Tag: nevin manimala

Pharmacol Res. 2023 Oct 4:106949. doi: 10.1016/j.phrs.2023.106949. Online ahead of print.

ABSTRACT

OBJECTIVES: A cost-utility analysis was conducted to evaluate pharmacogenomic (PGx)-guided treatment compared to the standard-of-care intervention among patients diagnosed with colorectal cancer (CRC) in Italy.

METHODS: Data derived from a prospective, open-label, block randomized clinical trial, as a part of the largest PGx study worldwide (355 patients in both arms) were used. Mortality was used as the primary health outcome to estimate life years (LYs) gained in treatment arms within a survival analysis context. PGx-guided treatment was based on established drug-gene interactions between capecitabine, 5-fluorouracil and irinotecan with DPYD and/or UGT1A1 genomic variants. Utility values for the calculation of Quality Adjusted Life Year (QALY) was based on Visual Analog Scale (VAS) score. Missing data were imputed via the Multiple Imputation method and linear interpolation, when possible, while censored cost data were corrected via the Replace-From-The-Right algorithm. The Incremental Cost-Effectiveness Ratio (ICER) was calculated for QALYs. Raw data were bootstrapped 5,000 times in order to produce 95% Confidence Intervals based on non-parametric percentile method and to construct a cost-effectiveness acceptability curve. Cost differences for study groups were investigated via a generalized linear regression model analysis. Total therapy cost per patient reflected all resources expended in the management of any adverse events, including medications, diagnostics tests, devices, surgeries, the utilization of intensive care units, and wards.

RESULTS: The total cost of the study arm was estimated at €380 (~ US$416; 95%CI: 195-596) compared to €565 (~ US$655; 95%CI: 340-724) of control arm while the mean survival in study arm was estimated at 1.58 (+0.25) LYs vs 1.50 (+0.26) (Log Rank test, X2=4.219, df=1, p-value=0.04). No statistically significant difference was found in QALYs. ICER was estimated at €13418 (~ US$14695) per QALY, while the acceptability curve indicated that when the willingness-to-pay was under €5000 (~ US$5476), the probability of PGx being cost-effective overcame 70%. The most frequent adverse drug event in both groups was neutropenia of severity grade 3 and 4, accounting for 82.6% of total events in the study arm and 65.0% in the control arm. Apart from study arm, smoking status, Body-Mass-Index and Cumulative Actionability were also significant predictors of total cost. Subgroup analysis conducted in actionable patients (7.9% of total patients) indicated that PGx-guided treatment was a dominant option over its comparator with a probability greater than 92%. In addition, a critical literature review was conducted, and these findings are in line with those reported in other European countries.

CONCLUSION: PGx-guided treatment strategy may represent a cost-saving option compared to the existing conventional therapeutic approach for colorectal cancer patient management in the National Health Service of Italy.

PMID:37802427 | DOI:10.1016/j.phrs.2023.106949

Ophthalmology. 2023 Oct 4:S0161-6420(23)00710-8. doi: 10.1016/j.ophtha.2023.09.031. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare topical PHMB (polihexanide) 0.02% (0.2 mg/ml) + propamidine 0.1% (1 mg/ml) [PHMB 0.02%+propamidine] to PHMB 0.08% (0.8 mg/ml) with placebo [PHMB 0.08%] for Acanthamoeba keratitis (AK) treatment.

DESIGN: Prospective randomized, double-masked, active-controlled, multicentre, Phase3 study (ClinicalTrials.gov NCT03274895).

PARTICIPANTS: 135 at six European centres between 08/17/2017 to 06/18/2021.

METHODS: Principal inclusion criteria: ≥12 years old; in vivo confocal microscopy (IVCM) with clinical findings consistent with AK. Also included were participants with concurrent bacterial keratitis, using topical steroids, antiviral and antifungal drugs before randomisation. Principal exclusions: concurrent herpes or fungal keratitis, use of anti-amoebic therapy (AAT).

