Nevin Manimala

Eur Urol Oncol. 2023 Aug 19:S2588-9311(23)00161-X. doi: 10.1016/j.euo.2023.07.018. Online ahead of print.

ABSTRACT

BACKGROUND: The European Association of Urology guidelines include the lutetium-177 (¹⁷⁷Lu) PSMA-617 prostate-specific membrane antigen (PSMA) ligand as a therapy option for metastatic castration-resistant prostate cancer (mCRPC). A major challenge in clinical practice is to pursue a personalized treatment approach based on robust predictive biomarkers.

OBJECTIVE: To assess the performance of ¹⁷⁷Lu PSMA in real-world practice and to elaborate clinical biomarkers for evaluating treatment responses.

DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective observational study including 233 patients with mCRPC treated with ¹⁷⁷Lu PSMA in eight high-volume European centers.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Baseline characteristics and clinical parameters during and after ¹⁷⁷Lu PSMA treatment were documented. Correlations to treatment response were analyzed using χ² and log-rank tests, with differences between groups with and without disease progression calculated using a Mann-Whitney U test. Univariate and multivariate-adjusted hazard ratios (HRs) were measured using Cox proportional hazards models.

RESULTS AND LIMITATIONS: A prostate-specific antigen (PSA) decrease of ≥30% was observed in 41.7%, 63.5%, and 77.8% of patients after the first, second, and third treatment cycle, respectively. Restaging performed via PSMA positron emission tomography-computed tomography revealed that 33.7% of patients had an imaging-based response, including two patients with a complete response, while 13.4% had stable disease. The median time to progression was 5 mo and the median time until the start of a consecutive antineoplastic therapy was 8.5 mo. Of importance, a PSA decrease ≥30% after the first two cycles of ¹⁷⁷Lu PSMA (1 cycle: p = 0.0003; 2 cycles: p = 0.004), absolute PSA after the first three cycles (1 cycle: p = 0.011; 2 cycles: p = 0.0005; 3 cycles: p = 0.002), and a PSA doubling time >6 mo (p = 0.009) were significantly correlated to treatment response. Furthermore, gamma-glutamyl transferase ≤31 U/L at the start of ¹⁷⁷Lu PSMA therapy was correlated with 1.5 times higher risk of progression for patients without but not with visceral metastases (p = 0.046).

CONCLUSIONS: ¹⁷⁷Lu PSMA is an effective treatment option in mCRPC in the real-world setting. A PSA decrease ≥30% after the first two cycles is an early marker of response that can be easily implemented in clinical practice.

PATIENT SUMMARY: ¹⁷⁷Lu PSMA is a radioactive agent approved for treatment of advanced prostate cancer. We reviewed its use outside of clinical trials for patients treated at eight European centers. We found that ¹⁷⁷Lu PSMA is an effective treatment option in real-world practice. A PSA (prostate-specific antigen) decrease of ≥30% after the first two therapy cycles is an early indicator of response to treatment and can be used in personalizing treatments for patients.

PMID:37604763 | DOI:10.1016/j.euo.2023.07.018

Parkinsonism Relat Disord. 2023 Aug 17:105809. doi: 10.1016/j.parkreldis.2023.105809. Online ahead of print.

ABSTRACT

INTRODUCTION: Deep Brain Stimulation (DBS) is an effective treatment for the motor symptoms of Parkinson’s Disease. The targeted physiological structure for lead location is commonly the subthalamic nucleus (STN). The efficacy of DBS for improving motor symptoms is assessed via the Unified Parkinson’s Disease Rating III Scale (UPDRS-III). In this study, we sought to compare the efficacy of frequency settings utilized for STN-DBS.

METHODS: Following PRISMA Guidelines, a search on PUBMED and MEDLINE was performed to include full-length randomized controlled trials evaluating STN-DBS. The frequency stimulation parameters and Unified Parkinson’s Disease Rating Scale (UPDRS-III) outcomes were extracted in the search. High-frequency stimulation (HFS) was defined as ≥100 Hz and low-frequency stimulation (LFS) was defined as <100 Hz. A frequentist network meta-analysis was performed with odds ratios (OR) and pooling performed using the Mantel-Haenszel method. Statistics are presented as OR [95% CI].

