The KORE-INNOVATION trial, a prospective controlled multi-site clinical study to implement and assess the effects of an innovative peri-operative care pathway for patients with ovarian cancer: rationale, methods and trial design.

BACKGROUND: Advanced ovarian cancer is managed by extensive surgery, which could be associated with high morbidity. A personalized pre-habilitation strategy combined with an 'enhanced recovery after surgery' (ERAS) pathway may decrease post-operative morbidity. PRIMARY OBJECTIVE: To analyze the effects of a combined multi-modal pre-habilitation and ERAS strategy on severe post-operative morbidity for patients with ovarian cancer (primary diagnosis or first recurrence) undergoing cytoreductive surgery. STUDY HYPOTHESIS: A personalized multi-modal pre-habilitation algorithm entailing a physical fitness intervention, nutritional and psycho-oncological support, completed by an ERAS pathway, reduces post-operative morbidity. TRIAL DESIGN: This is a prospective, controlled, non-randomized, open, interventional two-center clinical study. Endpoints will be compared with a three-fold control: (a) historic control group (data from institutional ovarian cancer databases); (b) prospective control group (assessed before implementing the intervention); and (c) matched health insurance controls. INCLUSION CRITERIA: Patients with ovarian, fallopian, or primary peritoneal cancer undergoing primary surgical treatment (primary ovarian cancer or first recurrence) can be included. The intervention group receives an additional multi-level study treatment: (1) standardized frailty assessment followed by (2) a personalized tri-modal pre-habilitation program and (3) peri-operative care according to an ERAS pathway. EXCLUSION CRITERIA: Inoperable disease or neoadjuvant chemotherapy, simultaneous diagnosis of simultaneous primary tumors, in case of interference with the overall prognosis (except for breast cancer); dementia or other conditions that impair compliance or prognosis. PRIMARY ENDPOINT: Reduction of severe post-operative complications (according to Clavien- Dindo Classification (CDC) III-V) within 30 days after surgery. SAMPLE SIZE: Intervention group (n=414, of which approximately 20% insure with the participating health insurance); historic control group (n=198); prospective control group (n=50), health insurance controls (for those intervention patients who are members of the participating health insurance). ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: The intervention phase started in December 2021 and will continue until June 2023. As of March 2023, 280 patients have been enrolled in the intervention group. The expected completion of the entire study is September 2024. TRIAL REGISTRATION: NCT05256576.

High Prevalence of Multimorbidity and Polypharmacy in Elderly Patients With Chronic Pain Receiving Home Care are Associated With Multiple Medication-Related Problems.

Aim: To measure the extent of polypharmacy, multimorbidity and potential medication-related problems in elderly patients with chronic pain receiving home care. Methods: Data of 355 patients aged ≥65 years affected by chronic pain in home care who were enrolled in the ACHE study in Berlin, Germany, were analyzed. History of chronic diseases, diagnoses, medications including self-medication were collected for all patients. Multimorbidity was defined as the presence of ≥2 chronic conditions and levels were classified by the Charlson-Comorbidity-Index. Polypharmacy was defined as the concomitant intake of ≥5 medications. Potentially clinically relevant drug interactions were identified and evaluated; underuse of potentially useful medications as well as overprescription were also assessed. Results: More than half of the patients (55.4%) had moderate to severe comorbidity levels. The median number of prescribed drugs was 9 (range 0-25) and polypharmacy was detected in 89.5% of the patients. Almost half of them (49.3%) were affected by excessive polypharmacy (≥10 prescribed drugs). Polypharmacy and excessive polypharmacy occurred at all levels of comorbidity. We detected 184 potentially relevant drug interactions in 120/353 (34.0%) patients and rated 57 (31.0%) of them as severe. Underprescription of oral anticoagulants was detected in 32.3% of patients with atrial fibrillation whereas potential overprescription of loop diuretics was observed in 15.5% of patients. Conclusion: Multimorbidity and polypharmacy are highly prevalent in elderly outpatients with chronic pain receiving home care. Medication-related problems that could impair safety of drug treatment in this population are resulting from potentially relevant drug interactions, overprescribing as well as underuse.

