Nevin Manimala

JAMA Psychiatry. 2025 Sep 3. doi: 10.1001/jamapsychiatry.2025.2039. Online ahead of print.

ABSTRACT

IMPORTANCE: Lithium augmentation is an effective treatment for patients with major depression after inadequate antidepressant response, but therapeutic outcomes vary considerably between individuals. Molecular studies may provide novel insights into treatment prediction and guide personalized therapy.

OBJECTIVE: To investigate the association of polygenic risk scores (PRS) for schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) with clinical outcomes after lithium augmentation.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study analyzed prospectively assessed treatment outcomes in patients who underwent lithium augmentation. Disorder-specific PRS were calculated using well-powered genome-wide association study summary statistics. Participants were recruited from 13 psychiatric hospitals, primarily in the greater Berlin area, between 2008 and 2020. They were patients with MDD who showed inadequate response to at least 1 antidepressant, a baseline score of 12 or more on the 17-item Hamilton Depression Rating Scale (HAMD-17), adequate treatment duration (≥4 weeks), and no diagnostic or co-medication changes. Data analysis was conducted between June 2022 and November 2023.

EXPOSURE: Polygenic risk scores for MDD, SCZ, or BIP.

MAIN OUTCOMES AND MEASURES: Response was defined as a 50% or greater reduction in HAMD-17 score, remission as a HAMD-17 score of 7 or less. Cox proportional hazards models, adjusted for ancestry, demographic, and clinical covariates, were used to estimate hazard ratios (HRs) for favorable outcomes.

RESULTS: Among 193 patients (mean [SD] age, 49.5 [13.4] years; 118 [61.1%] female and 75 [38.9%] male), higher BIP-PRS were associated with both response (HR, 1.29; 95% CI, 1.02-1.63; P = .03) and remission (HR, 1.52; 95% CI, 1.14-2.04; P = .004), explaining 2.51% and 4.53% of the variability in treatment outcomes, respectively. Individuals in the highest tertile of the BIP-PRS distribution had a 2.02-fold (95% CI, 1.15-3.53) higher likelihood of response and a 2.26-fold (95% CI, 1.17-4.36) higher chance of remission compared with those in the lowest tertile. Additionally, lower MDD-PRS was associated with better response to lithium augmentation (HR, 0.81; 95% CI, 0.66-1.00; P = .048; Nagelkerke R2 = 1.99%). No significant associations were observed between SCZ-PRS and response (HR, 1.00; 95% CI, 0.80-1.24; P = .97) or remission (HR, 1.12; 95% CI, 0.85-1.48; P = .42).

CONCLUSIONS AND RELEVANCE: Individuals carrying a higher polygenic burden for BIP and lower polygenic risk for MDD are more likely to benefit from lithium augmentation. Our findings suggest that disease-related PRS may aid in developing treatment prediction models for lithium augmentation response in depression, potentially informing clinical decision-making.

PMID:40900576 | DOI:10.1001/jamapsychiatry.2025.2039

JAMA Surg. 2025 Sep 3. doi: 10.1001/jamasurg.2025.3221. Online ahead of print.

ABSTRACT

IMPORTANCE: Traumatic rib fractures are associated with significant morbidity, including pulmonary complications and prolonged opioid use. Identifying adjunctive treatments that can reduce opioid consumption without compromising safety remains a clinical priority, particularly in nonintubated trauma patients.

OBJECTIVE: To evaluate whether adding dexmedetomidine to standard multimodal analgesia reduces opioid consumption in nonintubated patients in the intensive care unit (ICU) with traumatic rib fractures. It was hypothesized that adjunctive dexmedetomidine would reduce opioid use and improve numerical pain scores.

DESIGN, SETTING, AND PARTICIPANTS: This prospective, randomized, double-blind, placebo-controlled clinical trial was conducted from July 2021 to October 2023. Data were analyzed during January 2024. The study took place at a single academic level I trauma center ICU. Participants included nonintubated adult trauma patients (18 years or older) with 3 or more rib fractures who were admitted to the ICU. Exclusion criteria included a Glasgow Coma Scale score less than 14, bradycardia, hypotension, pregnancy, cirrhosis, chronic opioid use, or inability to consent. Of 41 enrolled patients, 19 received dexmedetomidine (46.3%).

EXPOSURE: Continuous intravenous infusion of dexmedetomidine (0.4 to 0.6 µg/kg per hour) or placebo (normal saline) for up to 48 hours, in addition to standard multimodal pain management.

MAIN OUTCOMES AND MEASURES: The primary outcome was the numerical pain score (NPS) over 48 hours. Secondary outcomes included oral morphine equivalents (OME) at 24 and 48 hours and pulmonary complications.

