Category: Nevin Manimala

Clin Park Relat Disord. 2023 Jun 28;9:100208. doi: 10.1016/j.prdoa.2023.100208. eCollection 2023.

ABSTRACT

INTRODUCTION: Data on Huntington’s disease (HD) epidemiology, treatment patterns, and economic burden in Israel are scarce.

METHODS: Annual prevalence and incidence of HD (ICD-9-CM 333.4) were assessed in the Israel-based Maccabi Healthcare Services (MHS) database 2016-2018. Adherence (medication possession rate [MPR], proportion of disease covered) were assessed for adult people with HD (PwHD) 2013-2018. Healthcare resources utilization (HCRU) and costs related to inpatient and outpatient visits and all medications in 2018 were assessed for PwHD, who were randomly matched to MHS members without HD (1:3) by birth-year and sex.

RESULTS: Overall, 164 patients had at least one HD diagnosis. Annual prevalence and incidence were 4.45 and 0.24/100,000, respectively. A total of 67.0% of adult patients (n = 106) were taking tetrabenazine (median MPR and proportion of disease covered, 74.3% and 30.2%, respectively), 65.1% benzodiazepines (75.8% and 32.3%), and 11.3% amantadine (79.2% and 6.0%). Over a 1-year follow-up, PwHD (n = 81) had significantly more neurologist, psychiatrist, physiotherapist, and speech therapist visits (P < 0.05 for each) and more hospitalization days (P < 0.0001) compared with matched controls (n = 243). Total healthcare and medication costs per patient (US dollars) were significantly higher for PwHD than controls ($7,343 vs. $3,625; P < 0.001).

DISCUSSION/CONCLUSION: PwHD have greater annual HCRU and medical costs than MHS members without HD in Israel. Among those who have taken medications, adherence was lower than 80% (both MPR and proportion of disease covered), which may translate into suboptimal symptom relief and quality of life.

PMID:37497383 | PMC:PMC10366633 | DOI:10.1016/j.prdoa.2023.100208

BMJ Open. 2023 Jul 26;13(7):e073232. doi: 10.1136/bmjopen-2023-073232.

ABSTRACT

INTRODUCTION: Although interest in including non-randomised studies of interventions (NRSIs) in meta-analysis of randomised controlled trials (RCTs) is growing, estimates of effectiveness obtained from NRSIs are vulnerable to greater bias than RCTs. The objectives of this study are to: (1) explore how NRSIs can be integrated into a meta-analysis of RCTs; (2) assess concordance of the evidence from non-randomised and randomised trials and explore factors associated with agreement; and (3) investigate the impact on estimates of pooled bodies of evidence when NRSIs are included.

METHODS AND ANALYSIS: We will conduct a systematic survey of 210 systematic reviews that include both RCTs and NRSIs, published from 2017 to 2022. We will randomly select reviews, stratified in a 1:1 ratio by Core vs non-Core clinical journals, as defined by the National Library of Medicine. Teams of paired reviewers will independently determine eligibility and abstract data using standardised, pilot-tested forms. The concordance of the evidence will be assessed by exploring agreement in the relative effect reported by NRSIs and RCT addressing the same clinical question, defined as similarity of the population, intervention/exposure, control and outcomes. We will conduct univariable and multivariable logistic regression analyses to examine the association of prespecified study characteristics with agreement in the estimates between NRSIs and RCTs. We will calculate the ratio of the relative effect estimate from NRSIs over that from RCTs, along with the corresponding 95% CI. We will use a bias-corrected meta-analysis model to investigate the influence on pooled estimates when NRSIs are included in the evidence synthesis.

ETHICS AND DISSEMINATION: Ethics approval is not required. The findings of this study will be disseminated through peer-reviewed publications, conference presentations and condensed summaries for clinicians, health policymakers and guideline developers regarding the design, conduct, analysis, and interpretation of meta-analysis that integrate RCTs and NRSIs.

PMID:37495391 | DOI:10.1136/bmjopen-2023-073232

BMJ Open. 2023 Jul 26;13(7):e071108. doi: 10.1136/bmjopen-2022-071108.

ABSTRACT

OBJECTIVE: Since rapid population growth challenges longitudinal population-based HIV cohorts in Africa to maintain coverage of their target populations, this study evaluated whether the exclusion of some residents due to growing population size biases key HIV metrics like prevalence and population-level viremia.

