Categories
Nevin Manimala Statistics

Improving Indirect Methods for Calculating Reference Limits for Nerve Conduction Studies From Historical Data

Muscle Nerve. 2026 May 19. doi: 10.1002/mus.70281. Online ahead of print.

ABSTRACT

INTRODUCTION/AIMS: High quality reference limits for nerve conduction studies (NCS) are essential for diagnosis of neuromuscular disorders. Examining healthy controls to calculate reference limits directly is expensive and time consuming. Indirect methods, including extrapolated norms (E-norms), extrapolated reference values (E-Ref), and multivariate extrapolated reference values (MeRef), use historical hospital data instead. These methods sort the historical measurements in increasing order, creating so-called S-curves, and select normal measurements based on the shape of these S-curves. Current versions of these methods have several limitations, and we aimed to improve them by modifying how they select normal measurements.

METHODS: E-norms, E-Ref, and MeRef were modified with new S-curve selection algorithms. The modified versions of the methods were used to calculate reference limits for common NCS measurements from a large historical database. The results were compared to reference limits calculated from 680 healthy subjects using Youden’s J statistic and z-score deviation.

RESULTS: The modified methods provided reference limits with Youden’s J > 0.8 and z-score deviation < 0.9 for most types of NCS measurements and similar or higher Youden’s J than the unmodified methods. In most cases, the methods required at least 500 measurements and fewer than 20% abnormal measurements for good performance.

DISCUSSION: Changing the S-curve selection algorithms improves E-norms, E-Ref, and MeRef. The modifications require a sufficient number and proportion of normal measurements in the historical database. When these prerequisites are met, a combination of indirect methods can be used when developing reference limits from historical patient data.

PMID:42156990 | DOI:10.1002/mus.70281

Categories
Nevin Manimala Statistics

Differential effects of prior versus concomitant Steroid and Antibiotic Treatment on Immunotherapy Efficacy – A Pooled Analysis of the RAMONA, INTEGA, OPTIM, ELDORANDO, FORCE, TITAN-RCC and TITAN-TCC Trials of the German AIO Study Group

Br J Cancer. 2026 May 19. doi: 10.1038/s41416-026-03428-8. Online ahead of print.

ABSTRACT

BACKGROUND: We explored the association of immune-related adverse events (irAE), along with prior and concomitant antibiotic and steroid use, on oncological outcomes following immune checkpoint inhibitor (ICI) treatment in various solid tumours.

METHODS: Pooled data from seven trials on ICI therapy across multiple cancer types (head and neck, non-small cell lung cancer, gastroesophageal junctional adenocarcinoma, oesophageal, renal cell, and urothelial carcinoma) was analysed, focusing on overall survival (OS) and progression-free survival (PFS) and antibiotic or steroid use before and during the study.

RESULTS: Of 693 patients, 80 used steroids and 52 used antibiotics prior to the study, while 360 and 331, respectively, used them concomitantly. Lack of prior antibiotic use was associated with longer OS (No vs. Yes: HR 0.552, 95%-CI 0.370-0.822, p = 0.0035) and PFS (No vs. Yes: HR 0.703, 95%-CI 0.485-1.019, p = 0.0625), whereas concomitant antibiotic use had no such effect. Patients with concomitant steroid use demonstrated longer PFS (No vs. Yes: HR 1.359, 95%-CI 1.091-1.693, p = 0.0061).

DISCUSSION: Our study confirmed associations between antibiotic and steroid use and ICI efficacy in cancer. Prior, but not concomitant, antibiotic use was linked to reduced OS, supporting the role of microbiome diversity in tumour response. Concomitant steroid use was associated with improved PFS, potentially reflecting its link to irAE occurrence.

PMID:42156980 | DOI:10.1038/s41416-026-03428-8

Categories
Nevin Manimala Statistics

iPad Eye Tracking Reproduces Clinical Grade Oculomotor Differences in Parkinson’s Disease

NPJ Digit Med. 2026 May 19. doi: 10.1038/s41746-026-02753-9. Online ahead of print.

