Nevin Manimala

R I Med J (2013). 2025 Jan 2;108(1):30-34.

ABSTRACT

BACKGROUND/OBJECTIVE: Pediatric sepsis is a significant cause of morbidity and mortality in the United States, and its early recognition is crucial but challenging. This study assessed clinicians’ self-reported preparedness for recognizing and managing pediatric sepsis in the Rhode Island region.

METHODS: A cross-sectional, survey was developed and sent to community emergency medicine clinicians in greater Rhode Island. Results were analyzed using descriptive statistics.

RESULTS: Survey responses were received from 35 participants across 10 Emergency Departments. Ninety-seven percent (97%) felt confident managing adult sepsis with shock, but only 51% felt confident managing pediatric sepsis with shock. Lack of pediatric procedural experience and familiarity with pediatric dosing were barriers to providing care to pediatric patients with sepsis for 74.2% and 62.8% of participants, respectively.

CONCLUSION: Many community ED clinicians lack confidence in managing pediatric sepsis. Structured educational initiatives focused on clinical examination, procedural skills, and medication dosing may enhance confidence in managing these patients.

PMID:39693532

R I Med J (2013). 2025 Jan 2;108(1):23-29.

ABSTRACT

BACKGROUND: With increasing use of diazoxide for hyperinsulinemic hypoglycemia (HH), reporting of serious side effects of diazoxide such as pulmonary hypertension (PHT) increased.

METHODS: Charts of all children diagnosed with HH during the study period and evaluated by Pediatric Endocrinology division of the Hasbro Children’s Hospital were reviewed. We analyzed diazoxide use among infants with HH with focus on infants born small for gestational age (SGA) and preterm infants.

RESULTS: Average timing of diazoxide initiation was later after 6/2017 compared to prior in preterm infants (45 days versus 4 days, p < 0.001) and in SGA infants (28 days versus 13 days, p < 0.001). Prescribing patterns changed further over time, corresponding with development of diazoxide-associated PHT in three infants between 10/2018-5/2020. Delays in diazoxide initiation were observed after 5/2020 compared to prior in full-term, non-SGA infants: 18 days versus12 days (p = 0.01). The proportion of SGA infants who received diazoxide was lower after 5/2020 compared to prior (23% versus 65%, p = 0.03). PHT developed in 12.5% of infants treated with diazoxide in this cohort, 75% of whom were preterm and/or SGA, and 75% were born to mothers with preeclampsia.

CONCLUSIONS: Patterns of diazoxide use changed over time, with delayed use in preterm and/or SGA infants observed after 6/2017, reduced use in SGA infants, and delayed initiation in all infants after 5/2020. PHT was not rare in our cohort, and was more likely in infants born SGA, preterm, or to a mother with preeclampsia.

PMID:39693531

Ophthalmic Epidemiol. 2024 Dec 18:1-10. doi: 10.1080/09286586.2024.2442367. Online ahead of print.

ABSTRACT

PURPOSE: To identify factors that are associated with no-shows and cancellations in a glaucoma clinic.

METHODS: Retrospective observational study of patients seen at a glaucoma clinic over a two-year period (6/2017-5/2019). Demographics and clinic information were recorded from the electronic medical record. A total of 36,810 visits from 7,383 patients were studied. Weather data was collected from the National Centers for Environmental Information. Distance analysis was calculated utilizing Bing Maps application programming interface (API) on Microsoft Excel. Visits were divided into three groups based on appointment status: kept, cancelled, and no-show.

RESULTS: Bivariate analysis found a statistically significant difference in various factors amongst patients based on appointment status. Patients <15 miles from clinic had a higher rate of no-show, but a lower rate of cancellations compared to those farther (p < 0.0001) Using multivariable logistic regression, the following factors were associated with the likelihood of patient cancellation: average snowfall (Odds Ratio = 1.37); presence of storm event (OR = 1.12), new visit (OR = 1.82), follow-up appointments (OR = 1.90), and travel distance > 15 miles (OR = 1.11). The following factors were associated with patient no-show: resident clinic (OR = 1.79), new visit (OR = 2.24), follow-up appointments (OR = 2.18), age (OR = 0.99), average snowfall (OR = 1.27), presence of storm event (OR = 1.41), average windspeed (OR = 0.98), and travel distance > 15 miles (OR = 0.67).

CONCLUSION: Patient age, gender, travel distance, appointment type, and weather were all significantly associated with rates of patient cancellations and no-shows. These risk factors could lead to interventions to improve appointment adherence and patient retention. Weather is an under-analyzed factor in patient follow-up rates that warrants further investigation.

PMID:39693515 | DOI:10.1080/09286586.2024.2442367

Transl Behav Med. 2024 Dec 18:ibae071. doi: 10.1093/tbm/ibae071. Online ahead of print.