DESIGN, SETTING AND PARTICIPANTS: Data were obtained from the Rakai Community Cohort Study (RCCS) in south central Uganda, an open population-based cohort which began excluding some residents of newly constructed household structures within its surveillance boundaries in 2008. The study includes adults aged 15-49 years who were censused from 2019 to 2020.

MEASURES: We fit ensemble machine learning models to RCCS census and survey data to predict HIV seroprevalence and viremia (prevalence of those with viral load >1000 copies/mL) in the excluded population and evaluated whether their inclusion would change overall estimates.

RESULTS: Of the 24 729 census-eligible residents, 2920 (12%) residents were excluded from the RCCS because they were living in new households. The predicted seroprevalence for these excluded residents was 10.8% (95% CI: 9.6% to 11.8%)-somewhat lower than 11.7% (95% CI: 11.2% to 12.3%) in the observed sample. Predicted seroprevalence for younger excluded residents aged 15-24 years was 4.9% (95% CI: 3.6% to 6.1%)-significantly higher than that in the observed sample for the same age group (2.6% (95% CI: 2.2% to 3.1%)), while predicted seroprevalence for older excluded residents aged 25-49 years was 15.0% (95% CI: 13.3% to 16.4%)-significantly lower than their counterparts in the observed sample (17.2% (95% CI: 16.4% to 18.1%)). Over all ages, the predicted prevalence of viremia in excluded residents (3.7% (95% CI: 3.0% to 4.5%)) was significantly higher than that in the observed sample (1.7% (95% CI: 1.5% to 1.9%)), resulting in a higher overall population-level viremia estimate of 2.1% (95% CI: 1.8% to 2.4%).

CONCLUSIONS: Exclusion of residents in new households may modestly bias HIV viremia estimates and some age-specific seroprevalence estimates in the RCCS. Overall, HIV seroprevalence estimates were not significantly affected.

PMID:37495389 | DOI:10.1136/bmjopen-2022-071108

J Neurosci. 2023 Jul 26:JN-RM-0451-23. doi: 10.1523/JNEUROSCI.0451-23.2023. Online ahead of print.

ABSTRACT

The overrepresentation of centrifugal motion in the middle temporal visual area (area MT) has long been thought to provide an efficient coding strategy for optic flow processing. However, this overrepresentation compromises the detection of approaching objects, which is essential for survival. In the present study, we revisited this long-held notion by reanalyzing motion selectivity in area MT of three macaque monkeys (2 males, 1 female) using random-dot stimuli instead of spot stimuli. We found no differences in the number of neurons tuned to centrifugal versus centripetal motion; however, centrifugally tuned neurons showed stronger tuning than centripetally tuned neurons. This was attributed to the heightened suppression of responses in centrifugal neurons to centripetal motion compared to that of centripetal neurons to centrifugal motion. Our modeling implies that this intensified suppression accounts for superior detection performance for weak centripetal motion stimuli. Moreover, through Fisher information analysis, we establish that the population sensitivity to motion direction in peripheral vision corresponds well with retinal motion statistics during forward locomotion. While these results challenge established concepts, considering the interplay of logarithmic Gaussian receptive fields and spot stimuli can shed light on the previously documented overrepresentation of centrifugal motion. Significantly, our findings reconcile a previously found discrepancy between MT activity and human behavior, highlighting the proficiency of peripheral MT neurons in encoding motion direction efficiently.Significance StatementThe efficient coding hypothesis states that sensory neurons are tuned to specific, frequently experienced stimuli. Whereas previous work has found that neurons in the middle temporal (MT) area favor centrifugal motion, which results from forward locomotion, we show here that there is no such bias. Moreover, we found that the response of centrifugal neurons for centripetal motion was more suppressed than that of centripetal neurons for centrifugal motion. Combined with modeling, this provides a solution to a previously known discrepancy between reported centrifugal bias in MT and better detection of centripetal motion by human observers. Additionally, we show that population sensitivity in peripheral MT neurons conforms to an efficient code of retinal motion statistics during forward locomotion.

PMID:37495384 | DOI:10.1523/JNEUROSCI.0451-23.2023

J Matern Fetal Neonatal Med. 2023 Dec;36(2):2238863. doi: 10.1080/14767058.2023.2238863.

ABSTRACT

OBJECTIVE: To investigate the effects of chromosome polymorphism on the clinical outcomes of in vitro fertilization/embryo transfer (IVF/ET)-assisted reproductive technology.