RESULTS: Among 41 patients (median age, 62 years; median injury severity score, 20), no significant differences were found in baseline characteristics between groups. Mean OME at 24 hours was 59.2 mg (dexmedetomidine) vs 54.9 mg (placebo) and 125.5 mg vs 87.1 mg at 48 hours. Median NPS was 4 in both groups. Pulmonary complication rates and ICU length of stay were also similar. Dexmedetomidine was discontinued in 47.4% of patients due to adverse events or patient request.

CONCLUSIONS AND RELEVANCE: Adjunctive dexmedetomidine did not reduce opioid consumption, improve pain scores, or lower pulmonary complication rates in nonintubated patients in the ICU with traumatic rib fractures. These findings do not support routine use of dexmedetomidine for analgesia in this patient population.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05321121.

PMID:40900569 | DOI:10.1001/jamasurg.2025.3221

Eur J Gastroenterol Hepatol. 2025 Jul 14. doi: 10.1097/MEG.0000000000003030. Online ahead of print.

ABSTRACT

Tegoprazan, a novel potassium-competitive acid blocker, has emerged as a potential alternative to proton pump inhibitors (PPIs) for the treatment of erosive esophagitis (EE), especially in light of long-term safety concerns associated with PPIs. This study aimed to assess the efficacy and safety of tegoprazan compared to PPIs in patients with EE. A systematic review and meta-analysis were conducted following preferred reporting items for systematic reviews and meta-analyses guidelines, including three randomized controlled trials with a total of 658 patients diagnosed with EE. The primary outcomes were cumulative endoscopic healing rates across 4-8 weeks and at 4 and 8 weeks, while secondary outcomes included any adverse events, drug-related treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs). Tegoprazan demonstrated noninferior healing rates at 4 weeks [relative risk (RR) = 1.05, 95% confidence interval (CI): 0.96-1.16; P = 0.28; I² = 51%] and 8 weeks (RR = 1.01, 95% CI: 0.96-1.06; P = 0.73; I² = 0%) compared to PPIs. There was no statistically significant difference in the overall incidence of adverse events or SAEs (RR = 1.19, 95% CI: 0.92-1.53; P = 0.19; I² = 24%). However, a significantly higher rate of drug-related TEAEs was observed in the tegoprazan group (RR = 1.23, 95% CI: 1.03-1.48; P = 0.02; I² = 0%). In conclusion, tegoprazan is an effective treatment option for EE, with comparable efficacy to PPIs, though further studies are warranted to evaluate its long-term safety before routine clinical use.

PMID:40900566 | DOI:10.1097/MEG.0000000000003030

Eur J Gastroenterol Hepatol. 2025 Jul 14. doi: 10.1097/MEG.0000000000003031. Online ahead of print.

ABSTRACT

OBJECTIVE: Most of the existing instruments assessing quality of care (QoC) are based on the perception of healthcare providers that may differ from that of healthcare users. We aimed to measure QoC through the patient’s eyes in a Greek cohort of patients with inflammatory bowel disease (GR QUOTE-IBD) and to investigate putative sociodemographic and disease-related QoC predictors.

METHODS: GR QUOTE-IBD questionnaire was delivered to patients at their regular follow-up visit, and adequate time was offered to fill it in. The outcome of the analysis was associated with epidemiological and disease-related characteristics. Statistical analysis was performed with SPSS (version 29, SPSS Inc., Chicago, Illinois, USA).

RESULTS: GR QUOTE-IBD questionnaire was completed by 150 patients from three IBD clinics, 93 with Crohn’s disease (CD), with a median disease duration of 10 years (range 0.6-43 years). Quality Index (QI) for total care was >9 in all three hospitals. Quality deficit QI <9 was found only for accessibility to IBD care in two of three clinics. Autonomy in decision-making was rated as the least important dimension of QoC from the patients’ perspective. A positive association was found between CD diagnosis and QI scores for total care (P = 0.013). Steroid treatment over two times in lifetime was negatively associated with QI scores for total care (P = 0.019).

CONCLUSION: Total QoC from patients’ perspective is high in Crete. CD and disease severity seem to affect patients’ perceptions of IBD care. Gastroenterologists in Crete should improve accessibility to IBD care and empower patients’ involvement in shared decision-making.

PMID:40900548 | DOI:10.1097/MEG.0000000000003031

Rev Bras Enferm. 2025 Jun 27;78Suppl 1(Suppl 1):e20240245. doi: 10.1590/0034-7167-2024-0245. eCollection 2025.

ABSTRACT

OBJECTIVES: to develop and validate an educational booklet on HIV Pre-Exposure Prophylaxis (PrEP).

METHODS: quantitative validation study aimed at developing and validating an educational booklet by experts and the target audience. For validation with experts, we used the Health Education Content Validation Index developed in a virtual environment. For the target audience, we used a questionnaire with questions related to organization, writing style, appearance, and motivation.

