Nevin Manimala

BMC Pediatr. 2025 Apr 14;25(1):289. doi: 10.1186/s12887-025-05646-0.

ABSTRACT

BACKGROUND: In Japan, the number of pharmaceuticals with pediatric indications is low, and some are approved only in Europe or the USA but not in Japan. As the approval review report by the Japanese health authority contains any detailed items considered for drug approval, this study aimed to analyze the review reports and elucidate data types that facilitate the approval of pediatric drugs in Japan.

METHODS: We identified products approved in Japan, extracted relevant product- and review-related information, and summarized the characteristics of pediatric drug clinical data and drug approval procedures.

RESULTS: Among 625 products (approved 04/2019-02/2024), 171 with pediatric indications were analyzed. The approval review considered orphan drug designation for 56 products, public knowledge-based application for 16 products, mandatory post-marketing surveillance for 42 products, and investigator-initiated studies for 11 products. For only 10 products, confirmatory studies were completed exclusively in Japanese children. Among the other 161 products, extrapolation from non-Japanese children and Japanese adults and/or older children was discussed for 93 and 100 products, respectively. Extrapolation-based reviews focused on ethnic and population factors and consistency of exposure dose, efficacy, and safety. Statistical confirmation is not always necessary for approval. Administrative incentives are often applied, including for orphan drugs and Sakigake designation and public knowledge-based applications.

CONCLUSIONS: The appropriateness or sufficiency of the clinical data package can refer to the PMDA. By considering joining a multinational study and determining the required number of Japanese patients, a path toward the approval of pediatric drugs in Japan can be identified.

PMID:40223100 | DOI:10.1186/s12887-025-05646-0

J Health Popul Nutr. 2025 Apr 13;44(1):117. doi: 10.1186/s41043-025-00861-y.

ABSTRACT

OBJECTIVE: To investigate the relationship between dietary microorganism intake and mortality risk among hypertensive adults with depression in the United States.

METHODS: This study utilizes data from the 2005-2018 National Health and Nutrition Examination Survey, focusing on individuals with hypertension. The Kaplan-Meier (K-M) curve is employed to preliminarily explore the relationship between dietary microorganism intake, depression, and mortality risk in hypertensive individuals. The Cox proportional hazards model is used for both individual and combined analyses of these relationships. Mediation analysis assesses the mediating effect of depression on the association between dietary microorganisms and mortality, while subgroup and sensitivity analysis evaluates the stability of the model.

RESULTS: This cohort study included 11,602 hypertensive participants (5,904 men and 5,698 women), with 1,201 having depression. During follow-up period, 2,085 died from all causes, 692 due to cardiovascular events. Preliminary analysis using the K-M curve reveals that hypertensive individuals with higher dietary microorganism intake and those without depression have lower mortality risks. Cox proportional hazards model analysis shows that increased dietary microorganism intake is associated with reduced mortality risk in hypertensive individuals (HR_ALL-cause=0.654, 95%CI: 0.555-0.771; HR_CVD-cause:0.675, 95%CI: 0.472,0.967). High intake of diets rich in dietary microorganisms may mitigate the ALL-cause mortality risk of depression in hypertensive populations(HR_ALL-cause=0.493, 95%CI: 0.256-0.947). Mediation analysis revealed that depression serves as a partial mediator in the process of dietary microorganisms improving the long – term prognosis of the hypertensive population. Results of subgroup analysis and sensitivity analysis showed that the beneficial effect of dietary microorganism intake on prognosis remained stable in most of the hypertensive population.

CONCLUSION: Patients with depression among those suffering from hypertension can reduce the risk of all-cause mortality caused by depression by increasing their intake of dietary microorganisms. This provides clinicians with a new non-pharmacological intervention approach and offers a direction for the optimization of clinical combined treatment regimens.

PMID:40223098 | DOI:10.1186/s41043-025-00861-y

Respir Res. 2025 Apr 13;26(1):141. doi: 10.1186/s12931-025-03216-7.

