Nevin Manimala

PLoS One. 2022 Sep 23;17(9):e0274026. doi: 10.1371/journal.pone.0274026. eCollection 2022.

ABSTRACT

Fibromyalgia-syndrome (FMS) is a complex disease characterized by chronic widespread pain and additional symptoms including depression, cognitive dysfunction (“fibro-fog”) and maldigestion. Our research team examined whether FMS-related pain parameters assessed by quantitative sensory testing (QST) and psychological disturbances are accompanied by alterations of the fecal microbiome. We recruited 25 patients with FMS and 26 age- and sex-matched healthy controls. Medical background, food habits, psychopathology and quality of life were assessed through questionnaires. Stool samples were analyzed by 16S rRNA gene amplification and sequencing. QST was performed according to the protocol of the German Network for Neuropathic Pain. QST showed that both lemniscal and spinothalamic afferent pathways are altered in FMS patients relative to healthy controls and that peripheral as well as central pain sensitization processes are manifest. Psychometric assessment revealed enhanced scores of depression, anxiety and stress. In contrast, neither the composition nor the alpha- and beta-diversity of the fecal microbiome was changed in FMS patients. FMS patients segregate from healthy controls in various parameters of QST and psychopathology, but not in terms of composition and diversity of the fecal microbiome. Despite consideration of several confounding factors, we conclude that the contribution of the gut microbiome to the pathophysiology of FMS is limited.

PMID:36149895 | DOI:10.1371/journal.pone.0274026

PLoS Biol. 2022 Sep 23;20(9):e3001804. doi: 10.1371/journal.pbio.3001804. Online ahead of print.

ABSTRACT

Following the initiation of the unprecedented global vaccination campaign against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), attention has now turned to the potential impact of this large-scale intervention on the evolution of the virus. In this Essay, we summarize what is currently known about pathogen evolution in the context of immune priming (including vaccination) from research on other pathogen species, with an eye towards the future evolution of SARS-CoV-2.

PMID:36149891 | DOI:10.1371/journal.pbio.3001804

ACS Nano. 2022 Sep 23. doi: 10.1021/acsnano.2c04089. Online ahead of print.

ABSTRACT

The diffusion and mobility in biomembranes are crucial for various cell functions; however, the mechanisms involved in such processes remain ambiguous due to the complex membrane structures. Herein, we investigate how the heterogeneous nanostructures cause anomalous diffusion in dipalmitoylphosphatidylcholine (DPPC) monolayers. By identifying the existence of condensed nanodomains and clarifying their impact, our findings renew the understanding of the hydrodynamic description and the statistical feature of the diffusion in the monolayers. We find a universal characteristic of the multistage mean square displacement (MSD) with an intermediate crossover, signifying two membrane viscosities at different scales: the short-time scale describes the local fluidity and is independent of the nominal DPPC density, and the long-time scale represents the global continuous phase taking into account nanodomains and increases with DPPC density. The constant short-time viscosity reflects a dynamic equilibrium between the continuous fluid phase and the condensed nanodomains in the molecular scale. Notably, we observe an “anomalous yet Brownian” phenomenon exhibiting an unusual double-peaked displacement probability distribution (DPD), which is attributed to the net dipolar repulsive force from the heterogeneous nanodomains around the microdomains. The findings provide physical insights into the transport of membrane inclusions that underpin various biological functions and drug deliveries.

PMID:36149751 | DOI:10.1021/acsnano.2c04089

JMIR Med Inform. 2022 Sep 23;10(9):e39746. doi: 10.2196/39746.

ABSTRACT

Electronic health records (EHRs) were originally developed for clinical care and billing. As such, the data are not collected, organized, and curated in a fashion that is optimized for secondary use to support the Learning Health System. Population health registries provide tools to support quality improvement. These tools are generally integrated with the live EHR, are intended to use a minimum of computing resources, and may not be appropriate for some research projects. Researchers may require different electronic phenotypes and variable definitions from those typically used for population health, and these definitions may vary from study to study. Establishing a formal registry that is mapped to the Observation Medical Outcomes Partnership common data model provides an opportunity to add custom mappings and more easily share these with other institutions. Performing preprocessing tasks such as data cleaning, calculation of risk scores, time-to-event analysis, imputation, and transforming data into a format for statistical analyses will improve efficiency and make the data easier to use for investigators. Research registries that are maintained outside the EHR also have the luxury of using significant computational resources without jeopardizing clinical care data. This paper describes a virtual Diabetes Registry at Atrium Health Wake Forest Baptist and the plan for its continued development.