RESULTS: thirty-two experts and 13 PrEP users participated in the study. The analysis was structured on the principles of descriptive statistics, and domains that presented a Content Validity Index equal to or greater than 0.80 were considered satisfactory. The final version of the material was made available in online and printed formats.

CONCLUSIONS: the educational booklet was developed and validated by experts and the target audience, serving as an educational tool to support self-care and awareness of HIV prevention for PrEP users.

PMID:40900539 | DOI:10.1590/0034-7167-2024-0245

Eur J Gastroenterol Hepatol. 2025 Jul 14. doi: 10.1097/MEG.0000000000003036. Online ahead of print.

ABSTRACT

OBJECTIVE: Refractory celiac disease-type II (RCDII) is the more severe and adverse form of celiac disease; however, its association with other autoimmune diseases remains unclear. We conducted a phenome-wide association study (PheWAS) to examine the association between the polygenic risk score (PRS) for RCDII and autoimmune diseases.

METHODS: To construct the PRS-RCDII, we extracted summary statistics for three non-human leukocyte antigen genetic variants, which were independently associated with RCDII (r2 < 0.001; P < 5 × 10-5) in a genome-wide association study. We then conducted a PRS-PheWAS in the UK Biobank to investigate the associations of PRS-RCDII with 27 autoimmune diseases, adjusting for age, sex, genetic batch, and genetic ancestry. False discovery rate (FDR < 0.05) correction was applied to account for multiple comparisons.

RESULTS: Our study population comprised 373 022 UK Biobank participants (mean age: 57.2 years), of whom 202 865 (54.4%) were females. We constructed the PRS-RCDII, using three genetic variants, namely rs2041570 on chromosome 7p14.3 (FAM188B), rs7324708 on chromosome 13q22.1 (KLF12), and rs205047 on chromosome 17p12 (SHISA6). In the PRS-PheWAS, two phenotypes were initially associated with RCDII at a nominal P value threshold, ankylosing spondylitis and systemic sclerosis; however, after adjusting for multiple comparisons, only the association with ankylosing spondylitis remained statistically significant (odds ratioper 1 SD increase = 1.13; 95% confidence interval: 1.04-1.22; PFDR = 0.023). Sex-stratified and single-nucleotide polymorphism (SNP)-by-SNP analyses revealed no significant heterogeneity.

CONCLUSION: Our study identified an association between the genetic risk score for RCDII and ankylosing spondylitis, but not with other autoimmune diseases. This finding may have clinical importance for people with RCDII, although replication in future studies is needed.

PMID:40900534 | DOI:10.1097/MEG.0000000000003036

Photobiomodul Photomed Laser Surg. 2025 Sep 3. doi: 10.1177/25785478251376142. Online ahead of print.

ABSTRACT

Background: Photodynamic therapy (PDT) combined with biliary stenting reportedly has better efficacy and safety in the treatment of extrahepatic cholangiocarcinoma (EHC). Considering the shortcomings of traditional PDT methods, we proposed a novel modified approach, defined as initial biliary stent placement followed by PDT, for the treatment of EHC. The study aimed to evaluate the effect and safety of biliary stent placement prior to PDT versus only stent placement on the treatment of EHC. Methods: A total of 30 patients diagnosed with EHC between January 2017 and December 2024 were included in the retrospective study. Ten patients underwent biliary stent placement, followed by PDT (Stenting with PDT group). Survival time, surgical success rate, and postoperative adverse events were compared to 20 patients receiving biliary stent placement alone (Stenting only group). Results: The success rate of all operations in both groups was 100%. After 96 months of follow-up, the stenting with PDT group had significantly longer median survival after stent placement than the stenting only group (10.5 vs. 4.0 months, p = 0.028). There were no statistically significant differences in the rates of postoperative total adverse events (5 [25%] vs. 2 [20%], p = 1.000), asymptomatic hyperamylasemia (1 [5%] vs. 1 [10%], p = 1.000), acute pancreatitis (4 [20%] vs. 1 [10%], p = 0.272), and postoperative acute cholangitis (0 vs. 1 [10%], p = 0.333) between the two groups. Conclusions: Compared with stenting alone, modified stenting combined with PDT resulted in longer survival in patients with unresectable EHC without significant adverse events.

PMID:40900522 | DOI:10.1177/25785478251376142

Epidemiol Serv Saude. 2025 Sep 1;34:e20250516. doi: 10.1590/S2237-96222025v34e20250516.en. eCollection 2025.

ABSTRACT

Report on a field investigation into the outbreak of skin infections by Mycobacterium abscessus subsp. abscessus following cosmetic procedures.