RANDOMISATION: 1:1 computer-generated, block size 4. This was a superiority trial having a predefined non-inferiority margin. The sample size of 130 participants gave approximately 80% power to detect 20 percentage point superiority for PHMB 0.08% for the primary outcome of the medical cure rate (without surgery or change of AAT) within 12 months (MCR_12), cure defined by clinical criteria 90 days after discontinuing anti-inflammatories and AAT. A prespecified multivariable analysis adjusted for baseline imbalances in risk factors affecting outcomes.

MAIN OUTCOME MEASURES: The MCR_12. Secondary outcomes included best-corrected visual acuity (BCVA) and treatment failure rates. Safety outcomes included adverse event rates.

RESULTS: 135 participants were randomised providing 127 in the full analysis subset (61 on PHMB 0.02%+propamidine and 66 on PHMB 0.08%) and 134 in the safety analysis subset. The adjusted MCR_12 was 86.6% (unadjusted 88.5%) for PHMB 0.02%+propamidine and 86.7% (unadjusted 84.9%) for PHMB 0.08%; the non-inferiority requirement for PHMB 0.08% was met (adjusted difference 0.1 percentage points, lower one-sided 95% confidence limit -8.3 percentage points). Secondary outcomes were similar for both treatments and not analysed statistically: median BCVA of 20/20, an overall treatment failure rate of 17/127 (13.4%) of whom 8/127 (6.3%) required therapeutic keratoplasty. There were no serious drug related adverse events.

CONCLUSIONS: PHMB 0.08% monotherapy may be as effective (or at worse only eight percentage points less effective) as dual therapy with PHMB 0.02%+propamidine (a widely used therapy) with medical cure rates of >86%, when used with the Trial treatment delivery protocol, in AK populations with similar disease severity.

PMID:37802392 | DOI:10.1016/j.ophtha.2023.09.031

Sci Total Environ. 2023 Oct 4:167567. doi: 10.1016/j.scitotenv.2023.167567. Online ahead of print.

ABSTRACT

The aim of this research was to examine how particulate matter (PM) pollution affects the life history of the two-spotted spider mite (TSSM), Tetranychus urticae (Trombidiformes: Tetranychidae), in modelled urban conditions. For this purpose, experimental populations of TSSM were cultured on the foliage of small-leaved lime (Tilia cordata) contaminated with PM at intensities corresponding to differing city zones such as a park, a busy road and an industrial area. The control samples in the study were washed, unpolluted leaves. The spider mite was selected as a model organism due to its cosmopolitan distribution, broad host spectrum, resistance to a variety of pesticides and food-intake mode involving cell-content sucking, while T. cordata is widely planted in cities and has demonstrated a considerable capability for PM capture. Data on the longevity and mortality of particular instars and on female fecundity at different pollution levels were collected and statistically evaluated. Concentrations of PM typical for roads and industrial city zones significantly reduced total female fecundity (avg. 53.9 and 55.9 eggs/female, respectively, vs 79.2 in control), which entailed a slower population increase, while the survival rate of particular developmental instars (P = 0.52) and fertility curves (P = 0.19) remained unchanged. The presence of PM caused physiological effects in the mites, despite the lack of direct consumption of the pollutant by adult and juvenile instars. Considering the incomparable resilience of TSSM to unfavourable environmental factors, it is predicted that the detrimental influence of PM on other representatives of urban arthropods may be even more severe. The results suggest that there is a need for further investigations into the ecological ramifications of air purification provided by urban green spaces.

PMID:37802333 | DOI:10.1016/j.scitotenv.2023.167567

J Subst Use Addict Treat. 2023 Oct 4:209180. doi: 10.1016/j.josat.2023.209180. Online ahead of print.

ABSTRACT

BACKGROUND: Sleep disturbance is commonly reported among individuals meeting criteria for cannabis use disorder (CUD), and cannabis users frequently report sleep disturbance as a contributor to failed quit attempts. The purpose of this study was to measure sleep in individuals enrolled in treatment for CUD, and to determine whether use of hypnotic medication during treatment increased abstinence rates.

