Nevin Manimala

Orv Hetil. 2022 Nov 20;163(47):1862-1871. doi: 10.1556/650.2022.32640. Print 2022 Nov 20.

ABSTRACT

INTRODUCTION: Several international studies have already confirmed the importance of the socioeconomic status of acute myocardial infarction patients in terms of patient care and prognosis. To our knowledge, a nationwide examination of this kind has not yet taken place in Hungary. The investigation of this problem field was made possible by the fact that from January 1, 2014, all healthcare providers must record the data of patients treated with a diagnosis of acute myocardial infarction in the database of the Hungarian Myocardial Infarction Registry (HUMIR).

OBJECTIVE: In this study, the authors searched for an answer to whether the complex development index (CDI) in Hungary’s 174 districts and 23 capital districts influences the treatment and prognosis of acute myocardial infarction patients.

METHOD: Based on the CDI worked out by the Hungarian Central Statistical Office, the authors divided the Hungarian districts into low (CDI_L), medium (CDI_M) and high (CDI_H) CDI groups according to their values. They examined the incidence, hospital treatment and prognosis of acute myocardial infarction in these administrative-territorial units. The HUMIR included 66,253 patients treated by myocardial infarction between 2015 and 2019. Their place of residence could be identified based on the zip code and in which district it was located. In the examined population, 29,101 patients with ST-elevation (STEMI) and 37,152 without ST-elevation (NSTEMI) received treatment for acute myocardial infarction.

RESULTS: In the population over 15 years of age, the age-standardized incidence of STEMI was 68.8 per 100,000 inhabitants a year in the CDI_L group and 52.7 per 100,000 inhabitants a year in the CDI_H group. Almost the same values were found in all three CDI subgroups of NSTEMI incidence (69.5 and 67 per 10,000 inhabitants a year). The frequency of percutaneous coronary intervention in the case of STEMI was higher than in NSTEMI, but within the groups, CDI did not influence the performance of this treatment. In the case of STEMI, the rates of patients who underwent percutaneous coronaria intervention in all three CDI subgroups (CDI_L, CDI_M, CDI_H) were 83.5%, 83.7%, 83.5%, while in the case of NSTEMI they were 57.4%, 57.7%, 57.3%. The authors applied a Cox multivariate regression analysis to examine myocardial infarction mortality. The CDI did not affect the 30-day mortality rates in the case of any myocardial infarction: the hazard ratio (HR) values were 0.906 and 0.914 (p = 0.04659; p = 0.04686) in the case of STEMI, while 1.067 and 1.001 (p = 0.16520; p = 0.98933) in the case of NSTEMI. In the case of a STEMI diagnosis, the risk of the 30-364-day and the 1-year mortality in the subgroup of CDI_H was significantly lower (HR = 0.822 and 0.816) than in the subgroup of CDI_L (p = 0.00096 and p = 0.00001). In the case of NSTEMI diagnosis, the authors found a difference in the risk of beyond 1-year mortality by comparing the districts in the subgroup of CDI_L with the districts in CDI_H: in the latter case, the HR of the mortality was 0.876, which was significantly lower (p = 0.00029) than in the subgroup of CDI_L.

CONCLUSION: The CDI has independent prognostic significance in determining the late prognosis of acute myocardial infarction patients. Orv Hetil. 2022; 163(47): 1862-1871.

PMID:36422687 | DOI:10.1556/650.2022.32640

Physiol Int. 2022 Nov 21. doi: 10.1556/2060.2022.00113. Online ahead of print.

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) resulted in a worldwide pandemic, due to its great capacity to invade the human body. Previous studies have shown that the primary route of invasion of this virus is the human respiratory tract via the co-expression of ACE2 receptor and TMPRSS2, a serine protease on the cellular surface. Interestingly, this condition is present not only on the respiratory epithelium but on the conjunctival mucosa, as well. Thus, we hypothesized that SARS-CoV-2 is present on the conjunctival mucosa.