A retrospective cohort study was conducted using secondary data from the Epidemiology Program Applied to SUS Services (EpiSUS) about the investigation conducted in 2022, in partnership with Paraguay’s Field Epidemiology Training Program. Clinical, laboratory, and environmental information and surgical records were analyzed to characterize the cases, define the exposed population, and analyze the risk. Relative risk (RR) was estimated with a 95% confidence interval (95%CI) and Fisher’s exact test was used for statistical evaluation.

Of the 108 individuals who underwent surgery in the period investigated, 10 became ill. Relative risk of illness was 6.50 (95%CI 2.28; 18.49; p-value 0.003) for surgeries performed in the critical period (December to January) and 10.29 (95%CI 1.37; 77.19; p-value 0.004) for lipoabdominoplasty.

Mycobacterium abscessus subsp. abscessus outbreak occurred among women undergoing cosmetic surgeries performed by the same professional in a hospital in Paraguay, with a higher risk associated with a specific period and type of procedure. Our findings highlight the importance of health surveillance in bordering regions and international cooperation in response to cross-border events. Educational, regulatory, and inspection strategies targeting medical tourism are essential to prevent new events.

PMID:40900520 | DOI:10.1590/S2237-96222025v34e20250516.en

Ann Clin Transl Neurol. 2025 Sep 3. doi: 10.1002/acn3.70174. Online ahead of print.

ABSTRACT

OBJECTIVE: Chronic pain is prevalent among people living with Parkinson’s disease (PD). We analyzed data from 10,631 Australian individuals with PD to assess the prevalence, age and sex differences, severity, anatomical distribution, clinical history, and associated factors.

METHODS: We analysed data from 10,631 participants with PD enrolled in the Australian Parkinson’s Genetics Study (APGS), an ongoing nationwide cohort. Participants completed an online or paper-based questionnaire assessing sociodemographic factors, PD-related variables, and chronic pain characteristics. Chronic pain was defined as pain persisting for more than 3 months and occurring most days or daily. Statistical analyses included descriptive statistics, correlation analyses, and group comparisons using chi-squared tests, Fisher’s exact tests, and independent samples t-tests.

RESULTS: Two-thirds (66.2%) reported chronic pain, with females experiencing higher prevalence (70.8%) and severity (4.7 vs. 4.3 on a 10-point scale). Common pain sites included the buttocks (35.6%), lower back (25.4%), neck (19.4%), and knees (17.2%). Chronic pain was strongly linked to comorbid depression, sleep disorders, and osteoarthritis (p < 0.05). Environmental exposures such as pesticides, heavy metals, and alcohol were associated with higher pain prevalence, especially in males (p < 0.05).

INTERPRETATION: These findings emphasise the substantial burden of chronic pain in PD, highlighting sex differences and strong links to multimorbidity. Further research is warranted to clarify sex-specific treatments and identify novel therapeutic targets.

PMID:40899387 | DOI:10.1002/acn3.70174

Dent Med Probl. 2025 Jul-Aug;62(4):721-729. doi: 10.17219/dmp/182891.

ABSTRACT

BACKGROUND: Cleaning overdentures is challenging due to their complex metallic structures, which often create small and irregular areas that are difficult to clean. Thus, it is necessary to find an effective and safe method for their maintenance.

OBJECTIVES: The aim of the study was to evaluate the effects of hygiene methods on the dimensional changes and retention force of the O-ring system over a simulated two-year period.

MATERIAL AND METHODS: A total of 54 specimens with 2 O-rings each were distributed into 9 groups: control – no cleaning; brushing – blue®m toothpaste (BM); brushing – Trihydral toothpaste (TR); immersion – NitrAdine® (Ni); immersion – 5 mg/mL chitosan solution (Ch); and combined methods: BM+Ni, BM+Ch, TR+Ni, TR+Ch. The deformation and retention force were evaluated every 6 months for 2 years. The statistical analysis was performed using two-way analysis of variance (ANOVA) and Pearson’s correlation test (α = 0.05).

RESULTS: The BM+Ch group exhibited smaller changes in diameter after 6 months (Δ(T1-T0)) than the control and BM+Ni groups, both internally and externally (p < 0.001). In addition, the BM+Ch group demonstrated greater retention forces at 6 months (p = 0.024) and 18 months (p = 0.028) in comparison to the TR+Ch group. The TR+Ch group exhibited a negative correlation with changes in the external diameter (r = -0.334, p = 0.021), while BM+Ch showed a negative correlation with changes in the internal diameter (r = -0.334, p = 0.021). The Ni group demonstrated a negative relationship with changes in both the internal (r = -0.296, p = 0.041) and external diameters (r = -0.405, p = 0.004).

CONCLUSIONS: A combination of brushing with blue®m toothpaste and immersion in the chitosan solution demonstrated satisfactory results in maintaining the retention force of the O-ring system.

PMID:40899382 | DOI:10.17219/dmp/182891