Category: Nevin Manimala

Haematologica. 2023 Nov 30. doi: 10.3324/haematol.2023.284154. Online ahead of print.

ABSTRACT

Immunoparesis (IP) in multiple myeloma (MM) patients can be measured by classic assessment of immunoglobulin (Ig) levels or by analysis of the uninvolved heavy/light chain pair of the same immunoglobulin (uHLC) by the Hevylite® assay. In this study we evaluate the prognostic value of recovery from IP measured by classic total Ig and uHLC assessment in newly diagnosed MM transplant-eligible (NDMM-TE) patients with intensive treatment and its association with Minimal Residual Disease (MRD). Patients were enrolled and treated in the PETHEMA/GEM2012MENOS65 trial and continued in the PETHEMA/GEM2014MAIN trial. Total Ig (IgG, IgA and IgM) and uHLC were analyzed in a central laboratory at diagnosis, after consolidation treatment and after the first year of maintenance. MRD was analyzed by next generation flow cytometry after consolidation (sensitivity level 2×10-6). We found no differences in progression free survival (PFS) between patients who recovered and patients who didn’t recover from IP after consolidation when examining classic total Ig and uHLC. However, after the first year of maintenance, in contrast to patients with classic IP, patients with recovery from uHLC IP had longer PFS than patients without recovery, with hazard ratio of 0.42 (CI95% 0.21-0.81; p=0.008). Multivariate analysis with Cox proportional-hazards regression models confirmed recovery from uHLC IP after the first year of maintenance as an independent prognostic factor for PFS, with an increase in C-statistic of 0.05 (-0.04-0.14; p<0.001) when adding uHLC IP recovery. Moreover, we observed that MRD status and uHLC IP recovery affords complementary information for risk stratification. In conclusion, recovery from uHLC IP after one year of maintenance is an independent prognostic factor for PFS in NDMM-TE patients who receive intensive treatment. Immune reconstitution, measured as recovery from uHLC IP, provides complementary prognostic information to MRD assessment.

PMID:38031761 | DOI:10.3324/haematol.2023.284154

J Endovasc Ther. 2023 Nov 30:15266028231212761. doi: 10.1177/15266028231212761. Online ahead of print.

ABSTRACT

PURPOSE: Covered stents and bare metal stents (BMS) have been regarded as viable treatment options for aortoiliac arterial diseases. We performed this systematic review and meta-analysis to compare the efficacy of covered stents with BMS for aortoiliac arterial diseases.

MATERIALS AND METHODS: The Cochrane Library, Embase, and Medline databases were searched by 2 authors (C.Z. and Z.W.) to retrieve all studies comparing the outcomes of covered stents vs BMS for aortoiliac arterial diseases. The Cochrane tool and the Newcastle-Ottawa scale were used to assess the risk of bias in randomized controlled trials and observational studies, respectively. The outcomes at the same stage reported in at least 2 studies were pooled together. The fixed effects model combined the data when I²<50%, otherwise the random effects model was applied. The results for dichotomous variables were presented as odds ratio (OR) or risk difference and 95% confidence interval (CI); continuous variables were reported as mean difference and 95% CI.

RESULTS: Herein, 10 studies with a total of 1695 limbs were included. The covered stents significantly increased the freedom from target lesion revascularization (OR 2.85, 95% CI: 1.28-6.33, p=0.010) compared to the BMS during a 24-month follow-up. However, no statistically significant difference was found in the technical success, primary patency, secondary patency, major adverse events (MAEs), ankle-brachial index (ABI) improvement, limb salvage, and survival between the two groups.

CONCLUSION: Compared to BMS, covered stents appear to have similar technical success, primary patency, secondary patency, MAEs, ABI improvement, limb salvage, and survival but may have advantages in reducing target lesion revascularization. More well-designed, prospective studies are warranted to determine such findings.

CLINICAL IMPACT: Covered stents may increase freedom from target lesion revascularization (TLR) compared to bare metal stents (BMS) in the treatment of aortoiliac arterial diseases. However, technical success, primary patency, secondary patency, major adverse events (MAEs), ABI improvement, limb salvage, and survival were similar. The aforementioned results are still not sufficient to draw a solid conclusion about the selection of stents for aortoiliac arterial diseases. More well-designed, prospective studies are warranted to determine such findings.

PMID:38031669 | DOI:10.1177/15266028231212761

Jpn J Nurs Sci. 2023 Nov 30:e12574. doi: 10.1111/jjns.12574. Online ahead of print.

