Category: Nevin Manimala

JMIR Form Res. 2023 Dec 21;7:e48296. doi: 10.2196/48296.

ABSTRACT

BACKGROUND: Cancer treatment is a key component of health care systems, and the increasing number of cancer medicines is expanding the treatment landscape. However, evidence of the impact on patients has been focused more on chemotherapy toxicity and symptom control and less on the effect of cancer medicines more broadly on patients’ lives. Evolving electronic patient-reported outcome measures (ePROMs) presents the opportunity to secure early engagement of patients and clinicians in shaping the collection of quality-of-life metrics and presenting these data to better support the patient-clinician decision-making process.

OBJECTIVE: The aim of this study was to obtain initial feedback from patients and clinicians on the wireframes of a digital solution (patient app and clinician dashboard) for the collection and use of cancer medicines ePROMs.

METHODS: We adopted a 2-stage, mixed methods approach. Stage 1 (March to June 2019) consisted of interviews and focus groups with cancer clinicians and patients with cancer to explore the face validity of the wireframes, informed by the technology acceptance model constructs (perceived ease of use, perceived usefulness, and behavioral intention to use). In stage 2 (October 2019 to February 2020), the revised wireframes were assessed through web-based, adapted technology acceptance model questionnaires. Qualitative data (stage 1) underwent a framework analysis, and descriptive statistics were performed on quantitative data (stage 2). Clinicians and patients with cancer were recruited from NHS Greater Glasgow & Clyde, the largest health board in Scotland.

RESULTS: A total of 14 clinicians and 19 patients participated in a combination of stage 1 interviews and focus groups. Clinicians and patients indicated that the wireframes of a patient app and clinician dashboard for the collection of cancer medicines ePROMs would be easy to use and could focus discussions, and they would be receptive to using such tools in the future. In stage 1, clinicians raised the potential impact on workload, and both groups identified the need for adequate IT skills to use each technology. Changes to the wireframes were made, and in stage 2, clinicians (n=8) and patients (n=16) indicated it was “quite likely” that the technologies would be easy to use and they would be “quite likely” to use them in the future. Notably, clinicians indicated that they would use the dashboard to enable treatment decisions “with around half” of their patients.

CONCLUSIONS: This study emphasizes the importance of consulting both patients and clinicians in the design of digital solutions. The wireframes were perceived positively by patients and clinicians who were willing to use such technologies if available in the future as part of routine care. However, challenges were raised, and some differences were identified between participant groups, which warrant further research.

PMID:38127422 | DOI:10.2196/48296

Viral Immunol. 2023 Dec;36(10):642-648. doi: 10.1089/vim.2023.0047.

ABSTRACT

Maternal immunoglobulin G (IgG) antibodies that are passively transferred to newborns through the placenta confer protection if they are exposed to measles virus. A measles outbreak occurred in several European countries including Greece, between 2016 and 2018. A prospective study was conducted in the General Hospital of Lakonia, regarding the measles seropositivity status of mother and newborn pairs. IgG antibody titer for measles was measured in serum samples acquired from pairs of mothers and newborns. The samples were analyzed through quantitative enzyme-linked immunosorbent assay, and antimeasles IgG >200 IU/mL was considered to be protective. Demographic data for mothers and neonates and data regarding immunization status of mothers were analyzed. Study population included 206 mothers and their newborns. In total, 12.6% of mothers (n = 26) and 10.7% of newborns (n = 22) did not have protective serology. A statistically significant positive linear association between maternal and neonatal antibodies was found (rho = 0.924) (p = 0.001). Neonates whose mothers were seropositive had higher antibodies [geometric mean concentration (GMC): 804.8 (728.3-889.2)] than neonates whose mothers were seronegative/borderline [GMC: 97.7 (64.2-148.8)] (p = 0.001). In the study area, a significant rate of mothers and newborns was found to have nonprotective measles serology that exceeds the limit required for herd immunity. Vaccination coverage in women of reproductive age should be increased to reduce potential for future measles epidemics.

PMID:38127419 | DOI:10.1089/vim.2023.0047

J Chem Phys. 2023 Sep 28;159(12):124118. doi: 10.1063/5.0160465.