METHODS: The case data of 2740 patients treated between January 2018 and January 2019 were retrospectively analyzed. The patients were organized into two groups: a case group and a control group. In the case group (n = 81), one or both parents were characterized by chromosomal polymorphism; in the control group (n = 2659), both parents had normal chromosome karyotyping. The primary outcomes included clinical pregnancy rate (clinical pregnancy rate of fresh transfer cycles = number of clinical pregnancy cycles/number of fresh embryo transfer cycles × 100%) and live birth rate (live birth rate per fresh transfer cycles = number of live births/numbers of fresh embryo transfer cycles × 100%). The propensity score matching (PSM) method was used for statistical analysis.

RESULTS: After PSM 1:2 matching for the patients in the two groups, 72 patients were successfully matched. The clinical pregnancy rate and live birth rate in the case group were lower than in the control group before PSM (clinical pregnancy rate: 33.30% case group vs. 46.60% control group, p = .020; live birth rate: 30.90% case group vs. 47.90% control group, p = .03). The differences were statistically significant (p < .05). The live birth rate in the case group was also significantly lower than in the control group after PSM (34.98% case group vs. 74.52% control group; p = .028). The correlation coefficient between clinical pregnancy and grouping (i.e. if there was a characteristic chromosome polymorphism) was -.045 (p = .02), while the correlation coefficient between live birth and grouping was -.046.

CONCLUSION: Chromosome polymorphism is weakly negatively correlated with live birth in IVF/ET-assisted reproduction and can significantly reduce the live birth rate of patients.

PMID:37495374 | DOI:10.1080/14767058.2023.2238863

JACC Cardiovasc Interv. 2023 Jul 24;16(14):1794-1803. doi: 10.1016/j.jcin.2023.05.005.

ABSTRACT

BACKGROUND: Drug-coated balloons (DCB) represent 1 of the most promising innovations in interventional cardiology and may represent a valid alternative to drug-eluting stents. Currently, some sirolimus-coated balloons (SCB) are being investigated for several coronary artery disease applications.

OBJECTIVES: This study sought to understand the role of a novel SCB for the treatment of coronary artery disease.

METHODS: EASTBOURNE (All-Comers Sirolimus-Coated Balloon European Registry) is a prospective, multicenter, investigator-driven clinical study that enrolled real-world patients treated with SCB. Primary endpoint was target lesion revascularization (TLR) at 12 months. Secondary endpoints were procedural success, myocardial infarction (MI), all-cause death, and major adverse clinical events (a composite of death, MI, and TLR). All adverse events were censored and adjudicated by an independent clinical events committee.

RESULTS: A total population of 2,123 patients (2,440 lesions) was enrolled at 38 study centers in Europe and Asia. The average age was 66.6 ± 11.3 years, and diabetic patients were 41.5%. De novo lesions (small vessels) were 56%, in-stent restenosis (ISR) 44%, and bailout stenting occurred in 7.7% of the patients. After 12 months, TLR occurred in 5.9% of the lesions, major adverse clinical events in 9.9%, and spontaneous MI in 2.4% of the patients. The rates of cardiac/all-cause death were 1.5% and 2.5%, respectively. The primary outcome occurred more frequently in the ISR cohort (10.5% vs 2.0%; risk ratio: 1.90; 95% CI: 1.13-3.19). After multivariate Cox regression model, the main determinant for occurrence of the primary endpoint was ISR (OR: 5.5; 95% CI: 3.382-8.881).

CONCLUSIONS: EASTBOURNE, the largest DCB study in the coronary field, shows the safety and efficacy of a novel SCB in a broad population of coronary artery disease including small vessels and ISR patients at mid-term follow-up. (The All-Comers Sirolimus-Coated Balloon European Registry [EASTBOURNE]; NCT03085823).

PMID:37495352 | DOI:10.1016/j.jcin.2023.05.005

JACC Clin Electrophysiol. 2023 Jul;9(7 Pt 2):1121-1133. doi: 10.1016/j.jacep.2022.11.021. Epub 2023 Feb 22.

ABSTRACT

BACKGROUND: There are limited data regarding the benefit of early rhythm control therapy for secondary prevention for stroke in patients with atrial fibrillation (AF).

OBJECTIVES: This study aimed to compare the risk of recurrent stroke between early rhythm control therapy and usual care in patients with new-onset AF and a history of prior stroke.

