Seasonal variation of platelets in a cohort of Italian blood donors: a preliminary report

Massimo Gallerani1*, Roberto Reverberi2, Raffaella Salmi1, Michael H Smolensky3 and Roberto Manfredini4 Author Affiliations 1 Internal Medicine, Azienda Ospedaliera-Universitaria, Ferrara, Italy 2 Immunohematological and Transfusional Service, Azienda Ospedaliera-Universitaria, Ferrara, Italy 3 Department of Biomedical Engineering, The University of Texas at Austin, Austin, USA 4 Clinica Medica, Azienda Ospedaliera-Universitaria, Ferrara, ItalyBackground: Since available data are not univocal, the aim of this study was to explore the existence of a seasonal variation in platelet count. Methods: The study was based on the database of the Italian Association of Blood Volunteers (AVIS), section of Ferrara, Italy, 2001–2010. Hematological data (170,238 exams referring to 16,422 donors) were categorized into seasonal and monthly intervals, and conventional and chronobiological analyses were applied. Results: Platelets and plateletcrit were significantly higher in winter-autumn, with a main peak in December-February (average +3.4% and +4.6%, respectively, P <0.001 for both). Conclusions: Although seasonal variations have been reported for several acute cardiovascular diseases, it is extremely unlikely that such a slight increase in platelet count in winter alone may be considered as a risk factor.Biomedical [email protected]

A seasonal periodicity in relapses of multiple sclerosis? A single-center, population-based, preliminary study conducted in Bologna, Italy

Fabrizio Salvi, Ilaria Bartolomei, Angelo Lorusso, and Elena Barbarossa are with the Department of Neuroscience, Multiple Sclerosis Center, Bellaria Hospital, Bologna, Italy -- Michael H. Smolensky is with the Department of Biomedical Engineering, the University of Texas at Austin, USA -- Ann Maria Malagoni, Paolo Zamboni, and Roberto Manfredini are with the Vascular Diseases Center, University of Ferrara, Italy -- Roberto Manfredini is with the Department of Internal Medicine, Hospital of the Delta, Azienda Unità Sanitaria Locale, Ferrara, Italy and the Department of Clinical and Experimental Medicine, Clinica Medica and Vascular Diseases Center, University of Ferrara, ItalyBackground: Temporal, i.e., 24-hour, weekly, and seasonal patterns in the occurrence of acute cardiovascular and cerebrovascular events are well documented; however, little is known about temporal, especially seasonal, variation in multiple sclerosis (MS) and its relapses. This study investigated, by means of a validated chronobiological method, whether severe relapses of MS, ones requiring medical specialty consultation, display seasonal differences, and whether they are linked with seasonal differences in local meteorological variables. Results: We considered 96 consecutive patients with severe MS relapse (29 men, 67 women, mean age 38.5 ± 8.8 years), referred to the Multiple Sclerosis Center, Bellaria Hospital, Bologna, Italy, between January 1, 2007 and December 31, 2008. Overall, we analyzed 164 relapses (56 in men, 108 in women; 115 in patients aged < 40 years, 49 in patients ≥40 years). Relapses were more frequent in May and June (12.2% each) and the least frequent in September (3.7%). Chronobiological analysis showed a biphasic pattern (major peak in May-June, secondary peak in November-December, p = 0.030). Analysis of monthly mean meteorological data showed a significant seasonal pattern in ambient temperature (peak in July, p < 0.001), relative humidity (peak in January, p < 0.001), and wind speed (peak in June, p = 0.011). Conclusions: In this Italian setting we found a biphasic pattern, peaks in spring and autumn, in severe MS relapses requiring medical consultation by doctors of the MS specialty center apparently unrelated to meteorological variables. Confirmations of the findings on larger multi-center populations residing in different climatic conditions are needed to further explore the potential seasonality of MS relapses and associated environmental triggers.Biomedical [email protected]

Seasonal pattern of peptic ulcer hospitalizations: analysis of the hospital discharge data of the Emilia-Romagna region of Italy

BACKGROUND: Previous studies have reported seasonal variation in peptic ulcer disease (PUD), but few large-scale, population-based studies have been conducted. METHODS: To verify whether a seasonal variation in cases of PUD (either complicated or not complicated) requiring acute hospitalization exists, we assessed the database of hospital admissions of the region Emilia Romagna (RER), Italy, obtained from the Center for Health Statistics, between January 1998 and December 2005. Admissions were categorized by sex, age ( or = 75 yrs), site of PUD lesion (stomach or duodenum), main complication (hemorrhage or perforation), and final outcome (intended as fatal outcome: in-hospital death; nonfatal outcome: patient discharged alive). Temporal patterns in PUD admissions were assessed in two ways, considering a) total counts per single month and season, and b) prevalence proportion, such as the monthly prevalence of PUD admissions divided by the monthly prevalence of total hospital admissions, to assess if the temporal patterns in the raw data might be the consequence of seasonal and annual variations in hospital admissions per se in the region. For statistical analysis, the chi2 test for goodness of fit and inferential chronobiologic method (Cosinor and partial Fourier series) were used. RESULTS: Of the total sample of PUD patients (26,848 [16,795 males, age 65 +/- 16 yrs; 10,053 females, age 72 +/- 15 yrs, p or = 75 yrs of age. There were more cases of duodenal (DU). (89.8%) than gastric ulcer (GU) (3.6%), and there were 1,290 (4.8%) fatal events. Data by season showed a statistically difference with the lowest proportion of PUD hospital admissions in summer (23.3%) (p < 0.001), for total cases and rather all subgroups. Chronobiological analysis identified three major peaks of PUD hospitalizations (September-October, January-February, and April-May) for the whole sample (p = 0.035), and several subgroups, with nadir in July. Finally, analysis of the monthly prevalence proportions yielded a significant (p = 0.025) biphasic pattern with a main peak in August-September-October, and a secondary one in January-February. CONCLUSIONS: A seasonal variation in PUD hospitalization, characterized by three peaks of higher incidence (Autumn, Winter, and Spring) is observed. When data corrected by monthly admission proportions are analyzed, late summer-autumn and winter are confirmed as higher risk periods. The underlying pathophysiologic mechanisms are unknown, and need further studies. In subjects at higher risk, certain periods of the year could deserve an appropriate pharmacological protection to reduce the risk of PUD hospitalization

