Nevin Manimala

Pediatrics. 2023 Jan 25:e2022057860. doi: 10.1542/peds.2022-057860. Online ahead of print.

ABSTRACT

CONTEXT: Discovering new interventions to improve neurodevelopmental outcomes is a priority; however, clinical trials are challenging and methodological issues may impact the interpretation of intervention efficacy.

OBJECTIVES: Characterize the proportion of infant neurodevelopment trials reporting a null finding and identify features that may contribute to a null result.

DATA SOURCES: The Cochrane library, Medline, Embase, and CINAHL databases.

STUDY SELECTION: Randomized controlled trials recruiting infants aged <6 months comparing any “infant-directed” intervention against standard care, placebo, or another intervention. Neurodevelopment assessed as the primary outcome between 12 months and 10 years of age using a defined list of tools.

DATA EXTRACTION: Two reviewers independently extracted data and assessed quality of included studies.

RESULTS: Of n = 1283 records screened, 21 studies (from 20 reports) were included. Of 18 superiority studies, >70% reported a null finding. Features were identified that may have contributed to the high proportion of null findings, including selection and timing of the primary outcome measure, anticipated effect size, sample size and power, and statistical analysis methodology and rigor.

LIMITATIONS: Publication bias against null studies means the proportion of null findings is likely underestimated. Studies assessing neurodevelopment as a secondary or within a composite outcome were excluded.

CONCLUSIONS: This review identified a high proportion of infant neurodevelopmental trials that produced a null finding and detected several methodological and design considerations which may have contributed. We make several recommendations for future trials, including more sophisticated approaches to trial design, outcome assessment, and analysis.

PMID:36695068 | DOI:10.1542/peds.2022-057860

Stat Med. 2023 Jan 25. doi: 10.1002/sim.9658. Online ahead of print.

ABSTRACT

One of the main challenges when using observational data for causal inference is the presence of confounding. A classic approach to account for confounding is the use of propensity score techniques that provide consistent estimators of the causal treatment effect under four common identifiability assumptions for causal effects, including that of no unmeasured confounding. Propensity score matching is a very popular approach which, in its simplest form, involves matching each treated patient to an untreated patient with a similar estimated propensity score, that is, probability of receiving the treatment. The treatment effect can then be estimated by comparing treated and untreated patients within the matched dataset. When missing data arises, a popular approach is to apply multiple imputation to handle the missingness. The combination of propensity score matching and multiple imputation is increasingly applied in practice. However, in this article we demonstrate that combining multiple imputation and propensity score matching can lead to over-coverage of the confidence interval for the treatment effect estimate. We explore the cause of this over-coverage and we evaluate, in this context, the performance of a correction to Rubin’s rules for multiple imputation proposed by finding that this correction removes the over-coverage.

PMID:36695043 | DOI:10.1002/sim.9658

Trials. 2023 Jan 24;24(1):53. doi: 10.1186/s13063-022-06981-8.

ABSTRACT

BACKGROUND: External randomised pilot trials aim to determine whether a future definitive randomised controlled trial (RCT) should be conducted, and if so, how. However, not every pilot trial that suggests that a definitive trial will be feasible will progress to a definitive study. In this study, we surveyed corresponding authors of external randomised pilot trial publications to assess pilot trial outcomes in terms of feasibility and progression.

METHODS: Web-based surveys were sent to corresponding authors of external randomised pilot trial publications, open for four weeks between January and February 2022. Four surveys were produced depending on whether the corresponding author had published a trial protocol or results publication, and whether progression criteria were reported. Surveys asked whether a future RCT was considered feasible, whether progression criteria were met (if applicable), what other factors informed the assessment of pilot trial feasibility, and whether the pilot trial has progressed to further research. Data was analysed using descriptive statistics and conventional content analysis.

RESULTS: 98 of 276 corresponding authors completed the survey (average response rate of 36% across all surveys). Of these, 89 respondents indicated that their trial had completed. Ninety per cent of respondents who were corresponding authors of completed pilot trials stated that their pilot trial was either feasible (42/89, 47%) or feasible with changes to the trial design (38/89, 43%), yet only 66% (59/89) reported the intention to conduct a future definitive trial. Availability of funding for a future definitive trial and changing priorities of the Chief Investigator were the most common barriers to progression identified. Qualitative research findings was the most frequent factor considered both by corresponding authors who reported and who did not report progression criteria when determining trial feasibility.

CONCLUSIONS: Just under one quarter (21/89, 24%) of respondents who considered their external randomised pilot trial to be feasible, or feasible with changes, did not intend to conduct a definitive trial highlighting research inefficiency and waste.

TRIAL REGISTRATION: Open Science Framework osf.io/d28hr [20 December 2021].

PMID:36694266 | DOI:10.1186/s13063-022-06981-8

BMC Med Educ. 2023 Jan 24;23(1):56. doi: 10.1186/s12909-023-04032-7.