ABSTRACT

BACKGROUND: Despite significant advances in the treatment of lung cancer (LC), there are no reliable biomarkers to effectively predict therapy response and overall survival (O/S) in non-small cell lung cancer (NSCLC) subtypes. While targeted therapies have improved survival rates in lung adenocarcinoma (LUAD), effective treatment options for lung squamous cell carcinoma (LUSC) are still limited. Recent evidence indicates that exosome-bound WNT5A may significantly contribute to disease progression. Our study assessed the WNT5A protein as a potential biomarker for diagnosing patients and predicting prognosis to assist in therapy selection.

METHODS: Primary tumor tissue and serum samples were collected from a cohort of 60 patients with histologically confirmed NSCLC before therapy. Healthy serum donors served as controls. Exosomes were isolated, then exosome number and size were measured, and WNT5A protein levels were identified in tissue and in vesicle-free, vesicle-bound fractions of the serum by ELISA.

RESULTS: Extensive statistical analysis (ROC, AUC, Cox, etc.) revealed that elevated WNT5A levels on the serum-exosome surface correlated with distant metastasis, advanced disease stage, and lymph node involvement in LUSC but not in LUAD patients. Moreover, a high WNT5A exosome surface expression was associated with a poor response to therapy and shorter O/S in LUSC patients. Additionally, serum-exosome surface + cargo WNT5A content distinguished LUAD and LUSC subtypes.

CONCLUSIONS: WNT5A, particularly its serum exosome-bound form, may serve as a valuable biomarker after further validation for differentiating NSCLC subtypes and predicting disease progression. Importantly, the information can become available from a simple serum sample at the time of diagnosis.

PMID:40223089 | DOI:10.1186/s12931-025-03216-7

BMC Oral Health. 2025 Apr 13;25(1):567. doi: 10.1186/s12903-025-05959-7.

ABSTRACT

BACKGROUND: It has been reported that periodontitis was a risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD). The aim of this study is to investigate the impact of periodontitis on all-cause and cause-specific mortality of MASLD patients.

METHODS: We included 11,019 individuals with metabolic dysfunction-associated steatotic liver disease (MASLD) from the National Health and Nutrition Examination Survey. Multivariable Cox proportional hazards models were utilized to analyze the estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality and cause-specific mortality among participants with different periods of periodontitis status. Additionally, we employed restricted cubic splines (RCS) curves to explore the dose-response relationship between clinical attachment level (CAL) and pocket probing depth (PPD) and mortality rates. Finally, a series of sensitivity analyses and stratification analyses were conducted to test the reliability and robustness of the results.

RESULTS: In this study, moderate to severe periodontitis significantly increased the all-cause mortality (HR 1.29, 95% CI 1.08-1.55; P = 0.003) and cardiovascular disease (CVD)-related mortality (HR 1.41, 95% CI 1.10-1.79; P = 0.006) among MASLD participants. However, no significant effects of different periodontal statuses on cancer mortality were observed among MASLD participants.

CONCLUSIONS: A nationwide large-sample longitudinal study indicated that MASLD patients with moderate to severe periodontitis experienced significantly higher all-cause and CVD-related mortality rates compared to those with no or mild periodontitis.

PMID:40223086 | DOI:10.1186/s12903-025-05959-7

Malar J. 2025 Apr 13;24(1):120. doi: 10.1186/s12936-025-05356-z.

ABSTRACT

BACKGROUND: Despite a significant reduction in malaria cases in America, Venezuela has experienced a substantial increase between 2000 and 2019. Asymptomatic malaria, prevalent in both low- and high-endemic regions, poses a challenge due to the absence of clinical manifestations and often low parasitaemia. This study aims to determine the current prevalence of asymptomatic malaria in four rural communities of Sucre, the third most endemic state in the country.

METHODS: A community-based cross-sectional study was conducted from October to December 2022 (high seasonality period). Individuals were interviewed in their households and assessed for malaria using rapid diagnostic tests (RDTs), thick and thin blood smear microscopy, and polymerase chain reaction (PCR). Asymptomatic individuals with PCR positive (PCR+) for Plasmodium were classified as cases, while PCR negative individuals were classified as controls. Descriptive statistics were used to analyse the data. The normality of numerical variables was assessed with the Kolmogorov-Smirnov test. Based on this assessment, Student’s t-test was applied to normally distributed variables and Mann-Whitney U-test to non-normally distributed ones. For categorical variables, Pearson’s chi-square test was used when less than 25.0% of cells had an expected frequency below five; otherwise, Fisher’s exact test was employed.

