Nevin Manimala

JMIR Med Educ. 2024 Oct 17;10:e53462. doi: 10.2196/53462.

ABSTRACT

BACKGROUND: Although digital health is essential for improving health care, its adoption remains slow due to the lack of literacy in this area. Therefore, it is crucial for health professionals to acquire digital skills and for a digital competence assessment and accreditation model to be implemented to make advances in this field.

OBJECTIVE: This study had two objectives: (1) to create a specific map of digital competences for health professionals and (2) to define and test a digital competence assessment and accreditation model for health professionals.

METHODS: We took an iterative mixed methods approach, which included a review of the gray literature and consultation with local experts. We used the arithmetic mean and SD in descriptive statistics, P values in hypothesis testing and subgroup comparisons, the greatest lower bound in test diagnosis, and the discrimination index in study instrument analysis.

RESULTS: The assessment model designed in accordance with the competence content defined in the map of digital competences and based on scenarios had excellent internal consistency overall (greatest lower bound=0.91). Although most study participants (110/122, 90.2%) reported an intermediate self-perceived digital competence level, we found that the vast majority would not attain a level-2 Accreditation of Competence in Information and Communication Technologies.

CONCLUSIONS: Knowing the digital competence level of health professionals based on a defined competence framework should enable such professionals to be trained and updated to meet real needs in their specific professional contexts and, consequently, take full advantage of the potential of digital technologies. These results have informed the Health Plan for Catalonia 2021-2025, thus laying the foundations for creating and offering specific training to assess and certify the digital competence of such professionals.

PMID:39418092 | DOI:10.2196/53462

JAMA. 2024 Oct 17. doi: 10.1001/jama.2024.16954. Online ahead of print.

ABSTRACT

IMPORTANCE: Previous studies on the comparative effectiveness between buprenorphine and methadone provided limited evidence on differences in treatment effects across key subgroups and were drawn from populations who use primarily heroin or prescription opioids, although fentanyl use is increasing across North America.

OBJECTIVE: To assess the risk of treatment discontinuation and mortality among individuals receiving buprenorphine/naloxone vs methadone for the treatment of opioid use disorder.

DESIGN, SETTING, AND PARTICIPANTS: Population-based retrospective cohort study using linked health administrative databases in British Columbia, Canada. The study included treatment recipients between January 1, 2010, and March 17, 2020, who were 18 years or older and not incarcerated, pregnant, or receiving palliative cancer care at initiation.

EXPOSURES: Receipt of buprenorphine/naloxone or methadone among incident (first-time) users and prevalent new users (including first and subsequent treatment attempts).

MAIN OUTCOMES AND MEASURES: Hazard ratios (HRs) with 95% compatibility (confidence) intervals were estimated for treatment discontinuation (lasting ≥5 days for methadone and ≥6 days for buprenorphine/naloxone) and all-cause mortality within 24 months using discrete-time survival models for comparisons of medications as assigned at initiation regardless of treatment adherence (“initiator”) and received according to dosing guidelines (approximating per-protocol analysis).

RESULTS: A total of 30 891 incident users (39% receiving buprenorphine/naloxone; 66% male; median age, 33 [25th-75th, 26-43] years) were included in the initiator analysis and 25 614 in the per-protocol analysis. Incident users of buprenorphine/naloxone had a higher risk of treatment discontinuation compared with methadone in initiator analyses (88.8% vs 81.5% discontinued at 24 months; adjusted HR, 1.58 [95% CI, 1.53-1.63]), with limited change in estimates when evaluated at optimal dose in per-protocol analysis (42.1% vs 30.7%; adjusted HR, 1.67 [95% CI, 1.58-1.76]). Per-protocol analyses of mortality while receiving treatment exhibited ambiguous results among incident users (0.08% vs 0.13% mortality at 24 months; adjusted HR, 0.57 [95% CI, 0.24-1.35]) and among prevalent users (0.08% vs 0.09%; adjusted HR, 0.97 [95% CI, 0.54-1.73]). Results were consistent after the introduction of fentanyl and across patient subgroups and sensitivity analyses.

