RESUMEN
Current hypertension guidelines fail to provide a recommendation on when-to-treat, thus disregarding relevant circadian rhythms that regulate blood pressure (BP) level and 24 h patterning and medication pharmacokinetics and pharmacodynamics. The ideal purpose of ingestion-time (chronopharmacology, i.e. biological rhythm-dependent effects on the kinetics and dynamics of medications, and chronotherapy, i.e. the timing of pharmaceutical and other treatments to optimize efficacy and safety) trials should be to explore the potential impact of endogenous circadian rhythms on the effects of medications. Such investigations and outcome trials mandate adherence to the basic standards of human chronobiology research. In-depth review of the more than 150 human hypertension pharmacology and therapeutic trials published since 1974 that address the differential impact of upon-waking/morning versus at-bedtime/evening schedule of treatment reveals diverse protocols of sometimes suboptimal or defective design and conduct. Many have been "time-of-day," i.e. morning versus evening, rather than circadian-time-based, and some relied on wake-time office BP rather than around-the-clock ambulatory BP measurements (ABPM). Additionally, most past studies have been of too small sample size and thus statistically underpowered. As of yet, there has been no consensual agreement on the proper design, methods and conduct of such trials. This Position Statement recommends ingestion-time hypertension trials to follow minimum guidelines: (i) Recruitment of participants should be restricted to hypertensive individuals diagnosed according to ABPM diagnostic thresholds and of a comparable activity/sleep routine. (ii) Tested treatment-times should be selected according to internal biological time, expressed by the awakening and bed times of the sleep/wake cycle. (iii) ABPM should be the primary or sole method of BP assessment. (iv) The minimum-required features for analysis of the ABPM-determined 24 h BP pattern ought to be the asleep (not "nighttime") BP mean and sleep-time relative BP decline, calculated in reference to the activity/rest cycle per individual. (v) ABPM-obtained BP means should be derived by the so-called adjusted calculation procedure, not by inaccurate arithmetic averages. (vi) ABPM should be performed with validated and calibrated devices at least hourly throughout two or more consecutive 24 h periods (48 h in total) to achieve the highest reproducibility of mean wake-time, sleep-time and 48 h BP values plus the reliable classification of dipping status. (vii) Calculation of minimum required sample size in adherence with proper statistical methods must be provided. (viii) Hypertension chronopharmacology and chronotherapy trials should preferably be randomized double-blind, randomized open-label with blinded-endpoint, or crossover in design, the latter with sufficient washout period between tested treatment-time regimens.
Asunto(s)
Monitoreo Ambulatorio de la Presión Arterial , Hipertensión , Antihipertensivos/uso terapéutico , Presión Sanguínea , Cronoterapia , Ritmo Circadiano , Ingestión de Alimentos , Humanos , Hipertensión/tratamiento farmacológico , Reproducibilidad de los Resultados , Factores de Riesgo , Factores de TiempoRESUMEN
Quality of care in medicine is not necessarily proportional to quantity of care and excess is often useless or even more, potentially detrimental to our patients. Adhering to the European Federation of Internal Medicine's initiative, the Romanian Society of Internal Medicine (SRMI) launched the Choosing Wisely in Internal Medicine Campaign, aiming to cut down diagnostic procedures or therapeutics overused in our country. A Working Group was formed and from 200 published recommendations from previous international campaigns, 36 were voted as most important. These were submitted for voting to the members of the SRMI and posted on a social media platform. After the two voting rounds, the top six recommendations were established. These were: 1. Stop medicines when no further benefit is achieved or the potential harms outweigh the potential benefits for the individual patient. 2. Don't use antibiotics in patients with recent C. difficile without convincing evidence of need. 3. Don't regularly prescribe bed rest and inactivity following injury and/or illness unless there is scientific evidence that harm will result from activity. Promote early mobilization. 4. Don't initiate an antibiotic without an identified indication and a predetermined length of treatment or review date. 5. Don't prescribe opioids for treatment of chronic or acute pain for sensitive jobs such as operating motor vehicles, forklifts, cranes or other heavy equipment. 6. Transfuse red cells for anemia only if the hemoglobin concentration is less than 7 g/dL or if the patient is hemodynamically unstable or has significant cardiovascular or respiratory comorbidity. Don't transfuse more units of blood than absolutely necessary.
Asunto(s)
Prescripción Inadecuada/prevención & control , Medicina Interna/métodos , Sociedades Médicas , Procedimientos Innecesarios/estadística & datos numéricos , Adulto , Femenino , Humanos , Prescripción Inadecuada/estadística & datos numéricos , Medicina Interna/normas , Medicina Interna/estadística & datos numéricos , Masculino , Pautas de la Práctica en Medicina/estadística & datos numéricos , RumaníaRESUMEN
Correlation between systolic (SBP) and diastolic (DBP) blood pressure (BP) level and target organ damage, cardiovascular disease (CVD) risk, and long-term prognosis is much greater for ambulatory BP monitoring (ABPM) than daytime office measurements. The 2013 ABPM guidelines specified herein are based on ABPM patient outcomes studies and constitute a substantial revision of current knowledge. The asleep SBP mean and sleep-time relative SBP decline are the most significant predictors of CVD events, both individually as well as jointly when combined with other ABPM-derived prognostic markers. Thus, they should be preferably used to diagnose hypertension and assess CVD and other associated risks. Progressive decrease by therapeutic intervention in the asleep BP mean is the most significant predictor of CVD event-free interval. The 24 h BP mean is not recommended to diagnose hypertension because it disregards the more valuable clinical information pertaining to the features of the 24 h BP pattern. Persons with the same 24 h BP mean may display radically different 24 h BP patterns, ranging from extreme-dipper to riser types, representative of markedly different risk states. Classification of individuals by comparing office with either the 24 h or awake BP mean as "masked normotensives" (elevated clinic BP but normal ABPM), which should replace the terms of "isolated office" or "white-coat hypertension", and "masked hypertensives" (normal clinic BP but elevated ABPM) is misleading and should be avoided because it disregards the clinical significance of the asleep BP mean. Outcome-based ABPM reference thresholds for men, which in the absence of compelling clinical conditions are 135/85 mmHg for the awake and 120/70 mmHg for the asleep SBP/DBP means, are lower by 10/5 mmHg for SBP/DBP in uncomplicated, low-CVD risk, women and lower by 15/10 mmHg for SBP/DBP in male and female high-risk patients, e.g., with diabetes, chronic kidney disease (CKD), and/or past CVD events. In the adult population, the combined prevalence of masked normotension and masked hypertension is >35%. Moreover, >20% of "normotensive" adults have a non-dipper BP profile and, thus, are at relatively high CVD risk. Clinic BP measurements, even if supplemented with home self-measurements, are unable to quantify 24 h BP patterning and asleep BP level, resulting in potential misclassification of up to 50% of all evaluated adults. ABPM should be viewed as the new gold standard to diagnose true hypertension, accurately assess consequent tissue/organ, maternal/fetal, and CVD risk, and individualize hypertension chronotherapy. ABPM should be a priority for persons likely to have a blunted nighttime BP decline and elevated CVD risk, i.e., those who are elderly and obese, those with secondary or resistant hypertension, and those diagnosed with diabetes, CKD, metabolic syndrome, and sleep disorders.