RESULTS: The study involved 351 individuals, mostly women (54.7%), of mixed (non-indigenous) race (61.3%), with primary (6 years) education (40.7%). The most common occupations were students (30.5%), housekeepers (27.6%), and farmers (16.5%). Over half (54.4%) had lived at their current address for over 10 years. The prevalence of asymptomatic malaria by RDTs and microscopy was 0.3% (n = 1/351) as determined. However, PCR detected a higher prevalence of 24.8% (87 positive cases, 95.0% CI = 20.5-29.5), primarily caused by P. vivax (73.6%). The highest prevalences were observed in individuals aged over 15 years (27.1%, 95.0% CI = 21.6-33.1), males (28.3%, 95.0% CI = 21.7-35.6), those with a college (14 years) education (33.3%, 95.0% CI = 17.2-53.2), and educators (41.7%, 95.0% CI = 18-68.8). The rural community with the highest prevalence was Chacopata (30.6%, 95.0% CI = 17.4-46.7), followed by El Paujil (28.6%, 95.0% CI = 21.9-36.1), Yaguaraparo (23.2%, 95.0% CI = 15.1-33.1), and Cristóbal Colón (16.5%, 95.0% CI = 9.6-25.8). Two-thirds (66.7%) reported a malaria history, predominantly caused by P. vivax (70.5%), with a median of 3 previous episodes. At least one-third (35.5%) had non-adherence to treatment during their most recent malarial episode. No statistically significant differences were observed between sociodemographic characteristics and malaria history of individuals with asymptomatic malaria (PCR+) and controls.

CONCLUSION: RDTs and microscopy only managed to diagnose less than 1.0% of asymptomatic malaria cases. Active surveillance systems with high sensitivity such as PCR may provide accurate estimates of asymptomatic malaria prevalence needed for opportune diagnosis and treatment.

PMID:40223077 | DOI:10.1186/s12936-025-05356-z

BMC Med. 2025 Apr 14;23(1):219. doi: 10.1186/s12916-025-04051-9.

ABSTRACT

BACKGROUND: Studies investigating the associations of 24-h movement behaviours (including moderate-to-vigorous-intensity physical activity (MVPA), light-intensity PA (LPA), sedentary time (ST) and sleep) with depressive symptoms are scarce. It is also unclear whether possible associations differ between urban and rural residents. Hence, we aimed to investigate these associations in a population-based sample of middle-aged Finnish adults.

METHODS: The study population consisted of 4295 adults, aged 46 years, from the Northern Finland Birth Cohort 1966. The participants wore a hip-worn accelerometer for 14 days. Time spent in sedentary, LPA and MVPA was obtained from accelerometer data and then combined with self-reported sleep duration to obtain the 24-h composition. The residential environment was classified as urban or rural based on the participants’ home addresses. Depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II). Multivariable adjusted regression analysis using a compositional data analysis approach based on isometric log-ratio transformation was used to determine the associations between movement behaviours and depressive symptoms in urban and rural residential environments.

RESULTS: The 24-h movement behaviour composition was significantly associated with the BDI-II score both in urban and rural residential environment. More time spent in sleep relative to other behaviours was associated with lower BDI-II score in rural residential environments. More time spent in ST among urban residents and in LPA among rural residents was associated with higher BDI-II scores. When modelling pairwise reallocations of time, more MVPA or more sleep at the expense of LPA or ST was associated with lower BDI-II score among rural residents. For urban residents, reallocating time from ST to any other behaviour was associated with lower BDI-II score.

CONCLUSIONS: Our findings showed that more relative time spent in MVPA and sleep was associated with lower levels of depressive symptoms among rural residents, and more relative time spent in any other behaviour at the expense of ST was associated with lower levels of depressive symptoms among urban residents. These differences should be considered in the prevention and treatment of depressive symptoms. Due to the cross-sectional design of this study, causality cannot be inferred, and further research exploring the mechanisms underlying these associations in diverse populations and longitudinal study settings are needed.