RESULTS: 15 studies consisting of 298 patients were included for analysis. Bilateral HFS -0.68 [-0.89; -0.46] was associated with better UPDRS-III scores compared to bilateral LFS. On the other hand, bilateral LFS with medications (MEDS) was favored over HFS with MEDS (-0.28 [-0.63; 0.07]). Bilateral LFS and MEDS, HFS and MEDS, stimulation (STIM) OFF MEDS ON, HFS, LFS, STIM OFF MEDS OFF UPDRS outcomes were ranked from best to worst outcomes.

DISCUSSION: The outcomes of this study suggest that bilateral HFS has better utility for those with no response to medication, while LFS has additive benefits to medication by improving unique symptoms via different neurophysiological mechanisms.

PMID:37604755 | DOI:10.1016/j.parkreldis.2023.105809

Br J Gen Pract. 2023 Jul 4:BJGP.2023.0007. doi: 10.3399/BJGP.2023.0007. Online ahead of print.

ABSTRACT

BACKGROUND: There are inequalities in the geographical distribution of the primary care workforce in England. Primary care networks (PCNs), and the associated Additional Roles Reimbursement Scheme (ARRS) funding, have stimulated employment of new healthcare roles. However, it is not clear whether this will impact inequalities.

AIM: To examine whether the ARRS impacted inequality in the distribution of the primary care workforce.

DESIGN AND SETTING: A retrospective before-and-after study of English PCNs in 2019 and 2022.

METHOD: The study combined workforce, population, and deprivation data at network level for March 2019 and March 2022. The change was estimated between 2019 and 2022 in the slope index of inequality (SII) across deprivation of full-time equivalent (FTE) GPs (total doctors, qualified GPs, and doctors-in-training), nurses, direct patient care, administrative, ARRS and non- ARRS, and total staff per 10 000 patients.

RESULTS: A total of 1255 networks were included. Nurses and qualified GPs decreased in number while all other staff roles increased, with ARRS staff having the greatest increase. There was a pro- rich change in the SII for administrative staff (-0.482, 95% confidence interval [CI] = -0.841 to -0.122, P<0.01) and a pro- poor change for doctors-in-training (0.161, 95% CI = 0.049 to 0.274, P<0.01). Changes in distribution of all other staff types were not statistically significant.

CONCLUSION: Between 2019 and 2022 the distribution of administrative staff became less pro-poor, and doctors-in-training became pro-poor. The changes in inequality in all other staff groups were mixed. The introduction of PCNs has not substantially changed the longstanding inequalities in the geographical distribution of the primary care workforce.

PMID:37604700 | DOI:10.3399/BJGP.2023.0007

Mult Scler Relat Disord. 2023 Aug 13;78:104931. doi: 10.1016/j.msard.2023.104931. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple Sclerosis (MS) is a chronic disease with a high prevalence of neuropsychiatric symptoms. Mindfulness is a practice that encourages individuals to cultivate a present-focused, acceptance-based approach for managing psychological distress. Its positive effect on MS has been demonstrated, but learning such technique is expensive and time-consuming. In this study, we investigated the feasibility and efficacy of an 8-week, at-home, smart-device aided mindfulness program in a cohort of MS patients. Specifically, we explored the role of a brain-sensing headband providing real-time auditory feedback as supportive tool for meditation exercises.

METHODS: The study included two visits, one at baseline and another after the mindfulness program. We measured adherence to the proposed mindfulness treatment and its effect on questionnaires investigating different psychological domains, cognition, fatigue, quality of life and quantitative EEG parameters. All participants received a smart biofeedback device to be used during the therapeutic program consisting of daily meditative exercises.

RESULTS: Twenty-nine patients were recruited for the present study. Among them, 27 (93%) completed the entire program and 17 (63%) completed more than 80% of the scheduled sessions. We observed a statistically significant reduction of the Ruminative Response Scale score and a significant increase of the Digit Span Backward. Regarding neurophysiological data, we found a significant reduction of the whole-scalp beta and parieto-occipital theta power post intervention.