ABSTRACT

INTRODUCTION: Imperial College Teddy Bear Hospital (ICSM-TBH) is a student-led volunteering group, which uses interactive, play-based teaching to educate school pupils aged 5-7 years about healthy lifestyles and healthcare. During the COVID-19 pandemic, volunteering sessions shifted online. The aim of this study was to compare the value of online and in-person ICSM-TBH volunteering for volunteers and school pupils.

METHODS: Undergraduate university students at Imperial College London (medicine can be taken as a first degree in the UK) who volunteered with ICSM-TBH between 2019 and 22 were invited to complete an anonymous online questionnaire evaluating their experiences of volunteering online and in-person through Likert-scale questions. Those who completed the questionnaire were also invited to an interview. Teachers who hosted online ICSM-TBH sessions were also invited to an in-person interview, exploring their view of their pupils’ experiences with these sessions. Questionnaire results were analysed through descriptive statistics. Interviews were analysed through inductive thematic analysis.

RESULTS: Thirty-two university students completed the questionnaire. Of these, 9 experienced both in-person and online volunteering, all of whom preferred in-person volunteering. For those who only volunteered in-person, 92% reported that ICSM-TBH sessions were a positive experience, compared to 100% who volunteered online; 92% in person volunteers agreed or strongly agreed that ICSM-TBH volunteering in person improved their mood, compared to 89% online; and 100% agreed or strongly agreed that ICSM-TBH volunteering in person helped them feel part of a community, compared to 84% online. A total of 12 volunteers and 4 teachers were interviewed, from whom five themes emerged: interaction and engagement (interaction and engagement between pupils and volunteers was more readily achieved in-person); personal and professional development (both online and in-person sessions enabled volunteers to gain valuable skills); community and social (greater sense of community was established in-person); emotional wellbeing and enjoyment (both modalities were enjoyed by volunteers and pupils); and workload (online sessions were more convenient for volunteers but with risk of screen fatigue).

CONCLUSION: Overall, both in-person and online volunteering were of substantial benefit to volunteers and school pupils. However, most teachers and volunteers preferred in-person volunteering.

PMID:36694256 | DOI:10.1186/s12909-023-04032-7

BMC Psychol. 2023 Jan 25;11(1):20. doi: 10.1186/s40359-023-01051-3.

ABSTRACT

BACKGROUND: Marriage dissolution, divorce, or separation from a spouse or common-law partner is a serious public health concern due to its increasing prevalence and devastating health and socio-economic consequences. Evidence suggests an increased risk of marital instability in Ethiopia. In addition, the extent of marital dissolution and other related factors have increased in the study area. Despite these, the prevalence of marital dissolution and the influence of associated factors (main reason for marriage, and parental history of marital dissolution) on marital dissolution has not been assessed in the study area. Therefore, the aim of this study was to investigate the prevalence of marital dissolution and its associated factors among residents of Hosanna town in southwestern Ethiopia in 2022.

METHODS: We conducted a community-based cross-sectional study among 459 randomly selected Hosanna Township residents. We used structured questionnaires to collect data. Descriptive statistics and logistic regression were performed to describe the data and test-associated factors, respectively. A p-value less than 0.05 was used to define statistical significance. We used STATA 14 and IBM SPSS 25.0 computer packages to process data.

RESULTS: Out of the 459 potentially eligible individuals, 450 participants properly responded to the questionnaires yielding a response rate of 98.04%. Of these, 218 (52.9%) were female. The commonly reported reason for marriage was to have children 150 (36.9%). The prevalence rate of marital dissolution was 26.0% (95% CI: (21.7%, 30.3%)). The participant’s level of education and the primary reasons (motives) why they get married were statistically significantly associated with marital dissolution. The odds of marital dissolution was higher among participants who completed secondary education (AOR = 3.2, 95% CI = 1.26-8.17) compared to those having no formal education. The participants who married for companionship reasons (AOR = 0.31, 95% CI = 0.11-0.83) had significantly lower odds of marriage dissolution compared with those who married for financial security.

CONCLUSIONS: In this study, the prevalence of marital dissolution was high. The participant’s level of education and the primary reasons (motives) why they getting married were significantly associated with marital dissolution. Therefore, an integrated, community-based approach should be developed to prevent marital dissolution.

PMID:36694249 | DOI:10.1186/s40359-023-01051-3

Biomark Res. 2023 Jan 24;11(1):9. doi: 10.1186/s40364-023-00455-y.

