Category: Nevin Manimala

J Prim Prev. 2021 Oct 17. doi: 10.1007/s10935-021-00650-3. Online ahead of print.

ABSTRACT

Although vaccination is one of the most cost-effective ways of preventing disease, vaccine hesitancy has been included among the ten threats of global health. Addressing low adult vaccination rates requires an adequate understanding of people’s views. We explored perceived barriers to immunization among under-vaccinated adults to identify potential differences among vaccine supporters, refuters, and those who are undecided. We conducted a multi-center, mixed-methods study at 23 primary care practices in Greece. Each day, we asked three new randomly-selected adult healthcare users who attended the practice over the course of 30 consecutive working days. We used thematic content analysis to analyze their written answers to open-ended questions that addressed reasons for not getting vaccinated. Out of 1571 participants, two-thirds reported they were under-vaccinated as adults, thus accounting for three out of five of the supporters and the vast majority of the undecided and refuters. “Concerns/fears,” a “perception of low susceptibility to disease due to good health status,” the “absence of healthcare professional’s recommendation,” and “previous negative experiences” were four themes common to all three groups. Additional barriers reported by supporters and the undecided included “knowledge gaps about the necessity of adult vaccination,” “negligence,” and lack of “accessibility.” Among refuters, additional themes identified were “mistrust in pharmaceutical companies” and “disbelief in vaccine effectiveness.” In conclusion, under-vaccination is common, not only among refuters or the undecided, but also among supporters of adult vaccination. We found similarities and differences in under-vaccinated adults’ perceived barriers, depending on their individual perspectives. Physicians and public health services should take into consideration the impact of the wide range of attitudes and beliefs in their effort to address the underlying barriers to vaccination compliance as they attempt to increase vaccination coverage in adults.

PMID:34657269 | DOI:10.1007/s10935-021-00650-3

BioDrugs. 2021 Oct 16. doi: 10.1007/s40259-021-00502-w. Online ahead of print.

ABSTRACT

BACKGROUND: AVT02 (adalimumab) is a proposed biosimilar to Humira^®. AVT02 is produced at a 100 mg/mL concentration with a citrate-free formulation.

OBJECTIVES: The aim of this study was to compare the efficacy, safety and immunogenicity of AVT02 versus Humira^® in subjects with moderate to severe chronic plaque psoriasis.

METHODS: This double-blind, randomised, parallel group, active control study of adult subjects compared (at a 1:1 ratio) AVT02 with originator adalimumab 80 mg subcutaneously in Week 1, then 40 mg every other week. At Week 16, subjects who had received originator adalimumab were re-randomised at a 1:1 ratio to continue receiving originator adalimumab, or to switch to AVT02, every other week until Week 48, with final efficacy endpoint at Week 50. Subjects who initially received AVT02 continued to receive AVT02 from Week 16 to Week 48. The primary endpoint was percentage improvement in Psoriasis Area and Severity Index (PASI) score at Week 16. Secondary efficacy endpoints included percentage improvement in PASI score at additional timepoints, change from baseline in Dermatology Life Quality Index (DLQI) score and number and percentage of subjects achieving static Physician’s Global Assessment (sPGA) responses of ‘clear’ or ‘almost clear’. Additional secondary endpoints included comparison of adverse event profiles, anti-drug antibodies and neutralising antibodies, and serum trough levels of adalimumab at steady state.

RESULTS: A total of 413 subjects were randomised (205 to AVT02 and 208 to originator). The percentage improvement in PASI score at Week 16 was 91.6% for AVT02-treated subjects and 89.6% for originator adalimumab. The 90% confidence intervals for the primary endpoint were within the pre-defined equivalence margin of ±10% (90% CI – 0.76 to 5.29; 95% CI – 1.34 to 5.88), and a comparable pattern for DLQI score (11.4-point and 10.6-point improvement in AVT02-treated and originator adalimumab-treated groups, respectively) and sPGA (90.5% in both groups achieving ‘clear’ or ‘almost clear’) at Week 16 supported the assessment. Efficacy persisted through Week 50 of the study in all treatment groups, including those who switched from originator adalimumab to AVT02, for percent improvement in PASI score, quality-of-life assessment and sPGA. The safety, tolerability and immunogenicity profiles between AVT02 and originator adalimumab were similar at Week 16, and this persisted in the switched and continued groups through Week 50.