ABSTRACT

AIM: To determine the effectiveness of a caregiver education (needs tailored) and telephone follow-up intervention for caregivers of people with moderate stage Alzheimer’s disease on caregiver burden, caregiving impact on life, and patients’ neuropsychiatric symptoms, dependence on activities of daily living.

METHODS: This quasi-experimental study sampled caregivers of people with moderate stage Alzheimer’s. Caregivers in the intervention group received education and telephone follow-up over 12 weeks, while the control group received routine care. Caregivers were assessed for burden, changes in life, and patients for neuropsychiatric symptoms, and dependence on daily living activities.

RESULTS: The caregiver burden, life changes, distress, and patients’ neuropsychiatric symptom scores showed apparent trend toward betterment, but no statistically significant differences were found in study outcomes between the two groups (P > .05).

CONCLUSION: The caregiver need-based, structured education and telephone follow-up intervention was not empirically effective. With the promising effect from this study, managing behavioral symptoms with need-based, structured, and skill-oriented training has the potential to alleviate the burden on caregivers.

PMID:38031663 | DOI:10.1111/jjns.12574

Aging Cell. 2023 Nov 29:e14052. doi: 10.1111/acel.14052. Online ahead of print.

ABSTRACT

Schizophrenia is often regarded as a disorder of premature aging. We investigated (a) whether polygenic risk for schizophrenia (PRS_sch ) relates to pace of epigenetic aging and (b) whether personal dispositions toward active and emotionally close relationships protect against accelerated epigenetic aging in individuals with high PRS_sch . The sample came from the population-based Young Finns Study (n = 1348). Epigenetic aging was measured with DNA methylation aging algorithms such as AgeAccel_Hannum , EEAA_Hannum , IEAA_Hannum , IEAA_Horvath , AgeAccel_Horvath , AgeAccel_Pheno , AgeAccel_Grim , and DunedinPACE. A PRS_sch was calculated using summary statistics from the most comprehensive genome-wide association study of schizophrenia to date. Social dispositions were assessed in terms of extraversion, sociability, reward dependence, cooperativeness, and attachment security. We found that PRS_sch did not have a statistically significant effect on any studied indicator of epigenetic aging. Instead, PRS_sch had a significant interaction with reward dependence (p = 0.001-0.004), cooperation (p = 0.009-0.020), extraversion (p = 0.019-0.041), sociability (p = 0.003-0.016), and attachment security (p = 0.007-0.014) in predicting AgeAccel_Hannum , EEAA_Hannum , or IEAA_Hannum . Specifically, participants with high PRS_sch appeared to display accelerated epigenetic aging at higher (vs. lower) levels of extraversion, sociability, attachment security, reward dependence, and cooperativeness. A rather opposite pattern was evident for those with low PRS_sch . No such interactions were evident when predicting the other indicators of epigenetic aging. In conclusion, against our hypothesis, frequent social interactions may relate to accelerated epigenetic aging in individuals at risk for psychosis. We speculate that this may be explained by social-cognitive impairments (perceiving social situations as overwhelming or excessively arousing) or ending up in less supportive or deviant social groups.

PMID:38031635 | DOI:10.1111/acel.14052

Int J Behav Nutr Phys Act. 2023 Nov 29;20(1):141. doi: 10.1186/s12966-023-01543-w.

ABSTRACT

BACKGROUND: We previously demonstrated that a heuristic (i.e., evidence-based, rounded yet practical) cadence threshold of ≥ 100 steps/min was associated with absolutely-defined moderate intensity physical activity (i.e., ≥ 3 metabolic equivalents [METs]) in older adults 61-85 years of age. Although it was difficult to ascertain achievement of absolutely-defined vigorous (6 METs) intensity, ≥ 130 steps/min was identified as a defensible threshold for this population. However, little evidence exists regarding cadence thresholds and relatively-defined moderate intensity indicators, including ≥ 64% heart rate [HR] maximum [HR_max = 220-age], ≥ 40% HR reserve [HRR = HR_max-HR_resting], and ≥ 12 Borg Scale Rating of Perceived Exertion [RPE]; or vigorous intensity indicators including ≥ 77%HR_max, ≥ 60%HRR, and ≥ 14 RPE.

PURPOSE: To analyze the relationship between cadence and relatively-defined physical activity intensity and identify relatively-defined moderate and vigorous heuristic cadence thresholds for older adults 61-85 years of age.