PMID:40223075 | DOI:10.1186/s12916-025-04051-9

BMC Pediatr. 2025 Apr 14;25(1):290. doi: 10.1186/s12887-025-05586-9.

ABSTRACT

OBJECTIVE: To retrospectively investigate the utilization patterns and clinical indications of acupuncture within the pediatric population in general hospitals from 2015 to 2020, including disease spectrum characteristics and relevance to pediatric subspecialties.

METHODS: The clinical data of pediatric inpatients consulted by Acupuncture-Moxibustion and Tuina Department of Qilu Hospital of Shandong University was collected from January 1, 2015, to December 31, 2020. The data collected include the number of wards in which consultation was requested, the diseases that require consultation, the distribution of pediatric tertiary disciplines and the system of disease affiliation.

RESULTS: This study summarizes 55 types of pediatric diseases treated with acupuncture. The most common health issues addressed include peripheral facial paralysis, diarrhea, reduced limb mobility or decreased muscle strength, postoperative bloating, and Guillain-Barré syndrome. Acupuncture is utilized across all pediatric subdisciplines, with notable applications in neurology, critical care medicine, general surgery, respiratory medicine, and orthopedics. The classification of diseases for acupuncture consultations primarily focuses on disorders of the nervous system, respiratory system, neoplasms, and digestive system (according to ICD-11).

CONCLUSIONS: In summary, acupuncture has a broad range of applications in the treatment of pediatric diseases and can serve as a valuable complementary and alternative therapy. The advancement of Traditional Chinese Medicine (TCM) acupuncture in general hospitals is closely linked to the involvement of pediatric practices. The findings of this study provide valuable insights for clinical practice, acupuncture education, pediatric healthcare systems, and social research.

PMID:40223074 | DOI:10.1186/s12887-025-05586-9

BMC Oral Health. 2025 Apr 13;25(1):564. doi: 10.1186/s12903-025-05895-6.

ABSTRACT

BACKGROUND: Ni-Ti instruments with varying design features may lead to different levels of postoperative pain, which is a significant clinical concern, particularly in previously asymptomatic teeth. Therefore, the purpose of this randomized clinical trial is to compare postoperative pain following instrumentation with TruNatomy versus ProTaper Next Ni-Ti systems in mandibular molars with asymptomatic apical periodontitis.

METHODS: 90 healthy participants were randomly assigned to two groups: TruNatomy (TN) or ProTaper Next (PTN) instruments. After single-visit root canal treatments, participants were asked to rate their postoperative pain levels at 6, 12, 24, 48, and 72 h and seven days later, using the Numerical Rating Scale (NRS) through an online questionnaire. In cases of pain, 400 mg of ibuprofen was prescribed. Data from 80 participants were finally included in the analysis. Data were analyzed using the Mann-Whitney U, Friedman, and Fisher’s Chi-Square tests (p < 0.05).

RESULTS: There was no statistically significant difference in postoperative pain intensity at 6, 12, 24, and 48 h and seven days between the groups (p > 0.05). At the 72-hour time point, TN group showed statistically higher postoperative pain intensity (p < 0.05). No statistically significant differences in the incidence of postoperative pain were observed at any of the time points (p > 0.05). Analgesic intake and flare-up incidence were not significantly different between the groups (p > 0.05).

CONCLUSION: Postoperative pain levels were not significantly influenced by the type of rotary Ni-Ti instrument. Both TN and PTN instruments led to low-level and similar postoperative pain intensity, minimal analgesic use, and a low incidence of flare-ups in teeth with asymptomatic apical periodontitis.

TRIAL REGISTRATION: ClinicalTrials.gov ID NCT06545773, Registration Date 8 August 2024 (retrospectively registered).

PMID:40223067 | DOI:10.1186/s12903-025-05895-6

BMC Oral Health. 2025 Apr 13;25(1):560. doi: 10.1186/s12903-025-05961-z.