CONCLUSION: Our results show that an at-home, smart-device aided mindfulness program is feasible for people with MS. The efficacy in terms of reappraisals of stress, cognitive and emotional coping responses is also supported by our neurophysiological data. Further studies are warranted to better explore the role of such approaches in managing the psychological impact of MS diagnosis.

PMID:37603929 | DOI:10.1016/j.msard.2023.104931

Mult Scler Relat Disord. 2023 Jul 22;78:104909. doi: 10.1016/j.msard.2023.104909. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: disease-modifying treatments (DMT) for Multiple Sclerosis (MS) have expanded in recent years making the shared-decision process challenging. Moreover, no head-to-head studies are available within the first-line options. Our aim is to compare therapeutic persistence within first-line DMT: teriflunomide (TER), dimethyl fumarate (DMF), and injectable drugs (INJ) in a real-world setting.

METHODS: Retrospective observational study analyzing diagnosed with Relapsing-Remitting Multiple Sclerosis (RRMS) who started DMT between January 2015 and April 2022 (TER=117, DMF=117, INJ=123). Clinical, radiological, and demographic variables were collected. The primary outcome was the median time to discontinuation of any DMT. Dropout was defined as discontinuation for 6 months for any reason.

RESULTS: Of the total of 357 patients, 155 withdraw with a median time-to-discontinuation of 1.427 years (IQR 2.410). The discontinuation rate was higher in the injectable group, 49.6%; compared to teriflunomide 40.2%, and dimethyl fumarate 39.8% (p = 0.201). The most frequent reason of discontinuation differs within groups (lack of efficacy in TER, 63.8%, and adverse effects in DMF and INJ (40.4% and 40.9% respectively). No difference in persistence was observed between DMT (p = 0.30). After 2018 there has been a tendency to treat in a quick and early manner (lower EDSS; relapse rate and number of naïve patients), statistically significant for TER (p = 0.005, p = 0.010, and p = 0.045).

CONCLUSIONS: Our study demonstrated no differences in persistence between the actual first-line DMT in a real-world setting, although a trend to favor oral-DMT was seen. Reasons for discontinuation differs within groups.

PMID:37603928 | DOI:10.1016/j.msard.2023.104909

Ecotoxicol Environ Saf. 2023 Aug 19;263:115384. doi: 10.1016/j.ecoenv.2023.115384. Online ahead of print.

ABSTRACT

BACKGROUND: Ambient particulate matter with aerodynamic diameter ≤ 2.5 µm (PM_2.5) consists of various toxic constituents. However, the health effect of PM_2.5 may differ depending on its constituents, but the joint effect of PM_2.5 constituents remains incompletely understood.

OBJECTIVE: Our goal was to evaluate the joint effect of long-term PM_2.5 constituent exposures on dyslipidemia and identify the most hazardous chemical constituent.

METHODS: This study included 67,015 participants from the China Multi-Ethnic Cohort study. The average yearly levels of PM_2.5 constituents for all individuals at their residences were assessed through satellite remote sensing and chemical transport modeling. Dyslipidemia was defined as one or more following abnormal blood lipid concentrations: total cholesterol (TC) ≥ 6.22 mmol/L, triglycerides (TG) ≥ 2.26 mmol/L, high-density lipoprotein cholesterol (HDL-C) < 1.04 mmol/L, and low-density lipoprotein cholesterol (LDL-C) ≥ 4.14 mmol/L. The logistic regression model was utilized to examine the single effect of PM2.5 constituents on dyslipidemia, while the weighted quantile sum regression model for the joint effect.