METHOD: The study enrolled 127 adults seeking treatment for CUD in a 12-week clinical trial and randomized to receive extended-release zolpidem (zolpidem-XR) or placebo. All participants received computerized behavioral therapy and abstinence-based contingency management. The study conducted in-home ambulatory polysomnography (PSG) assessments at baseline and during treatment to objectively measure sleep. Self-report measures of recent sleep, Insomnia Severity Index (ISI), and drug use (Timeline Follow-Back) were collected at each study visit, and the study confirmed self-reported abstinence via quantitative urine drug testing.

RESULT: Participants randomized to placebo, but not zolpidem-XR exhibited significant sleep disturbance during week 1 of treatment. Sleep disturbance emerged in the zolpidem-XR group after study medication was stopped at the end of treatment. Though participants assigned to the zolpidem-XR condition had qualitatively greater rates of abstinence compared with placebo (27 % versus 15 % negative at end of treatment), the difference was not statistically significant. Treatment retention was poor (about 50 % drop out in both groups) and medication adherence was a challenge without the use of contingent incentives.

CONCLUSION: Results from this randomized controlled trial suggest that zolpidem-XR can attenuate abstinence-induced sleep disturbance early in treatment for CUD, but that sleep problems are likely to emerge after the medication is stopped. Further research should identify alternative pharmacotherapies and behavioral treatments for CUD and elucidate the role of sleep disturbance in the development and maintenance of CUD.

PMID:37802317 | DOI:10.1016/j.josat.2023.209180

Kathmandu Univ Med J (KUMJ). 2023 Jan-Mar;21(81):69-73.

ABSTRACT

Background The median nerve is subjected to compression in the carpal tunnel giving rise to a constellation of symptoms known as carpal tunnel syndrome. It is the most frequent form of peripheral entrapment neuropathies and is most prevalent in the middle age females. The most common cause of this syndrome is idiopathic. One of the known secondary causes is pregnancy. Objective To compare the mean cross sectional area of median nerve using ultrasound in pregnant and non-pregnant females at carpal tunnel inlet and its variations with different trimesters. Method The study was conducted during a period of one year (October 2014 to September 2015). A total of 204 participants were evaluated among which 102 were nonpregnant and 102 were pregnant. Among the 102 pregnant participants, 34 females each were in the first, second, and third trimesters. A convenience sampling technique was used for the selection of the participants. The mean cross-sectional area of the median nerve was calculated in both of these groups in both hands by using the direct method. The mean cross-sectional area of non-pregnant female was used as the reference value to which that of pregnant female were compared. Data obtained were compiled and analyzed using Statistical Package for Social Sciences Version 16. Result The overall mean cross-sectional area of the median nerve in non-pregnant females was 6.76 ± 1.05 mm2 and in pregnant females was 6.84 ± 1.09 mm. No statistically significant difference was noted in the mean cross-sectional area of the median nerve in either hand in both pregnant and non-pregnant females. No statistically significant difference was noted in the overall mean cross-sectional area between the non-pregnant and pregnant females. There was no significant difference in the mean cross-sectional area within the different trimesters in both hands on intergroup comparisons. Conclusion Ultrasound examination of the median nerve and measurement of its crosssectional area is a useful diagnostic tool in the evaluation of carpal tunnel syndrome. Ultrasound has the advantage of easy availability, low cost, quick scan time, able to scan a long segment of nerve and examine the structures in both static and dynamic states. Besides, it also helps in the identification of various anatomic variants and pathologies within or adjacent to carpal tunnel.

PMID:37800429

Kathmandu Univ Med J (KUMJ). 2023 Jan-Mar;21(81):28-32.