ABSTRACT

BACKGROUND: It has been believed that traditional handcrafted radiomic features extracted from magnetic resonance imaging (MRI) of tumors are normally shallow and low-ordered. Recent advancement in deep learning technology shows that the high-order deep radiomic features extracted automatically from tumor images can capture tumor heterogeneity in a more efficient way. We hypothesize that MRI-based deep radiomic phenotypes have significant associations with molecular profiles of breast cancer tumors. We aim to identify deep radiomic features (DRFs) from MRI, evaluate their significance in predicting breast cancer (BC) clinical characteristics and explore their associations with multi-level genomic factors.

METHODS: A denoising autoencoder was built to retrospectively extract 4,096 DRFs from 110 BC patients’ MRI. Visualization and clustering were applied to these DRFs. Linear Mixed Effect models were used to test their associations with multi-level genomic features (GFs) (risk genes, gene signatures, and biological pathway activities) extracted from the same patients’ mRNA expression profile. A Least Absolute Shrinkage and Selection Operator model was used to identify the most predictive DRFs for each clinical characteristic (tumor size (T), lymph node metastasis (N), estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status).

RESULTS: Thirty-six conventional radiomic features (CRFs) for 87 of the 110 BC patients provided by a previous study were used for comparison. More than 1,000 DRFs were associated with the risk genes, gene signatures, and biological pathways activities (adjusted P-value < 0.05). DRFs produced better performance in predicting T, N, ER, PR, and HER2 status (AUC > 0.9) using DRFs. These DRFs showed significant powers of stratifying patients, linking to relevant biological and clinical characteristics. As a contrast, only eight risk genes were associated with CRFs. The RFs performed worse in predicting clinical characteristics than DRFs.

CONCLUSIONS: The deep learning-based auto MRI features perform better in predicting BC clinical characteristics, which are more significantly associated with GFs than traditional semi-auto MRI features. Our radiogenomic approach for identifying MRI-based imaging signatures may pave potential pathways for the discovery of genetic mechanisms regulating specific tumor phenotypes and may enable a more rapid innovation of novel imaging modalities, hence accelerating their translation to personalized medicine.

PMID:36694221 | DOI:10.1186/s40364-023-00455-y

Lipids Health Dis. 2023 Jan 24;22(1):11. doi: 10.1186/s12944-023-01775-6.

ABSTRACT

OBJECTIVE: This study investigated the correlation of liver fat content (LFC) with metabolic characteristics and its association with chronic complications in type 2 diabetes mellitus (T2DM) patients.

METHODS: Eighty-one prospectively enrolled T2DM patients were divided into non-alcoholic fatty liver disease (NAFLD) group and the non-NAFLD group according to the presence of NAFL complications. LFC was determined by MRI IDEAL-IQ Sequence, and patients were divided into 4 groups according to LFC by quartile method. Basic information, metabolic indexes, and occurrence of chronic complications in different groups were analyzed and compared.

RESULTS: BMI, SBP, DBP, TG, ALT, AST, GGT, UA, HbA1c, FCP, 2 h CP, HOMA-IR, and HOMA-IS in the NAFLD group were significantly higher than the non-NAFLD group (P < 0.05). The incidences of chronic complications in the NAFLD group were higher than in the non-NAFLD group but not statistically significant (P > 0.05). BMI, SBP, DBP, TC, TG, ALT, AST, FCP, 2 h CP, HOMA-IR, and HOMA-IS showed significant differences between the patients with different LFC, and these indexes were significantly higher in patients with higher LFC than those with lower LFC (P < 0.05). Moreover, diabetes duration, TC, HOMA-IR, and LFC were the risk factors for ASCVD complications, while diabetes duration, TG, and LDL-C were risk factors for DN complications. Also, diabetes duration and SBP were risk factors for both DR and DPN complications in T2DM patients (P < 0.05).

CONCLUSION: LFC is positively correlated with the severity of the systemic metabolic disorder and chronic complications in T2DM patients.

PMID:36694216 | DOI:10.1186/s12944-023-01775-6

BMC Psychol. 2023 Jan 24;11(1):18. doi: 10.1186/s40359-023-01057-x.

ABSTRACT

BACKGROUND: Residual depression can cause functional impairment. This study aimed to assess personality traits among individuals with depression, to compare the results with personality traits found in outpatients without psychiatric disorders recruited from general practitioner settings, and to study the association between personality traits and the age-onset of depression, duration of treatment, and the presence of depressive residual symptoms.

METHODS: A case-control study surveyed Thai individuals with depression and outpatients without psychiatric disorders recruited from general practitioner settings at an outpatient clinic of Songklanagarind hospital, in 2022. The questionnaires were: (1) demographic data, (2) the PHQ-9 Thai version, and (3) the International Personality Item Pool-NEO (IPIP-NEO) Thai version. The difference between personality traits and the assigned clinical group were analyzed using the Student’s t-test and the Wilcoxon rank sum test. A generalized linear model was performed to examine differences of personality traits between the assigned clinical group (case-control), and the presence of depressive residual symptoms. The association between personality traits and treatment profiles was assessed by using an analysis of the variance test and the Kruskal-Wallis test.