PMID:36149742 | DOI:10.2196/39746

JMIR Res Protoc. 2022 Sep 23;11(9):e38608. doi: 10.2196/38608.

ABSTRACT

BACKGROUND: Sleep disturbances post concussion have been associated with more frequent and severe concussion symptoms and may contribute to poorer recovery. Cognitive behavioral therapy for insomnia (CBT-I) is an effective treatment for insomnia; however, it remains unclear if this treatment method is effective in improving sleep outcomes and reducing concomitant postconcussion symptoms.

OBJECTIVE: The hypotheses for this study are that (1) CBT-I will improve sleep outcomes and (2) CBT-I will improve concomitant postconcussion symptoms.

METHODS: In total, 40 individuals who are within ≥4 weeks of postconcussion injury and have insomnia symptoms will be enrolled in this randomized controlled trial. Participants will be randomized into either a group that starts a 6-week CBT-I program immediately after baseline or a waitlist control group that starts CBT-I following a 6-week waiting period. All participants will be reassessed 6, 12, and 18 weeks after baseline. Standardized assessments measuring sleep outcomes, postconcussion symptoms, and mood will be used. Linear regression and t tests will be used for statistical analyses.

RESULTS: Enrollment of 40 participants was completed July 2022, data collection will be completed in November 2022, and publication of main findings is anticipated in May 2023. It is anticipated that participants experience reduced insomnia symptoms and postconcussion symptoms following CBT-I and these improvements will be retained for at least 12 weeks. Additionally, we expect to observe a positive correlation between sleep and postconcussion symptom improvement.

CONCLUSIONS: Successful completion of this pilot study will allow for a better understanding of the treatment of insomnia and postconcussion symptoms in individuals following a concussion.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04885205; https://clinicaltrials.gov/ct2/show/NCT04885205.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/38608.

PMID:36149737 | DOI:10.2196/38608

JMIR Ment Health. 2022 Sep 23;9(9):e38067. doi: 10.2196/38067.

ABSTRACT

BACKGROUND: While mental health applications are increasingly becoming available for large populations of users, there is a lack of controlled trials on the impacts of such applications. Artificial intelligence (AI)-empowered agents have been evaluated when assisting adults with cognitive impairments; however, few applications are available for aging adults who are still actively working. These adults often have high stress levels related to changes in their work places, and related symptoms eventually affect their quality of life.

OBJECTIVE: We aimed to evaluate the contribution of TEO (Therapy Empowerment Opportunity), a mobile personal health care agent with conversational AI. TEO promotes mental health and well-being by engaging patients in conversations to recollect the details of events that increased their anxiety and by providing therapeutic exercises and suggestions.

METHODS: The study was based on a protocolized intervention for stress and anxiety management. Participants with stress symptoms and mild-to-moderate anxiety received an 8-week cognitive behavioral therapy (CBT) intervention delivered remotely. A group of participants also interacted with the agent TEO. The participants were active workers aged over 55 years. The experimental groups were as follows: group 1, traditional therapy; group 2, traditional therapy and mobile health (mHealth) agent; group 3, mHealth agent; and group 4, no treatment (assigned to a waiting list). Symptoms related to stress (anxiety, physical disease, and depression) were assessed prior to treatment (T1), at the end (T2), and 3 months after treatment (T3), using standardized psychological questionnaires. Moreover, the Patient Health Questionnaire-8 and General Anxiety Disorders-7 scales were administered before the intervention (T1), at mid-term (T2), at the end of the intervention (T3), and after 3 months (T4). At the end of the intervention, participants in groups 1, 2, and 3 filled in a satisfaction questionnaire.