ABSTRACT

In a recent study, we developed a kinetic-energy density functional that can be utilized in orbital-free quantum mechanical/molecular mechanical (OF-QM/MM) simulations. The functional includes the nonlocal term constructed from the response function of the reference system of the QM solute. The present work provides a method to combine the OF-QM/MM with a theory of solutions based on the energy representation to compute the solvation free energy of the QM solute in solution. The method is applied to the calculation of the solvation free energy Δμ of a QM water solute in an MM water solvent. It is demonstrated that Δμ is computed as -7.7 kcal/mol, in good agreement with an experimental value of -6.3 kcal/mol. We also develop a theory to map the free energy δμ due to electron density polarization onto the coordinate space of electrons. The free energy density obtained by the free-energy mapping for the QM water clarifies that each hydrogen atom makes a positive contribution (+34.7 kcal/mol) to δμ, and the oxygen atom gives the negative free energy (-71.7 kcal/mol). It is shown that the small polarization free energy -2.4 kcal/mol is generated as a result of the cancellation of these counteracting energies. These analyses are made possible by the OF-QM/MM approach combined with a statistical theory of solutions.

PMID:38127397 | DOI:10.1063/5.0160465

J Chem Phys. 2023 Sep 28;159(12):124101. doi: 10.1063/5.0160631.

ABSTRACT

Ultrafast spectroscopy is a powerful technique that utilizes short pulses on the femtosecond time scale to generate and probe coherent responses in molecular systems. While the specific ultrafast methodologies vary, the most common data analysis tools rely on discrete Fourier transformation for recovering coherences that report on electronic or vibrational states and multi-exponential fitting for probing population dynamics, such as excited-state relaxation. These analysis tools are widely used due to their perceived reliability in estimating frequencies and decay rates. Here, we demonstrate that such “black box” methods for parameter estimation often lead to inaccurate results even in the absence of noise. To address this issue, we propose an alternative approach based on Bayes probability theory that simultaneously accounts for both population and coherence contributions to the signal. This Bayesian inference method offers accurate parameter estimations across a broad range of experimental conditions, including scenarios with high noise and data truncation. In contrast to traditional methods, Bayesian inference incorporates prior information about the measured signal and noise, leading to improved accuracy. Moreover, it provides estimator error bounds, enabling a systematic statistical framework for interpreting confidence in the results. By employing Bayesian inference, all parameters of a realistic model system may be accurately recovered, even in extremely challenging scenarios where Fourier and multi-exponential fitting methods fail. This approach offers a more reliable and comprehensive analysis tool for time-resolved coherent spectroscopy, enhancing our understanding of molecular systems and enabling a better interpretation of experimental data.

PMID:38127370 | DOI:10.1063/5.0160631

JAMA Ophthalmol. 2023 Dec 21. doi: 10.1001/jamaophthalmol.2023.5751. Online ahead of print.

ABSTRACT

IMPORTANCE: Dry eye is a common ocular disease that can have substantial morbidity. Systematic reviews provide evidence for dry eye interventions and can be useful for patients, clinicians, and clinical guideline developers. Overviews of reviews use explicit and systematic methods to synthesize findings from multiple systematic reviews, but currently, there are no overviews of systematic reviews investigating interventions for dry eye.

OBJECTIVE: To summarize the results of reliable systematic reviews of dry eye interventions and to highlight the evidence gaps identified.

EVIDENCE REVIEW: We searched the Cochrane Eyes and Vision US satellite database and included reliable systematic reviews evaluating dry eye interventions published from 2016 to 2022. We reported the proportion of systematic reviews that were reliable with reasons for unreliability. Critical and important outcomes from reliable systematic reviews were extracted and verified. Critical outcomes included dry eye-related patient-reported outcome measures. Results were synthesized from reliable systematic reviews to provide summaries of evidence for each intervention. Evidence for each intervention was defined as conclusive or inconclusive depending on whether high-certainty evidence across systematic reviews was available according to Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria and whether findings reached statistical or clinical significance. Recommendations were made for further research.

FINDINGS: Within the Cochrane Eyes and Vision US satellite database, 138 potentially relevant systematic reviews were identified, 71 were considered eligible, and 26 (37%) were assessed as reliable. Among reliable systematic reviews, no conclusive evidence was identified for any dry eye intervention. Inconclusive evidence suggested that environmental modifications, dietary modifications, artificial tears and lubricants, punctal occlusion, intense pulsed light therapy, vectored thermal pulsation therapy (Lipiflow), topical corticosteroids, topical cyclosporine A, topical secretagogues, and autologous serum may be effective. Only unreliable systematic reviews evaluated lifitegrast, oral antibiotics, and moisture chamber devices.