METHODS: Ninety-seven ostensibly healthy adults (72.7 ± 6.9 years; 49.5% women) completed up to nine 5-min treadmill walking bouts beginning at 0.5 mph (0.8 km/h) and progressing by 0.5 mph speed increments (with 2-min rest between bouts). Directly-observed (and video-recorded) steps were hand-counted, HR was measured using a chest-strapped monitor, and in the final minute of each bout, participants self-reported RPE. Segmented mixed model regression and Receiver Operating Characteristic (ROC) curve analyses identified optimal cadence thresholds associated with relatively-defined moderate (≥ 64%HR_max, ≥ 40%HRR, and ≥ 12 RPE) and vigorous (≥ 77%HR_max, ≥ 60%HRR, and ≥ 14 RPE) intensities. A compromise between the two analytical methods, including Youden’s Index (a sum of sensitivity and specificity), positive and negative predictive values, and overall accuracy, yielded final heuristic cadences.

RESULTS: Across all relatively-defined moderate intensity indicators, segmented regression models and ROC curve analyses identified optimal cadence thresholds ranging from 105.9 to 112.8 steps/min and 102.0-104.3 steps/min, respectively. Comparable values for vigorous intensity indicators ranged between126.1-132.1 steps/min and 106.7-116.0 steps/min, respectively. Regardless of the relatively-defined intensity indicator, the overall best heuristic cadence threshold aligned with moderate intensity was ≥ 105 steps/min. Vigorous intensity varied between ≥ 115 (greater sensitivity) or ≥ 120 (greater specificity) steps/min.

CONCLUSIONS: Heuristic cadence thresholds align with relatively-defined intensity indicators and can be useful for studying and prescribing older adults’ physiological response to, and/or perceived experience of, ambulatory physical activity.

TRIAL REGISTRATION: Clinicaltrials.gov NCT02650258. Registered 24 December 2015.

PMID:38031156 | DOI:10.1186/s12966-023-01543-w

J Cardiovasc Magn Reson. 2023 Nov 30;25(1):72. doi: 10.1186/s12968-023-00986-1.

ABSTRACT

BACKGROUND: The 2019 arrhythmogenic right ventricular cardiomyopathy (ARVC) risk model has proved insufficient in the capability of predicting ventricular arrhythmia (VA) risk in non-classical arrhythmogenic cardiomyopathy (ACM). Furthermore, the prognostic value of ringlike late gadolinium enhancement (LGE) of the left ventricle in non-classical ACM remains unknown. We aimed to assess the incremental value of ringlike LGE over the 2019 ARVC risk model in predicting sustained VA in patients with non-classical ACM.

METHODS: In this retrospective study, consecutive patients with non-classical ACM who underwent CMR from January 2011 to January 2022 were included. The pattern of LGE was categorized as no, non-ringlike, and ringlike LGE. The primary outcome was defined as the occurrence of sustained VA. Univariable and multivariable Cox regression analysis was used to evaluate the impact of LGE patterns on sustained VA and area under curve (AUC) was calculated for the incremental value of ringlike LGE.

RESULTS: A total of 73 patients were collected in the final cohort (mean age, 39.3 ± 14.4 years, 51 male), of whom 10 (13.7%) had no LGE, 33 (45.2%) had non-ringlike LGE, and 30 (41.1%) had ringlike LGE. There was no statistically significant difference in the 5-year risk score among the three groups (P = 0.190). During a median follow-up of 34 (13-56) months, 34 (46.6%) patients experienced sustained VA, including 1 (10.0%), 13 (39.4%) and 20 (66.7%) of patients with no, non-ringlike and ringlike LGE, respectively. After multivariable adjustment, ringlike LGE remained independently associated with the presence of sustained VA (adjusted hazard ratio: 6.91, 95% confidence intervals: 1.89-54.60; P = 0.036). Adding ringlike LGE to the 2019 ARVC risk model showed significantly incremental prognostic value for sustained VA (AUC: 0.80 vs. 0.67; P = 0.024).

CONCLUSION: Ringlike LGE provides independent and incremental prognostic value over the 2019 ARVC risk model in patients with non-classical ACM.

PMID:38031154 | DOI:10.1186/s12968-023-00986-1

BMC Oral Health. 2023 Nov 29;23(1):944. doi: 10.1186/s12903-023-03570-2.

ABSTRACT

BACKGROUND: Premature loss of primary molars can be treated with a band loop space maintainer (SM). However, fabricating a conventional band loop SM requires multiple clinical and laboratory procedures, which can potentially affect the accuracy of the SM. Moreover, the conventional SM is unable to fully restore masticatory function and maintain the vertical dimension of the edentulous space. In this current study, a fully digital workflow to fabricate a semi-rigid bridge SM made from polyetheretherketone (PEEK) has been described and evaluated for its clinical effectiveness.