RESULTS: Despite randomization, statistically significant differences between groups were present at T1. Group 4 showed lower levels of anxiety and depression compared with group 1, and lower levels of stress compared with group 2. Comparisons between groups at T2 and T3 did not show significant differences in outcomes. Analyses conducted within groups showed significant differences between times in group 2, with greater improvements in the levels of stress and scores related to overall well-being. A general worsening trend between T2 and T3 was detected in all groups, with a significant increase in stress levels in group 2. Group 2 reported higher levels of perceived usefulness and satisfaction.

CONCLUSIONS: No statistically significant differences could be observed between participants who used the mHealth app alone or within the traditional CBT setting. However, the results indicated significant differences within the groups that received treatment and a stable tendency toward improvement, which was limited to individual perceptions of stress-related symptoms.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04809090; https://clinicaltrials.gov/ct2/show/NCT04809090.

PMID:36149730 | DOI:10.2196/38067

JMIR Form Res. 2022 Sep 23;6(9):e35648. doi: 10.2196/35648.

ABSTRACT

BACKGROUND: Social media sites, dating apps, and information search sites have been used to reach individuals at high risk for HIV infection. However, it is not clear which platform is the most efficient in promoting home HIV self-testing, given that the users of various platforms may have different characteristics that impact their readiness for HIV testing.

OBJECTIVE: This study aimed to compare the relative effectiveness of social media sites, dating apps, and information search sites in promoting HIV self-testing among minority men who have sex with men (MSM) at an increased risk of HIV infection. Test kit order rates were used as a proxy to evaluate promotion effectiveness. In addition, we assessed differences in characteristics between participants who ordered and did not order an HIV test kit.

METHODS: Culturally appropriate advertisements were placed on popular sites of three different platforms: social media sites (Facebook, Instagram), dating apps (Grindr, Jack’D), and information search sites (Google, Bing). Advertisements targeted young (18-30 years old) and minority (Black or Latinx) MSM at risk of HIV exposure. Recruitment occurred in 2 waves, with each wave running advertisements on 1 platform of each type over the same period. Participants completed a baseline survey assessing sexual or injection use behavior, substance use including alcohol, psychological readiness to test, attitudes toward HIV testing and treatment, and HIV-related stigma. Participants received an electronic code to order a free home-based HIV self-test kit. Follow-up assessments were conducted to assess HIV self-test kit use and uptake of pre-exposure prophylaxis (PrEP) at 14 and 60 days post enrollment.

RESULTS: In total, 271 participants were enrolled, and 254 were included in the final analysis. Among these 254 participants, 177 (69.7%) ordered a home HIV self-test kit. Most of the self-test kits were ordered by participants enrolled from dating apps. Due to waves with low enrollment, between wave statistical comparisons were not feasible. Within wave comparison revealed that Jack’D showed higher order rates (3.29 kits/day) compared to Instagram (0.34 kits/day) and Bing (0 kits/day). There were no associations among self-test kit ordering and HIV-related stigma, perceptions about HIV testing and treatment, and mistrust of medical organizations.

CONCLUSIONS: Our findings show that using popular dating apps might be an efficient way to promote HIV self-testing. Stigma, perceptions about HIV testing and treatment, or mistrust of medical organizations may not affect order rates of HIV test kits promoted on the internet.

TRIAL REGISTRATION: ClinicalTrials.gov NCT04155502; https://clinicaltrials.gov/ct2/show/NCT04155502.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/20417.

PMID:36149729 | DOI:10.2196/35648

J Palliat Med. 2022 Sep 23. doi: 10.1089/jpm.2022.0338. Online ahead of print.