ABSTRACT

OBJECTIVES: Mini implant retained overdentures have been treated in edentulous patients with promising long-term results. However, various attachment systems in this process remain insufficiently investigated. This systematic review and meta-analysis aimed to compare the effects of the ball and other attachments used in mini-implant overdentures. Marginal bone loss, bite force, implant survival rate, prosthetic maintenance, and complications were assessed.

MATERIALS AND METHODS: A systematic search was conducted across PubMed, Cochrane Library, and Scopus databases until 25th February 2025. This systematic review aimed to find studies that compare ball attachments with other attachment systems in mini dental implant (MDI) overdentures. The primary outcome was marginal bone loss, while the secondary outcomes were maximum bite force, implant survival rate, prosthetic maintenance, and complications. The risk of bias was assessed using the Cochrane risk-of-bias tool for RCTs, and a quantitative meta-analysis was performed.

RESULTS: Of the 561 publications, six randomized clinical trials (101 participants, 234 mini-implants) met the inclusion criteria. Risk of bias assessment revealed three studies with a low risk of bias and three studies with some concerns for risk of bias. There was no significant difference in the marginal bone loss between the ball attachments and others (WMD = 0.15, 95% CI -0.50 to 0.81, p = 0.65), though ball attachments performed better than telescopic ones (P < 0.05) in subgroup analysis. No significant difference in bite force was found (WMD = -5.29, 95% CI -33.46 to 22.87, p = 0.71). Two-year survival rates were 90.9% for ball and 97.8% for bar attachments. The ERA^® (Extra-Coronal Resilient Attachment) group required five interventions (sore spot adjustments, relining, nylon replacements), while the ball attachment group required only two (denture repair, nylon cap replacement) over the one-year follow-up period.

CONCLUSIONS: Within the limitations of the study, it can be concluded that ball, bar, and ERA^® attachments yield similar outcomes in marginal bone loss while telescopic attachments show more statistically significant marginal bone loss (p < 0.05). The type of attachment does not significantly affect maximum bite force.

PROSPERO REGISTRATION NUMBER: CRD42024610018.

PMID:40223059 | DOI:10.1186/s12903-025-05961-z

BMC Oral Health. 2025 Apr 13;25(1):563. doi: 10.1186/s12903-025-05955-x.

ABSTRACT

PURPOSE: To evaluate the influence of guide support on the accuracy of sCAIS using a keyless guiding system in different cases of partial edentulism.

METHODS: Sixty polyamide models of partially edentulous maxillae, simulating anterior and posterior single-tooth gaps as well as anterior and distal extended edentulous areas, were fabricated. Full-arch, 2-teeth, and 4-teeth supported surgical guides were used to place implants at FDI 15, 17, 21, 26 sites in Model A and at FDI 12, 22, 15 sites in Model B. In total, 210 replica implants were placed using 120 surgical guides in seven implantation sites. Three-dimensional crestal and apical, angular and vertical deviations from the planned implant positions were compared using the Kruskal-Wallis H test with Dunn’s procedure for multiple pairwise comparisons.

RESULTS: Overall median 3D crestal and apical deviations of implants placed with 2-teeth guide support (0.62 mm [0.45-0.84], 0.92 mm [0.69-1.25]) and 4-teeth guide support (0.65 mm [0.52-0.81], 1.01 mm [0.8-1.26]) were significalty lower compared to the full-arch support group (0.86 mm [0.63-0.98], 1.26 mm [0.98-1.52]) with values of p < 0.017. Overall angular and vertical deviations of implants placed with 2-teeth guide support (2.61° [1.71-3.75], 0.32 mm [0.15-0.44]) were significantly lower compare to the full-arch support group (3.22° [2.25-4.41], 0.46 mm [0.24-0.62]). In the subgroup analysis, implants placed at the FDI 12, 22, and 15 positions exhibited significantly higher 3D and angular deviations with full-arch guide support, whereas the 3D apical and angular deviations of were significantly lower with 2-teeth guide support at the FDI 21 site.

CONCLUSIONS: The deviations in all guide support groups did not exceed the recommended safety margins. Statistically significant differences were found between guide support groups, with influence of guide support on the accuracy of sCAIS varying across different implantation sites.

TRIAL REGISTRATION: Not applicable.

PMID:40223057 | DOI:10.1186/s12903-025-05955-x