Tag: nevin manimala

Health Econ Rev. 2024 Apr 12;14(1):27. doi: 10.1186/s13561-024-00503-9.

ABSTRACT

BACKGROUND: Based on the legal framework laid down in section 130b (9) of Book V of the German Social Code, various criteria are relevant for the negotiated price for new patented drugs in Germany. European reference prices (ERPs) are one criterion. The ERP is based on the ex-factory prices (EFPs) of the countries included in the European country basket. However, in some of these countries, the EFP is not published due to confidential wholesale margins. Wholesale margins must therefore be estimated and deducted from purchase prices. In this context literature-based estimates to date do not assume regressive margins with higher pharmaceutical prices. This assumption is questionable and can lead to systematically underestimated country prices, especially for high-priced drugs. Percentage wholesale margins in the majority of European countries develop to a comparable extent regressively with increasing prices. It should therefore be examined (1) whether statistical models can predict the margins of individual countries, in principle and especially for countries where margins are unknown and regressive trends are likely, and (2) to what extent the estimation of margins improves when regressive statistical models are used to estimate margins instead of cross-price averages published in the literature.

METHODS: Qualitative preliminary research explores the basic wholesale pricing mechanisms in countries with confidential wholesale margins. Wholesale margins for reimbursable drugs were then modeled for regulated European countries. Estimation quality and impact of the model was compared to estimations based on average margins.

RESULTS: In both regulated countries and in countries with confidential wholesale margins, percentage margins of wholesalers develop regressively as drug prices rise. Regressive courses of margins can be resiliently modeled for the regulated countries using a power distribution with significantly lower mean squared errors in a linear mixed model in comparison to literature-based estimations with country-specific cross-price averages.

CONCLUSION: If there is reason to believe that margins are regressive, confidential wholesale margins are expected to be better estimated by the power function based on margins of regulated countries than by the published country-specific average margins, reducing significantly inaccurate effects on margin estimations of high-price drugs.

PMID:38607501 | DOI:10.1186/s13561-024-00503-9

Environ Sci Pollut Res Int. 2024 Apr 12. doi: 10.1007/s11356-024-33038-x. Online ahead of print.

ABSTRACT

Understanding the nexus of land use and water quality can potentially underline the influences within the groundwater management. The study envisages land use-specific qualitative assessment of the groundwater resources in Ghaziabad district, in western Uttar Pradesh, India. For encountering the relative impacts of land use on the groundwater quality, chemometric analysis has been employed to apportion the pollution sources. The integration of quality parameters, in the information entropy index modeling, has segregated the quality classes and visualized the seasonal suitability trends as per potability standards along with non-carcinogenic health hazard risk assessment (HHRA). The qualitative assessment of the groundwater resources, along with spatial distribution, has deciphered a polluting impact, specifically in western and south western parts of district, and observed the linkages with direct and indirect discharges/seepages from densely populated residential and industrial land use types localized in urbanized areas. Statistically significant annual and seasonal variations have been found exclusively for EC, Mg²⁺, F^–, Cd, Cr_(total), Ni, and Pb which inferred variable concentrations, whereas land use types showed a non-significant variation within groundwater quality. Chemometric-based source apportioning and hierarchical cluster analysis (HCA) have derived salinization and enrichment of dissolved salts, arising from mixed sources and contributes to metal pollution, i.e., mainly from anthropogenic sources. Information EWQI derived poor to extremely poor category represented degraded potability specifically for fewer sites located within western and southern parts on the Yamuna-Hindon flood plains for limited sites of residential, industrial, and agricultural in an urbanized region. However, majority of the samples fall under excellent to good groundwater quality, recommendable in the north and north-eastern (peri-urban) regions. Non-carcinogenic HHRA has shown that majority of the samples categorized under unsafe value for hazard index (HI > 1), for females and children and thus, presumed probable health hazard risk from metal groundwater pollution in south-western part, eastern, and northern regions.