AIM: To prove that SARS-CoV-2 can be detected in the conjunctiva.

METHODS: Previously nasopharyngeal swab-sample based real-time polymerase chain reaction (PCR) positive COVID-19 infected patients were selected at the COVID Care Centers of Semmelweis University, Budapest, Hungary. The study was approved by the ethical committee of Semmelweis University. During their recovery, both nasopharyngeal and conjunctival swab-samples were taken and PCR method was used to detect the presence of SARS-CoV-2 RNA. Appropriate statistical analysis was performed.

RESULTS: The study population consisted of 97 patients, 49 females (50.5%) and 48 males (49.5%), with a mean age of 67.2 ± 11.9 years. During recovery, with nasopharyngeal swabs, the PCR test was positive in 55 cases (56.70%), whereas with conjunctival swabs it was positive in 8 cases (8.25%). Both tests were positive in 5 cases (5.15%). In some patients, ocular symptoms were observed as well. The rest of the patients (29 cases) had negative nasopharyngeal PCR tests during recovery.

CONCLUSIONS: Although only in few cases, the data of the present study provides a proof of concept that SARS-CoV-2 can be present on the conjunctival mucosa even in nasopharyngeal negative patients, a finding, which can have clinical importance. Also, on the basis of these findings one can hypothesize that – in addition to the respiratory tract – the conjunctiva can be an entrance route for SARS-CoV-2 to the human body. Thus, in high-risk conditions, in addition to covering the mouth and nose with mask, the protection of the eyes is also strongly recommended.

PMID:36422684 | DOI:10.1556/2060.2022.00113

Eur Arch Psychiatry Clin Neurosci. 2022 Nov 24. doi: 10.1007/s00406-022-01527-0. Online ahead of print.

ABSTRACT

Samples can be prone to ascertainment and attrition biases. The Australian Genetics of Depression Study is a large publicly recruited cohort (n = 20,689) established to increase the understanding of depression and antidepressant treatment response. This study investigates differences between participants who donated a saliva sample or agreed to linkage of their records compared to those who did not. We observed that older, male participants with higher education were more likely to donate a saliva sample. Self-reported bipolar disorder, ADHD, panic disorder, PTSD, substance use disorder, and social anxiety disorder were associated with lower odds of donating a saliva sample, whereas anorexia was associated with higher odds of donation. Male and younger participants showed higher odds of agreeing to record linkage. Participants with higher neuroticism scores and those with a history of bipolar disorder were also more likely to agree to record linkage whereas participants with a diagnosis of anorexia were less likely to agree. Increased likelihood of consent was associated with increased genetic susceptibility to anorexia and reduced genetic risk for depression, and schizophrenia. Overall, our results show moderate differences among these subsamples. Most current epidemiological studies do not search for attrition biases at the genetic level. The possibility to do so is a strength of samples such as the AGDS. Our results suggest that analyses can be made more robust by identifying attrition biases both on the phenotypic and genetic level, and either contextualising them as a potential limitation or performing sensitivity analyses adjusting for them.

PMID:36422680 | DOI:10.1007/s00406-022-01527-0

Cancer. 2022 Nov 24. doi: 10.1002/cncr.34565. Online ahead of print.

ABSTRACT

BACKGROUND: Immunotherapy using a checkpoint inhibitor (CPI) alone or in combination with chemotherapy is the standard of care for treatment-naive patients with advanced non-small cell lung cancer (NSCLC) without driver mutations for which targeted therapies have been approved. It is unknown whether continuing CPI treatment beyond disease progression results in improved outcomes.

METHODS: Patients who experienced progressive disease (PD) after a clinical benefit from chemotherapy plus a CPI were enrolled. Patients received pembrolizumab (200 mg every 3 weeks) plus next-line chemotherapy. The primary end point was progression-free survival (PFS) according to the Response Evaluation Criteria in Solid Tumors (version 1.1). Key secondary end points included the overall survival (OS), clinical benefit rate, and toxicity. The authors’ hypothesis was that continuing pembrolizumab beyond progression would improve the median PFS to 6 months in comparison with a historical control of 3 months with single-agent chemotherapy alone.