ABSTRACT

Healthcare providers (HCPs) face high rates of distress, experienced as burnout, moral distress, compassion fatigue, and grief. HCPs are also experiencing a crisis in meaning whereby distress is associated with disconnection from meaning in work and, in turn, a lack of meaning in work can further perpetuate distress for HCPs. Although scalable systems-level solutions are needed to tackle multidimensional HCP distress, it is also necessary to address HCP suffering at individual, team, and institutional levels. Targeted interventions to alleviate HCP distress are limited. Meaning-centered psychotherapy (MCP), a brief, evidence-based, intervention first developed for persons with advanced cancer, holds promise to mitigate HCP distress. This study adapted MCP for HCPs through feedback from a multidisciplinary sample of clinicians trained in MCP and working in healthcare settings. A survey was distributed electronically between November and December 2023 to HCPs previously trained in MCP assessing quantitative and qualitative feedback on the appropriateness of MCP for HCPs, the relevance of MCP session topics and exercises, and implementation barriers and facilitators. Descriptive statistics on relevant participant ratings were calculated; a matrix analysis approach was used for qualitative data. Forty participants, primarily mental health providers, expressed that MCP principles were highly relevant for HCPs and offered key insights on appropriate intervention modifications, including the need for a primary focus on meaning in professional life, reduced intervention length, and delivery in group format. Feedback informed critical adjustments to promote appropriateness and acceptability of MCP-HCP which is poised for pilot testing to determine its feasibility and preliminary efficacy for HCPs.

PMID:39693501 | DOI:10.1093/tbm/ibae071

Anal Chem. 2024 Dec 18. doi: 10.1021/acs.analchem.4c04418. Online ahead of print.

ABSTRACT

Mixture analysis is crucial in many areas of chemistry, and a wide variety of separation methods are in use. A common method for physical separation is high-performance liquid chromatography (HPLC), but resolution is a problem: chemically similar species coelute. An alternative approach is diffusion-ordered NMR spectroscopy (DOSY), in which the signals of mixture components are separated according to the diffusion coefficient. Again, separation is limited if species diffuse similarly or have overlap in their NMR spectra. Using the two techniques in combination can resolve both NMR spectra and the elution profiles of individual components, even where both techniques fail when used in isolation. Recording diffusion NMR data as a function of HPLC retention time gives a three-dimensional (3D) data set that can be analyzed using multiway statistical methods. PARAFAC analysis of diffusion NMR data measured from HPLC eluate for commercial “monoacetin” (a mixture of glycerol and its mono-, di-, and triacetates) yielded fully resolved and quantitative NMR spectra and elution profiles for all four components, whereas neither HPLC nor diffusion NMR applied independently was able to resolve the components.

PMID:39693498 | DOI:10.1021/acs.analchem.4c04418

AIDS. 2024 Dec 17. doi: 10.1097/QAD.0000000000004093. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to evaluate the efficacy of combination nicotine replacement therapy (c-NRT) for smoking cessation among people with HIV (PWH) in South Africa.

DESIGN: We conducted an open label, individually randomized clinical trial.

METHODS: Using a two-armed approach, PWH who smoke were randomized to receive either 1) intensive anti-smoking behavioral counseling (BC) or 2) intensive anti-smoking BC plus c-NRT (nicotine patches augmented by nicotine gum). Self-reported smoking abstinence was biochemically validated with exhaled breath carbon monoxide (CO) and urine cotinine at six months. Recruitment, provision of trial interventions, and follow-up of participants took place March 2014 through June 2016.

RESULTS: We randomly assigned 280 participants to the BC arm and 281 participants to the BC + c-NRT arm. 438 (78%) participants were male and 123 (22%) were female. For our primary outcome of biochemically verified abstinence at six months, 41 (15%) were quit in the BC + c-NRT arm versus 28 (10%) in the BC arm, resulting in a 5% (95% CI -1%, 10%) absolute difference in relative risk and an adjusted odd ratio of 1.47 (95% CI: 0.86, 2.52) comparing the BC + c-NRT to the BC arm.

CONCLUSIONS: Although our results did not reach statistical significance, we found augmentation of BC with c-NRT to increase smoking abstinence at six months, which is consistent with performance in the general population. PWH in low-resource settings may benefit from the addition of c-NRT to existing tobacco cessation interventions.

PMID:39693492 | DOI:10.1097/QAD.0000000000004093

Reprod Fertil. 2024 Dec 1:RAF-24-0046. doi: 10.1530/RAF-24-0046. Online ahead of print.