PMID:38607485 | DOI:10.1007/s11356-024-33038-x

Environ Sci Pollut Res Int. 2024 Apr 12. doi: 10.1007/s11356-024-33261-6. Online ahead of print.

ABSTRACT

Computational techniques, such as quantitative structure-property relationships (QSPRs), can play a significant role in exploring the important chemical features essential for the degree of sorption or sludge/water partition coefficient (K_d) towards sewage sludge of wastewater treatment process to evaluate the environmental consequence and risk of pharmaceuticals. The current research work aims to construct a predictive QSPR model for the sorption of 148 diverse active pharmaceutical ingredients (APIs) in sewage sludge during wastewater treatment. For the development of the model, we employed easily computable 2D descriptors as independent variables. The model has been developed following the Organization for Economic Cooperation and Development’s (OECD) guidelines. It has undergone internal and external validation using a variety of methodologies, as well as been tested for its applicability domain. A measure of hydrophobicity, i.e., MLOGP2, showed the most promising contribution in modeling the sorption coefficient of APIs. Among other parameters, the number of tertiary aromatic amines, the presence of electronegative atoms like N, O, and Cl, the size of a molecule, the number of aromatic hydroxyl groups, the presence of substituted aromatic nitrogen atoms and alkyl-substituted tertiary carbon atoms were also found to be influential for the regulation of solid water partition coefficient of APIs during the wastewater treatment process. The statistical validity tests performed on the developed partial least squares (PLS) model showed that it is statistically evident, robust, and predictive (R²_Train = 0.750, Q²_LOO = 0.683, Q²_F1 = 0.655, Q²_F2 (or R²_Test) = 0.651). In addition, the predictivity of the constructed model was further inspected by using the “prediction reliability indicator” tool for 14 external APIs.

PMID:38607482 | DOI:10.1007/s11356-024-33261-6

Intensive Care Med Exp. 2024 Apr 12;12(1):36. doi: 10.1186/s40635-024-00620-z.

ABSTRACT

BACKGROUND: In refractory out-of-hospital cardiac arrest, the patient is commonly transported to hospital with mechanical continuous chest compressions (CCC). Limited data are available on the optimal ventilation strategy. Accordingly, we compared arterial oxygenation and haemodynamics during manual asynchronous continuous ventilation and compressions with a 30:2 compression-to-ventilation ratio together with the use of 10 cmH₂O positive end-expiratory pressure (PEEP).

METHODS: Intubated and anaesthetized landrace pigs with electrically induced ventricular fibrillation were left untreated for 5 min (n = 31, weight ca. 55 kg), after which they were randomized to either the CCC group or the 30:2 group with the the LUCAS® 2 piston device and bag-valve ventilation with 100% oxygen targeting a tidal volume of 8 ml/kg with a PEEP of 10 cmH₂O for 35 min. Arterial blood samples were analysed every 5 min, vital signs, near-infrared spectroscopy and electrical impedance tomography (EIT) were measured continuously, and post-mortem CT scans of the lungs were obtained.

RESULTS: The arterial blood values (median + interquartile range) at the 30-min time point were as follows: PaO₂: 180 (86-302) mmHg for the 30:2 group; 70 (49-358) mmHg for the CCC group; PaCO₂: 41 (29-53) mmHg for the 30:2 group; 44 (21-67) mmHg for the CCC group; and lactate: 12.8 (10.4-15.5) mmol/l for the 30:2 group; 14.7 (11.8-16.1) mmol/l for the CCC group. The differences were not statistically significant. In linear mixed models, there were no significant differences between the groups. The mean arterial pressures from the femoral artery, end-tidal CO₂, distributions of ventilation from EIT and mean aeration of lung tissue in post-mortem CTs were similar between the groups. Eight pneumothoraces occurred in the CCC group and 2 in the 30:2 group, a statistically significant difference (p = 0.04).