CONCLUSION: Objective and subjective measures of efficacy supported the evaluation of biosimilarity between AVT02 and originator adalimumab at Week 16 and until Week 50, in switched and continued treatment groups. AVT02 was safe and well tolerated, with a safety and immunogenicity profile similar to that observed in originator adalimumab with no clinically meaningful difference between the two.

CLINICAL TRIAL REGISTRATION: EudraCT: 2017-003367-35; ClinicalTrials.gov: NCT03849404.

PMID:34657274 | DOI:10.1007/s40259-021-00502-w

Environ Sci Pollut Res Int. 2021 Oct 16. doi: 10.1007/s11356-021-16792-0. Online ahead of print.

ABSTRACT

Activated carbon prepared from grape branches was used as a remarkable adsorbent to uptake naproxen and treat a synthetic mixture from aqueous solutions. The material presented a highly porous texture, a surface area of 938 m² g^-1, and certain functional groups, which were key factors to uptake naproxen from effluents. The maximum adsorption capacity predicted by the Langmuir model for naproxen was 176 mg g^-1. The thermodynamic study revealed that the adsorption process was endothermic and spontaneous. The linear driving force (LDF) model presented a good statistical adjustment to the experimental decay data. A suitable interaction pathway of naproxen adsorption onto activated carbon was proposed. The adsorbent material was highly efficient to treat a synthetic mixture containing several drugs and salts, reaching 95.63% removal. Last, it was found that the adsorbent can be regenerated up to 7 times using an HCl solution. Overall, the results proved that the activated carbon derived from grape branches could be an effective and sustainable adsorbent to treat wastewaters containing drugs.

PMID:34657260 | DOI:10.1007/s11356-021-16792-0

Mol Biol Rep. 2021 Oct 16. doi: 10.1007/s11033-021-06763-6. Online ahead of print.

ABSTRACT

BACKGROUND: The present study evaluates the development of edema, the change in the AQP3, AQP4, p53 and Bax gene expressions, and the protective effects of melatonin in rat hearts administered with cisplatin.

METHODS AND RESULTS: A total of 28 Wistar albino rats were divided into four groups. The vehicle was administered intraperitoneally (i.p.) to the rats in the control group. The melatonin group (Mel) received melatonin at a dose of 10 mg/kg for 13 days. The cisplatin group (Cis) received cisplatin on days 1, 5, 9 and 13 at a dose of 4 mg/kg. The rats in the cisplatin + melatonin (Cis+Mel) group underwent the procedures both in the Mel and Cis groups. Blood and left ventricular samples were taken and analyzed on day 14 of the study. AQP3, p53 and Bax gene expressions were found to be significantly increased following cisplatin administration compared to the control, while melatonin administration significantly decreased the expression of these genes (p < 0.05). Melatonin administration also significantly decreased the level of AQP4 gene expression compared to the cis. On histological examination, congestion, hemorrhage, extracellular and intracellular edema, and degenerative changes were significantly more common in the Cis than in the control. Melatonin administration significantly decreased intracellular edema (p = 0.010) and degenerative changes (p = 0.010), and the improvement in extracellular edema was close to statistical significance (p = 0.051) in melatonin.

CONCLUSIONS: These results indicate that melatonin had an ameliorative effect on myocardial edema and AQP channels, and that it may be used as a protective molecule against myocardial edema secondary to cisplatin administration.

PMID:34657253 | DOI:10.1007/s11033-021-06763-6

Environ Sci Pollut Res Int. 2021 Oct 16. doi: 10.1007/s11356-021-16738-6. Online ahead of print.

ABSTRACT

Passenger cars are responsible for a great amount of energy consumption and emissions in the world. Turkey is one of the world’s twenty largest emission producers. The reason behind this study is to determine the most appropriate energy source for passenger cars particularly in Turkey in terms of main vehicle emissions. The results will be supportive for general inferences also. The impact of technological year, vehicle type, fuel type, fuel production, and electricity generation from different energy sources on well-to-wheel emissions for Turkey has been analyzed using the GREET software in this study. In the realization of emission analysis, transportation statistics of Turkey in the last 10 years have been evaluated. In addition, different scenarios have been presented for the years 2030 and 2050. It is found that average emissions emitted from passenger cars in Turkey decrease by year, and the use of LPG and CNG in plug-in hybrid cars generates lower emissions in future scenarios.

PMID:34657255 | DOI:10.1007/s11356-021-16738-6

J Pharmacokinet Pharmacodyn. 2021 Oct 16. doi: 10.1007/s10928-021-09789-2. Online ahead of print.