RESULTS: Between May 2017 and February 2020, 35 patients were enrolled. The patient and disease characteristics were as follows: 51.4% were male; 82.9% were current or former smokers; and 74.3%, 20%, and 5.7% had adenocarcinoma, squamous cell carcinoma, and NSCLC not otherwise specified, respectively. The null hypothesis that the median PFS would be 3 months was rejected (p < .05). The median PFS was 5.1 months (95% confidence interval [CI], 3.6-8.0 months). The median OS was 24.5 months (95% CI, 15.6-30.9 months). The most common treatment-related adverse events were fatigue (60%), anemia (54.3%), and nausea (42.9%). There were no treatment-related deaths.

CONCLUSIONS: Pembrolizumab plus next-line chemotherapy in patients with advanced NSCLC who experienced PD after a clinical benefit from a CPI was associated with statistically significant higher PFS in comparison with historical controls of single-agent chemotherapy alone.

PMID:36420773 | DOI:10.1002/cncr.34565

Trop Med Int Health. 2022 Nov 24. doi: 10.1111/tmi.13831. Online ahead of print.

ABSTRACT

OBJECTIVES: To determine the comparative efficacy and safety of a fixed dose of benznidazole (BZN) with an adjusted-dose for T. cruzi-seropositive adults without cardiomyopathy.

METHODS: We conducted a systematic review and individual participant data (IPD) meta-analysis following Cochrane methods, and the PRISMA-IPD statement for reporting. Randomized controlled trials (RCTs) allocating participants to fixed or adjusted doses of BZN for T. cruzi-seropositive adults without cardiomyopathy were included. We searched (December 2021) Cochrane, MEDLINE, EMBASE, LILACS and trial registries and contacted Chagas experts. Selection, data extraction, risk of bias assessment using the Cochrane tool, and a GRADE summary of finding tables were performed independently by pairs of reviewers. We conducted a random-effects IPD meta-analysis using the one-stage strategy, or, if that was impossible, the two-stage strategy.

RESULTS: Five RCTs (1198 patients) were included, none directly comparing fixed with adjusted doses of BZN. Compared to placebo, BZN therapy was strongly associated with negative qPCR and sustainable parasitological clearance regardless of the type of dose and subgroup analyzed. For negative qPCR, the fixed/adjusted rate of odds ratios (ROR^F/A ) was 8.83 (95%CI 1.02-76.48); for sustained parasitological clearance it was 4.60 (95%CI 0.40-52.51), probably indicating at least non-inferior effect of fixed doses, with no statistically significant interactions by scheme for global and most subgroup estimations. The ROR^F/A for treatment interruption due to adverse events was 0.44 (95%CI, 0.14-1.38), probably indicating no worse tolerance of fixed doses.

CONCLUSIONS: We found no direct comparison between fixed and adjusted doses of BZN. However, fixed doses vs. placebo are probably not inferior to weight-adjusted doses of BZN vs. placebo in terms of parasitological efficacy and safety. Network IPD meta-analysis, through indirect comparisons, may well provide the best possible answers in the near future.

REGISTRATION: The study protocol was registered in PROSPERO (CRD42019120905).

PMID:36420767 | DOI:10.1111/tmi.13831

J Radiat Res. 2022 Nov 24:rrac078. doi: 10.1093/jrr/rrac078. Online ahead of print.

