Inconvenient Truths on Merger Retrospective Studies

The evidence that cigarette smoking and atmospheric pcllution are causes of lung cancer is largely statistical. The first evidence was indirect; that is, i1. was noticed that in many countries the incidence of lung cancer had increased and that the increase could be correlated with changes in the prevalence of cigarette smoking and of certain types of atmospheric pollution.Since then much direct evidence has been obtained. The relationship between cigarette smoking and lung cancer has been demonstrated retrospectively by comparing the smoking habits of patients with and without lung cancer and prospectively by observing the mortality from lung cancer in groups of persons of known smoking habits. Conclusions can be drawn from these studies only after careful examination of the results. In particular it is important in retrospective studies to test a) the reproducibility of the data, b) the representativeness of the data, and c) the comparability of the special series and their controls. The resul1.s of retrospective studies are all similar and all show a close relationship between cigarette smoking and the disease.The results have been confirmed by pro~pective studies which are lesF. open to bias. The results can be explained if cigarette smoking causes lung cancer or if both are related to some third common factor. Ancillary data (pathological changes in the bronchial mucosa, animal experiments, etc.) support the causal hypothesis.The evidence relating to atmospheric pollution is less definite and it is difficult to get direct evidence of a relationship in the individual. It is clear that pollution has little effect in the absence of smoking, but the mortality associated with a given amount of smoking is generally greater in large towns than in the countryside and among men who have emigrated from Britain than among men who have lived all their lives in less polluted countries.

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A 5 years retrospective studies looking at trends in water deprivation tests and roles for endocrine specialist nurses

Endocrine Abstracts ◽

10.1530/endoabs.37.ep745 ◽

2015 ◽

Author(s):

Phillip Yeoh ◽

Pierre Bouloux ◽

Shern Chew ◽

Bernard Khoo ◽

Paul Carroll ◽

...

Keyword(s):

Water Deprivation ◽

Retrospective Studies ◽

Specialist Nurses

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Influence of cyp2d6 polymorphisms on pharmacokinetics, efficacy and safety of antipsychotics

Психическое здоровье ◽

10.25557/2074-014x.2018.01.26-39 ◽

2018 ◽

pp. 26-39

Author(s):

А.А. Курылев ◽

Б.В. Андреев

Keyword(s):

Genetic Polymorphisms ◽

Atypical Antipsychotics ◽

Retrospective Studies ◽

Pharmacokinetic Parameters ◽

Clinical Routine ◽

Elimination Half ◽

Daily Dose ◽

Comparison Groups ◽

Cyp2d6 Polymorphisms ◽

Positive Significant Correlation

Несмотря на доступность в клинической практике широкого круга классических и атипичных антипсихотиков (АП), по-прежнему наблюдается широкая вариабельность ответа на психофармакотерапию. Эта вариабельность обусловлена генетической гетерогенностью как самой шизофрении, так и метаболизма АП. Стандартные назначаемые дозы АП далеко не всегда являются оптимальными. Генетическая вариабельность систем биотрансформации и биодоступности АП могут играть значимую роль в формировании ответа на терапию и развитии нежелательных реакций. Целью исследования стало проведение обзора литературы по проблеме клинической эффективности применения генотипирования полиморфизмов CYP2D6 при терапии антипсихотиками. Большинство фармакокинетических исследований обнаруживают сильную достоверную положительную корреляцию метаболического статуса CYP2D6, определенного путем генотипирования полиморфизмов CYP2D6 и фармакокинетических параметров АП (AUC, период полувыведения, клиренс). Однако статистически достоверных связей между полиморфизмами CYP2D6 и эффективностью терапии АП в большинстве исследований обнаружено не было, прежде всего из-за недостаточного количества участников, гетерогенности сравниваемых когорт, применении различных АП и использовании разных критериев эффективности. Перспективные исследования с хорошо сбалансированными группами сравнения, а также масштабные ретроспективные исследования демонстрируют достоверную корреляцию метаболического статуса CYP2D6 и частоты развития нежелательных реакций АП (лекарственный паркинсонизм и поздняя дискинезия). Для более точной оценки величины вклада генетических полиморфизмов CYP2D6 в эффективность и безопасность психофармакотерапии необходимы масштабные перспективные клинические исследования. Although a number of typical and atypical antipsychotics (AP) have been discovered and used in psychiatric clinical practice the variability in response to AP is quite high. This variability is partially explained by a genetic heterogeneity of schizophrenia and metabolism of AP. The standard prescribed antipsychotic daily dose is not always optimal. Genetic variability of biotransformation and bioavailability of AP may significantly influence on therapeutic effect and tolerability. The aim of the study was to perform literature review of studies evaluating the correlation of CYP2D6 genetic polymorphisms and AP pharmacokinetics, effectiveness and safety. Most pharmacokinetics studies show high positive significant correlation between CYP2D6 metabolic activity, determined by CYP2D6 polymorphisms genotyping and AP pharmacokinetic parameters (AUC, elimination half-life, clearance etc.). However the majority of studies were failed to demonstrate significant correlation between CYP2D6 polymorphisms and AP effectiveness mainly due to inadequate number of patient, heterogeneous cohorts, different AP and effectiveness criteria used. Prospective studies with balanced comparison groups and large retrospective studies showed significant correlation between CYP2D6 metabolic status and the frequency of AP induced AEs (parkinsonism and tardive dyskinesia). To better assess the influence of CYP2D6 genetic polymorphisms on AP effectiveness and safety in clinical routine large prospective well designed clinical studies are needed.