RESULTS: The odds ratio with a 95 % confidence interval for dyslipidemia positively related to per-SD increase in the three-year average was 1.29 (1.20-1.38) for PM_2.5 mass, 1.25 (1.17-1.34) for black carbon, 1.24 (1.16-1.33) for ammonium, 1.33 (1.24-1.43) for nitrate, 1.34 (1.25-1.44) for organic matter, 1.15 (1.08-1.23) for sulfate, 1.30 (1.22-1.38) for soil particles, and 1.12 (1.05-1.92) for sea salt. Stronger associations were observed in individuals < 65 years of age, males, and those with low physical activity. Joint exposure to PM_2.5 constituents was positively related to dyslipidemia (OR: 1.09, 95 %CI: 1.05-1.14). Nitrate was identified as the constituent with the largest weight (weighted at 0.387).

CONCLUSIONS: Long-term exposure to PM_2.5 constituents poses a significant risk to dyslipidemia and nitrate might be the most responsible for the risk. These findings indicate that reducing PM_2.5 constituent exposures, especially nitrate, could be beneficial to alleviate the burden of disease attributed to PM_2.5-related dyslipidemia.

PMID:37603926 | DOI:10.1016/j.ecoenv.2023.115384

J Pediatr Nurs. 2023 Aug 19;73:34-43. doi: 10.1016/j.pedn.2023.08.015. Online ahead of print.

ABSTRACT

AIM: The present study to determine the level of therapeutic communication skills among the students undertaking the pediatric nursing course and explore the associated influencing factors.

METHODS: This descriptive cross-sectional study was conducted with 140 nursing students who took the pediatric nursing course. Data were collected using a Nursing Student Information Form and the Therapeutic Communication Skills Scale for Nursing Students. The mean and percentage calculations, t-test, ANOVA test, and regression analysis were conducted to analyze the correlations between the participants’ descriptive characteristics and their mean scores on the scales.

RESULTS: The participants’ mean scores obtained on the total Therapeutic Communication Skills Scale for Nursing Students and all of its subdimensions were observed to have a statistically significant correlation with variables such as gender, grade point average, willingness to select the nursing department, satisfaction with the nursing department, difficulty in establishing communication, perceived ability to establish social relations, difficulty in communicating with a child, perception of childhood life, experience with child care, fondness for children, interest in playing therapeutic games with children, and perceived ability to communicate with children. In Model 1, certain descriptive characteristics (satisfaction with the nursing department, difficulty in communicating with a child, experience with child care, interest in playing therapeutic games with children, and perceived ability to communicate with children) explained 52.4% of the therapeutic communication skills scores of the pediatric nursing students and were statistically significantly.

CONCLUSIONS: In this study, it was determined that some of the descriptive characteristics of the students who took the pediatric nursing course had a significant effect on their therapeutic communication skills.

IMPLICATIONS FOR PRACTICE: In order to develop the therapeutic communication skills of students undertaking a pediatric nursing course, it is necessary to support these students with a standard curriculum that includes student-centered, innovative, and interactive educational methods, such as role play, case analysis, and video-based learning. It is also recommended to conduct comparative studies on different educational approaches for nursing students undertaking pediatric nursing courses or meta-analyses to evaluate the effectiveness of such approaches.

PMID:37603925 | DOI:10.1016/j.pedn.2023.08.015

Cancer Treat Rev. 2023 Aug 16;120:102617. doi: 10.1016/j.ctrv.2023.102617. Online ahead of print.

ABSTRACT

BACKGROUND: Primary cardiac angiosarcoma (PCA) is the most prevalent histological type of cardiac sarcoma but its rarity poses a challenge for standardizing treatment protocols. Moreover, published studies are limited by small patient numbers and lack of randomization, making it challenging to establish evidence-based treatment strategies. This systematic review aims to consolidate the heterogeneous published data and identify factors related to the treatment outcome of PCA patients.

METHODS: The PubMed and Scopus bibliographic databases were systematically searched for original articles reporting clinical, treatment and outcome data for PCA patients. Kaplan-Meier analysis was used to calculate the time to progression and survival. The Log-Rank test was used to compare progression-free and overall survival data. The Cox proportional hazards regression model was used for univariate and multivariate analysis of survival data.