METHODS: A total of 15 children (eight males and seven females) between the ages of 4-8 years, who experienced the premature loss of a single primary molar, were included in this study. Digital impressions were taken using the CEREC CAD/CAM chair system and imported into CAD software to design the semi-rigid bridge SM, which was fabricated using PEEK block as the maintainer material. The digital SM was tried-in and bonded to the abutment with resin cement. The edentulous space was measured immediately after bonding (T0) and 1 month (T1), 3 months (T2), and 6 months (T3) after treatment. The periodontal condition and mobility of the SM and abutment were also examined.

RESULTS: The use of digital impressions resulted in a decreased occurrence of the pharyngeal reflex. The digital semi-rigid bridge SM, fabricated with PEEK, was both convenient and aesthetically pleasing, and successfully restored the anatomy and masticatory function of the missing primary molar. None of the 15 semi-rigid bridge SMs or abutments became loose or fell off during the study, and only one child presented with gingivitis. Furthermore, the difference in the edentulous space at T0, T1, T2, and T3 was not statistically significant (all P > 0.05).

CONCLUSIONS: The digital semi-rigid bridge SM fabricated with PEEK was clinically effective in maintaining the missing space and had advantages over the traditional band/crown loop SM.

PMID:38031148 | DOI:10.1186/s12903-023-03570-2

Adv Rheumatol. 2023 Nov 29;63(1):56. doi: 10.1186/s42358-023-00340-0.

ABSTRACT

BACKGROUND: Some studies have suggested the HLA-B27 gene may protect against some infections, as well as it could play a benefit role on the viral clearance, including hepatitis C and HIV. However, there is lack of SARS-CoV-2 pandemic data in spondyloarthritis (SpA) patients.

AIM: To evaluate the impact of HLA-B27 gene positivity on the susceptibility and severity of COVID-19 and disease activity in axial SpA patients.

METHODS: The ReumaCoV-Brasil is a multicenter, observational, prospective cohort designed to monitor immune-mediated rheumatic diseases patients during SARS-CoV-2 pandemic in Brazil. Axial SpA patients, according to the ASAS classification criteria (2009), and only those with known HLA-B27 status, were included in this ReumaCov-Brasil’s subanalysis. After pairing them to sex and age, they were divided in two groups: with (cases) and without (control group) COVID-19 diagnosis. Other immunodeficiency diseases, past organ or bone marrow transplantation, neoplasms and current chemotherapy were excluded. Demographic data, managing of COVID-19 (diagnosis, treatment, and outcomes, including hospitalization, mechanical ventilation, and death), comorbidities, clinical details (disease activity and concomitant medication) were collected using the Research Electronic Data Capture (REDCap) database. Data are presented as descriptive analysis and multiple regression models, using SPSS program, version 20. P level was set as 5%.

RESULTS: From May 24th, 2020 to Jan 24th, 2021, a total of 153 axial SpA patients were included, of whom 85 (55.5%) with COVID-19 and 68 (44.4%) without COVID-19. Most of them were men (N = 92; 60.1%) with mean age of 44.0 ± 11.1 years and long-term disease (11.7 ± 9.9 years). Regarding the HLA-B27 status, 112 (73.2%) patients tested positive. There were no significant statistical differences concerning social distancing, smoking, BMI (body mass index), waist circumference and comorbidities. Regarding biological DMARDs, 110 (71.8%) were on TNF inhibitors and 14 (9.15%) on IL-17 antagonists. Comparing those patients with and without COVID-19, the HLA-B27 positivity was not different between groups (n = 64, 75.3% vs. n = 48, 48%, respectively; p = 0.514). In addition, disease activity was similar before and after the infection. Interestingly, no new episodes of arthritis, enthesitis or extra-musculoskeletal manifestations were reported after the COVID-19. The mean time from the first symptoms to hospitalization was 7.1 ± 3.4 days, and although the number of hospitalization days was numerically higher in the B27 positive group, no statistically significant difference was observed (5.7 ± 4.11 for B27 negative patients and 13.5 ± 14.8 for B27 positive patients; p = 0.594). Only one HLA-B27 negative patient died. No significant difference was found regarding concomitant medications, including conventional or biologic DMARDs between the groups.

CONCLUSIONS: No significant difference of COVID-19 frequency rate was observed in patients with axial SpA regarding the HLA-B27 positivity, suggesting a lack of protective effect with SARS-CoV-2 infection. In addition, the disease activity was similar before and after the infection.