ABSTRACT

Background Alarm fatigue is a well-recognized patient safety concern in critical care settings. It occurs when nurses become overwhelmed by the total number of alarm signals which can result in alarm desensitization and eventually contributes to missing of serious and important changes in a patient’s condition, thus failing to respond properly. Objective To find out alarm fatigue and its associated factors among nurses working in critical care setting. Method A cross-sectional study design with convenient sampling technique was used to select 56 nurses working at different critical care settings in Dhulikhel Hospital. A selfconstructed semi structured questionnaire and nurses alarm fatigue questionnaire was used for the survey. Frequency, percentage, mean and standard deviation were used for descriptive statistics whereas Independent t-test and One-way ANOVA were used for inferential statistics. Result The result shows that more than half of the nurses were less than 25 years, single and more than two-third of the participants worked in Adult Intensive Care Unit. Out of total obtainable score 44, the overall mean score of the Alarm Fatigue was 28.03±12.813. The result showed that there was no significant difference between alarm fatigue and selected socio-demographic and work related characteristics. Conclusion The alarm fatigue among nurses working in critical care settings was found to be higher in this study. Since alarm fatigue is directly related to patients’ safety, the effective management of medical device alarms can reduce alarm fatigue and prevent potentially dangerous outcomes.

PMID:37800422

J Sports Med Phys Fitness. 2023 Oct 6. doi: 10.23736/S0022-4707.23.15003-1. Online ahead of print.

ABSTRACT

BACKGROUND: The influence of COVID-19 infection on elite athletes remains largely unknown, especially on baseball players. The goal of this study is to examine the actual performance of infected elite baseball players from the Chinese Professional Baseball League (CPBL) from a sabermetric point of view.

METHODS: This was a retrospective observational cohort study. CPBL players who were infected with COVID-19 from April 27^th to May 31^st, 2022, were eligible for this study. The performance of study participants before and after COVID-19 infection was compared, and statistics from the batters and pitchers were analyzed separately.

RESULTS: During the study interval, 56 players were infected with COVID-19, including 35 batters and 21 pitchers. After excluding injured players and players with inadequate playing opportunities, 23 batters and 12 pitchers were enrolled. For batters, there were no significant differences before and after COVID-19 infection. However, batters older than 28 years of age showed a decline in slugging percentage (0.372 vs. 0.292, P=0.049). Analysis of pitchers revealed significantly boosted fastball velocity after COVID-19 infection (142.10 km/h vs. 142.82 km/h, P=0.028) and improved strikeouts per nine innings (6.89 vs. 8.56, P=0.021).

CONCLUSIONS: COVID-19 might have a potential influence on professional baseball players. For batters, veteran players more than 28 years of age were more likely to be negatively affected by COVID-19, whereas the effect of COVID-19 on pitchers was generally positive, with significantly improved fastball velocity and K/9 numbers.

PMID:37800400 | DOI:10.23736/S0022-4707.23.15003-1

Birth. 2023 Oct 6. doi: 10.1111/birt.12776. Online ahead of print.

ABSTRACT

BACKGROUND: In 2014, the National University Hospital of Iceland (NUHI) merged a mixed-risk birth unit and a midwifery-led low-risk unit into one mixed-risk unit. Interprofessional preventative and mitigating measures were implemented since there was a known threat of cultural contamination between mixed-risk and low-risk birth environments. The aim of the study was to assess whether the NUHI’s goal of protecting the rates of birth without intervention had been achieved and to support further development of labor services.

METHODS: A retrospective cohort study of all women who had singleton births at NUHI birth units in two 2-year periods, 2012-2013 and 2015-2016. The primary outcome variables, birth without intervention, with or without artificial rupture of membranes (AROM), were adjusted for confounding variables using logistic regression analysis. Secondary outcome variables (individual interventions and maternal and neonatal complications) were analyzed using descriptive statistics, t test, and Chi-square test.

RESULTS: The rate of births without interventions, both with and without AROM, increased significantly after the unit merger and accompanying preventative measures. The rates of AROM, oxytocin augmentation, episiotomies, and epidural analgesia decreased significantly. The rate of induction increased significantly. There were no significant differences in maternal or neonatal complication rates.