ABSTRACT

Background: Patients with hepatocellular cancer (HCC) are at risk for poor quality of life (QoL) and high symptom burden, coupled with limited treatment options. Palliative care (PC) can play an important role in reducing the suffering of this population, but remains underutilized. Aim: To demonstrate feasibility of an outpatient PC intervention within HCC care. Methods: This is a pilot randomized controlled trial conducted at an academic center. All stages of HCC patients (except Barcelona Clinic Liver Cancer stage D) with a scheduled hepatology appointment were eligible. Patients were randomized to receive PC intervention or usual care (control arm). In the PC arm, patients received PC from a PC provider at enrollment and at three months from the baseline visit, in addition to continued standard of care. Control arm received only standard care. All patients completed FACT-Hep (Functional Assessment of Cancer Therapy-Hepatobiliary Cancer) and modified Edmonton Symptom Assessment Scale at baseline and at three-month visit. Descriptive statistics were utilized to summarize questionnaires, and change in QoL and symptoms from baseline to three months were compared between the two study groups. Results: Of the 109 approached, 57 patients (52.3%) consented to enroll, and 52 (91%) completed the study. QoL and symptom burden assessments demonstrated impaired QoL and high symptom burden in both arms of the study. At least 50% of enrolled patients in each arm had some degree of fatigue, pain, sleep disturbance, and appetite loss, at baseline. Post-intervention, symptom burden and QoL improved in the intervention arm and remained same or worsened in the control group. All FACT-Hep scores decreased numerically among controls and increased numerically among patients in the PC intervention group. Conclusion: Outpatient PC intervention within routine HCC care is feasible, and can potentially improve QoL and symptoms.

PMID:36149682 | DOI:10.1089/jpm.2022.0338

JAMA Netw Open. 2022 Sep 1;5(9):e2233088. doi: 10.1001/jamanetworkopen.2022.33088.

ABSTRACT

IMPORTANCE: Obesity and metabolic syndrome are highly prevalent among the US population and are associated with the dysregulation of sex hormones. An increase in obesity and metabolic syndrome may also be associated with exposure to phthalates. The association of exposure to phthalate metabolites with sex hormones and metabolic health has been understudied in the female population.

OBJECTIVE: To evaluate the association between exposure to common phthalate metabolites with total testosterone (TT) levels, sex hormone-binding globulin (SHBG) levels, obesity, and metabolic syndrome among women.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data collected from the National Health and Nutrition Examination Survey during 2013 to 2016. Female participants aged 15 years or older with urinary profiles containing common phthalate metabolites were included in this study. Statistical analyses were performed from March 15, 2021, to April 30, 2022.

EXPOSURES: Urinary concentrations of phthalate metabolites were classified into tertiles, and the lowest tertile was used as a reference category. The concentrations of phthalate metabolites and their composite scores based on clustering were also used in the analysis.

MAIN OUTCOMES AND MEASURES: Serum concentrations of TT and SHBG were dichotomized into high TT levels (>46 ng/dL [to convert to nanomoles per liter, multiply by 0.0347] for age <50 years and >32 ng/dL for age ≥50 years) and low SHBG levels (<2.85 μg/mL [to convert to nanomoles per liter, multiply by 10.53]) as established for the female population. Obesity was defined as a body mass index of 30 or more (calculated as weight in kilograms divided by height in meters squared), and metabolic syndrome was defined using the National Cholesterol Education Program criteria. The serum concentrations of TT and SHBG were also included in the validation analyses. Modified Poisson models were used to estimate the adjusted relative risk (RR) with 95% CIs for the associations.

RESULTS: Among the 2004 women included in this study, the mean (SD) age was 46.6 (18.5) years (14.7% Hispanic participants, 62.7% non-Hispanic White participants, and 13.2% non-Hispanic Black participants; 17.4% of participants were born outside the US [weighted percentages]; 230 (11.8%) had high TT levels, 210 (10.4%) had low SHBG levels, 825 (39.8%) had obesity, and 965 (45.5%) had metabolic syndrome (weighted percentages). Of the 13 phthalate metabolites, 8 had the highest tertile level greater than 6.2 ng/mL (range, 0.5-75.2 ng/mL). High levels of exposure to mono(2-ethyl-5-carboxypentyl) phthalate (RR, 1.84 [95% CI, 1.33-2.54]), mono(2-ethyl-5-oxohexyl) phthalate (RR, 1.77 [95% CI, 1.21-2.59]), mono(2-ethyl-5-hydroxyhexyl) phthalate (RR, 1.94 [95% CI, 1.34-2.81]), and monobenzyl phthalate (RR, 1.75 [95% CI, 1.21-2.54]) were associated with low SHBG levels but not with high TT levels. High levels of exposure to some of these metabolites were also associated with obesity and metabolic syndrome. Most associations were specific to premenopausal or postmenopausal women.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, exposure to certain phthalate metabolites could be associated with low SHBG levels, obesity, and metabolic syndrome depending on menopausal status.

