[Equality across ages : addressing gender discrimination among older patients]. / Égalité à tous les âges : aborder la discrimination de genre chez les patient-e-s âgé-e-s.

The aim of this article is to draw attention to sex- and gender-related differences in the management of elderly patients. This issue is illustrated with two diseases linked to gender and sex: osteoporosis and high blood pressure. On one hand, patients of the sex less affected by the disease may feel less concerned; on the other hand, these patients are at greater risk of being under-diagnosed by medical and nursing staff. In addition, studies tend to overlook patients of the less-affected sex, resulting in guidelines that do not take account of sex or gender specific characteristics. There is even less literature on gender-related disparities in care in the elderly population than in the young, but it can be assumed that this risk of disparities exists even more in relation to specificities in diagnosis and care of elderly patients.

Cet article vise à attirer l'attention sur le risque de différences de prise en charge des patient-e-s âgé-e-s liées au sexe et au genre, illustré par deux pathologies considérées l'une comme féminine, l'autre comme masculine : l'ostéoporose et l'hypertension artérielle. Dans ce type de pathologies, les patient-e-s du sexe le moins touché par la maladie peuvent se sentir moins concerné-e-s et ont un risque accru de sous-diagnostic de la part du corps médicosoignant. De plus, les études tendent à négliger les patient-e-s du sexe moins touché, aboutissant à des guidelines ne tenant pas compte de spécificités liées au sexe ou au genre. La littérature sur les disparités de prise en charge liées au genre dans la population âgée est encore très limitée. Néanmoins, il est important de prendre en compte les spécificités liées au genre au même titre que celles liées à l'âge avancé.

[New perspectives in the diagnosis and treatment of heart failure with preserved ejection fraction (HFpEF)]. / Avancées dans le diagnostic et traitement de l'insuffisance cardiaque à fraction d'éjection préservée.

Heart failure with preserved ejection fraction (HFpEF), defined as ≥50 %, affects 1 to 3 % of the population and represents a diagnostic challenge. Clinical scores have been developed to facilitate the diagnosis of affected patients, who can now benefit from new treatments. Recent studies have shown a reduction in cardiovascular morbidity and mortality with sodium-glucose cotransporter-2 (SGLT-2) inhibitors in this population. Other promising drugs, currently in the study phase, could potentially change the management approach in the near future. Finally, controlling symptoms, signs of congestion and the frequently encountered comorbidities in this population remain crucial.

L'insuffisance cardiaque à fraction d'éjection préservée (HFpEF), soit ≥ 50 %, touche 1 à 3 % de la population et représente un défi diagnostique. Des scores cliniques ont été développés pour faciliter l'identification des patients concernés qui peuvent désormais bénéficier de nouveaux traitements. Des études récentes ont en effet montré une diminution de la morbimortalité cardiovasculaire grâce aux inhibiteurs du cotransporteur sodium-glucose de type 2 (iSGLT2) dans cette population. D'autres médicaments prometteurs actuellement en phase d'étude pourraient aussi changer la prise en charge dans un futur proche. Enfin, le contrôle des symptômes et signes de congestion ainsi que le traitement des comorbidités fréquemment rencontrées dans cette population restent essentiels.

Drinking patterns of alcohol and risk of major adverse cardiovascular events after an acute coronary syndrome.

AIM: To evaluate the risk of alcohol consumption after acute coronary syndromes (ACS). METHODS: A total of 6557 patients hospitalized for ACS at 4 Swiss centres were followed over 12 months. Weekly alcohol consumption was collected at baseline and 12 months. Binge drinking was defined as consumption of ≥6 units of alcohol on one occasion. Major adverse cardiovascular events (MACE) were defined as a composite of cardiac death, myocardial infarction, stroke or clinically indicated target vessel coronary revascularization. Cox regression analysis was performed to assess the risk of MACE in patients with heavy (>14 standard units/week), moderate (7-14 standard units per week), light consumption (<1 standard unit/week) or abstinence, and with binge drinking episodes, adjusted for baseline differences. RESULTS: At baseline, 817 (13.4%) patients reported heavy weekly alcohol consumption. At one-year follow-up, 695/1667 (41.6%) patients reported having at least one or more episodes of binge drinking per month. The risk for MACE was not significantly higher in those with heavy weekly consumption compared to abstinence (8.6% vs. 10.2%, HR 0.97, 95%CI 0.69-1.36) or light consumption (8.6% vs. 8.5 %, HR 1.41, 95%CI 0.97-2.06). Compared to patients with no-binge drinking, the risk of MACE was dose-dependently higher in those with binge drinking with less than one episode per month (9.2% vs 7.8%, HR 1.61, 95%CI 1.23-2.11), or one or more episodes per month (13.6% vs 7.8%, HR 2.17, 95%CI 1.66-2.83). CONCLUSION: Binge drinking during the year following an ACS, even less than once per month, is associated with worse clinical outcomes.