Lifestyle, psychological, socioeconomic and environmental factors and their impact on hypertension during the coronavirus disease 2019 pandemic.

SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic considerably affects health, wellbeing, social, economic and other aspects of daily life. The impact of COVID-19 on blood pressure (BP) control and hypertension remains insufficiently explored. We therefore provide a comprehensive review of the potential changes in lifestyle factors and behaviours as well as environmental changes likely to influence BP control and cardiovascular risk during the pandemic. This includes the impact on physical activity, dietary patterns, alcohol consumption and the resulting consequences, for example increases in body weight. Other risk factors for increases in BP and cardiovascular risk such as smoking, emotional/psychologic stress, changes in sleep patterns and diurnal rhythms may also exhibit significant changes in addition to novel factors such as air pollution and environmental noise. We also highlight potential preventive measures to improve BP control because hypertension is the leading preventable risk factor for worldwide health during and beyond the COVID-19 pandemic.

Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19.

Systemic arterial hypertension (referred to as hypertension herein) is a major risk factor of mortality worldwide, and its importance is further emphasized in the context of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to as COVID-19. Patients with severe COVID-19 infections commonly are older and have a history of hypertension. Almost 75% of patients who have died in the pandemic in Italy had hypertension. This raised multiple questions regarding a more severe course of COVID-19 in relation to hypertension itself as well as its treatment with renin-angiotensin system (RAS) blockers, e.g. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We provide a critical review on the relationship of hypertension, RAS, and risk of lung injury. We demonstrate lack of sound evidence that hypertension per se is an independent risk factor for COVID-19. Interestingly, ACEIs and ARBs may be associated with lower incidence and/or improved outcome in patients with lower respiratory tract infections. We also review in detail the molecular mechanisms linking the RAS to lung damage and the potential clinical impact of treatment with RAS blockers in patients with COVID-19 and a high cardiovascular and renal risk. This is related to the role of angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 entry into cells, and expression of ACE2 in the lung, cardiovascular system, kidney, and other tissues. In summary, a critical review of available evidence does not support a deleterious effect of RAS blockers in COVID-19 infections. Therefore, there is currently no reason to discontinue RAS blockers in stable patients facing the COVID-19 pandemic.

Reviewing the effects of thiazide and thiazide-like diuretics as photosensitizing drugs on the risk of skin cancer.

BACKGROUND: Thiazide diuretics and particularly hydrochlorothiazide were recently linked to an increased risk of skin cancer, which was attributed to the photosensitizing properties of these drugs. Given the widespread use of thiazide diuretics, a potential skin cancer promoting effect would impose an important public health concern. OBJECTIVE: To critically appraise in a narrative review, the association between use of thiazide and thiazide-like diuretics and risk of skin cancer. METHODS: We evaluated chemical structures and photosensitizing potential of selected thiazide and thiazide-like diuretics. Moreover, we searched PubMed up to December 2018 for observational studies assessing the association between use of thiazide or thiazide-like diuretics and risk of skin cancer. Study quality was assessed for major methodological biases. RESULTS: Commonly used thiazide and thiazide-like diuretics carry resonating structural components, such as sulfonamide groups that contribute to their photosensitizing activity. Overall, 13 observational (9 case-control, 4 cohort) studies assessed the association between use of different thiazide or thiazide-like diuretics and risk of several skin cancer types. Of those, nine studies showed positive associations ranging from 3% increased risk for bendroflumethiazide and basal cell carcinoma to 311% increased risk for thiazide diuretics and squamous cell carcinoma. All studies had important design-related methodological limitations including potential confounding by indication, detection bias, and time-window bias. CONCLUSION: Commonly used thiazide and thiazide-like diuretics have photosensitizing potential, and some observational studies with important methodological limitations have linked their use to an increased risk of skin cancer. Well designed observational studies are needed to provide more solid evidence on this possible association.