CONCLUSIONS AND RELEVANCE: This overview of systematic reviews found some evidence that dry eye interventions may be effective, but no conclusive evidence was available. The conduct and reporting of most systematic reviews for dry eye interventions warrant improvement, and reliable systematic reviews are needed to evaluate lifitegrast, oral antibiotics, and moisture chamber devices.

PMID:38127364 | DOI:10.1001/jamaophthalmol.2023.5751

JAMA Netw Open. 2023 Dec 1;6(12):e2348914. doi: 10.1001/jamanetworkopen.2023.48914.

ABSTRACT

IMPORTANCE: Studies elucidating determinants of residential neighborhood-level health inequities are needed.

OBJECTIVE: To quantify associations of structural racism indicators with neighborhood prevalence of chronic kidney disease (CKD), diabetes, and hypertension.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used public data (2012-2018) and deidentified electronic health records (2017-2018) to describe the burden of structural racism and the prevalence of CKD, diabetes, and hypertension in 150 residential neighborhoods in Durham County, North Carolina, from US census block groups and quantified their associations using bayesian models accounting for spatial correlations and residents’ age. Data were analyzed from January 2021 to May 2023.

EXPOSURES: Global (neighborhood percentage of White residents, economic-racial segregation, and area deprivation) and discrete (neighborhood child care centers, bus stops, tree cover, reported violent crime, impervious areas, evictions, election participation, income, poverty, education, unemployment, health insurance coverage, and police shootings) indicators of structural racism.

MAIN OUTCOMES AND MEASURES: Outcomes of interest were neighborhood prevalence of CKD, diabetes, and hypertension.

RESULTS: A total of 150 neighborhoods with a median (IQR) of 1708 (1109-2489) residents; median (IQR) of 2% (0%-6%) Asian residents, 30% (16%-56%) Black residents, 10% (4%-20%) Hispanic or Latino residents, 0% (0%-1%) Indigenous residents, and 44% (18%-70%) White residents; and median (IQR) residential income of $54 531 ($37 729.25-$78 895.25) were included in analyses. In models evaluating global indicators, greater burden of structural racism was associated with greater prevalence of CKD, diabetes, and hypertension (eg, per 1-SD decrease in neighborhood White population percentage: CKD prevalence ratio [PR], 1.27; 95% highest density interval [HDI], 1.18-1.35; diabetes PR, 1.43; 95% HDI, 1.37-1.52; hypertension PR, 1.19; 95% HDI, 1.14-1.25). Similarly in models evaluating discrete indicators, greater burden of structural racism was associated with greater neighborhood prevalence of CKD, diabetes, and hypertension (eg, per 1-SD increase in reported violent crime: CKD PR, 1.15; 95% HDI, 1.07-1.23; diabetes PR, 1.20; 95% HDI, 1.13-1.28; hypertension PR, 1.08; 95% HDI, 1.02-1.14).

CONCLUSIONS AND RELEVANCE: This cross-sectional study found several global and discrete structural racism indicators associated with increased prevalence of health conditions in residential neighborhoods. Although inferences from this cross-sectional and ecological study warrant caution, they may help guide the development of future community health interventions.

PMID:38127347 | DOI:10.1001/jamanetworkopen.2023.48914

JAMA Netw Open. 2023 Dec 1;6(12):e2349026. doi: 10.1001/jamanetworkopen.2023.49026.

ABSTRACT

IMPORTANCE: Many multimodality treatment regimens exist for gastric adenocarcinoma, including neoadjuvant vs adjuvant chemotherapy, radiation, or both. Neoadjuvant therapy is recommended in the United States for patients with locally advanced gastric cancer; however, it is unknown whether the outcomes of neoadjuvant therapy are associated with race and ethnicity.

OBJECTIVE: To evaluate the differences in outcomes by race and ethnicity of patients with noncardia gastric cancer undergoing surgical procedures with and without neoadjuvant therapy.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study examined the National Cancer Database from the American College of Surgeons for patients with clinical stage II or III gastric adenocarcinoma, excluding gastric cardia tumors, undergoing surgical resection procedures from January 2006 to December 2019. Statistical analysis was performed from December 2021 to May 2023.

EXPOSURE: Patients were stratified by race and ethnicity, and their outcomes were analyzed for those who received and did not receive neoadjuvant therapy.