The cardiovascular risk of alcohol consumption and of binge drinking episodes after acute coronary syndrome (ACS) has not been established. Our data suggested the following: After ACS, regular weekly alcohol consumption is not associated with the risk of major adverse cardiovascular events (MACE), except for patients reporting binge drinking who have a two-fold increased risk of MACE within one year of the index event.After ACS, episodes of binge drinking, even less than once per month, are associated with worse clinical outcomes. It is not the frequency, but rather the quantity of alcohol intake in a binge drinking episode, that is associated with worse prognosis in patients after an ACS.

Physical activity matters for everyone's health, but individuals with multimorbidity benefit more.

Multimorbidity, defined as the presence of two or more chronic conditions, is increasingly prevalent and is a major contributor to ill health in old age. Physical activity (PA) is a key protective factor for health and individuals with multimorbidity could particularly benefit from engaging in PA. However, direct evidence that PA has greater health benefits in people with multimorbidity is lacking. The objective of the present study was to investigate whether the associations between PA and health were more pronounced in individuals with (vs. without) multimorbidity. We used data from 121,875 adults aged 50 to 96 years (mean age = 67 ± 10 years, 55% women) enrolled in the Survey of Health, Ageing and Retirement in Europe (SHARE). Multimorbidity and PA were self-reported. Health indicators were assessed using tests and validated scales. Variables were measured up to seven times over a 15-year period. Confounder-adjusted linear mixed-effects models were used to investigate the moderating role of multimorbidity on the associations of PA with the levels and trajectories of health indicators across aging. Results showed that multimorbidity was associated with declines in physical, cognitive, and mental health, as well as poorer general health. Conversely, PA was positively associated with these health indicators. We found a significant interaction between multimorbidity and PA, revealing that positive associations between PA and health indicators were strengthened in people with multimorbidity - although this stronger association became less pronounced in advanced age. These findings suggest that the protective role of PA for multiple health indicators is enhanced in individuals with multimorbidity.

Sex Differences Among Patients Receiving Edoxaban vs Vitamin K Antagonist for Atrial Fibrillation After TAVR.

Background: In the ENVISAGE-TAVI AF (Edoxaban vs Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation-Atrial Fibrillation) trial, edoxaban was noninferior to vitamin K antagonists (VKA) for a composite outcome of ischemic and bleeding complications but increased major bleeding in patients with atrial fibrillation after successful transcatheter aortic valve replacement. Women are at higher risk of bleeding and stroke than men after transcatheter aortic valve replacement. It is unclear whether the effect of edoxaban on these complications varies in relation to sex. Objectives: This study was to assess the effect of edoxaban vs VKA according to sex in the ENVISAGE-TAVI AF trial. Methods: The primary outcomes were net adverse cardiovascular events (NACE) and major bleeding, assessed considering the effective time on study medication (safety analysis). Results: Out of 1,377 patients, 658 (47.8%) were women. Risks for ischemic and major bleeding outcomes were similar between women and men. Edoxaban compared to VKA was associated with a similar risk of NACE in women (HR: 1.16; 95% CI: 0.81-1.65) and men (HR: 1.08; 95% CI: 0.76-1.53; P for interaction = 0.820) and a higher risk of major bleeding in both sexes (P for interaction = 0.170). The risk increase of major bleeding was attenuated in women (HR: 1.11; 95% CI: 0.69-1.79) as compared to men (HR: 1.75; 95% CI: 1.07-2.85). There were no treatment-related differences for ischemic complications in both sexes. Conclusions: Edoxaban compared to VKA was associated with a similar risk of NACE and higher risk of major bleeding in both sexes. The increase in bleeding complications with edoxaban was attenuated in women.