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Crizotinib Versus Chemotherapy on ALK-positive NSCLC: A Systematic Review of Efficacy and Safety

Current Cancer Drug Targets ◽

10.2174/1568009617666170623115846 ◽

2018 ◽

Vol 19 (1) ◽

pp. 41-49 ◽

Cited By ~ 2

Author(s):

Mingxia Wang ◽

Guanqi Wang ◽

Haiyan Ma ◽

Baoen Shan

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Objective Response Rate ◽

Retrospective Studies ◽

Response Rate ◽

Objective Response ◽

Treated Group ◽

Efficacy And Safety ◽

Alk Positive

Introduction: Crizotinib was approved to treat anaplastic lymphoma kinase (ALK)- positive non-small cell lung cancer (NSCLC) by the Food and Drug Administration in 2011.We conducted a systematic review of clinical trials and retrospective studies to compare the efficacy and safety of crizotinib with chemotherapy. </P><P> Methods: We searched electronic databases from inception to Dec. 2016. Clinical trials and retrospective studies regarding crizotinib and crizotinib versus chemotherapy in treatment of NSCLC were eligible. The primary outcomes were the objective response rate (ORR) and disease control rate (DCR). Results: Nine studies (five clinical trials and four retrospective studies) including 729 patients met the inclusion criteria. Crizotinib treatment revealed 1-year OS of 77.1% and PFS of 9.17 months. And crizotinib had a better performance than chemotherapy in ORR (OR: 4.97, 95%CI: 3.16 to 7.83, P<0.00001, I2=35%). DCR revealed superiority with crizotinib than chemotherapy (OR: 3.42, 95% CI: 2.33 to 5.01, P<0.00001, I2=0%). PR (partial response) were significant superior to that of chemotherapy through direct systematic review. No statistically significant difference in CR (complete response) was found between crizotinib-treated group and chemotherapy-treated group. Regarding SD (stable disease), chemotherapy-treated group had a better performance than crizotinib-treated group. Common adverse events associated with crizotinib were visual disorder, gastrointestinal side effects, and elevated liver aminotransferase levels, whereas common adverse events with chemotherapy were fatigue, nausea, and hematologic toxicity. This systematic review revealed improved objective response rate and increased disease control rate in crizotinib group comparing with chemotherapy group. Crizotinib treatment would be a favorable treatment option for patients with ALK-positive NSCLC. ALK inhibitors may have future potential applications in other cancers driven by ALK or c-MET gene mutations.

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Evidence-based management of arrhythmogenic right ventricular cardiomyopathy in pregnancy

Future Cardiology ◽

10.2217/fca-2020-0127 ◽

2020 ◽

Author(s):

Jagjit Khosla ◽

Reshma Golamari ◽

Alice Cai ◽

Jamal Benson ◽

Wilbert S Aronow ◽

...