PMID:36149653 | DOI:10.1001/jamanetworkopen.2022.33088

JAMA Netw Open. 2022 Sep 1;5(9):e2233094. doi: 10.1001/jamanetworkopen.2022.33094.

ABSTRACT

IMPORTANCE: Because stroke causes diverse functional deficits, understanding the long-term recovery pattern of each functional domain may inform prognosis and therapeutic strategies.

OBJECTIVE: To observe long-term changes in functional status and residual disability in survivors of first-time stroke.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study was an interim analysis of the Korean Stroke Cohort for Functioning and Rehabilitation. Between August 2012 and May 2015, 7858 of 10 636 screened patients with first-time strokes from 9 district hospitals in Korea provided informed consent to participate. Data were analyzed from September 2021 through February 2022.

EXPOSURE: First-time stroke.

MAIN OUTCOMES AND MEASURES: Study data include multifaceted face-to-face functional assessments obtained at 8 to 9 points until 60 months after stroke onset. The Korean Mini-Mental State Examination (K-MMSE), Fugl-Meyer Assessment, Functional Ambulatory Category, American Speech-Language-Hearing Association National Outcome Measurement System Swallowing Scale, and Short Korean version of the Frenchay Aphasia Screening Test were performed from 7 days to 60 months after stroke. The Korean Modified Barthel Index was measured from 3 months to 60 months after stroke.

RESULTS: A total of 4443 patients (2649 men [59.62%]; mean [SD] age 62.13 [12.43] years) who underwent repeated functional assessments for 60 months after stroke (3508 patients with ischemic and 935 patients with hemorrhagic stroke) were included. Overall, functions plateaued between 12 and 18 months after stroke and declined after 30 months; for example, mean (SD) K-MMSE improved from 7 days (22.89 [7.89]) to 12 months (26.03 [5.48]) (P < .001), plateaued until 36 months (26.03 [5.84]), and decreased to 48 months (26.02 [5.82]) (P < .001). Interaction associations were found between time after stroke and age, stroke severity, and stroke type in functional assessment outcomes. For example, mean (SE) FMA for ages 65 years or younger vs older than 65 years was 81.64 (0.63) vs 80.69 (0.68) at 7 days and 91.28 (0.47) vs 88.46 (0.58) at 6 months (P for interaction < .001), and for IS vs HS, it was 84.46 (0.47) vs 69.02 (1.24) at 7 days and 91.20 (0.38) vs 85.51 (0.98) at 6 months (P for interaction < .001). Mean (SE) FMA was 94.39 (0.21) at 7 days and 97.57 (0.14) at 6 months for mild stroke, 44.69 (1.18) at 7 days and 70.43 (1.21) at 6 months for moderate stroke, and 13.22 (0.99) at 7 days and 48.07 (2.62) at 6 months for severe stroke (P for interaction < .001). Factors associated with activities of daily living independence at 60 months included older age (β per 1-year increase = -0.35; standard error [SE], 0.03; P < .001), male sex (β = 2.12; SE, 0.73; P = .004), and hemorrhagic stroke type (β vs ischemic stroke = 2.35; SE, 0.81; P = .004).

CONCLUSIONS AND RELEVANCE: This study found that long-term recovery patterns in multifaceted functional domains differed from one another and varied by patient age, stroke severity, and stroke type. Understanding the diversity of long-term functional recovery patterns and factors associated with these outcomes in survivors of stroke may help clinicians develop strategies for effective stroke care and rehabilitation.

PMID:36149652 | DOI:10.1001/jamanetworkopen.2022.33094