[Dilated cardiomyopathy: a toxic cause?] / Cardiomyopathies dilatées d'origine toxique.

Dilated cardiomyopathy is defined by the presence of left ventricular dilatation and contractile dysfunction in the absence of abnormal loading conditions and severe coronary artery disease. Once dilated cardiomyopathy is discovered, a careful and detailed history with laboratory tests may reveal a potential toxic cause. In this article, we present the case of a patient with suspected toxic dilated cardiomyopathy, and then discuss the common causes and treatment of toxic dilated cardiomyopathy.

La cardiomyopathie dilatée est définie par la présence d'une dilatation ventriculaire gauche et d'un dysfonctionnement contractile en l'absence de conditions de charge anormales et de coronaropathie sévère. Une fois qu'une cardiomyopathie dilatée est découverte, une anamnèse minutieuse et détaillée associée à des tests de laboratoire exhaustifs peut révéler une cause toxique potentielle. Dans cet article, nous présentons le cas d'une patiente avec suspicion de cardiomyopathie dilatée d'origine toxique, puis discutons des causes fréquentes et du traitement de la cardiomyopathie dilatée d'origine toxique.

Cardiovascular therapy use, modification, and in-hospital death in patients with COVID-19: A cohort study.

AIMS: To assess the associations of exposure and modifications in exposure (i.e., discontinuation on admission, initiation during hospitalization) to eight common cardiovascular therapies with the risk of in-hospital death among inpatients with coronavirus disease 2019 (COVID-19). METHODS: In this observational study including 838 hospitalized unvaccinated adult patients with confirmed COVID-19, the use of cardiovascular therapies was assessed using logistic regression models adjusted for potential confounders. RESULTS: No cardiovascular therapy used before hospitalization was associated with an increased risk of in-hospital death. During hospitalization, the use of diuretics (aOR 2.59 [1.68-3.98]) was associated with an increase, and the use of agents acting on the renin-angiotensin system (aOR 0.39 [0.23-0.64]) and lipid-lowering agents (aOR 0.41 [0.24-0.68]) was associated with a reduction in the odds of in-hospital death. Exposure modifications associated with decreased survival were the discontinuation of an agent acting on the renin-angiotensin system (aOR 4.42 [2.08-9.37]), a ß-blocker (aOR 5.44 [1.16-25.46]), a lipid-modifying agent (aOR 3.26 [1.42-7.50]) or an anticoagulant (aOR 5.85 [1.25-27.27]), as well as the initiation of a diuretic (aOR 5.19 [2.98-9.03]) or an antiarrhythmic (aOR 6.62 [2.07-21.15]). Exposure modification associated with improved survival was the initiation of an agent acting on the renin-angiotensin system (aOR 0.17 [0.03-0.82]). CONCLUSION: In hospitalized and unvaccinated patients with COVID-19, there was no detrimental association of the prehospital use of any regular cardiovascular medication with in-hospital death, and these therapies should be continued as recommended.

Prevalence and forms of gender discrimination and sexual harassment among medical students and physicians in French-speaking Switzerland: a survey.

OBJECTIVES: The aim of this study was to determine the prevalence and forms of gender discrimination and sexual harassment experienced by medical students and physicians in French-speaking part of Switzerland. DESIGN AND SETTING: We conducted an online survey using a questionnaire of 9 multiple-choice and 2 open questions between 24 January 2019 and 24 February 2019. Our target population was medical students and physicians working at hospitals and general practitioners from the French-speaking part of Switzerland. The online survey was sent via social media platforms and direct emails. We compared answers between male-determined and female-determined respondents using either χ2 or Fisher's exact tests. RESULTS: Among 1071 responders, a total of 893 were included (625 females, 264 males, 4 non-binary and 1 non-binary and male). 178 were excluded because they did not mention their working place or were working only outside Switzerland. Because of the small number of non-binary participants, they were not contemplated in further statistical analysis. Of 889 participants left, 199 (31.8%) women and 18 (6.8%) men reported having personally experienced gender discrimination, in terms of sexism, difficulties in career development and psychological pressure. Among women, senior attendings were the most affected (55.2%), followed by residents (44.1%) and junior attendings (41.1%). Sexual harassment was equally observed among women (19.0%) and men (16.7%). Compared with men (47.0%), women (61.4%) expressed the need to promote equality and inclusivity in medicine more frequently (p<0.001), as well as the need for support in their professional development (38.7% women and 23.9% men; p<0.001). CONCLUSIONS: Gender discrimination in medicine in French-speaking Switzerland affects one-third of women, in particular, those working in hospital settings and senior positions.