MAIN OUTCOMES AND MEASURES: The Cox proportional hazard model was used to compare overall survival (OS) between racial and ethnic groups (Asian, Black, Hispanic, and White) overall and according to receipt of neoadjuvant therapy. Among those who received neoadjuvant therapy, proportional differences in pathological responses were calculated in each group.

RESULTS: Among a total of 6938 patients in the cohort, 4266 (61.4%) were male; mean (SD) age was 65.9 (12.8) years; 1046 (15.8%) were Asian, 1606 (24.3%) were Black, 1175 (17.8%) were Hispanic, and 3540 (53.6%) were White. Compared with other races and ethnicities, the group of White patients had significantly more who were 65 years or older with more comorbidities. White patients underwent surgical resection procedures alone without neoadjuvant or adjuvant therapy more frequently than other races and ethnicities. Asian and Black patients had the highest proportion of being downstaged or achieving pathological complete response after neoadjuvant therapy. In multivariate models, perioperative chemotherapy was associated with improved OS (HR, 0.79 [95% CI, 0.69-0.90]), whereas number of positive lymph nodes and surgical margins were associated with the largest decreases in OS. Asian and Hispanic race and ethnicity were associated with significantly improved OS compared with Black and White races (eg, Asian patients: HR, 0.64 [95% CI, 0.58-0.72]; and Hispanic patients: HR, 0.77 [95% CI, 0.69-0.85]). Black race was associated with improved OS compared with White race when receiving neoadjuvant therapy (HR, 0.78 [95% CI, 0.67-0.90]).

CONCLUSIONS AND RELEVANCE: In this large nationwide cohort study of survival outcomes among patients with resected clinical stage II or III gastric cancer, there were significant differences in response to treatment and OS between different racial and ethnic groups.

PMID:38127346 | DOI:10.1001/jamanetworkopen.2023.49026

JAMA Netw Open. 2023 Dec 1;6(12):e2349098. doi: 10.1001/jamanetworkopen.2023.49098.

ABSTRACT

IMPORTANCE: Despite the availability of several empirically supported trauma-focused interventions, retention in posttraumatic stress disorder (PTSD) psychotherapy is poor. Preliminary efficacy data shows that brief, family-based interventions may improve treatment retention in a veteran’s individual PTSD treatment, although whether this occurs in routine clinical practice is not established.

OBJECTIVE: To characterize receipt of family therapy among veterans diagnosed with PTSD and evaluate whether participation in family therapy is associated with an increased likelihood of completing individual trauma-focused treatment.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used the Veterans Health Administration (VHA) Informatics and Computing Infrastructure to extract electronic health record data of participants. All participants were US veterans diagnosed with PTSD between October 1, 2015, and December 31, 2019, who attended at least 1 individual trauma-focused treatment session. Statistical analysis was performed from May to August 2023.

EXPOSURES: Receipt of any family psychotherapy and subtype of family-based psychotherapy.

MAIN OUTCOMES AND MEASURES: Minimally adequate individual trauma-focused treatment completion (ie, 8 or more sessions of trauma-focused treatment in a 6-month period).

RESULTS: Among a total of 1 516 887 US veterans with VHA patient data included in the study, 58 653 (3.9%) received any family therapy; 334 645 (23.5%) were Black, 1 006 168 (70.5%) were White, and 86 176 (6.0%) were other race; 1 322 592 (87.2%) were male; 1 201 902 (79.9%) lived in urban areas; and the mean (SD) age at first individual psychotherapy appointment was 52.7 (15.9) years. Among the 58 653 veterans (3.9%) who received any family therapy, 36 913 (62.9%) received undefined family therapy only, 15 528 (26.5%) received trauma-informed cognitive-behavioral conjoint therapy (CBCT) only, 5210 (8.9%) received integrative behavioral couples therapy (IBCT) only, and 282 (0.5%) received behavioral family therapy (BFT) only. Compared with receiving no family therapy, the odds of completing individual PTSD treatment were 7% higher for veterans who also received CBCT (OR, 1.07 [95% CI, 1.01-1.13]) and 68% higher for veterans received undefined family therapy (OR, 1.68 [95% CI, 1.63-1.74]). However, compared with receiving no family therapy care, veterans had 26% lower odds of completing individual PTSD treatment if they were also receiving IBCT (OR, 0.74 [95% CI, 0.66-0.82]).