CONCLUSIONS: The 30:2 and CCC protocols with a PEEP of 10 cmH₂O resulted in similar gas exchange and vital sign outcomes in an experimental model of prolonged cardiac arrest with mechanical compressions, but the CCC protocol resulted in more post-mortem pneumothoraces.

PMID:38607459 | DOI:10.1186/s40635-024-00620-z

J Nucl Cardiol. 2024 Mar 29:101854. doi: 10.1016/j.nuclcard.2024.101854. Online ahead of print.

ABSTRACT

BACKGROUND: Myocardial flow reserve (MFR) by positron emission tomography (PET) is a validated measure of cardiovascular risk. Elevated resting rate pressure product (RPP = heart rate x systolic blood pressure) can cause high resting myocardial blood flow (MBF), resulting in reduced MFR despite normal/near-normal peak stress MBF. When resting MBF is high, it is not known if RPP-corrected MFR (MFRcorrected) helps reclassify CV risk. We aimed to study this question in patients without obstructive coronary artery disease (CAD).

METHODS: We retrospectively studied patients referred for rest/stress cardiac PET at our center from 2006-2020. Patients with abnormal perfusion (summed stress score > 3) or prior coronary artery bypass grafting (CABG) were excluded. MFRcorrected was defined as stress MBF/corrected rest MBF where corrected rest MBF = rest MBF x 10,000/RPP. The primary outcome was major cardiovascular events (MACE): cardiovascular death or myocardial infarction. Associations of MFR and MFRcorrected with MACE were assessed using unadjusted and adjusted Cox regression.

RESULTS: 3,276 patients were followed for a median of 7 (IQR 3-12) years. 1,685 patients (51%) had MFR < 2.0, and of those 366 (22%) had an MFR ≥ 2.0 after RPP correction. MFR < 2.0 was associated with an increased absolute risk of MACE (HR 2.24 [1.79-2.81], p<0.0001). Among patients with MFR < 2.0, the risk of MACE was not statistically different between patients with a MFRcorrected ≥ 2.0 compared with those with MFRcorrected < 2.0 (1.9% vs 2.3% MACE/year, HR 0.84 [0.63-1.13], p=0.26) even after adjustment for confounders (p=0.66).

CONCLUSIONS: In patients without overt obstructive CAD and MFR< 2.0, there was no significant difference in cardiovascular risk between patients with discordant (≥2.0) and concordant (<2) MFR following RPP correction. This suggests that RPP-corrected MFR may not consistently provide accurate risk stratification in patients with normal perfusion and MFR < 2.0. Stress MBF and uncorrected MFR should be reported to more reliably convey cardiovascular risk beyond perfusion results.

PMID:38606610 | DOI:10.1016/j.nuclcard.2024.101854

J Glob Health. 2024 Apr 12;14:04068. doi: 10.7189/jogh-14-04068.

ABSTRACT

BACKGROUND: Central and bridge nodes can drive significant overall improvements within their respective networks. We aimed to identify them in 16 prevalent chronic diseases during the coronavirus disease 2019 (COVID-19) pandemic to guide effective intervention strategies and appropriate resource allocation for most significant holistic lifestyle and health improvements.

METHODS: We surveyed 16 512 adults from July 2020 to August 2021 in 30 territories. Participants self-reported their medical histories and the perceived impact of COVID-19 on 18 lifestyle factors and 13 health outcomes. For each disease subgroup, we generated lifestyle, health outcome, and bridge networks. Variables with the highest centrality indices in each were identified central or bridge. We validated these networks using nonparametric and case-dropping subset bootstrapping and confirmed central and bridge variables’ significantly higher indices through a centrality difference test.