Changes of lipoprotein(a) levels with endogenous steroid hormones.

BACKGROUND: Lipoprotein(a) [Lp(a)] is an LDL-like molecule that is likely causal for cardiovascular events and Lp(a) variability has been shown to be mostly of genetic origin. Exogenous hormones (hormone replacement therapy) seem to influence Lp(a) levels, but the impact of endogenous hormone levels on Lp(a) is still unknown. The aim of the study was to assess the effect of endogenous steroid hormone metabolites on Lp(a). METHODS: Lipoprotein(a) levels were measured in 1,021 participants from the Swiss Kidney Project on Genes in Hypertension, a family-based, multicentre, population-based prospective cohort study. Endogenous levels of 28 steroid hormone precursors were measured in 24-h urine collections from 883 individuals. Of the participants with Lp(a) data, 1,011 participants had also genotypes available. RESULTS: The participants had an average age of 51 years and 53% were female. Median Lp(a) levels were 62 mg/L, and the 90th percentile was 616 mg/L. The prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. Forty-three per cent of Lp(a) variability was explained respectively by: age (2%, p < .001), LDL-C (1%, p = .001), and two SNPs (39%, p value<2⋅10-16 ). Of the 28 endogenous steroid hormones assessed, androstenetriol, androsterone, 16α-OH-DHEA and estriol were nominatively associated with serum Lp(a) levels in univariable analyses and explained 0.4%-1% of Lp(a) variability, but none of them reached significance in multivariable models. CONCLUSIONS: In this contemporary population-based study, the prevalence of a Lp(a) elevation ≥700 mg/L was 3.2%. The effect of endogenous steroid hormone levels of Lp(a) variability was small at best, suggesting a negligible impact on the wide range of Lp(a) variability.

Symptoms and quality of life at 1-year follow up of patients discharged after an acute COVID-19 episode.

AIM OF THE STUDY: Patients surviving COVID-19 have been described as being at risk of developing sequelae. We aimed to investigate and elicit persistent symptoms, emotional status and quality-of-life in patients discharged after an acute COVID-19 episode. METHODS: Patient-reported outcome measures were collected during a telephone interview 30 days and 1 year after discharge. Patients' general health status was evaluated using questions based on their symptoms, emotional status was assessed using the items 9 to 12 of the HeartQoL questionnaire and quality of life was assessed at 1 year through the EQ-5D-5L. In patients with a history of cardiovascular disease, all 14 items of the HeartQoL questionnaire were completed to derive the HeartQoL global score. RESULTS: Among 687 patients who survived after being hospitalised for COVID-19 at the University Hospitals of Geneva between 26 February and 26 April 2020, 184 (27%) and 165 (24%), respectively, participated in the follow-up at 30 days and 1 year. Of these 184 participants, 62% were male, median age was 58 years and 21% had a past medical history of cardiovascular disease. At one month after discharge, 61% (113/184) of patients presented fatigue and 28% (52/184) dyspnoea. One year after discharge, the main complaints were persistent fatigue in 27% (45/165) of patients, neurological problems in 17% (28/165) and dyspnoea in 14% (23/165). Eight percent (14/184) of patients declared being significantly worried 1 month after discharge and 5% (9/184) feeling depressed. The number of patients reporting being significantly worried or depressed at 1 year was lower. Regarding the quality of life at 1 year, the median EQ-5D-5L visual analogue scale score was 80 (interquartile range 70-90). CONCLUSIONS: Approximately half of patients reported some symptoms 1 year after discharge following an acute episode of COVID-19. The predominant symptom was persistent fatigue both at 1-month and at 1-year follow-up. Emotional status and quality of life appeared satisfactory.

[Cardiac rehabilitation : a multidisciplinary program of cardiovascular prevention of essential importance]. / La réadaptation cardiaque : un programme multidisciplinaire de prévention cardiovasculaire indispensable.