ABSTRACT

Clinical trials in patients with ulcerative colitis (UC) face the challenge of high and variable placebo response rates. The Mayo Clinical Score (MCS) is used widely as the primary endpoint in clinical trials to describe the clinical status of patients with UC. The MCS is comprised of four subscores, each scored 0, 1, 2 and 3: rectal bleeding (RB), stool frequency (SF), physician’s global assessment (PGA), and endoscopy (ENDO) subscore. Excluding the PGA subscore gives the modified MCS. Quantitative insight on the placebo response, and its impact on the components of the MCS over time, can better inform clinical trial design and interpretation. Longitudinal modeling of the MCS, and the modified MCS, can be challenging due to complex clinical trial design, population heterogeneity, and limited assessments for the ENDO subscore. The current study pooled patient-level placebo/standard of care (SoC) arm data from five clinical trials in the TransCelerate database to develop a longitudinal placebo response model that describes the MCS over time in patients with UC. MCS subscores were modeled using proportional odds models, and the removal of patients from the placebo/SoC arm, or “dropout”, was modeled using logistic regression models. The subscore and dropout models were linked to allow for the prediction of the MCS and the modified MCS. Stepwise covariate modeling identified prior exposure to TNF-α antagonists as a statistically significant predictor on the RB + SF subscore. Patients with prior exposure to TNF-α antagonists had higher post-baseline RB + SF subscores than naive patients.

PMID:34657238 | DOI:10.1007/s10928-021-09789-2

Clin Drug Investig. 2021 Oct 16. doi: 10.1007/s40261-021-01087-6. Online ahead of print.

ABSTRACT

Allogeneic haematopoietic stem cell transplantation (alloHSCT) offers a potentially curative therapy for patients suffering from diseases of the haematopoietic system but requires a high level of expertise and is both resource intensive and expensive. A frequent and life-threatening complication is graft-versus-host disease (GvHD). Acute GvHD (aGvHD) generally causes skin, gastrointestinal and liver symptoms, but chronic GvHD (cGvHD) has a different pathophysiology and may affect nearly every organ or tissue of the body. In Europe, GvHD prophylaxis is generally a calcineurin inhibitor in combination with methotrexate, with high-dose systemic steroids used for advanced GvHD treatment. Between 39% and 59% of alloHSCT patients will develop aGvHD and around 36-37% will develop cGvHD. Steroid response decreases with increasing disease severity, which in turn leads to an increase in non-relapse mortality. GvHD imposes a financial burden on healthcare systems, significantly increasing post-alloHSCT costs. Increased GvHD disease severity magnifies this. Balancing immunosuppression to control the GvHD whilst maintaining a degree of immunocompetence against infection is critical. European GvHD guidelines acknowledge the lack of evidence to support a standard second-line therapy, and improved long-term outcomes and quality-of-life (QoL) remain an unmet need. Evidence generation for potential treatments is challenging. Issues to overcome include choice of comparator (extensive off-label usage); blinding; selection of relevant patient-reported outcome measures (PROMs); and rarity of the condition, which may infeasibly increase timescales to achieve clinical and statistical relevance.

PMID:34657244 | DOI:10.1007/s40261-021-01087-6

Ir J Med Sci. 2021 Oct 16. doi: 10.1007/s11845-021-02783-0. Online ahead of print.

ABSTRACT

INTRODUCTION: Lung cancer is the leading cause of cancer deaths in many Western countries, but its incidence has never been studied in Northern Ireland.

AIMS: Accordingly, the present study was mounted to determine, for the first time, the incidence of the condition in Northern Ireland and to compare the findings with other regions in the British Isles.

METHODS: A notification study of the incidence of lung cancer (ICD 162) was conducted in Northern Ireland during 1991/1992. Notifications from 6 sources were computerised and linked. Incident cases were identified and analysed in relation to Age, Sex and Geographical region-Northern Ireland, England and Wales, Scotland and the Republic of Ireland.

RESULTS: Some 900 incident cases of lung cancer were identified. The incidence rate per 100,000 population was found to be 57.04. Mortality underestimated incidence by 12.5%. ([Formula: see text]). The male to female incidence ratio was 2.1: 1, and this ratio was similar in other regions, except Scotland, where the ratio was 1.7:1. The null hypothesis of a common incidence distribution across regions was formally rejected. A variety of models were fitted and a model in which the log-odds on incidence was a quadratic function of age fitted most of the regional data.