ABSTRACT

iPad-based eye tracking could support Parkinson’s disease (PD) screening and longitudinal monitoring by enabling objective, low-cost, portable assessment of oculomotor function. We previously validated an iPad-based eye-tracking system against the EyeLink 1000 Plus for temporal and spatial saccade metrics. Here, in a convenience sample of 19 healthy controls (HC) and 12 patients with PD, we recorded eye movements simultaneously with both devices during pro-saccade, anti-saccade (AS), memory-guided saccade (MGS), and self-generated saccade tasks. Across all pre-specified metrics, statistically significant PD-HC differences and null results were concordant between devices. In addition, saccade-level mixed-effects models showed small group × device interaction effects that remained below literature-based benchmarks for clinically meaningful PD-HC differences, indicating that iPad-based measurements preserved benchmark clinical-grade group-level effects. A compact three-metric iPad-based classifier comprising AS directional error rate, AS gain, and MGS gain supported strong subject-level PD-HC discrimination, with an area under the receiver operating characteristic curve of 0.98, sensitivity of 0.91, specificity of 1.00, and accuracy of 0.96. These findings support scalable tablet-based oculomotor assessment for PD-related screening and longitudinal monitoring.

PMID:42156978 | DOI:10.1038/s41746-026-02753-9

Categories
Nevin Manimala Statistics

Resonance frequency versus fixed 0.1 Hz breathing in HRV biofeedback: a four-week randomized comparison

Sci Rep. 2026 May 19. doi: 10.1038/s41598-026-53333-6. Online ahead of print.

ABSTRACT

Heart rate variability biofeedback (HRVB) is increasingly examined as an adjunctive method for reducing psychological symptoms. Standard protocols involve identifying each participant’s resonance frequency (RF); however, it remains unclear whether this individualized calibration offers advantages over training at a fixed breathing rate of 0.1 Hz. We conducted a randomized trial with three groups (RF, 0.1 Hz, Control) to compare the effectiveness of a four-week HRVB intervention using an individually determined RF versus a fixed breathing frequency of 0.1 Hz. Participants (N = 88) completed pre- and post-intervention assessments of perceived stress, anxiety, depressive symptoms (DASS-21), and resting HRV. Both HRVB groups showed significant reductions in stress, anxiety, and depressive symptoms relative to the control group, with no meaningful differences between them. Bayesian analysis provided anecdotal evidence favoring the null hypothesis of no difference between groups. The intervention did not produce significant changes in resting HRV. The present study does not permit firm conclusions regarding whether breathing at the RF confers additional benefits over breathing at a fixed rate of 0.1 Hz or whether the two approaches differ in effectiveness. Future studies aimed at detecting small differences between these approaches should include larger samples.Trial registration: The study was retrospectively registered at isrctn.com (Identifier ISRCTN17808563 date of first registration 20/01/2026, https//doi.org/10.1186/ISRCTN17808563). The full trial protocol and statistical analysis plan can be accessed via the registry.

PMID:42156977 | DOI:10.1038/s41598-026-53333-6

Categories
Nevin Manimala Statistics

Optimising patient centred drug development to realise impact

Commun Med (Lond). 2026 May 19;6(1):285. doi: 10.1038/s43856-026-01634-2.

NO ABSTRACT

PMID:42156971 | DOI:10.1038/s43856-026-01634-2

Categories
Nevin Manimala Statistics

Effect of the sterilization cycle on the flexural strength of titanium orthodontic mini-screws: an in vitro study

Sci Rep. 2026 May 19. doi: 10.1038/s41598-026-52979-6. Online ahead of print.

