OBJECTIVE: We hypothesized that Cav1.3 blockade by cinnarizine may achieve similar, or greater, reduction in aldosterone secretion than nonselective Cav1.2/1.3 blockade by nifedipine.
METHODS: Separate wells of angiotensin II-stimulated HAC15 cells were treated with either cinnarizine (1-30 μM) or nifedipine (1-100 μM). Aldosterone concentrations were measured in culture medium; RNA extraction and quantitative polymerase chain reaction were performed to evaluate CYP11B2 expression. A prospective, open-label, crossover study was conducted of 15 adults with PA, treated with 2 weeks of cinnarizine 30 mg 3 times a day or nifedipine extended release 60 mg daily, separated by a 2-week washout. The hierarchical primary outcome was change in aldosterone-to-renin ratio (ARR), urinary tetrahydroaldosterone (THA), and plasma aldosterone concentration (PAC). Blood pressure change was a secondary outcome. Parametric analysis was undertaken on log-transformed data. (ClinicalTrials.gov: NCT05686993).
RESULTS: Both drugs reduced aldosterone concentrations and CYP11B2 expression in vitro. Mean changes ± SEM in fold change of aldosterone concentrations and CYP11B2 were -0.47 ± 0.05 and -0.56 ± 0.07, respectively, with cinnarizine 30 μM and -0.59 ± 0.05 and -0.78 ± 0.07 with nifedipine 100 μM. In the clinical crossover trial, ARR was reduced by nifedipine but not cinnarizine (F = 3.25; P = .047); PAC rose with both drugs (F = 4.77; P = .013), but urinary THA was unchanged.
CONCLUSION: A Cav1.3 ligand, cinnarizine, reduced aldosterone secretion from adrenocortical cells, but at maximum-soluble concentrations was less effective than the nonselective calcium blocker, nifedipine. At clinical doses, cinnarizine did not reduce plasma ARR in patients with PA, and, as in vitro, was inferior to nifedipine. The limited efficacy of high-dose nifedipine may be due to incomplete Cav1.3 blockade, or to a role for non-L-type calcium channels in aldosterone secretion.
OBJECTIVE: To investigate the association between smoking status or smoking cessation time and complications after cancer surgery.
DATA SOURCES: Embase, CINAHL, Medline COMPLETE, and Cochrane Library were systematically searched for studies published from January 1, 2000, to August 10, 2023.
STUDY SELECTION: Observational and interventional studies comparing the incidence of complications in patients undergoing cancer surgery who do and do not smoke.
DATA EXTRACTION AND SYNTHESIS: Two reviewers screened results and extracted data according to the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) reporting guidelines. Data were pooled with a random-effects model and adjusted analysis was performed.
MAIN OUTCOMES AND MEASURES: The odds ratio (OR) of postoperative complications (of any type) for people who smoke currently vs in the past (4-week preoperative cutoff), currently smoked vs never smoked, and smoked within shorter (2-week cutoff) and longer (1-year cutoff) time frames.
RESULTS: The meta-analyses across 24 studies with a pooled sample of 39 499 participants indicated that smoking within 4 weeks preoperatively was associated with higher odds of postoperative complications compared with ceasing smoking for at least 4 weeks (OR, 1.31 [95% CI, 1.10-1.55]; n = 14 547 [17 studies]) and having never smoked (OR, 2.83 [95% CI, 2.06-3.88]; n = 9726 [14 studies]). Within the shorter term, there was no statistically significant difference in postoperative complications between people who had smoked within 2 weeks preoperatively and those who had stopped between 2 weeks and 3 months in postoperative complications (OR, 1.19 [95% CI, 0.89-1.59]; n = 5341 [10 studies]), although the odds of complications among people who smoked within a year of surgery were higher compared with those who had quit smoking for at least 1 year (OR, 1.13 [95% CI, 1.00-1.29]; N = 31 238 [13 studies]). The results from adjusted analyses were consistent with the key findings.
CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis of smoking cessation and complications after cancer surgery, people with cancer who had stopped smoking for at least 4 weeks before surgery had fewer postoperative complications than those smoking closer to surgery. High quality, intervention-based evidence is needed to identify the optimal cessation period and inform clinicians on the trade-offs of delaying cancer surgery.
OBJECTIVE: To address this gap in research, this scoping review aims to determine the facilitators and barriers to implementing DHTs in LMIC hospital settings following the onset of the COVID-19 pandemic. Additionally, the review outlined the types of DHTs that have been implemented in LMICs' hospitals during this pandemic and finally developed a classification framework to categorize the landscape of DHTs.