CONCLUSIONS: Northern Ireland had the lowest incidence of lung cancer in the UK, but its overall rate was still 40% higher than that observed in the Republic of Ireland which had the lowest rate in the British Isles. Across regions, the pattern of incidence by age and sex was complicated, but a linear logistic model fitted all of the Irish data and the female data in Scotland, satisfactorily.

PMID:34657234 | DOI:10.1007/s11845-021-02783-0

Prev Vet Med. 2021 Sep 15;196:105494. doi: 10.1016/j.prevetmed.2021.105494. Online ahead of print.

ABSTRACT

Tanzania has the second largest livestock population in Africa and livestock keeping is an integral part of most people’s livelihoods. Foot-and-mouth disease (FMD) is a transboundary disease, affecting cloven-hoofed animals, that is currently endemic in Tanzania. The Tanzania Development Vision 2025 aspires to make the livestock sector more competitive. Part of this plan foresees establishing a FMD-free zone in the Rukwa region to be able to increase the export of animals and animal products. The aim of this study was to assess the economic efficiency and feasibility of establishing such an FMD-free zone and to advise policy makers on the profitability of the investment. A stochastic benefit-cost model, set-up in Palisade @Risk for Excel for a time frame of ten years, was developed to assess whether the benefits of establishing a FMD-free zone would outweigh the costs. Data were collated from reviewing literature, government statistics, and key informant interviews with farmers, traders and veterinarians in Tanzania, and complemented by informed assumptions and expert opinion. Moreover, feasibility aspects including underlying infrastructure, market structures and resource availability were discussed based on key informant interviews, literature review and historical analyses. The net present value for the establishment of a FMD-free zone was negative and the benefit-cost ratio was below one (mean 0.09, min 0.05 – max 0.15 in the scenario considering vaccination of all susceptible domestic animals, and mean 0.11, min 0.06 – max 0.20 when considering vaccinating cattle only), excluding potential benefits from trade. The sensitivity analysis showed that variables related to the cost of vaccination had the largest negative impact on the net present value. The proposed FMD-free zone in Rukwa region is unlikely to be cost-effective with the current FMD status and export trade prospects in Tanzania. Interviews with stakeholders revealed that vaccine availability, funding, farmers’ willingness to participate, and lack of staff continuity in key roles were the main barriers to establish a reliable FMD control programme in the country. Recommendations towards FMD control and potential short and middle term strategies are discussed.

PMID:34656049 | DOI:10.1016/j.prevetmed.2021.105494

Clin Nutr. 2021 Sep 4;40(11):5494-5499. doi: 10.1016/j.clnu.2021.08.022. Online ahead of print.

ABSTRACT

BACKGROUND & AIMS: Dietary intake of several specific macronutrients has been linked to risk of coronary heart disease (CHD). However, these associations may depend on overall macronutrient composition rather than effects of one single macronutrient. Therefore, we aimed to investigate the associations of macronutrient intake and CHD and its related risk factors, by taking into account different macronutrient substitutions.

METHODS: This study was performed among 5873 participants from the Rotterdam Study, a population-based cohort study. Macronutrient intake was measured using a semi-quantitative food-frequency questionnaire. Cox proportional hazard regression analyses were used to examine associations between intakes of macronutrients and CHD incidence; and linear regression analyses were used to examine associations with the related risk factors, including triglycerides, total, high-density and low-density cholesterol levels, body mass index (BMI), fat mass index (FMI), and fat-free mass index (FFMI).

RESULTS: We documented 669 CHD cases during 74,776 person-years of follow-up. In multivariable-adjusted models we observed no statistically significant associations between macronutrients and CHD incidence. Although non-significant, a higher plant protein intake tended to be associated with a lower risk of CHD when consumed at the expense of any of the other macronutrients. This association was strongest when 5% of energy (5 E%) of plant protein was consumed at the expense of animal protein (HR = 0.61; 95% CI 0.31, 1,21), mono- and disaccharides (HR = 0.62; 95% CI 0.29, 1.35) or saturated fat (HR = 0.61; 95% CI 0.31, 1.20). No consistent associations were observed for risk factors related to CHD.

CONCLUSIONS: Macronutrient composition was not significantly associated with CHD incidence or cardiometabolic risk factors in an adult population. Future studies should further investigate food sources and quality of macronutrients.

PMID:34656031 | DOI:10.1016/j.clnu.2021.08.022