Cardiovascular diseases and especially coronary artery disease remain the first cause of mortality in Switzerland. Comprehensive cardiac rehabilitation is a validated multidisciplinary intervention, which represents the most appropriate strategy of implementing an effective secondary cardiovascular prevention to reduce the impact of cardiovascular diseases. However, less than half of patients after a myocardial infarction and a tiny proportion of patients with heart failure participate in a rehabilitation program in our country. This article summarizes the current state of cardiac rehabilitation in Switzerland, as well as future developments of cardiac tele-rehabilitation that have accelerated due to the COVID-19 pandemic.

Les maladies cardiovasculaires, et en premier lieu la maladie coronarienne, restent la première cause de mortalité en Suisse. La réadaptation cardiaque intégrée est une intervention multidisciplinaire validée représentant le meilleur moyen de mettre en place une stratégie de prévention cardiovasculaire secondaire efficace pour réduire l'impact des maladies cardiovasculaires. Pourtant, moins de la moitié des patients victimes d'un infarctus du myocarde et une proportion infime de patients atteints d'une insuffisance cardiaque participent à un programme de réadaptation cardiaque dans notre pays. Cet article résume l'état actuel de la réadaptation cardiaque en Suisse ainsi que les futurs développements de téléréadaptation cardiaque qui se sont accélérés dans le contexte de la pandémie de Covid-19.

Mortality and high risk of major adverse events in patients with COVID-19 and history of cardiovascular disease.

OBJECTIVE: History of cardiovascular diseases (CVDs) may influence the prognosis of patients hospitalised for COVID-19. We investigated whether patients with previous CVD have increased risk of death and major adverse cardiovascular event (MACE) when hospitalised for COVID-19. METHODS: We included 839 patients with COVID-19 hospitalised at the University Hospitals of Geneva. Demographic characteristics, medical history, laboratory values, ECG at admission and medications at admission were collected based on electronic medical records. The primary outcome was a composite of in-hospital mortality or MACE. RESULTS: Median age was 67 years, 453 (54%) were males and 277 (33%) had history of CVD. In total, 152 (18%) died and 687 (82%) were discharged, including 72 (9%) who survived a MACE. Patients with previous CVD were more at risk of composite outcomes 141/277 (51%) compared with those without CVD 83/562 (15%) (OR=6.0 (95% CI 4.3 to 8.4), p<0.001). Multivariate analyses showed that history of CVD remained an independent risk factor of in-hospital death or MACE (OR=2.4; (95% CI 1.6 to 3.5)), as did age (OR for a 10-year increase=2.2 (95% CI 1.9 to 2.6)), male gender (OR=1.6 (95% CI 1.1 to 2.3)), chronic obstructive pulmonary disease (OR=2.1 (95% CI 1.0 to 4.2)) and lung infiltration associated with COVID-19 at CT scan (OR=1.9 (95% CI 1.2 to 3.0)). History of CVD (OR=2.9 (95% CI 1.7 to 5)), age (OR=2.5 (95% CI 2.0 to 3.2)), male gender (OR=1.6 (95% CI 0.98 to 2.6)) and elevated C reactive protein (CRP) levels on admission (OR for a 10 mg/L increase=1.1 (95% CI 1.1 to 1.2)) were independent risk factors for mortality. CONCLUSION: History of CVD is associated with higher in-hospital mortality and MACE in hospitalised patients with COVID-19. Other factors associated with higher in-hospital mortality are older age, male sex and elevated CRP on admission.

Impact of the COVID-19 pandemic on acute coronary syndromes.

AIM: To assess the impact of the first wave of the COVID-19 pandemic on acute coronary syndromes and on the delay from symptom onset to first medical contact among patients presenting with ST-segment elevation myocardial infarction (STEMI), as well as to investigate whether there were patient-related reasons related to COVID-19 for delaying first medical contact. METHODS AND RESULTS: All patients undergoing percutaneous coronary intervention (PCI) at the Geneva University Hospitals for acute coronary syndromes (ACS) during the first COVID-19 wave were compared with a control group consisting of all ACS patients who underwent PCI during the same period in 2019 and those treated in the period immediately preceding the pandemic. The primary outcome measure was the difference in the delay from symptom onset to first medical contact in the setting of STEMI between the COVID-19 period and the control period. Secondary outcome measures were the difference in ACS incidence and the impact of the COVID-19 pandemic on patients’ decisions to call the emergency services, assessed using a questionnaire. Delay from symptom onset to first medical contact was longer among patients suffering from STEMI in the COVID-19 period compared with the control period (112 min vs 60 min, p = 0.049). The incidence rate of ACS was lower during the COVID-19 period (incidence rate ratio 0.6, 95% confidence interval [CI] 0.449–0.905). ACS patients delayed their call to the emergency services mainly because of fear of contracting or spreading COVID-19 following hospital admission, as well as of adding burden to the healthcare system. CONCLUSION: We observed prolonged delays from symptom onset to first medical contact and a decline in overall ACS incidence during the first wave of the COVID-19 pandemic, with a higher threshold to call for help among ACS patients.