METHODS: Systematic searches were conducted on PubMed, Scopus, Web of Science, and Google Scholar for studies published from March 2020 to December 2023. We extracted data on authors, publication years, study objectives, study countries, disease conditions, types of DHTs, fields of clinical medicine where the DHTs are applied, study designs, sample sizes, characteristics of the study population, study location, and data collection methods of the included studies. Both quantitative and qualitative data were utilized to conduct a thematic analysis, using a deductive method based on the Practical, Robust Implementation and Sustainability Model (PRISM), to identify facilitators and barriers to DHT implementation. Finally, all accessible DHTs were identified and organized to create a novel classification framework.
RESULTS: Twelve studies were included from 292 retrieved articles. Telemedicine (n=5) was the most commonly used DHT in LMICs' hospitals, followed by hospital information systems (n=4), electronic medical records (n=2), and mobile health (n=1). These 4 DHTs, among the other existing DHTs, allowed us to develop a novel classification framework for DHTs. The included studies used qualitative methods (n=4), which included interviews and focus groups, quantitative methods (n=5), or a combination of both (n=2). Among the 64 facilitators of DHT implementation, the availability of continuous on-the-job training (n=3), the ability of DHTs to prevent cross-infection (n=2), and positive previous experiences using DHTs (n=2) were the top 3 reported facilitators. However, of the 44 barriers to DHT implementation, patients with poor digital literacy and skills in DHTs (n=3), inadequate awareness regarding DHTs among health care professionals and stakeholders (n=2), and concerns regarding the accuracy of disease diagnosis and treatment through DHTs (n=2) were commonly reported.
CONCLUSIONS: In the postpandemic era, telemedicine, along with other DHTs, has seen increased implementation in hospitals within LMICs. All facilitators and barriers can be categorized into 6 themes, namely, (1) Aspects of the Health Care System; (2) Perspectives of Patients; (3) External Environment; (4) Implementation of Sustainable Infrastructure; (5) Characteristics of Health Care Organization; and (6) Characteristics of Patients.
METHODS: Clinical and 30-day outcome data for inpatients with AKI who were hemodynamically stable and not on ventilation and who received intermittent hemodialysis (IHD) or continuous kidney replacement therapy (CKRT) in public hospitals in Kuwait from January 1 to December 31, 2021, were prospectively collected.
RESULTS: We recruited 229 patients (age: 59.9 years; males, 60.3%; baseline estimated baseline glomerular filtration [eGFR], 56 mL/min). CKRT accounted for 72.9% of cases due to lack of access to water treatment. No statistically significant differences were observed between groups in terms of age, baseline eGFR, sex, comorbidities, cause of AKI, or fluid administration. The intensive care unit contributed 21% of cases, with no significant difference between groups. More IHD patients received diuretics (62.9% vs. 43.1% for CKRT, p = 0.008). At 30 days, 21.8% of patients had died. There was no statistically significant difference in mortality between groups (16.1% for IHD vs. 24% for CKRT, p = 0.2). Final eGFR was 53.2 mL/min, with no difference between groups. Complete kidney recovery was greater with CKRT (33.1% vs. 13.5%, p = 0.009). Baseline eGFR < 60 mL/min did not influence mortality or kidney recovery.
CONCLUSION: Compared with IHD, CKRT did not lower mortality at 30 days, which is similar to that of randomized trials; however, it was associated with better complete kidney recovery, which was reported in observational studies.
STUDY SAMPLE: Retrospective data from 23 collaborating centres across 16 LMICs were collected. All participants were adults seeking help for hearing problems. A machine learning approach was utilised to classify the hearing threshold data and identify representative profiles. The study comprised 5773 participants.
RESULTS: The results revealed mildly sloping audiometric patterns with varying severity. The patterns differed from previous studies conducted in high-income regions which included more steeply sloping losses. The findings also indicated a higher proportion of more severe levels of hearing loss.
CONCLUSIONS: These variations could be attributed to population-level differences in the causative mechanisms of hearing loss in LMICs, such as a higher prevalence of infectious disease-related hearing loss. The results may also reflect differences in health seeking behaviours. This study highlights the need for tailored, scalable, hearing interventions for LMICs.
METHOD: A cross-sectional survey was developed using pilot testing with clinimetric sensibility assessment to ensure clarity and relevance, and the Open-Source Metric for Measuring Arabic Narratives (OSMAN) to assess readability. The Checklist for Reporting Internet E-Surveys (CHERRIES) was used to enhance the quality of the survey. The survey was distributed via social media to Arabic-speaking patients with self-reported RMDs. Collected data included demographics, disease characteristics, medication use, treatment satisfaction factors, perceived causes, and patient concerns.