CONCLUSIONS AND RELEVANCE: Receipt of methadone was associated with a lower risk of treatment discontinuation compared with buprenorphine/naloxone. The risk of mortality while receiving treatment was similar for buprenorphine/naloxone and methadone, although the CI estimate for the hazard ratio was wide.

PMID:39418046 | DOI:10.1001/jama.2024.16954

J Cataract Refract Surg. 2024 Oct 17. doi: 10.1097/j.jcrs.0000000000001571. Online ahead of print.

ABSTRACT

TOPIC: To examine the association between virtual postoperative follow-up care and patient outcomes after cataract surgery.

CLINICAL RELEVANCE: Cataract surgery is a safe and commonly performed surgery. Follow-up visits are used to monitor for complications. It is uncertain whether virtual follow-up provides a safe alternative to in-person review.

METHODS: Medline, Embase and CINAHL were searched from inception to October 2023 for relevant articles containing original data. Studies that: 1) included patients that were seen in a virtual follow-up (i.e., telephone or video call) for postoperative appointments after cataract surgery, and 2) reported patient outcomes were included. Risk of bias was assessed using the Newcastle-Ottawa and ROB2 assessment tools. Descriptive statistics were used to summarize findings. The review was registered in PROSPERO (registration number, CRD42023477207) and PRISMA guidelines were followed.

RESULTS: The search yielded 1710 records with seven studies included in this review. The seven studies reported on 2113 cataract surgeries in 1994 patients. The studies ranged between 2004 and 2020. Most of the studies (5/7) included only patients with uncomplicated cataract surgery. Virtual follow-ups were all conducted by telephone. The follow-up calls were made at varying timepoints including postoperative day 1 (n= 3), day 7 (n=2) and day 14 (n=1). Two observational studies directly compared patients who had a telephone follow-up to a control group who had an in-person follow-up. There were no significant differences in complication rates (p=0.22) or visual acuity (p=0.28) between these follow-up groups. None of the studies reported serious adverse outcomes from replacing in-person follow-up with telephone follow-up. One study used virtual follow-up in conjunction with in-person visits for elderly patients and found that additional telephone follow-up was associated with decreased surgical recovery time and decreased patient anxiety. Three studies reported on patient perceptions about telephone follow-up. A common theme was that patients preferred telephone reviews and found them to be more convenient than in-person follow-up.

CONCLUSIONS: For patients with uncomplicated cataract surgery, virtual follow-ups seem to be a safe alternative to in-person visits and were preferred by patients. These conclusions are preliminary given the limited literature base, and further study is needed.

PMID:39418044 | DOI:10.1097/j.jcrs.0000000000001571

JAMA Oncol. 2024 Oct 17. doi: 10.1001/jamaoncol.2024.4381. Online ahead of print.

ABSTRACT

IMPORTANCE: The combination of ifosfamide and etoposide (IE) is commonly used to treat relapsed or refractory osteosarcoma; however, second-line treatment recommendations vary across guidelines.

OBJECTIVE: To evaluate whether the addition of lenvatinib to IE (LEN-IE) improves outcomes in children and young adults with relapsed or refractory osteosarcoma.

DESIGN, SETTING, AND PARTICIPANTS: The OLIE phase II, open-label, randomized clinical trial was conducted globally across Europe, Asia and the Pacific, and North America. From March 22, 2020, through November 11, 2021, the trial enrolled patients aged 2 to 25 years with high-grade osteosarcoma, measurable or evaluable disease per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), and 1 to 2 prior lines of systemic treatment. The data analyses were performed between March 22, 2020 (first patient in) and June 22, 2022 (data cutoff for the primary analysis), and September 29, 2023 (end of study final database lock).

INTERVENTIONS: The OLIE trial assessed the efficacy and safety of lenvatinib (14 mg/m2 taken orally once daily) combined with up to 5 cycles of ifosfamide (3000 mg/m2 intravenously) and etoposide (100 mg/m2 intravenously) on days 1 to 3 of each cycle vs IE alone at the same doses. Patients randomized to IE could cross over to receive lenvatinib upon disease progression by independent imaging review.