METHODS: Using the Korean nationwide claims database, the investigators identified patients who were newly diagnosed with AF and had a history of prior stroke. Patients who received rhythm control therapy, including antiarrhythmic drug, direct current cardioversion, or AF catheter ablation, within 1 year after incident AF were defined as the early rhythm control group, and the others were the usual care group. The propensity score weighting method was used to balance baseline characteristics between the 2 groups. Incident stroke was evaluated as a primary outcome.

RESULTS: A total of 53,509 patients were included (12,455 in the early rhythm control group and 41,054 in the usual care group). All patients were prescribed oral anticoagulants. During a median 2.6 years of follow-up, 4,382 patients had an incident stroke (incidence rate: 2.6 per 100 person-years). Early rhythm control was associated with a lower risk of recurrent stroke compared to the risk associated with usual care (weighted HR: 0.720; 95% CI: 0.666-0.779; P < 0.001).

CONCLUSIONS: Early rhythm control within 1 year after AF diagnosis might be beneficial to prevent recurrent stroke in patients with incident AF and a history of stroke. Integrated care, including optimal rhythm control with appropriate anticoagulation, should be considered in this population.

PMID:37495321 | DOI:10.1016/j.jacep.2022.11.021

Fungal Biol. 2023 Jul-Aug;127(7-8):1241-1249. doi: 10.1016/j.funbio.2023.04.003. Epub 2023 Apr 14.

ABSTRACT

Candidiasis is a significant fungal infection with high mortality and morbidity rates worldwide. Candida albicans is the most dominant species responsible for causing different manifestations of candidiasis. Certain virulence traits as well as its resistance to antifungal drugs contribute to the pathogenesis of this yeast. This study was designed to determine the production of some virulence factors, such as biofilm formation and extracellular hydrolytic enzymes (esterase, coagulase, gelatinase, and catalase) by this fungus, as well as its antifungal resistance profile. A total of 304 clinical C. albicans isolates obtained from different clinical specimens were identified by a conventional diagnostic protocol. The antifungal susceptibility of C. albicans strains was determined by disk diffusion technique against commercially available antifungal disks, such as nystatin 50 μg, amphotericin B 100 unit, fluconazole 25 μg, itraconazole 10 μg, ketoconazole 10 μg, and voriconazole 1 μg. The assessment of biofilm formation was determined by the tube staining assay and spectrophotometry. Gelatinase, coagulase, catalase, and esterase enzyme production was also detected using standard techniques. A total of 66.1% (201/304) and 28.9% (88/304) of C. albicans strains were susceptible-dose dependent (SDD) to nystatin and itraconazole, respectively. Among the antifungal drugs, C. albicans strains showed high resistance to ketoconazole 24.7% (75/304); however, no statistically significant relationship between the clinical origin of C. albicans isolates and antifungal drug resistance pattern was detected. For virulence factors, the majority of the C. albicans strains actively produced biofilm and all hydrolytic enzymes. Biofilm formation was demonstrated by 88% (267/304) of the strains with a quantitative mean value 0.1762 (SD ± 0.08293). However, 100% (304/304) of isolates produced catalase enzyme, 69% (211/304) produced coagulase, 66% (197/304) produced gelatinase, and 52% (157/304) produced esterase enzyme. A significant relationship between the source of specimens and biofilm formation by C. albicans was observed; nevertheless, there was no significant relationship between different sources of C. albicans strains and the production of different enzymatic virulence factors. The study found that C. albicans strains have excellent potential to produce virulence markers and resistance to antifungals, which necessitates surveillance of these opportunistic pathogens to minimize the chances of severe invasive infections.

PMID:37495314 | DOI:10.1016/j.funbio.2023.04.003

J Am Coll Cardiol. 2023 Aug 1;82(5):401-410. doi: 10.1016/j.jacc.2023.05.042.

ABSTRACT

BACKGROUND: The RACING (randomized comparison of efficacy and safety of lipid-lowering with statin monotherapy versus statin/ezetimibe combination for high-risk cardiovascular diseases) trial examined the effects of combination therapy with moderate-intensity statin and ezetimibe in patients with atherosclerotic cardiovascular disease compared with high-intensity statin monotherapy.

OBJECTIVES: This observational study was conducted to evaluate the impact of 2 treatment strategies used in the RACING trial in clinical practice.