ABSTRACT

Chemotherapeutic agents result in the loss of growing follicles, which can manifest as amenorrhoea. Alkylating chemotherapy (AC) is known to be more gonadotoxic than non-alkylating chemotherapy (NAC). Anti-Mullerian Hormone (AMH), an indirect marker of ovarian reserve, and age have been investigated as predictors of ovarian function after chemotherapy, however little is known about the time to return of menses. This study aimed to assess how patient age and baseline serum AMH levels at cancer diagnosis affect the time to return of menses post-chemotherapy. This retrospective cohort study examined oncology patients (n=67) who underwent chemotherapy and were treated through the Reproductive Services Unit of two institutions in Melbourne, Australia. Primary outcomes included correlation between age and baseline AMH with time to return of menses after chemotherapy. Secondary outcomes include the change in AMH levels at 6- and 12-months post-completion of chemotherapy. Pairwise correlation of pre-chemotherapy AMH level and time to return of menses demonstrated statistical significance (Spearman’s coefficient, ρ = -0.40) for patients who underwent AC. This analysis in breast cancer patients who underwent AC displayed a negative correlation, however, was not statistically significant. No association was found between age and time to return of menses for all cancer (NAC or AC) or breast cancer patients who underwent AC. Higher AMH level prior to AC was associated with an earlier return of menses after chemotherapy. Age at the commencement of chemotherapy was not associated with return of menses. Further prospective research is required to assess post-chemotherapy recovery of AMH.

PMID:39693398 | DOI:10.1530/RAF-24-0046

Elife. 2024 Dec 18;13:RP97709. doi: 10.7554/eLife.97709.

ABSTRACT

The mis-folding and aggregation of intrinsically disordered proteins (IDPs) such as α-synuclein (αS) underlie the pathogenesis of various neurodegenerative disorders. However, targeting αS with small molecules faces challenges due to the lack of defined ligand-binding pockets in its disordered structure. Here, we implement a deep artificial neural network-based machine learning approach, which is able to statistically distinguish the fuzzy ensemble of conformational substates of αS in neat water from those in aqueous fasudil (small molecule of interest) solution. In particular, the presence of fasudil in the solvent either modulates pre-existing states of αS or gives rise to new conformational states of αS, akin to an ensemble-expansion mechanism. The ensembles display strong conformation-dependence in residue-wise interaction with the small molecule. A thermodynamic analysis indicates that small-molecule modulates the structural repertoire of αS by tuning protein backbone entropy, however entropy of the water remains unperturbed. Together, this study sheds light on the intricate interplay between small molecules and IDPs, offering insights into entropic modulation and ensemble expansion as key biophysical mechanisms driving potential therapeutics.

PMID:39693390 | DOI:10.7554/eLife.97709

J Gerontol A Biol Sci Med Sci. 2024 Dec 18:glae293. doi: 10.1093/gerona/glae293. Online ahead of print.

ABSTRACT

The population of older adults is exponentially expanding. Alongside aging comes the onset of chronic disease, decline of functional capacity, and reduced quality of life. Thus, this population increase will stress the capacity and financial viability of health and long-term care systems. Developing pre-clinical models for age-related functional decline is imperative to advancing therapies that extend healthspan and prolong independence. Previously in a cross-sectional study, we established a powerful composite scoring system we termed CFAB (comprehensive functional assessment battery). CFAB measures physical function and exercise capacity using well-validated determinants to measure overall motor function, fore-limb strength, four-limb strength/endurance, aerobic capacity, and volitional exercise/activity rate. In the current work, we used CFAB to track cohorts of male and female C57BL/6 mice over the lifespan (measuring CFAB at 6, 12, 18, 24, and 28 months of age). Overall, we found statistically significantly declining function as the mice aged, with some differences between males and females in trajectory and slope. We also determined that body mass changes presented differently between sexes, and tracked body composition (fat percentage, using magnetic resonance imagery) in females. In a subset of mice, we tracked in vivo contractile physiology noting declines in plantar flexor maximum isometric torque. In summary, our data suggest that males and females declined at different rates. We confirmed the efficacy of CFAB to track longitudinal changes in exercise capacity and physical fitness in both males and females, further validating the system to track age-related functional decline.

PMID:39693388 | DOI:10.1093/gerona/glae293

J Sports Sci. 2024 Dec 17:1-9. doi: 10.1080/02640414.2024.2440676. Online ahead of print.

ABSTRACT

The aim was to estimate national temporal trends in muscular fitness for French youth between 1999 and 2023. Data were obtained from five cross-sectional studies on 53,314 children and adolescents (age range: 6-16 years). Lower- and upper-body strength were assessed by standing broad jump (SBJ) and handgrip strength (HGS). BMI z-scores (BMIz) were calculated using WHO growth curves. We found a statistically significant negligible decline in SBJ performance (standardised effect size (ES) trend per decade [95%CI]: -0.08 [-0.10, -0.07] or -2.1 cm [95%CI: -2.4, -1.8]) and a statistically significant negligible improvement in HGS (ES trend per decade [95%CI]: 0.11 [0.08, 0.13]) or 0.6 kg [(95%CI: 0.4, 0.8]). We found evidence of significant increases in distributional variability and asymmetry, with poorer trends in the low performers (<25^th percentile) and better trends in the high performers (>75^th percentile) compared to the average performers. Our data suggest negligible trends in mean SBJ and HGS, coupled with increased distributional variability and asymmetry. Trends were not uniform across the population distribution with data suggesting an increase over time in the gap between low and high performers. These results reinforce the importance of interventions and programmes aiming at improving muscular fitness specifically in children and adolescents with low muscular strength.

PMID:39690442 | DOI:10.1080/02640414.2024.2440676