention and detection. The objective of this study is to assess the level of awareness of prostate cancer among male patients attending care in a urology unit in Ethiopia.

METHODS: We conducted a cross-sectional study among 241 male patients at Tikur Anbessa Specialized Hospital from February to April 2021. Data were collected using an interviewer-administered questionnaire adapted from published studies and cancer awareness measurement tools. We used EpiData V.4.6.0 and SPSS V.26 for data entry and analysis. Descriptive statistics and linear regressions were used for analyses. Bivariate and multivariate linear regression analysis identified factors associated with prostate cancer awareness. Adjusted odd ratio (AOR) at 95% CI and p value<0.05 were considered statistically significant.

RESULTS: A total of 250 patients were approached, and 241 (96.4%) responded. The mean scores for awareness of prostate cancer risk factors, symptoms, screening and prevention were 41.2%, 43.8%, 44.7% and 49.5%, respectively. Families with an average monthly income of more than 8900 ETB (Ethiopian birr), having heard about prostate cancer, having a regular source of care every six months or more, having a history of hospitalisation and having healthcare providers as the main source of information were all significantly associated with awareness of prostate cancer.

CONCLUSION: The findings of this study indicate that male patients have a relatively low level of awareness of prostate cancer risk factors, symptoms, screening and prevention. There should be more public awareness initiatives to educate men in Ethiopia on the risk factors, symptoms, screening and prevention of prostate cancer.

PMID:37553199 | DOI:10.1136/bmjopen-2023-073602

BMJ Open. 2023 Aug 8;13(8):e073080. doi: 10.1136/bmjopen-2023-073080.

ABSTRACT

OBJECTIVES: This study aimed to assess the cardiopulmonary resuscitation (CPR) knowledge and willingness of schoolteachers in Jordan.

DESIGN: This was a cross-sectional study conducted using an online questionnaire.

SETTING: For inclusion in this study, schoolteachers must be currently teaching at any level in schools across the country. Responses were collected from 1 April 2021 to 30 April 2021.

PARTICIPANTS: All schoolteachers actively working in public or private schools were included in our study.

PRIMARY AND SECONDARY OUTCOME MEASURES: Continuous variables were summarised as means and SD, whereas categorical variables were reported as frequencies and percentages (%). A χ² test for independence, independent sample t-tests and analysis of variance were used appropriately. A p-value less than 0.05 was used to determine statistical significance.

RESULTS: A total of 385 questionnaires were eligible for analyses. Only 14.5% of the participants received CPR training and overall correct knowledge answers were 18.8% of the total score. Those participants with previous CPR training had higher mean knowledge scores (2.34 vs 1.15, p<0.001). Trained participants were also more likely to provide hands-only CPR to various patient groups than untrained participants (p<0.05). Participants were more willing to provide standard CPR to family members than hands-only CPR (p<0.001), but more willing to provide hands-only CPR to friends (p<0.001), students (75.1% vs 58.2%, p<0.001), neighbour (p<0.001), stranger (p=0.001) and patient from the opposite gender (p<0.001).

CONCLUSIONS: Schoolteachers in Jordan possess limited knowledge of CPR. However, the study participants showed a positive attitude towards performing CPR. The study revealed that they were more inclined to provide hands-only CPR than standard CPR. Policymakers and public health officials can take advantage of these findings to incorporate CPR training programmes for schoolteachers, either as a part of their undergraduate studies or as continuing education programmes with an emphasis on hands-only CPR.

PMID:37553198 | DOI:10.1136/bmjopen-2023-073080

BMJ Open. 2023 Aug 8;13(8):e074142. doi: 10.1136/bmjopen-2023-074142.

ABSTRACT

BACKGROUND: The implementation of complex interventions is considered challenging, particularly in multi-site clinical trials and dynamic clinical settings. This study protocol is part of the family intensive care units (FICUS) hybrid effectiveness-implementation study. It aims to understand the integration of a multicomponent family support intervention in the real-world context of adult intensive care units (ICUs). Specifically, the study will assess implementation processes and outcomes of the study intervention, including fidelity, and will enable explanation of the clinical effectiveness outcomes of the trial.