RESULTS: A total of 127 studies containing data for 162 patients were analyzed. The median age of the patient cohort was 45 years, with males being 1.5 times more frequently affected than females. Tumors were primarily located on the right side of the heart, with a median size of 6 cm. Median progression-free and overall survival of 5 months and 12 months, respectively, were calculated. Age, sex, and resection margins did not have a significant impact on PCA survival, as determined by both univariate and multivariate analyses. The presence of metastases at diagnosis was associated with lower overall survival in univariate analysis, although this effect was not significant in multivariate analysis. Multimodality treatment that incorporated surgery and adjuvant chemo-radiotherapy was associated with a statistically significant survival benefit. Median overall survival increased from 6 months with surgery alone to 13 months and 27 months with adjuvant chemotherapy and chemo-radiotherapy, respectively.

CONCLUSION: Multimodality treatment including surgery and chemo-radiotherapy was found to offer the greatest survival benefit for PCA patients.

PMID:37603906 | DOI:10.1016/j.ctrv.2023.102617

J Craniofac Surg. 2023 Aug 21. doi: 10.1097/SCS.0000000000009628. Online ahead of print.

ABSTRACT

To evaluate the effect of training on increasing baseline knowledge of pediatrics and anesthesia residents about airway management of pediatric patients with tracheostomy. It is a prospective, descriptive, before and after survey study. A questionnaire was conducted to measure the baseline knowledge of pediatrics and anesthesia residents about airway management in patients with pediatric tracheotomy. The same questionnaire was repeated after the education. Of the 63 participants, 42 were pediatric residents and 21 were anesthesiology residents. While the number of participants who answered the cuff part, inner cannula part, obturator part and balloon part of the tracheostomy tube correctly before the training was 27, 4, 10, and 12, respectively, these numbers increased to 53, 52, 57, and 55 after the training. There was a statistically significant improvement after the training in the correct response of the cuff, inner cannula, obturator, and balloon sections. A statistically significant improvement was observed in the answers received after the training for all 7 questions regarding the clinical scenario of accidental decannulation and tracheostomy bleeding compared to the pre-training. There was a statistical improvement in part where the participants rated themselves. In conclusion, training increases the ability of healthcare professionals to cope with life-threatening complications related to pediatric tracheotomy. A standardized education program on pediatric tracheostomy should be included in the routine programs of associated departments such as emergency medicine, anesthesia, and pediatrics residencies.

PMID:37603891 | DOI:10.1097/SCS.0000000000009628

Acta Radiol. 2023 Aug 21:2841851231189998. doi: 10.1177/02841851231189998. Online ahead of print.

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a markedly increased prevalence of coronary artery disease (CAD). Radiomics features of pericoronary adipose tissue (PCAT) were correlated with inflammation, which may have potential value in the prediction of CAD.

PURPOSE: To determine whether radiomics analysis of PCAT captured by plain computed tomography (CT) could predict obstructive CAD in patients with T2DM.

MATERIAL AND METHODS: The study included 155 patients with T2DM with suspected CAD between January 2020 and December 2021. Volumes of right coronary artery of 10-50 mm were delineated in the plain CT to extract radiomics features and PCAT CT attenuation (PCATa). Least absolute shrinkage and selection operator was used to select the useful radiomics features to calculate the radiomics score (Rad-score). Univariate and multivariable logistic regression were applied to select independent predictors. The predictive performance was evaluated by the area under the receiver operating characteristics curve (AUC).

RESULTS: Rad-score (per 0.1 increments: odds ratio [OR] = 1.297; P < 0.001), coronary artery calcium score (CACS) (OR = 1.003; P = 0.037), and sex (OR = 3.245; P = 0.026) were identified as independent predictors for obstructive CAD. Rad-score (AUC = 0.835) outperformed CACS (AUC = 0.780), sex (AUC = 0.665), and PCATa (AUC = 0.550) in predicting obstructive CAD (P = 0.017 and 0.003 for Rad-score vs. sex and PCATa, respectively); however, the improvement between Rad-score and CACS had no statistical significance (P = 0.490).

CONCLUSION: Plain CT-derived Rad-score may be used as a preliminary screening tool for obstructive CAD in patients with T2DM.

PMID:37603886 | DOI:10.1177/02841851231189998