MAIN OUTCOMES AND MEASURES: The primary end point was progression-free survival (PFS) per RECIST 1.1 by independent imaging review. The Kaplan-Meier method was used to estimate the PFS distribution, with a prespecified 1-sided significance threshold of .025 by stratified log-rank test. Secondary end points included PFS rate at 4 months and overall survival. Adverse events were summarized using descriptive statistics.

RESULTS: A total of 81 patients were enrolled (median [IQR] age, 15.0 [12.0-18.0] years; 46 males [56.8%]), with 40 in the LEN-IE arm and 41 in the IE arm. Median PFS was 6.5 months (95% CI, 5.7-8.2 months) for the LEN-IE arm and 5.5 months (95% CI, 2.9-6.5 months) for the IE arm (hazard ratio [HR], 0.54; 95% CI, 0.27-1.08; 1-sided P = .04). The rate of PFS at 4 months was 76.3% (95% CI, 59.3%-86.9%) in the LEN-IE arm and 66.0% (95% CI, 47.7%-79.2%) in the IE arm. Median overall survival was 11.9 months (95% CI, 10.1 months to not estimable) with LEN-IE and 17.4 months (95% CI, 14.2 months to not estimable) with IE (HR, 1.28; 95% CI, 0.60-2.70; 1-sided nominal P = .75). Grade 3 or higher treatment-related adverse events occurred in 35 of 39 patients (89.7%) in the LEN-IE arm and 31 of 39 patients (79.5%) in the IE arm.

CONCLUSIONS AND RELEVANCE: Although LEN-IE did not meet prespecified statistical significance for improved PFS vs IE, this study demonstrates the importance of international collaboration and randomized clinical trials in patients with relapsed or refractory osteosarcoma and may inform future trial design.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04154189.

PMID:39418029 | DOI:10.1001/jamaoncol.2024.4381

JAMA Netw Open. 2024 Oct 1;7(10):e2437148. doi: 10.1001/jamanetworkopen.2024.37148.

ABSTRACT

IMPORTANCE: Elevated ambient fine particulate matter (PM2.5) air pollution exposure has been associated with poor health outcomes across several domains, but its associated outcomes among lung transplant recipients are poorly understood.

OBJECTIVE: To investigate whether greater PM2.5 exposure at the zip code of residence is associated with a higher hazard for mortality and graft failure in patients with lung transplants.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used panel data provided by the United Network for Organ Sharing, which includes patients receiving transplants across all active US lung transplant programs. Adult patients who received lung transplants between May 2005 and December 2016 were included, with a last follow-up of September 10, 2020. Data were analyzed from September 2022 to May 2023.

EXPOSURE: Zip code-level annual PM2.5 exposure was constructed using previously published North American estimates.

MAIN OUTCOMES AND MEASURES: The primary outcome was time to death or lung allograft failure after lung transplant. A gamma shared frailty Cox proportional hazards model was used to produce unadjusted and adjusted hazard ratios (HRs) to estimate the association of zip code PM2.5 exposure at the time of transplant with graft failure or mortality.

RESULTS: Among 18 265 lung transplant recipients (mean [SD] age, 55.3 [13.2] years; 7328 female [40.2%]), the resident zip code’s annual PM2.5 exposure level was greater than or equal to the Environmental Protection Agency (EPA) standard of 12μg/m3 for 1790 patients (9.8%) and less than the standard for 16 475 patients (90.2%). In unadjusted analysis, median graft survival was 4.87 years (95% CI, 4.57-5.23 years) for recipients living in high PM2.5 areas and 5.84 years (95% CI, 5.71-5.96 years) for recipients in the low PM2.5 group. Having an annual PM2.5 exposure level greater than or equal to the EPA standard 12 μg/m3 was associated with an increase in the hazard of death or graft failure (HR, 1.11; 95% CI, 1.05-1.18; P < .001) in the unadjusted analysis and after adjusting for covariates (HR, 1.08; 95% CI, 1.01-1.15; P = .02). Each 1 μg/m3 increase in exposure was associated with an increase in the hazard of death or graft failure (adjusted HR, 1.01; 95% CI, 1.00-1.02; P = .004) when treating PM2.5 exposure as a continuous variable.