CONCLUSIONS: Interprofessional preventative measures, implemented alongside a mixed-risk and low-risk birth unit merger, can increase rates of births without interventions in a mixed-risk hospital setting. However, it is necessary to maintain awareness of the possible effects of a mixed-risk birth environment on the use of childbirth interventions and examine the long-term effects of preventative measures.

PMID:37800388 | DOI:10.1111/birt.12776

Magn Reson Med. 2023 Oct 6. doi: 10.1002/mrm.29849. Online ahead of print.

ABSTRACT

PURPOSE: To demonstrate MR T₁ mapping in vivo as a method to non-invasively estimate vitreous oxygen concentration in ischemic eye disease.

METHODS: Patients with ischemic eye disease (central retinal vein occlusion, ocular ischemic syndrome, and proliferative diabetic retinopathy) were prospectively recruited. MRI was performed on each patient before any treatment, with T₁ mapping acquired using an inversion recovery TrueFISP sequence at several inversion times, from a single slice positioned through the center of both eyes in the axial oblique plane. A phantom study measuring seven different concentrations of vitronectin, a protein released in ischemic eye disease, was undertaken to determine its potential confounding effect on T₁ .

RESULTS: Ten participants were recruited (eight central retinal vein occlusion, one ocular ischemic syndrome, and one proliferative diabetic retinopathy). Of the eight central retinal vein occlusion cases, there was a statistically different vitreous T₁ in the diseased eye compared to the healthy control eye (4.306 vs. 4.518 s, p = 0.008). T₁ times did not significantly alter across the range of vitronectin concentrations.

CONCLUSIONS: Ischemic eye disease decreases vitreous T₁ , potentially implying an increase in vitreous partial pressure of oxygen (pO₂ ) concentration given what is known from the relationship between 1/T₁ and pO₂ . Potential theories for this unexpected result are discussed. This study provides further data on this technique, with potential clinical application in eye disease.

PMID:37800364 | DOI:10.1002/mrm.29849

J Am Geriatr Soc. 2023 Oct 6. doi: 10.1111/jgs.18625. Online ahead of print.

ABSTRACT

BACKGROUND: Home-based primary care promotes aging in place but is not immediately responsive to urgent needs. Community paramedicine leverages emergency medical services clinicians to expedite in-home care, though limited evidence supports this model. We evaluated the primary care and acute care use of older adults evaluated urgently by a community paramedic with telemedicine physician compared to a physician home visit model.

METHODS: This prospective cohort study enrolled older adults in home-based primary care who requested an urgent evaluation. We allocated participants to the physician home visit model or physician home visit plus community paramedic model by ZIP code. We observed primary care and acute care use for 6 months following enrollment. The primary outcome was the median number of primary care and acute care visits per participant. Secondary outcomes included 30-day readmission rates, median wait times, and physician productivity. Data analysis included descriptive statistics, comparison of means and proportions, and negative binomial regression modeling reported as incidence rate ratios (IRR).

RESULTS: We screened 255 participants, determined 203 eligible, allocated 199, and completed observation for 167 (84 community paramedicine, 83 physician home visit). Participants were mostly female, age 76-86 years, with 3-5 comorbidities, living in a home/apartment. Community paramedic participants had 29% more primary care visits (IRR 1.29, 95% confidence interval [CI] 1.06-1.57) and shorter wait times for urgent evaluations (1 vs. 5 days, p < 0.001) without increasing acute care use (IRR 0.75, 95% CI 0.48-1.18) or 30-day readmissions (IRR 1.32, 95% CI 0.49-3.55). Physician productivity increased 81% (40 vs. 22 visits/week, p < 0.001).

CONCLUSION: Older adults evaluated by a community paramedic for urgent needs were seen sooner, used acute care similarly to patients evaluated by a physician home visit, and nearly doubled physician efficiency. This suggests that older adults may benefit from combining emergency medical services and primary care resources for urgent evaluations.

PMID:37800363 | DOI:10.1111/jgs.18625