METHODS: After stabilized inverse probability of treatment weighting, a total of 72,050 patients who were prescribed rosuvastatin after drug-eluting stent implantation were identified from a nationwide cohort database: 10,794 patients with rosuvastatin 10 mg plus ezetimibe 10 mg (combination lipid-lowering therapy) and 61,256 patients with rosuvastatin 20 mg monotherapy. The primary endpoint was the 3-year composite event of cardiovascular death, myocardial infarction, coronary artery revascularization, hospitalization for heart failure treatment, or nonfatal stroke in accordance with the RACING trial.

RESULTS: Combination lipid-lowering therapy was associated with a lower occurrence of the primary endpoint (11.6% vs 15.2% for those with high-intensity statin monotherapy; HR: 0.75; 95% CI: 0.70-0.79; P < 0.001). Compared with high-intensity statin monotherapy, combination lipid-lowering therapy was associated with fewer discontinuations of statin (6.5% vs 7.6%; HR: 0.85; 95% CI: 0.78-0.94: P < 0.001) and a lower occurrence of new-onset diabetes requiring medication (7.7% vs 9.6%; HR: 0.80; 95% CI: 0.72-0.88; P < 0.001).

CONCLUSIONS: In clinical practice, combination lipid-lowering therapy with ezetimibe and moderate-intensity statin was associated with favorable clinical outcomes and drug compliance in patients treated with drug-eluting stent implantation. (CONNECT DES Registry; NCT04715594).

PMID:37495276 | DOI:10.1016/j.jacc.2023.05.042

J Dent. 2023 Jul 24:104631. doi: 10.1016/j.jdent.2023.104631. Online ahead of print.

ABSTRACT

OBJECTIVES: Tooth grinding produces a significant amount of aerosol particles. The aim of this study was to quantitatively assess particle contamination produced from tooth grinding with a speed-increasing handpiece across a real-world clinical setting.

METHODS: The crowns of all molars were pretreated into cylinders with a uniform cross-section diameter of 10 mm and a height of 5 mm. A novel computer-assisted numerical control system was used to fix the feed rate at 10 mm/min and the grinding depth at 30 μm, and to parametrically study the bur speed: from 20,000 (20 K) to 200,000 (200 K) revolutions per minute (rpm) at 20 K rpm intervals. 5-minute tooth grinding was performed in triplicate at each speed setting in a real dental operation room with the air conditioning off, and the window closed. Three online real-time particle counters (ORPC; TR-8301, TongrenCo.) with six particle-size channels (0.3, 0.5, 1.0, 2.5, 5.0, and 10.0 µm) were placed at 3 positions (0.5 m, 1.0 m, and 1.5 m) to evaluate particle production. All experimental instruments were controlled remotely. The data obtained were statistically analyzed using descriptive statistics and non-parametric tests (Scheirer-Ray-Hare and Kruskal-Wallis/ Dunn-Bonferroni tests, p < 0.05).

RESULTS: The concentration level of aerosol particles production during the grinding experiment was elevated above the control group for all conditions, and increased with bur speed at any location (the maximum peak, reaching 5.59 × 10⁷ particles/m³, at 200 K and 1 m), with differences between conditions. We noted that the effect of speed on the increment of particles across different channels compared to the control group was statistically significant among locations (p < 0.001). The simple main effect of location was not significant for the distribution difference of increment in 0.3 µm particles at 120 K (H = 4.314, p = 0.116), 0.5 µm at 180 K (H = 1.855, p = 0.396), and 5 µm at 40 K (H = 1.259, p = 0.533), while increments in other sizes particles at any speed setting showed significant differences (p < 0.05). Out of 171 post hoc pairwise comparisons of location, 130 showed significant differences (p < 0.05), with 50 between 0.5 m and 1.5 m (0.5 m – 1.5 m), and 40 in both the 1.5 m – 1 m and 0.5 m – 1 m. The simple main effect of speed was significant for the distribution difference of particle increment across all channels at any sampling location. In the post hoc pairwise comparisons of speed, there were 810 comparison groups, and those with speed differences below 80 K tended to show non-significant differences (p > 0.05), but all groups with a speed difference above 140 K showed significant differences (p < 0.05).

CONCLUSIONS: Statistically significant particle contamination was produced using a speed-increasing handpiece, but the contamination level for each experimental condition was reduced to baseline within 30 min, and most particles with a diameter greater than 1 μm produced at low speeds (80 K or lower) tended to settle within 1 m.

CLINICAL RELEVANCE: Our study suggested that the use of a speed-increasing handpiece below 80 K and 30 minutes of fallow time may lead to an adequate reduction in the health effects of particle contamination.

PMID:37495202 | DOI:10.1016/j.jdent.2023.104631