FINDINGS: Among the 48 networks, 44 were validated (all correlation-stability coefficients >0.25). Six central lifestyle factors were identified: less consumption of snacks (for the chronic disease: anxiety), less sugary drinks (cancer, gastric ulcer, hypertension, insomnia, and pre-diabetes), less smoking tobacco (chronic obstructive pulmonary disease), frequency of exercise (depression and fatty liver disease), duration of exercise (irritable bowel syndrome), and overall amount of exercise (autoimmune disease, diabetes, eczema, heart attack, and high cholesterol). Two central health outcomes emerged: less emotional distress (chronic obstructive pulmonary disease, eczema, fatty liver disease, gastric ulcer, heart attack, high cholesterol, hypertension, insomnia, and pre-diabetes) and quality of life (anxiety, autoimmune disease, cancer, depression, diabetes, and irritable bowel syndrome). Four bridge lifestyles were identified: consumption of fruits and vegetables (diabetes, high cholesterol, hypertension, and insomnia), less duration of sitting (eczema, fatty liver disease, and heart attack), frequency of exercise (autoimmune disease, depression, and heart attack), and overall amount of exercise (anxiety, gastric ulcer, and insomnia). The centrality difference test showed the central and bridge variables had significantly higher centrality indices than others in their networks (P < 0.05).

CONCLUSION: To effectively manage chronic diseases during the COVID-19 pandemic, enhanced interventions and optimised resource allocation toward central lifestyle factors, health outcomes, and bridge lifestyles are paramount. The key variables shared across chronic diseases emphasise the importance of coordinated intervention strategies.

PMID:38606605 | DOI:10.7189/jogh-14-04068

Psychol Med. 2024 Apr 12:1-12. doi: 10.1017/S0033291724000825. Online ahead of print.

ABSTRACT

BACKGROUNDS: Many autistic people in mental health are suicidal. This study evaluated the effectiveness of dialectical behavior therapy (DBT) v. treatment as usual (TAU) in reducing suicidal ideation and suicide attempts.

METHODS: At six Dutch mental health centers, 123 outpatients (18-65 years) with DSM-5 diagnosed autism spectrum disorder (ASD) and suicidal behavior were randomly assigned to the DBT intervention group (n = 63) or TAU control group (n = 60). Assessments were conducted at baseline, post-treatment at 6 months and 12-month follow-up. The primary outcomes were severity of suicidal ideation and frequency of suicide attempts. The severity of depression and social anxiety were secondary outcomes.

RESULTS: At end-of-treatment, DBT significantly reduced both suicidal ideation (z = -2.24; p = 0.025; b = -4.41; s.e. = 197.0) and suicide attempts (z = -3.15; p = 0.002; IRR = 0.046; s.e. = 0.045) compared to TAU, but lost statistical significance at the 12-month follow-up. Depression severity significantly decreased with DBT (z = -1.99; p = 0.046: b = -2.74; s.e. = 1.37) remaining so at 12 months (z = -2.46; p = 0.014; b = -3.37; s.e. = 1.37). No effects were observed on social anxiety. Severe adverse events included two suicides in the TAU condition.

CONCLUSIONS: DBT is an acceptable, safe, and short-term effective intervention to reduce suicidal ideation and suicide attempts in autistic adults with suicidal behavior.

PMID:38606582 | DOI:10.1017/S0033291724000825

Euro Surveill. 2024 Apr;29(15). doi: 10.2807/1560-7917.ES.2024.29.15.2400178.

ABSTRACT

Since the end of November 2023, the European Mortality Monitoring Network (EuroMOMO) has observed excess mortality in Europe. During weeks 48 2023-6 2024, preliminary results show a substantially increased rate of 95.3 (95% CI: 91.7-98.9) excess all-cause deaths per 100,000 person-years for all ages. This excess mortality is seen in adults aged 45 years and older, and coincides with widespread presence of COVID-19, influenza and respiratory syncytial virus (RSV) observed in many European countries during the 2023/24 winter season.

PMID:38606570 | DOI:10.2807/1560-7917.ES.2024.29.15.2400178

Br J Nutr. 2024 Apr 12:1-23. doi: 10.1017/S0007114524000709. Online ahead of print.