The 'de Winter' electrocardiogram pattern as a ST-elevation myocardial infarction equivalent: a case report.

BACKGROUND: A 'STEMI equivalent' electrocardiogram (ECG) pattern reflects an acute thrombotic occlusion of a large epicardial coronary artery without ST-segment elevation. These ECG patterns are less known by caregivers. CASE SUMMARY: We describe the case of a 56-year-old patient suffering from acute chest pain, presenting in our emergency department with a 'de Winter' ECG pattern: an upsloping ST-segment depression with tall symmetrical T waves associated with left anterior descending artery occlusion. DISCUSSION: The 'de Winter' ECG pattern, as other 'STEMI equivalent', must be recognized promptly and treated as soon as possible with emergent reperfusion by percutaneous coronary intervention.

[Long-term physical activity after a myocardial infarction : a permanent challenge]. / Activité physique au long cours après un infarctus du myocarde : un défi permanent.

Cardiac rehabilitation is a well-defined multidisciplinary program with the objective to reduce mortality and morbidity, while also improving the exercise capacity and quality of life of the patient following a myocardial infarction. Despite the fact that a cardiovascular rehabilitation program is now recommended by international guidelines for all patients who have suffered from an acute coronary syndrome, only half of all patients actually participate to such a program in Switzerland. Even worse, especially when taking into consideration the population in Geneva, less than 5 % of patients follow a long-term cardiac maintenance program (phase III). Since 2015, our project has been to encourage patients who have completed a phase II cardiac rehabilitation program, to resume regular physical activity in the long term.

La réadaptation cardiovasculaire (RCV) postinfarctus est un programme multidisciplinaire bien défini dont les objectifs sont non seulement d'améliorer la capacité fonctionnelle, la qualité de vie des patients, mais aussi de réduire leur morbi-mortalité cardiovasculaire. Même si la RCV est maintenant fortement recommandée dans les directives internationales pour tous les patients postinfarctus du myocarde, seule la moitié des patients y participe en Suisse. Pire encore, après une RCV de phase II, moins de 5 % des patients à Genève s'inscrivent dans un groupe de maintenance cardiovasculaire (phase III). Nous présentons, dans cet article, les projets que nous menons depuis 2015 afin de stimuler les patients qui ont terminé une RCV de phase II à poursuivre une activité physique régulière et au long cours.

Brugada Pattern Caused by a Flecainide Overdose.

BACKGROUND: Brugada pattern can be found on the electrocardiogram (ECG) of patients with altered mental status, usually with fever or drug intoxication. Diagnosis remains challenging, because the ECG changes are dynamic and variable. In addition, triggers are not always clearly identified. In patients with atrial fibrillation (AF), the use of class IC antidysrhythmic drugs can unmask a Brugada pattern on the ECG, especially if combined with other medications acting on sodium channels. CASE REPORT: A 62-year-old man with a medical history of AF was admitted to our emergency department for altered mental status. The ECG at the time of admission showed a Brugada pattern, triggered by a flecainide overdose (about 1 g), in association with an unknown dose of lamotrigine and quetiapine. After discontinuation of all medications, the Brugada pattern disappeared and his ECG showed no abnormalities. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In patients with AF, the use of class IC antidysrhythmic drugs, if overdosed, can trigger a Brugada ECG pattern, and therefore it can increase the risk for malignant dysrhythmias. It is important to provide, to all patients with a Brugada ECG pattern, a list of drugs to avoid, and to underline the synergistic interplay between drugs, taking into consideration all patients' comorbidities.