METHODS AND ANALYSIS: This mixed-methods multiple case study is guided by two implementation theories, the Normalisation Process Theory and the Consolidated Framework for Implementation Research. Participants are key clinical partners and healthcare professionals of eight ICUs allocated to the intervention group of the FICUS trial in the German-speaking part of Switzerland. Data will be collected at four timepoints over the 18-month active implementation and delivery phase using qualitative (small group interviews, observation, focus group interviews) and quantitative data collection methods (surveys, logs). Descriptive statistics and parametric and non-parametric tests will be used according to data distribution to analyse within and between cluster differences, similarities and factors associated with fidelity and the level of integration over time. Qualitative data will be analysed using a pragmatic rapid analysis approach and content analysis.

ETHICS AND DISSEMINATION: Ethics approval was obtained from the Cantonal Ethics Committee of Zurich BASEC ID 2021-02300 (8 February 2022). Study findings will provide insights into implementation and its contribution to intervention outcomes, enabling understanding of the usefulness of applied implementation strategies and highlighting main barriers that need to be addressed for scaling the intervention to other healthcare contexts. Findings will be disseminated in peer-reviewed journals and conferences.

PROTOCOL REGISTRATION NUMBER: Open science framework (OSF) https://osf.io/8t2ud Registered on 21 December 2022.

PMID:37553195 | DOI:10.1136/bmjopen-2023-074142

BMJ Open. 2023 Aug 8;13(8):e068402. doi: 10.1136/bmjopen-2022-068402.

ABSTRACT

OBJECTIVE: To investigate the relationship between burn-out and spiritual health among medical doctors.

DESIGN: Systematic literature review and narrative synthesis of cross-sectional studies.

SETTING: Any setting, worldwide.

DATA SOURCES: Five databases were searched from inception to March 2022, including Medline, Embase, PsycINFO, Scopus and Web of Science.

ELIGIBILITY CRITERIA: Any study design that involved medical doctors (and other healthcare staff if assessed alongside medical doctors), that measured (in any way) both burn-out (or similar) and spiritual health (or similar) medical doctors.

DATA EXTRACTION AND SYNTHESIS: All records were double screened. Data extraction was performed by one reviewer and a proportion (10%) checked by a second reviewer. Quality was assessed using the Appraisal of Cross-sectional Studies tool. Due to the heterogeneity of the included studies, a narrative review was undertaken without a meta-analysis.

RESULTS: Searches yielded 1049 studies. 40 studies met eligibility criteria and were included in this review. Low reported levels of spirituality were associated with high burn-out scores and vice versa. Religion was not significantly associated with lower levels of burn-out. Few studies reported statistically significant findings, few used validated spiritual scores and most were vulnerable to sampling bias.

CONCLUSIONS: Published research suggests that burn-out is linked to spiritual health in medical doctors but not to religion. Robust research is needed to confirm these findings and develop effective interventions.

PROSPERO REGISTRATION NUMBER: CRD42020200145.

PMID:37553194 | DOI:10.1136/bmjopen-2022-068402

J Nurs Meas. 2023 Aug 8:JNM-2022-0051.R1. doi: 10.1891/JNM-2022-0051. Online ahead of print.

ABSTRACT

Background and Purpose: Patients undergoing surgery are at risk of pressure injury development and should be assessed to ensure measures are taken for prevention. The study’s purpose was to examine the causal relationships and reliability of the Munro Pressure Injury Risk Assessment Scale for Perioperative Patients (Munro Scale). The Munro Scale is the first dynamic risk scale available for this patient population in the acute clinical setting. Methods: This study was a retrospective review to explore the relationships of the variables in the Munro Scale, identify the strongest predictors, and measure the reliability of previously collected data from two northeastern community hospitals. A total of 630 risk assessments were analyzed to obtain regression, correlation, and reliability evidence for the Munro Scale. Results: The correlation analysis among the 15 risk variables and combined comorbidities revealed commonalities among the variables and significant relationships to the final postoperative injury score. The model as a whole is significant to predict the final level of risk. Cronbach’s α revealed a lower than anticipated reliability when compared to the Chinese, Turkish, and Brazilian versions of the Munro Scale. Conclusions: There are significant relationships among the variables, and the scale is acceptable for use in the acute perioperative practice setting. This study has both clinical and statistical significance.

PMID:37553161 | DOI:10.1891/JNM-2022-0051