CONCLUSIONS AND RELEVANCE: In this study, elevated zip code-level ambient PM2.5 exposure was associated with an increased hazard of death or graft failure in lung transplant recipients. Further study is needed to better understand this association, which may help guide risk modification strategies at individual and population levels.

PMID:39418024 | DOI:10.1001/jamanetworkopen.2024.37148

JAMA Netw Open. 2024 Oct 1;7(10):e2440047. doi: 10.1001/jamanetworkopen.2024.40047.

ABSTRACT

IMPORTANCE: Associations of body mass index (BMI) with survival in pancreatic ductal adenocarcinoma (PDA) have substantial variability in literature, potentially due to heterogeneous patient populations and retrospective analyses. Additionally, BMI may inadequately describe body composition (ie, morphomics; including subcutaneous and visceral fats, muscle, and fascia), which might have independent biological roles and associations with survival.

OBJECTIVE: To study the associations of BMI and morphomics with survival and metabolomics in metastatic PDA.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study prospectively collected patient data, imaging, and serum on the phase 3 trial (Avenger500), which investigated the efficacy and safety of 5-fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) versus modified FOLFIRINOX plus devimistat. The randomized trial accrued 528 patients with chemotherapy-naive, metastatic PDA from Europe, Israel, Korea, and the US between 2018 and 2020. In the present study, per-protocol patients with L1 to L4, T10 to T12 vertebral levels were evaluated. Data analysis occurred from January 2023 to April 2024.

EXPOSURE: Patient data were collected by clinical staff. Morphomics were analyzed from baseline imaging. Metabolites were extracted from baseline serum.

MAIN OUTCOME AND MEASURES: A multifaceted statistical approach evaluated associations of BMI and morphomics with progression-free survival (PFS) and overall survival (OS). Associations of morphomics with metabolites were also studied.

RESULTS: Of the 528 initial patients, 476 (median [IQR] age, 63 [56-68] years; 280 male [58.8%]; median [IQR] BMI, 25.0 [22.1-25.9]) were evaluable for the present study. BMI (obese [≥30] compared with normal [18.5-24.9]) was not associated with OS (hazard ratio [HR], 0.90; 95% CI, 0.67-1.22; P for trend = .33). More subcutaneous fat was associated with longer OS (HR, 0.62; 95% CI, 0.41-0.94; P for trend = .02). Higher visceral fat density was associated with shorter PFS (HR, 1.74; 95% CI, 1.23-2.48; P for trend = .002) and OS (HR, 1.50; 95% CI, 1.12-2.00; P for trend = .008). A higher muscle-to-fascia ratio was associated with longer PFS (HR, 0.58; 95% CI, 0.40-0.84; P for trend = .005) and OS (HR, 0.56; 95% CI, 0.41-0.75; P for trend = 1.7 × 10-4). Subcutaneous fat was positively associated with long-chain fatty acid metabolism including pristanic acid, decanoylcarnitine, decenoylcarnitine, and octanoylcarnitine. Muscle-to-fascia was positively associated with metabolites including acetylcarnosine (β = 0.34; 95% CI, 0.21-0.47; P = 1.27 × 10-6).

CONCLUSIONS AND RELEVANCE: In cohort study of patients with metastatic PDA, BMI was not associated with survival. Higher visceral fat density, subcutaneous fat area, and muscle-to-fascia ratio were associated with survival independent of BMI. The latter 2 were associated with higher levels of animal product metabolism. These findings could represent novel focuses for prognostication and intervention to improve survival of patients with PDA.

PMID:39418020 | DOI:10.1001/jamanetworkopen.2024.40047

JAMA Ophthalmol. 2024 Oct 17. doi: 10.1001/jamaophthalmol.2024.4297. Online ahead of print.

ABSTRACT

IMPORTANCE: Evidence is limited to support therapies to treat submacular hemorrhage (SMH) secondary to neovascular age-related macular degeneration (AMD) as an adjunct to anti-vascular endothelial growth factor therapy (anti-VEGF).