TRIAL REGISTRATION: This study was approved by the Brazilian Committee of Ethics in Human Research (CONEP), CAAE 30186820.2.1001.8807, and was registered at the Brazilian Registry of Clinical Trials – REBEC, RBR-33YTQC. All patients read and signed the informed consent form before inclusion.

PMID:38031143 | DOI:10.1186/s42358-023-00340-0

J Pharm Policy Pract. 2023 Nov 29;16(1):162. doi: 10.1186/s40545-023-00609-1.

ABSTRACT

BACKGROUND: This study aimed to assess the general public’s perception of services provided by community pharmacies, their willingness to utilize these services, their satisfaction with and understanding of community pharmacists, and their views on dispensing separation and pharmacy medicines (P medicines).

METHODS: An online cross-sectional study was conducted, in which questionnaires were distributed among the general public. A novel questionnaire was designed and validated specifically for this study. It was composed of six sections: demographics, pharmacy usage and service preferences, understanding and satisfaction with pharmacists, views on dispensing separation, private community pharmacies, and knowledge of P medicines. Statistical analyses such as one-way ANOVA, independent t test, and binary logistic regression were employed, with a p value of < 0.05 considered statistically significant.

RESULTS: The study received 222 responses. The majority of the respondents were females within the 20-29-year-old age group (62.2%). Most respondents preferred to consult doctors for medical treatment, with their primary reason for visiting community pharmacies being to collect prescribed medicines. About 52.7% of respondents expressed their willingness to avail of screening services and treatment for minor illnesses at community pharmacies. A statistically significant difference was found among different age groups regarding their views on the dispensing separation system, with those aged 41-50 years demonstrating higher scores. However, the binary logistic regression analysis did not reveal any statistical significance when comparing the understanding of P medicines among respondents.

CONCLUSIONS: In general, the public prefers to consult doctors for medical treatment and visit community pharmacies predominantly to collect prescriptions or purchase over-the-counter medications. Nonetheless, they are also open to utilizing services provided by community pharmacists, particularly screening services and treatment for minor illnesses.

PMID:38031133 | DOI:10.1186/s40545-023-00609-1

Pilot Feasibility Stud. 2023 Nov 29;9(1):194. doi: 10.1186/s40814-023-01421-z.

ABSTRACT

BACKGROUND: Acquired brain injury (ABI) can lead to biopsychosocial changes such as depression, low self-esteem and fatigue. These changes can cause, and be caused by, sexual issues affecting relationships and wellbeing. Given the relationship between sexual wellbeing and mental health, it is feasible that supporting sexual wellbeing will benefit psychological wellbeing. However, neurorehabilitation is inconsistent and often fragmented across the UK, and psychological, sexual and social support are lacking. Research shows that self-management and peer-support programmes can improve quality of life, self-efficacy and psychological wellbeing after brain injury. This protocol describes a feasibility randomised controlled trial (RCT) of a digital self-management programme to support mental and sexual wellbeing (known as HOPE4ABI), co-designed with and for people with ABI.

METHODS: This mixed-methods feasibility RCT has two parallel trial arms of the 8-week digital HOPE4ABI self-management programme. Eligibility criteria include age > 18 years, diagnosed or suspected ABI > 3 months prior to trial entry, access to an Internet-enabled device and ability to engage with the intervention. Referrals to the study website will be made via the National Health Service (NHS), social media and partnering organisations. Sixty eligible participants will be randomised at a ratio of 1:1 to peer-supported (n = 30) or self-directed (n = 30) HOPE4ABI programmes. Primary feasibility outcomes include recruitment and retention rates, engagement, adherence and usage. Secondary outcomes related to standardised measures of quality of life, sexual wellbeing and mental wellbeing. Participants and peer facilitators will be interviewed after the course to assess acceptability across both trial arms.

DISCUSSION: This feasibility trial data is not sufficiently powered for inferential statistical analyses but will provide evidence of the feasibility of a full RCT. Quantitative trial data will be analysed descriptively, and participant screening data representing age, ethnicity and gender will be presented as proportions at the group level. These data may indicate trends in reach to particular demographic groups that can inform future recruitment strategies to widen participation. Progression to a definitive trial will be justified if predetermined criteria are met, relating to recruitment, retention, engagement and acceptability.

TRIAL REGISTRATION: ISRCTN46988394 registered on March 1, 2023.

PMID:38031132 | DOI:10.1186/s40814-023-01421-z