ABSTRACT

The aim of this study was to investigate the effect of sterilization cycles on the flexural strength (FS) of titanium mini-screws used in orthodontics. The study was conducted between 2024 and 2025 at the Department of Orthodontics, Faculty of Dentistry, Van Yüzüncü Yıl University, using 1.8 × 8 mm titanium mini-screws. A total of 30 specimens were used and divided into three equal groups: Group 1 received one sterilization cycle; Group 2 received 10 sterilization cycles; and Group 3 received 25 sterilization cycles. The screws were then embedded in acrylic blocks and tested. FS measurements were performed using a universal testing machine. Mini-screws fixed in acrylic blocks were placed parallel to the ground, and a force perpendicular to the length was applied to induce deformation. The significance of the results was assessed at p < 0.05. The mean FS values ​​were 278.00 ± 61.62 N in Group 1, 243.80 ± 51.26 N in Group 2, and 286.60 ± 41.91 N in Group 3. The FS values ​​of sterilized miniscrews did not differ statistically significantly according to the number of sterilization cycles (p > 0.05). The study found that the FS of titanium miniscrews, which have a wide range of applications in orthodontic practice, was not affected by repeated sterilization cycles of up to 25 cycles.

PMID:42156963 | DOI:10.1038/s41598-026-52979-6

Categories
Nevin Manimala Statistics

Prevalence of irritable bowel syndrome and its association with lifestyle factors among medical students in Jordan: a cross-sectional survey

Sci Rep. 2026 May 19. doi: 10.1038/s41598-026-52741-y. Online ahead of print.

ABSTRACT

Irritable Bowel Syndrome (IBS) is a common functional gastrointestinal disorder marked by chronic abdominal discomfort and altered bowel habits, including constipation, diarrhea, or a combination of both. It significantly impacts quality of life and is often linked to psychological stress and dietary factors. Given the scarcity of multi-university data from Jordan, this study aimed to determine the prevalence of IBS among medical students across three Jordanian universities and to identify associated lifestyle, psychological, and demographic risk factors using validated instruments. A cross-sectional survey was conducted among medical students from the University of Jordan, Mutah University, and Jordan University of Science and Technology across all academic levels. The Rome III criteria were employed to diagnose IBS. Sleep quality was evaluated using the SATED (Satisfaction, Alertness, Timing, Efficiency, and Duration) scale, and mental health status was assessed using the Hospital Anxiety and Depression Scale (HADS). A total of 572 students completed the questionnaire. IBS was identified in 33.74% of respondents. Among those with IBS, 31.1% had the constipation-predominant subtype, 18.1% had the diarrhea-predominant subtype, and 50.8% experienced mixed symptoms. Binary logistic regression revealed that a family history of IBS significantly increased the likelihood of having the disorder (OR: 1.95; 95% CI: 1.34-2.83). Other significant risk factors included smoking (OR: 1.43; 95% CI: 1.08-2.40) and anxiety borderline anxiety (OR: 1.76; 95% CI: 1.11-2.80; p = 0.01). Established anxiety (OR: 1.53; p = 0.06) did not reach statistical significance. Sixth-year students were found to be at highest risk (OR: 5.16; 95% CI: 1.84-14.41), possibly due to greater academic pressure. Regular physical activity was associated with lower IBS odds, though this did not reach statistical significance (OR: 0.6; p = 0.07). No significant association was found with gender, BMI, sleep quality, junk food consumption, or depression. IBS is prevalent among Jordanian medical students and is associated with both genetic predisposition and lifestyle factors. These findings underscore the importance of targeted mental health and lifestyle interventions – particularly for sixth-year students – and highlight the need for longitudinal research to establish causal pathways. To our knowledge, this is the first multi-university study in Jordan to simultaneously assess psychological, sleep, and lifestyle correlates of IBS in medical students using validated instruments, providing a foundation for evidence-based student health policy in the region.

PMID:42156949 | DOI:10.1038/s41598-026-52741-y

Categories
Nevin Manimala Statistics

Gut hormones in POTS and their relation to hemodynamic parameters and gastrointestinal symptoms

Sci Rep. 2026 May 19;16(1):15514. doi: 10.1038/s41598-026-52963-0.