Keyword(s):

Heart Failure ◽

Right Ventricular ◽

Retrospective Studies ◽

Arrhythmogenic Right Ventricular Cardiomyopathy ◽

Genetic Disorder ◽

Ventricular Myocardium ◽

Evidence Based ◽

Ventricular Cardiomyopathy ◽

Genes Encoding ◽

In Pregnancy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder resulting in fibrofatty replacement of the myocardium. Genetic mutations in genes encoding for desmosome proteins result in a ventricular myocardium prone to arrhythmias and heart failure. Although ARVC is known for a few decades, most of the outcomes in pregnancy are reported recently. Pregnancy leads to significant physiological changes with excess mechanical stress on the myocardium. All the retrospective studies suggest that pregnancy is well tolerated in these patients despite the high risk of arrhythmias and heart failure. Our review focuses on the most up-to-date evidence on the management of ARVC patients during the antepartum and postpartum period.

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Pneumomediastinum in COVID-19 disease: Outcomes and relation to the Macklin effect

Asian Cardiovascular and Thoracic Annals ◽

10.1177/02184923211010089 ◽

2021 ◽

pp. 021849232110100

Author(s):

João Brito ◽

Paulo Gregório ◽

Alessandro Mariani ◽

Paula D’ambrosio ◽

Mauro Filho ◽

...

Keyword(s):

Mortality Rate ◽

Retrospective Studies ◽

Underlying Mechanism ◽

Hemodynamic Instability ◽

Disease Course ◽

Lung Involvement ◽

Radiological Findings ◽

Disease Outcomes ◽

Macklin Effect ◽

Benign Course

Aim Pneumomediastinum (PM) is associated with several etiologies and mechanisms. Although it has been described more than 100 years ago, the literature is limited to small retrospective studies. This study aimed to follow patients with coronavirus disease (COVID-19) that developed PM during hospitalization and describe their clinical and radiological evolution. Methods A prospective cohort was developed with patients with PM, excluding those with aerodigestive trauma, inside a hospital COVID-19 dedicated hospital. Clinical variables including onset of symptoms, hemodynamic instability, associated complications, the need of interventions, and disease course were all recorded. Also, radiological findings such as the presence of the Macklin effect, extension of lung involvement by COVID-19, and characteristics of the PM were analyzed. Results Twenty-one patients with non-traumatic PM were followed, resulting in an overall incidence of 0.5% during the study period. Seven (33%) patients had associated pneumothorax and malignant/tension PM was observed in three (14%) cases. The Macklin effect could be found in 11 patients (52%) and the majority of them had more than 50% of lung involvement due to COVID-19. The mortality rate was 49%; however, no deaths were directly related to the PM. Conclusions PM incidence is probably increased in the severe acute respiratory syndrome caused by COVID-19, especially in those with greater involvement of the lungs, and the Macklin effect may be an important underlying mechanism of this complication. Usually, PM has a benign course, but complications like tension/malignant PM may occur requiring prompt detection and intervention.

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Is It Definitely Clear That Long-Term Survival after Breast Cancer Surgery Is Not Affected by Anaesthetics?

Cancers ◽

10.3390/cancers13143390 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3390

Author(s):

Mats Enlund

Keyword(s):

Breast Cancer ◽

Survival Data ◽

Retrospective Studies ◽

Breast Cancer Surgery ◽

Breast Cancer Patients ◽

Term Survival ◽

Long Term Survival ◽

Significant Difference ◽

One Year

Retrospective studies indicate that cancer survival may be affected by the anaesthetic technique. Propofol seems to be a better choice than volatile anaesthetics, such as sevoflurane. The first two retrospective studies suggested better long-term survival with propofol, but not for breast cancer. Subsequent retrospective studies from Asia indicated the same. When data from seven Swedish hospitals were analysed, including 6305 breast cancer patients, different analyses gave different results, from a non-significant difference in survival to a remarkably large difference in favour of propofol, an illustration of the innate weakness in the retrospective design. The largest randomised clinical trial, registered on clinicaltrial.gov, with survival as an outcome is the Cancer and Anesthesia study. Patients are here randomised to propofol or sevoflurane. The inclusion of patients with breast cancer was completed in autumn 2017. Delayed by the pandemic, one-year survival data for the cohort were presented in November 2020. Due to the extremely good short-term survival for breast cancer, one-year survival is of less interest for this disease. As the inclusions took almost five years, there was also a trend to observe. Unsurprisingly, no difference was found in one-year survival between the two groups, and the trend indicated no difference either.

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A161 PREVALENCE OF FINANCIAL CONFLICTS OF INTEREST (FCOI) AMONG PROPENSITY-SCORE MATCHED RETROSPECTIVE STUDIES EVALUATING BIOLOGIC THERAPEUTICS FOR IBD

Journal of the Canadian Association of Gastroenterology ◽

10.1093/jcag/gwab002.159 ◽

2021 ◽

Vol 4 (Supplement_1) ◽

pp. 168-170

Author(s):

K Elsolh ◽

D Tham ◽

M A Scaffidi ◽

R Bansal ◽

J Li ◽

...