ABSTRACT

Although mammalian fetuses have been suggested to be sensitive to radiation, an increased frequency of translocations was not observed in blood lymphocytes from atomic bomb (A-bomb) survivors who were exposed to the bomb in utero and examined as adults. Since experiments using hematopoietic cells of mice and rats confirmed this finding, it was hypothesized that either irradiated fetal hematopoietic stem cells (f-HSCs) cannot generate exchange-type chromosomal aberrations or cells bearing induced aberrations are eliminated before the animals reach adulthood. In the present study, pregnant mice (12.5-15.5 days post coitum [dpc]) were irradiated with 2 Gy of X-rays and long-term HSCs (LT-HSCs) were isolated 24 h later. Multicolor fluorescence in situ hybridization (mFISH) analysis of LT-HSC clones proliferated in vitro showed that nine out of 43 (21%) clones from fetuses and 21 out of 41 (51%) clones from mothers bore translocations. These results indicate that cells with translocations can arise in mouse f-HSCs but exist at a lower frequency than in the mothers 24 h after X-ray exposure. Thus, it seems likely that translocation-bearing f-HSCs are generated but subsequently disappear, so that the frequency of lymphocyte translocations may decrease and reach the control level by the time the animals reach adulthood.

PMID:36420765 | DOI:10.1093/jrr/rrac078

Cancer Med. 2022 Nov 24. doi: 10.1002/cam4.5470. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: In general, there are not many studies exploring the clinical value of adjuvant chemotherapy or maintenance chemotherapy (AC/MC) after induction chemotherapy and concurrent chemoradiotherapy (IC+CCRT+AC/MC). The purpose of this study was to establish a clinical nomogram for the use of AC/MC in patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC).

MATERIAL AND METHODS: Two centers (Guangzhou Medical University Cancer Center [N = 1226] and Zhongshan People’s Hospital [N = 150]) recruited 1376 patients with LA-NPC. All the patients underwent IC+CCRT; 560 patients received AC with cisplatin/nedaplatin plus docetaxel/paclitaxel (TP) or cisplatin/nedaplatin plus fluorouracil (PF), and 81 patients received MC with S-1. Multivariate Cox regression was used to confirm optimal predictors of progression-free survival (PFS), and a nomogram was established to identify patients into low-risk and high-risk cohorts. Additionally, bootstrap internal validation was performed to further verify our nomogram.

RESULTS: After propensity score matching (PSM), the survival curves were not statistically different between IC+CCRT+AC/MC and IC+CCRT (all p > 0.05). Then, a nomogram was developed based on variables that were screened by univariate and multivariate Cox regression, including N stage, cumulative platinum dose during CCRT, body mass index (BMI), IC cycles, IC regimen and cervical lymph node (CLN) necrosis and infiltration of adjacent tissues. The results of the nomogram showed that the high-risk cohort had greatly worse 5-year DMFS, LRFS, PFS and OS compared to low-risk cohort (all p < 0.05), and subgroup analysis found that the 5-year DMFS, PFS and OS of patients treated with IC+CCRT+AC/MC were better than those treated with IC+CCRT in high-risk cohort (all p < 0.05). Notably, the incidence of adverse effects for IC+CCRT+AC cohort was higher than that for IC+CCRT+MC cohort, especially leukocytopenia and neutropenia. IC+CCRT and IC+CCRT+MC were associated with similar incidences of adverse effects.

CONCLUSIONS: The addition of AC or MC to IC+CCRT could improve the DMFS of patients with high-risk NPC and prolong their survival. Additionally, our findings suggest a potential role of AC/MC following IC plus CCRT in the treatment of high-risk LA-NPC.

PMID:36420689 | DOI:10.1002/cam4.5470

Musculoskeletal Care. 2022 Nov 24. doi: 10.1002/msc.1716. Online ahead of print.

ABSTRACT

INTRODUCTION: The aim of this study was to evaluate patient reported outcome measures using the EQ5D-5L and EQ5D-5L visual analogue scale (VAS) following elective shoulder and elbow orthopaedic list delays. This was further correlated with patients’ intention to proceed with the planned surgery.

METHODS: Patients on the waiting list for more than 26 weeks were included in the study. Telephone interviews were conducted utilising the EQ5D-5L and the EQ5D-5L VAS at the time of addition to the waiting list and presently.