OBJECTIVE: To determine if intravitreal tissue plasminogen activator (TPA) or gas improves visual acuity or promotes resolution of SMH secondary to neovascular AMD in eyes treated with ranibizumab.

DESIGN, SETTING, AND PARTICIPANTS: This was a double-masked, sham-controlled, factorial randomized clinical trial and feasibility study that recruited participants from June 2014 to March 2019, with 12 months’ follow-up. Included in the trial were patients from 4 UK vitreoretinal units who had fovea-involving SMH of at least 1 disc area secondary to neovascular AMD and were evaluated within 14 days of onset.

INTERVENTIONS: Study eyes received baseline ranibizumab and were then randomized 2:1:1:1 to 1 of 4 intravitreal treatments: sham injection, perfluoropropane (C3F8), TPA, or combined C3F8 and TPA (C3F8 + TPA). All eyes received monthly pro re nata ranibizumab therapy over 12 months. Outcome assessors were masked to intervention assignment.

MAIN OUTCOME AND MEASURE: Best-corrected visual acuity (BCVA) at month 3.

RESULTS: Fifty-three of 56 participants (95%; mean [SD] age, 81.5 [8.1] years; 33 female [59%]) reached the primary end point. Study eyes were randomized to the following intravitreal treatments: sham injection (n = 23), C3F8 (n = 11), TPA (n = 11), or C3F8 + TPA (n = 11). On factorial analysis, the combined TPA groups had significantly better month 3 mean logMAR BCVA than those not receiving TPA: 0.66 vs 0.98 (μd = -0.32; 95% CI, -0.58 to -0.07; P = .02). There was no statistically significant difference comparing groups that did vs did not receive C3F8: 0.80 vs 0.90 (μd = -0.11; 95% CI, -0.37 to 0.16; P = .43). The combined TPA groups were less likely to have SMH present at month 1 (10 of 18 [55.6%] vs 21 of 24 [87.5%]; P = .03), a benefit not evident in the combined gas groups. The mean logMAR BCVA at 3 months was not significantly different between the groups: monotherapy control, 0.99; C3F8, 0.97 (vs control μd = -0.02; 95% CI, -0.48 to 0.44); TPA, 0.70 (vs control μd = -0.29; 95% CI, -0.79 to 0.21); combined C3F8 and TPA, 0.71 (vs control μd = -0.36; 95% CI, -0.82 to 0.11); P = .11. No safety differences were identified across the treatment groups.

CONCLUSIONS AND RELEVANCE: Results of this randomized clinical trial suggest that TPA may increase the chance of visual acuity gain when added to ranibizumab therapy for neovascular AMD in eyes with SMH, warranting consideration of additional clinical trials.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01835067.

PMID:39418015 | DOI:10.1001/jamaophthalmol.2024.4297

J Otolaryngol Head Neck Surg. 2024 Jan-Dec;53:19160216241288811. doi: 10.1177/19160216241288811.

ABSTRACT

IMPORTANCE: At present, there is no consensus on the concentration of epinephrine/physiological saline for subcutaneous injection into external auditory canal (EAC) under general anesthesia in otoendoscopic surgery. A randomized controlled trial (RCT) research is needed to provide reference, as this concentration can provide satisfactory surgical field clarity while maintaining patients’ hemodynamic stability.

OBJECTIVE: Comparison of the effect of subcutaneous injection of different concentrations of epinephrine/physiological saline into EAC under general anesthesia in otoendoscopic surgery on surgical field clarity and hemodynamics.

DESIGN: This double-blind, RCT study was about the effect of topical epinephrine injection in otoendoscopic surgery.

SETTING: This study was conducted at a single institution.

PARTICIPANTS: This study included 168 patients conformed to the inclusion criteria.

INTERVENTION: Patients were randomized to receive different concentrations of epinephrine/physiological saline injection (1:5000, 1:10,000, 1:20,000, or 1:40,000) into the junction of bone and cartilage at posterior wall of EAC during surgery.