CONCLUSIONS AND RELEVANCE: In this cohort study of US veterans, family-based psychotherapies were found to differ substantially in their associations with individual PTSD psychotherapy retention. These findings highlight potential benefits of concurrently providing family-based therapy with individual PTSD treatment but also the need for careful clinical attention to the balance between family-based therapies and individual PTSD treatment.

PMID:38127345 | DOI:10.1001/jamanetworkopen.2023.49098

JAMA Otolaryngol Head Neck Surg. 2023 Dec 21. doi: 10.1001/jamaoto.2023.4024. Online ahead of print.

ABSTRACT

IMPORTANCE: Despite the widespread use of fibula free flap (FFF) surgery for head and neck reconstruction, there are no studies assessing if early weight-bearing (EWB) affects postoperative recovery, and the timing of weight-bearing initiation following FFF surgery varies considerably across institutions. Therefore, it is important to understand the effect of EWB in these patients and whether it could improve postoperative recovery.

OBJECTIVE: To assess the association of EWB after FFF surgery with donor-site complications, length of stay, and discharge to home status.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study took place at Massachusetts Eye and Ear, a single tertiary care institution in Boston, Massachusetts. A total of 152 patients who received head and neck reconstruction with a fibula osteocutaneous free flap between January 11, 2010, and August 11, 2022, were included.

EXPOSURE: EWB on postoperative day 1 vs non-EWB on postoperative day 2 or later.

MAIN OUTCOMES AND MEASURES: Patient characteristics, including demographic characteristics and comorbidities, surgical characteristics, donor-site complications, length of stay, and discharge disposition, were recorded. Descriptive statistics and multivariate logistic regressions were used to compute effect sizes and 95% CIs to compare postoperative outcomes in EWB and non-EWB groups.

RESULTS: A total of 152 patients (median [IQR] age, 63 [55-70] years; 89 [58.6%] male) were included. The median (IQR) time to postoperative weight-bearing was 3 (1-5) days. Among all patients, 14 (9.2%) had donor-site complications. EWB on postoperative day 1 was associated with shorter length of stay (adjusted odds ratio [AOR], 0.10; 95% CI, 0.02-0.60), increased rate of discharge to home (AOR, 7.43; 95% CI, 2.23-24.80), and decreased donor-site complications (AOR, 0.11; 95% CI, 0.01-0.94). Conversely, weight-bearing 3 or more days postoperatively was associated with an increased risk of pneumonia (AOR, 6.82; 95% CI, 1.33-34.99).

CONCLUSIONS AND RELEVANCE: In this cohort study, EWB after FFF surgery was associated with shorter length of stay, increased rate of discharge to home, and decreased donor-site complications. These findings support the role of early mobilization to optimize postoperative recovery after FFF surgery.

PMID:38127340 | DOI:10.1001/jamaoto.2023.4024

Ital J Dermatol Venerol. 2023 Dec 21. doi: 10.23736/S2784-8671.23.07630-2. Online ahead of print.

ABSTRACT

BACKGROUND: Accumulating evidence suggests that oxidative stress is involved in the inflammatory process of atopic dermatitis (AD). Biopyrrins are the end products of the oxidative reaction of bilirubin with reactive oxygen species. The aim of our study was to explore the correlation between urinary biopyrrin levels and AD severity as well as to assess the possible modification of them in AD patients during biologic therapy with human monoclonal antibody dupilumab.

METHODS: For this purpose, 25 adult patients with moderate-severe AD who were candidates for dupilumab therapy independently from the study, and 15 healthy control subjects, matched by sex and age, were enrolled. Morning urine samples were collected from all study participants. For AD patients, a collection was planned before starting therapy with dupilumab (WO), after 8, 16, 52 weeks (W8, W16, W52, respectively), and two years (Y2) of treatment. The analysis of urinary levels of biopyrrins was performed by ELISA assay.

RESULTS: Our results demonstrated that urinary biopyrrin levels were significantly augmented in AD patients, and interestingly they correlated with disease severity. Furthermore, dupilumab therapy decreased levels of urinary biopyrrins in AD patients after eight and 16 weeks, maintaining the result after 52 weeks as well as after two years of treatment. The correlation analysis showed a statistically significant positive correlation between the urinary concentration of biopyrrins and EASI Index, circulating total IgE as well as plasma C reactive protein levels.

CONCLUSIONS: Dupilumab therapy was able to ameliorate oxidative state in AD patients.

PMID:38127318 | DOI:10.23736/S2784-8671.23.07630-2