Nevin Manimala

Cochrane Database Syst Rev. 2021 Oct 17;10:CD003654. doi: 10.1002/14651858.CD003654.pub5.

ABSTRACT

BACKGROUND: This is the first update of a review published in 2010. While calcium channel blockers (CCBs) are often recommended as a first-line drug to treat hypertension, the effect of CCBs on the prevention of cardiovascular events, as compared with other antihypertensive drug classes, is still debated.

OBJECTIVES: To determine whether CCBs used as first-line therapy for hypertension are different from other classes of antihypertensive drugs in reducing the incidence of major adverse cardiovascular events.

SEARCH METHODS: For this updated review, the Cochrane Hypertension Information Specialist searched the following databases for randomised controlled trials (RCTs) up to 1 September 2020: the Cochrane Hypertension Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2020, Issue 1), Ovid MEDLINE, Ovid Embase, the World Health Organization International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also contacted the authors of relevant papers regarding further published and unpublished work and checked the references of published studies to identify additional trials. The searches had no language restrictions.

SELECTION CRITERIA: Randomised controlled trials comparing first-line CCBs with other antihypertensive classes, with at least 100 randomised hypertensive participants and a follow-up of at least two years.

DATA COLLECTION AND ANALYSIS: Three review authors independently selected the included trials, evaluated the risk of bias, and entered the data for analysis. Any disagreements were resolved through discussion. We contacted study authors for additional information.

MAIN RESULTS: This update contains five new trials. We included a total of 23 RCTs (18 dihydropyridines, 4 non-dihydropyridines, 1 not specified) with 153,849 participants with hypertension. All-cause mortality was not different between first-line CCBs and any other antihypertensive classes. As compared to diuretics, CCBs probably increased major cardiovascular events (risk ratio (RR) 1.05, 95% confidence interval (CI) 1.00 to 1.09, P = 0.03) and increased congestive heart failure events (RR 1.37, 95% CI 1.25 to 1.51, moderate-certainty evidence). As compared to beta-blockers, CCBs reduced the following outcomes: major cardiovascular events (RR 0.84, 95% CI 0.77 to 0.92), stroke (RR 0.77, 95% CI 0.67 to 0.88, moderate-certainty evidence), and cardiovascular mortality (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence). As compared to angiotensin-converting enzyme (ACE) inhibitors, CCBs reduced stroke (RR 0.90, 95% CI 0.81 to 0.99, low-certainty evidence) and increased congestive heart failure (RR 1.16, 95% CI 1.06 to 1.28, low-certainty evidence). As compared to angiotensin receptor blockers (ARBs), CCBs reduced myocardial infarction (RR 0.82, 95% CI 0.72 to 0.94, moderate-certainty evidence) and increased congestive heart failure (RR 1.20, 95% CI 1.06 to 1.36, low-certainty evidence).

AUTHORS’ CONCLUSIONS: For the treatment of hypertension, there is moderate certainty evidence that diuretics reduce major cardiovascular events and congestive heart failure more than CCBs. There is low to moderate certainty evidence that CCBs probably reduce major cardiovascular events more than beta-blockers. There is low to moderate certainty evidence that CCBs reduced stroke when compared to angiotensin-converting enzyme (ACE) inhibitors and reduced myocardial infarction when compared to angiotensin receptor blockers (ARBs), but increased congestive heart failure when compared to ACE inhibitors and ARBs. Many of the differences found in the current review are not robust, and further trials might change the conclusions. More well-designed RCTs studying the mortality and morbidity of individuals taking CCBs as compared with other antihypertensive drug classes are needed for patients with different stages of hypertension, different ages, and with different comorbidities such as diabetes.

PMID:34657281 | DOI:10.1002/14651858.CD003654.pub5

Eur Arch Paediatr Dent. 2021 Oct 16. doi: 10.1007/s40368-021-00651-0. Online ahead of print.

ABSTRACT

PURPOSE: This study was aimed at evaluating the levels of knowledge of child abuse among students attending the School of Dental and Oral Medicine at the University of Hamburg- Eppendorf, Germany.

METHODS: This cross-sectional study utilized a self-administered and structured questionnaire, consisting of 23 multiple-choice questions; the questionnaire focused on rating the students’ knowledge of and ability to diagnose child abuse. Each question was analysed with simple descriptive statistics.

RESULTS: The students (181) were aware of their legal and ethical responsibilities towards the children and their parents. More than two-thirds (69.6%) responded positively when asked whether a dentist should be legally responsible to report cases of child abuse brought to their attention. The majority of the students (96.1%) agreed that dentists had an ethical duty to report such cases. However, the students were unable to define or describe the signs, symptoms, and social indicators of child abuse. Approximately 93.4% of the students lacked basic training related to child abuse, while 95.7% of them indicated that there was insufficient training in issues related to child abuse.

CONCLUSIONS: There is a general lack of information regarding child abuse among dentistry students. The majority of the students showed interest in the topic of child abuse and neglect, but were unable to clearly identify the signs and symptoms. More lectures and workshops relating to child abuse should be available to all dentists to reinforce their knowledge as well as to strengthen their confidence when confronted with suspected cases of child abuse.

PMID:34657276 | DOI:10.1007/s40368-021-00651-0

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

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

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

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

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

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

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

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