RESULTS: Of the 1050 responses received, 456 were complete and included in the analysis. Most respondents were female (81.4%) and between the ages of 25 and 44 (63.4%). The most frequently reported diseases were systemic lupus erythematosus, rheumatoid arthritis, and ankylosing spondylitis. Nearly all (97.1%) used medications within the previous three months, primarily hydroxychloroquine, glucocorticoids, and biologics. Key factors influencing treatment satisfaction were pain relief, laboratory result discussions, sleep quality, and mood improvement. Patients perceived immune system abnormalities (76.5%), psychological factors (54.8%), and genetics (41.7%) as primary disease causes. Main concerns included fear of disease complications, adverse drug reactions, and being a burden to others. Rheumatologists and internet search engines were the primary sources of information for patients. Most avoided alternative medicine, while 33.3% used it.
CONCLUSION: This survey is the first and largest in the MENA region, providing valuable insights into patient perspectives on RMD. It highlights the need for holistic management, enhanced education, and supportive services to improve quality of life. Key Points • The most commonly perceived causes of rheumatic and musculoskeletal diseases among patients with RMD were immune system abnormalities, psychological factors, genetic/hereditary influences, and envy. • Patients' top concerns included fear of future complications, adverse drug reactions, becoming a burden to others, physical disability, and issues related to marriage and childbirth. • Key factors influencing treatment satisfaction included pain relief, discussions of laboratory results, sleep quality, and mood improvement. • Approximately one-third of patients had consulted practitioners of complementary and alternative medicine.
METHOD: Formalin-fixed paraffin-embedded tissues of 30 CRC patients were retrieved and reviewed. DNA was isolated from selected tissues. Desirable quality check using Qubit and Nanoquant machine was done, and desirable libraries prepared were loaded into the sequencer for sequencing. Using Illumina BaseSpace and Illumina Variant interpreter, generated FastQ data were treated for annotation, alignment, and mapping with reference genome. Sequencing-runs with Phred-score ≥ 30 were selected as desirable runs. Finally, the variants were validated on NCBI-dsSNP and Ensembl databases for clinical consequence interpretations.
RESULTS: Overall, patient distribution consists of 12(40%) females and 18 (60%) males with mean age (53.2 + 5.3). most patients were in TNM stage-3: 53.3% (15/30) and the least was Stage-4: 20%(6/30) respectively. Overall, 73.3%: (22/30) completed the sequencing, and 552 mutations involving 29 genes and 12 chromosomes were detected. The most upregulated variants are KIT:68(12.3%), FGFR4:61(11.1%), EGFR:60(10.9%), ALK:53(9.6%), DCUN1D1:41(7.4%), PDGFR:40(7.2%), KRAS:33(6.0%), CDK4:27(4.9%), FGFR3:26(4.7%), MTOR:14(2.6), while NRAS, CDK6, PIK3CA, and RET each has 13(2.4%) apiece. Chromosomes 4:134/55(24.2%), chr7:84/552(15.2%), chr12:71/552(12.9%), chr5:64/552(11.6%), chr2:61/552(11.1%), chr3:54/552(9.8%), and chr1:43/552(7.8%) are the most involved chromosomes. Nine genes (APC, NRAS, ALK, PIK3CA, KRAS, IDH1, FGFR1, ERBB2, and ESR1) are identified as pathogenic-causing variants in CRC.
CONCLUSION: This is the first NGS-based molecular study on FFPE-CRC tissues in hospital-USM that showed the most upregulated variants in CRC and identified nine genes as crucial pathogenic variants.
RECENT FINDINGS: This case report presents the first documented instance of such a unique clinical scenario. The marked histological disparities between GCT and ECD further underscore the enigmatic nature of this case. The intricate interplay of genetic, environmental, and pathophysiological factors that led to the simultaneous development of two distinct neoplasms in the same patient is yet to be fully elucidated. This case not only challenges our understanding of the etiology of these conditions but also emphasizes the importance of a multidisciplinary approach to the evaluation and management of such complex cases. The confluence of rare entities, the diagnostic complexities they introduce, and the imperative need for tailored treatment strategies exemplify the intricate landscape of oncological care. This case serves as a compelling reminder of the many unknown facets of disease etiology and the significance of collaborative medical efforts in offering the best possible care for patients confronting exceptionally rare clinical presentations.