ABSTRACT

Postural orthostatic tachycardia syndrome (POTS) is associated with multiple autonomic symptoms, including gastrointestinal (GI) complaints, and has been linked to insulin resistance. We aimed to explore HbA1c, circulating metabolic hormones (insulin, C-peptide, GIP, GLP-1, glucagon, leptin, and peptide YY) and cortisol, and their associations with hemodynamic parameters and GI symptoms in POTS. Two POTS cohorts were studied and compared with matched controls. In the fasting cohort, blood samples were drawn in 42 patients and 41 controls, followed by active standing tests with measurement of pulse and blood pressure (BP) in supine and standing positions. In the non-fasting cohort, questionnaires assessed GI symptoms and HbA1c was measured in 43 patients and 52 controls. Fasting C-peptide and insulin levels correlated with BP in POTS (q = 0.002) but not in controls. Fasting insulin tended to be higher in POTS but was not statistically significant after adjustment for BMI (β = 6.85; 95% CI: -1.04-14.74; p = 0.085). Morning cortisol was comparable between groups. In the non-fasting cohort, HbA1c and metabolic hormones were comparable between groups, with no associations with GI symptoms. Together, these findings suggest a potential link between insulin-related pathways and BP regulation in POTS. Future studies are warranted to further investigate insulin dynamics in POTS.

PMID:42156945 | DOI:10.1038/s41598-026-52963-0

Categories
Nevin Manimala Statistics

The impact of pre-transplant extramedullary disease on the outcome of allogeneic hematopoietic cell transplantation for acute myeloid leukaemia in children- on behalf of PDWP/EBMT

Bone Marrow Transplant. 2026 May 19. doi: 10.1038/s41409-026-02908-y. Online ahead of print.

ABSTRACT

Extramedullary disease (EMD) is a rare presentation in Acute Myeloid Leukaemia (AML). On behalf of PDWP/EBMT we studied the effect of EMD compared to isolated BM involvement in the outcomes following non-TBI conditioning hematopoietic stem cell transplantation (HCT) for AML in children. Patients were grouped into three categories: BM involvement only (Group A), BM + CNS involvement only (Group B) and BM+ other EMD+/- CNS (Group C). A total of 958 patients were included, 685 (71.5%) in Group A, 135 (14.1%) in Group B and 138 (14.4%) in Group C. The median post HCT follow-up was 5.4 years. Five years LFS, OS, RI and NRM were 62%, 68.4%, 26.4% and 11.6%, respectively. Multivariate analysis showed higher RI in Group C compared to Group A (HR = 1.45 (1.01-2.06) p = 0.04). In the multivariate analysis patients with EMD had no significant difference in LFS, OS and NRM. Our findings suggest that children with AML and BM with EMD+/- CNS involvement (group C) have a higher incidence of relapse after HCT compared to those with BM only or BM + CNS only disease. However, the presence of EMD did not have an impact on overall, leukaemia-free survival or non-relapse mortality.

PMID:42156943 | DOI:10.1038/s41409-026-02908-y

Categories
Nevin Manimala Statistics

Prostate cancer screening: Decision-making when MRI results are inconclusive for cancer (PI-RADS 3)

Urol Oncol. 2026 May 19;44(7):243-247. doi: 10.1016/j.urolonc.2026.04.287. Online ahead of print.

ABSTRACT

Many patients who receive prostate magnetic resonance imaging are classified as Patient Imaging Reporting and Data Systems level 3 (PI-RADS 3), which is inconclusive for cancer. An important question is whether PI-RADS 3 patents should receive a biopsy. Prostate biopsy has a 4.6% chance of complications including a 1.3% chance of a hospital or emergency room visit. I critically examine the literature on the standard endpoint for PI-RADS 3 decision-making, namely clinically significant prostate cancer (csPCa) determined on biopsy. Some methods for estimating the probability of csPCa are statistically flawed. Importantly, even if there were no methodological flaws, these estimates have limited information for decision-making because the benefit of detecting csPCa on biopsy is not well established. Therefore, PI-RADS 3 patients should consider events after biopsy. The prostate testing for cancer and treatment trial of patients with localized prostate cancer found similar probabilities of prostate cancer death among patients randomized to active monitoring, prostatectomy, and radiotherapy. Adding perspective, based on calculations from the results of this trial, the probability of prostate cancer death is much smaller than the probability of death from other causes, particularly in older patients. Therefore, for PI-RADS 3 patients who would choose active monitoring if diagnosed with csPCa on biopsy, a reasonable decision is no biopsy with active monitoring.

PMID:42155163 | DOI:10.1016/j.urolonc.2026.04.287