RESULTS: 75 out of 324 screened patients were eligible. 62 (82.7%) patients still wanted to proceed with their planned procedure while 13 (17.3%) patients in the other group no longer wanted to proceed. There was no statistically significant difference in the mean age, gender, initial trial of conservative treatment and limb laterality between these groups (p < 0.05). There was a statistically significant difference in the mean duration of being on the waiting list between these groups (40.4 ± 19 vs. 62.9 ± 17.5 weeks respectively). Furthermore, statistically significant differences (p < 0.05) in the current EQ5D-5L VAS scores were observed between these groups (52.4 vs. 65.8 respectively).

CONCLUSION: This study has shown that majority of patients on elective shoulder and elbow orthopaedic lists with prolonged waiting list delays and improved EQ5D-5L scores are likely to decline the planned procedure and vice versa. Nevertheless, the unplanned ‘watchful waiting’ caused by the COVID-19 pandemic and leading to patients deciding to decline surgery, is not a substitute for timely planned surgery to alleviate patients’ suffering.

PMID:36420684 | DOI:10.1002/msc.1716

Hum Psychopharmacol. 2022 Nov 24:e2858. doi: 10.1002/hup.2858. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the impact of solriamfetol, a dopamine and norepinephrine reuptake inhibitor, on on-the-road driving performance in participants with narcolepsy.

METHODS: In this randomised, double-blind, placebo-controlled, crossover study, driving performance during a 1 h on-road driving test was assessed at 2 and 6 h post-dose following 7 days of treatment with solriamfetol (150 mg/day for 3 days, followed by 300 mg/day for 4 days) or placebo. The primary endpoint was standard deviation of lateral position (SDLP) at 2 h post-dose.

RESULTS: The study included 24 participants (54% male; mean age, 40 years); 22 had evaluable SDLP data. At 2 h post-dose, median SDLP was significantly lower (improved) with solriamfetol compared with placebo (19.08 vs. 20.46 cm [median difference, -1.9 cm], p = 0.002). Four participants on solriamfetol and 7 on placebo had incomplete driving tests. At 6 h post-dose, median SDLP was not statistically significantly different with solriamfetol compared with placebo (19.59 vs. 19.78 cm [median difference, -1.1 cm], p = 0.125). Three participants on solriamfetol and 10 on placebo had incomplete driving tests. Common adverse events (≥5%) included headache, decreased appetite, and somnolence.

CONCLUSIONS: Solriamfetol 300 mg/day improved on-the-road driving performance, at 2 h post-administration in participants with narcolepsy.

PMID:36420633 | DOI:10.1002/hup.2858

Artif Organs. 2022 Nov 24. doi: 10.1111/aor.14465. Online ahead of print.

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) became an accepted therapy for the treatment of severe acute respiratory distress syndrome and chronic obstructive pulmonary disease. However, ECMO systems are still prone to thrombus formation and decrease of gas exchange over time. Therefore, it is necessary to conduct qualified studies to identify parameters for optimization of ECMO systems, and especially the oxygenator. However, commercially marketed oxygenators are not always appropriate and available for certain research use cases. Therefore, we aimed to design an oxygenator, which is suitable for various test conditions such as blood tests, numerical simulation, and membrane studies, and can be modified in membrane area size and manufactured in laboratory.

METHODS: Main design criteria are a homogeneous blood flow without stagnation zones, low pressure drop, manufacturability in the lab, size variability with one set of housing parts and cost-efficiency. Our newly designed oxygenator was tested comparatively regarding blood cell damage, gas transfer performance and pressure drop to prove the validity of the design in accordance with a commercial device.

RESULTS: No statistically significant difference between the tested oxygenators was detected and our new oxygenator demonstrated sufficient hemocompatibility. Furthermore, our variable oxygenator has proven that it can be easily manufactured in the laboratory, allows to use various membrane fiber configurations and can be reopened easily and non-destructively for analysis after use, and the original geometry is available for numerical simulations.

CONCLUSION: Therefore, we consider this newly developed device as a valuable tool for basic experimental and numerical research on the optimization of oxygenators.

PMID:36420613 | DOI:10.1111/aor.14465