MAIN OUTCOME MEASURES: Surgical field clarity was assessed with surgical field clarity grading scale and tympanic membrane flap flipping time. Hemodynamic changes were monitored by clinical parameters of blood pressure, heart rate, and ST segment of ECG.

RESULTS: There were no statistically-significant differences in surgical field clarity grade (P = .577) and tympanic membrane flap flipping time (P = .490) among 4 concentration groups. Epinephrine injection did cause an increase in hemodynamic parameters when compared with baseline (P < .05). Compared with the relatively-lower concentration groups (1:20,000 and 1:40,000), the relatively-higher concentration groups (1:5000 and 1:10,000) had more significant and long-lasting effect until 30 minutes after injection.

CONCLUSIONS AND RELEVANCE: Four concentration groups of topical epinephrine injection in otoendoscopic surgery have the same effect on surgical field clarity. For the stability of patients’ hemodynamics, we would prefer to recommend the use of concentrations with minimal impact on hemodynamics, ranging from 1:20,000 to 1:40,000.

TRIAL REGISTRATION: Clinical Trial Registry-China: ChiCTRI1800016647.

PMID:39418011 | DOI:10.1177/19160216241288811

Eur Arch Paediatr Dent. 2024 Oct 17. doi: 10.1007/s40368-024-00948-w. Online ahead of print.

ABSTRACT

PURPOSE: The aim of the present was to assess the association between MIH and tooth agenesis (TA) in orthodontic patients from the Federal University of Rio Grande do Norte, Natal, Brazil.

METHODS: A cross-sectional study was performed to evaluate the presence of MIH and TA in a sample of 371 pretreatment orthodontic records from patients aged 9-18 years. Statistical analyses were performed using the Chi-square and Fisher’s exact tests, and logistic regressions.

RESULTS: There was a statistically significant association between the prevalence of tooth agenesis and MIH. A higher percentage of third molar agenesis, maxillary premolar agenesis, and mandibular second premolar agenesis was observed among children with MIH-affected teeth. Patients with MIH had a 2.43 times greater chance of third molar agenesis, and a 5.88 times higher likelihood of mandibular premolar agenesis.

CONCLUSION: There is a weak association between MIH and TA. Furthermore, the presence of hypomineralised molars increases the risk of tooth agenesis.

PMID:39417959 | DOI:10.1007/s40368-024-00948-w

Environ Sci Pollut Res Int. 2024 Oct 17. doi: 10.1007/s11356-024-35261-y. Online ahead of print.

ABSTRACT

This study evaluated the biofuel production potential of two algal species, Chlorella pyrenoidosa and Scenedesmus abundans, under stress conditions induced by nutrient supplementation or starvation at varying light intensities. Central composite face-centered design response surface methodology (CCFD-RSM) was employed to optimize stress conditions by varying the sodium nitrate (NaNO₃), potassium dihydrogen phosphate (KH₂PO₄), dipotassium hydrogen phosphate (K₂HPO₄), cultivation time, and light intensity. The study included both C. pyrenoidosa and S. abundans, which presented increased biomass yields when subjected to nutrient starvation. Under the optimized conditions, the dry biomass yield was 98.26 mg/L for C. pyrenoidosa and 110 mg/L for S. abundans. Lipid yields were approximately 22.47% for C. pyrenoidosa and 29.06% for S. abundans under these optimized growth conditions. The optimized parameters for maximum biomass and lipid production were identified as C. pyrenoidosa, and the optimized conditions required 0.805 g/L NaNO₃, 0.052 g/L K₂HPO₄, 0.099 g/L KH₂PO₄, 17 days of culture, and 5168.39 lx of light intensity. For S. abundans, the optimal conditions were 1.065 g/L NaNO₃, 0.071 g/L K₂HPO₄, 0.058 g/L KH₂PO₄, 22 days of cultivation, and 2897 lx of light intensity. Overall, both C. pyrenoidosa and S. abundans have emerged as promising candidates for sustainable biodiesel production, highlighting their potential under stress conditions induced by nutrient modulation and variable light intensities.

PMID:39417936 | DOI:10.1007/s11356-024-35261-y