RESULTS: In regards to 73 individuals with depression in the case group, and 73 gender-and age-matched outpatients without psychiatric disorders recruited from general practitioner settings in the control group; 78.1% of cases and 82.2% of controls were female. Thirty-eight (52.1%) cases had depressive residual symptoms. Regarding the IPIP-NEO Thai version, there was a statistically significant difference in Neuroticism, Extraversion, and Conscientiousness domains between the case and the control groups. In comparison to the control group, the case group scored higher on the Neuroticism domain, and lower on the Extraversion and Conscientiousness domains. Every 0.18-point reduction in the Neuroticism score and every 0.09-point increment in regards to the Openness score were associated with a 1-year increment of age-onset of depression. This study found an association between a higher score of Neuroticism and a lower score of Conscientiousness with the presence of depressive residual symptoms.

CONCLUSION: Different personality profiles were found between individuals with depression and outpatients without psychiatric disorders recruited from general practitioner settings. Individuals with depressive residual symptoms featured a higher score of Neuroticism and a lower score of Conscientiousness. A higher score of Neuroticism and a lower score of Openness were associated with age-onset of depression, but no personality traits were associated with treatment duration.

PMID:36694215 | DOI:10.1186/s40359-023-01057-x

Pediatr Rheumatol Online J. 2023 Jan 25;21(1):9. doi: 10.1186/s12969-023-00791-1.

ABSTRACT

BACKGROUND: In a chronic pain-causing disease such as juvenile idiopathic arthritis, the quality of coping with pain is crucial. Parents have a substantial influence on their children’s pain-coping strategies. This study aimed to develop scales for assessing parents’ strategies for coping with their children’s pain and a shorter improved scale for children usable in clinical practice.

METHODS: The number of items in the Finnish version of the pain-coping questionnaire for children was reduced from 39 to 20. A corresponding reduced scale was created for parental use. We recruited consecutive patients from nine hospitals evenly distributed throughout Finland, aged 8-16 years who visited a paediatric rheumatology outpatient clinic and reported musculoskeletal pain during the past week. The patients and parents rated the child’s pain on a visual analogue scale from 0 to 100 and completed pain-coping questionnaires and depression inventories. The selection process of pain questionnaire items was performed using factor analyses.

RESULTS: The average (standard deviation) age of the 130 patients was 13.0 (2.3) years; 91 (70%) were girls. Four factors were retained in the new, improved Pain-Coping Scales for children and parents. Both scales had 15 items with 2-5 items/factor. The goodness-of-fit statistics and Cronbach’s alpha reliability coefficients were satisfactory to good in both scaled. The criterion validity was acceptable as the demographic, disease related, and the depression and stress questionnaires correlated with the subscales.

CONCLUSIONS: We created a shorter, feasible pain-coping scale for children and a novel scale for caregivers. In clinical work, the pain coping scales may serve as a visualisation of different types of coping strategies for paediatric patients with pain and their parents and facilitate the identification of families in need of psychological support.

PMID:36694196 | DOI:10.1186/s12969-023-00791-1

BMC Oral Health. 2023 Jan 25;23(1):40. doi: 10.1186/s12903-023-02751-3.

ABSTRACT

BACKGROUND: Dental enamel, the hardest outermost layer of a human tooth, is subjected to occlusal forces throughout life during different oral function as talking, mastication etc. Due to this continuous stress, wear causes the loss of this protective shell. This study aimed to detect microscopic differences in enamel’s wear behavior among different age groups of adolescents and adults.

AIMS AND METHODS: Enamel specimens from immature open-apex and mature closed-apex premolars were subjected to simulated occlusal wear of impact and sliding wear test ISWT. Upper and lower enamel specimens were made to come in contact under controlled conditions. The enamel specimens’ surfaces were examined using different microscopes. The upper and lower specimens were subjected to the following tests; pre-test light microscopy examination, enamel specimens’ preparation for ISWT, scanning laser confocal microscopy of upper specimens, three-dimensional (3D) colored laser microscope and a Profilometer imaging of the lower specimens.

RESULTS: Wear characteristics, including wear areas, crater depths, and relation to enamel microstructures, differed among different age groups. Immature enamel from the upper specimens was more resistant to chipping than mature enamel with no statistically significant wear area difference. The immature enamel craters from the lower specimens were wider and deeper than those in the mature enamel; the wear areas in the mature enamel in the lower specimens were almost flat and smooth. The wear areas in the immature enamel in the lower specimens were significantly larger than those in the mature enamel.

CONCLUSIONS: Wear characteristics of the immature enamel are different from those of the mature enamel. Hence, it should be repaired using restorative materials with compatible wear properties.

PMID:36694188 | DOI:10.1186/s12903-023-02751-3