ABSTRACT

The ability to provide adequate nutrition is considered a key factor in evaluating the sustainability of foods and diets. Nutrient indices are used as functional units (FUs) in life cycle assessment of foods to include nutritional performance in the environmental assessment of a product. Several general and food group-specific nutrient indices exist but many lack validation, particularly when used as FU. In addition, the nutrient selection strategies and reference units for nutrient intake can vary considerably among studies. To validate intake-based product-group-specific nutrient indices previously developed for protein (NR-FI_prot) and carbohydrate (NR-FI_carb) foods and for fruits and vegetables (NR-FI_veg), we applied principal component analysis to investigate correlations between nutrients in foods and dishes representing a typical Finnish diet. The reference amounts for meal components were based on a plate model that reflected Finnish dietary recommendations. The portion sizes for the different food groups were anchored at 100 g, 135 g and 350 g for proteins, carbohydrates and fruits/vegetables, respectively. Statistical modelling largely validated the NR-FI indices, highlighting protein foods as sources of niacin, vitamin B12 and selenium, carbohydrate foods as sources of magnesium, iron and phosphorous, and fruits/vegetables as sources of potassium, vitamin K, vitamin C, fibre and thiamine. However, in contrast to the intake-based approach applied in NR-FI_prot, the dietary recommendation-based validation process suggested that fruits and vegetables should be favoured as sources of riboflavin and vitamin B6.

PMID:38606563 | DOI:10.1017/S0007114524000709

Eur J Heart Fail. 2024 Apr 12. doi: 10.1002/ejhf.3232. Online ahead of print.

ABSTRACT

AIMS: Carotid baroreflex activation therapy (BAT) restores baroreflex sensitivity and modulates the imbalance in cardiac autonomic function in patients with heart failure with reduced ejection fraction (HFrEF). We tested the hypothesis that treatment with BAT significantly reduces cardiovascular mortality and heart failure morbidity and provides long-term safety and sustainable symptomatic improvement.

METHODS AND RESULTS: BeAT-HF was a prospective, multicentre, randomized, two-arm, parallel-group, open-label, non-implanted control trial. New York Heart Association (NYHA) class III subjects, ejection fraction ≤35%, previous heart failure hospitalization or N-terminal pro-B-type natriuretic peptide (NT-proBNP) >400 pg/ml, no class I indication for cardiac resynchronization therapy and NT-proBNP <1600 pg/ml were randomized to BAT plus optimal medical management (BAT group) or optimal medical management alone (control). The primary endpoint was cardiovascular mortality and HF morbidity; additional pre-specified endpoints included durability of safety, quality of life (QOL), exercise capacity (6-min hall walk distance [6MHWD]), functional status (NYHA class), hierarchical composite win ratio, freedom from all-cause death, left ventricular assists device (LVAD) implantation, heart transplant. Overall, 323 patients had 332 primary events, median follow-up was 3.6 years/patient. Both primary endpoint (rate ratio 0.94, 95% confidence interval [CI] 0.57-1.57; p = 0.82) and components of the primary endpoints were not significantly different between BAT and control. The system- and procedure-related major adverse neurological and cardiovascular event-free rate remained 97% throughout the trial. Symptom improvement (QOL, 6MHWD, NYHA class, all nominal p < 0.001) in the BAT group was durable in time, sustainable in extent. Win ratio (1.26, 95% CI 1.02-1.58) and freedom from all-cause death, LVAD implantation, heart transplant (hazard ratio 0.66, 95% CI 0.43-1.01) favoured the BAT group but did not reach statistical significance.

CONCLUSION: The BeAT-HF primary endpoint was neutral; however, BAT provided safe, effective, and sustainable improvements in HFrEF patient’s functional status, 6MHWD and QOL.

PMID:38606555 | DOI:10.1002/ejhf.3232