Keyword(s):

Propensity Score ◽

Propensity Score Matching ◽

Retrospective Studies ◽

Conflicts Of Interest ◽

Cochrane Library ◽

High Burden ◽

Real World Evidence ◽

Full Text Retrieval ◽

Financial Conflicts Of Interest ◽

Matched Comparison

Abstract Background Inflammatory Bowel Disease (IBD) studies have commonly relied on real-world evidence to evaluate different therapies. An emerging idea has been the use of propensity score matching as a statistical method to account for baseline characteristics in IBD patients. In retrospective studies, propensity score matching of patients helps reduce treatment assignment bias and mimic the effects of randomization. Recently, propensity-score matching has become an important tool in IBD studies comparing biologic therapeutics. Biologic medications are among the highest-grossing drugs worldwide, and their pharmaceutical producers make considerable payments to physicians to market them. In spite of this, there is a lack of evidence examining the role of undue industry influence among propensity-score matched comparative studies evaluating biologic therapeutics for IBD. Aims Given the documented association between IBD biologics and FCOI, we hypothesize a high burden of FCOI in propensity-score matched studies. The aim of this study was to evaluate the prevalence of disclosed & undisclosed financial conflicts of Interest (FCOI) in propensity-score matched comparison studies evaluating biologics for IBD. Methods We developed & ran a librarian-reviewed systematic search on EMBASE, MEDLINE, and Cochrane Library databases for all propensity-score matched retrospective studies comparing biologics for the treatment of IBD. Full-text retrieval & screening was performed on all studies in duplicate. 16 articles were identified. Industry payments to authors were only considered FCOI if they were made by a company producing a biologic that was included in the comparison study. Disclosed FCOI were identified by authors’ interests disclosures in full-texts. Any undisclosed FCOI among US authors were identified using the Centre for Medicare and Medicaid Services (CMS) Open Payments Database, which collects industry payments to physicians. Results Based on a preliminary analysis of 16 studies, there was at least one author with a relevant FCOI in 14 (88%) of the 16 studies. 14 studies (88%) had at least one disclosed FCOI, while 6 studies (37.5%) had at least one undisclosed FCOI. Among studies with disclosed FCOI, a mean of 40.2% (SD = 23.4%) of authors/study reported FCOI. Among studies with undisclosed FCOI, a mean of 18.8% (SD = 7.0%) of authors/study reported FCOI. The total dollar value of FCOIs was $1,974,328.3. The median conflict dollar value was $5,576.6 (IQR: $321.6 to $36,394.9). Conclusions We found a high burden of undisclosed FCOI (37.5%) among authors of propensity-score matched studies evaluating IBD biologics. Given the potential for undue industry influence stemming from such payments, authors should ensure better transparency with industry relationships. Funding Agencies None

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Acute pulmonary embolism in COVID-19 patient: a case report of free-floating right heart thrombus successfully treated with fibrinolysis

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytaa388 ◽

2020 ◽

Author(s):

Fernando Scudiero ◽

Antonino Pitì ◽

Roberto Keim ◽

Guido Parodi

Keyword(s):

Pulmonary Embolism ◽

High Risk ◽

Retrospective Studies ◽

Right Heart ◽

Clinical Issue ◽

Systemic Thrombolysis ◽

Case Summary ◽

High Prevalence ◽

Life Threatening ◽

Complex Scenario

Abstract Background Despite the fast-growing understanding of the coronavirus disease 2019 (COVID-19), patient management remains largely empirical or based on retrospective studies. In this complex scenario, an important clinical issue appears to be represented by the high prevalence of thromboembolic events, but the data regarding high-risk pulmonary embolism (PE) is still not available. Case summary A patient with COVID-19 developed sudden shortness of breath and hypoxia. Early echocardiographic diagnosis of high-risk PE related to right heart thrombus was performed. Systemic thrombolysis was administered with excellent clinical and haemodynamic response. Discussion Pulmonary thromboembolism is a common occurrence in severe COVID-19 infection. In our experience, systemic thrombolysis proved to be effective and for this reason may be considered for life-threatening PE in COVID-19 patients.

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