Ambulatory Blood Pressure Monitoring (ABPM) as the reference standard for diagnosis of hypertension and assessment of vascular risk in adults

New information has become available since the ISC, AAMCC, and SECAC released their first extensive guidedelines to improve the diagnosis and treatment of adult arterial hypertension. A critical assessment of evidence and a comparison of what international guidelines now propose are the basis for the following statements, which update the recommendations first issued in 2013. Office blood pressure (BP) measurements should no longer be considered to be the ‘‘gold standard’’ for the diagnosis of hypertension and assessment of cardiovascular risk. Relying on office BP, even when supplemented with at-home wake-time self-measurements, to identify high-risk individuals, disregarding circadian BP patterning and asleep BP level, leads to potential misclassification of 50% of all evaluated persons. Accordingly, ambulatory BP monitoring is the recommended reference standard for the diagnosis of true hypertension and accurate assessment of cardiovascular risk in all adults 18 yrs of age, regardless of whether office BP is normal or elevated. Asleep systolic BP mean is the most significant independent predictor of cardiovascular events. The sleep-time relative SBP decline adds prognostic value to the statistical model that already includes the asleep systolic BP mean and corrected for relevant confounding variables. Accordingly, the asleep systolic BP mean is the recommended protocol to diagnose hypertension, assess cardiovascular risk, and predict cardiovascular event-free interval. In men, and in the absence of compelling clinical conditions, reference thresholds for diagnosing hypertension are 120/70mmHg for the asleep systolic/diastolic BP means derived from ambulatory BP monitoring. However, in women, in the absence of complicating co-morbidities, the same thresholds are lower by 10/5 mmHg, i.e., 110/65 mmHg for the asleep means. In high-risk patients, including those diagnosed with diabetes or chronic kidney disease, and/or those having experienced past cardiovascular events, the thresholds are even lower by 15/10 mmHg, i.e., 105/60 mmHg. Bedtime treatment with the full daily dose of ≥1 hypertension medications is recommended as a cost-effective means to improve the management of hypertension and reduce hypertension-associated risk. Bedtime treatment entailing the full daily dose of ≥1 conventional hypertension medications must be the therapeutic regimen of choice for the elderly and those with diabetes, resistant and secondary hypertension, chronic kidney disease, obstructive sleep apnea, and medical history of past cardiovascular events, among others, given their documented high prevalence of sleep-time hypertensio

Chronotherapy of blood pressure medications to improve management of hypertension and reduce vascular risk

Correlation between blood pressure (BP) and target organ damage, cardiovascular disease (CVD) risk, and long-term prognosis is greater for ambulatory BP monitoring (ABPM) than daytime in-clinic measurements. Additionally, consistent evidence of numerous studies substantiates the ABPM-determined asleep BP mean is an independent and stronger predictor of CVD risk than the awake or 24h means. Hence, cost-effective adequate control of sleep-time BP is of marked clinical relevance. Ingestion time, according to circadian rhythms, of hypertension medications of six different classes and their combinations significantly impacts their beneficial and/or adverse effects. For example, because the high-amplitude circadian rhythm of the renin-angiotensin-aldosterone system activates during nighttime sleep, bedtime versus morning ingestion of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARB) better controls the asleep BP mean, with additional benefit, independent of medication terminal half-life, of converting the 24h BP profile into more normal dipper patterning. The MAPEC Study, first prospective randomized treatment-time investigation testing the worthiness of bedtime chronotherapy with ≥1 conventional hypertension medications to specifically target attenuation of asleep BP, demonstrated, relative to conventional morning therapy, significant reduction of CVD risk: adjusted hazard ratio (HR) of total CVD events (HR=0.39 95%CI [0.29-0.51]; P<0.001) and major CVD events, i.e., CVD deaths, myocardial infarctions, and ischemic and hemorrhagic strokes (HR=0.33 [0.19-0.55]; P<0.001). CVD risk reduction was strongest when bedtime treatment included an ARB. The MAPEC Study not only documents the asleep BP mean is the most significant prognostic marker of CVD and stroke morbidity and mortality, but it also substantiates attenuation of the asleep BP mean by a bedtime hypertension treatment strategy with the entire daily dose of ≥1 hypertension medications significantly reduces CVD risk, both in the general hypertension population and in patients of greater vulnerability and enhanced CVD risk, i.e., those diagnosed with chronic kidney disease, diabetes, and resistant hypertension

Pharmacogenomics and circadian rhythms as mediators of cardiovascular drug-drug interactions

: This article summarizes the current literature and documents new evidence concerning drug-drug interactions (DDI) stemming from pharmacogenomic and circadian rhythm determinants of therapies used to treat common cardiovascular diseases (CVD), such as atherosclerosis and hypertension. Patients with CVD often have more than one pathophysiologic condition, namely metabolic syndromes, hypertension, hyperlipidemia, and hyperglycemia, among others, which necessitate polytherapeutic or polypharmaceutic management. Interactions between drugs, drugs and food/food supplements, or drugs and genetic/epigenetic factors may have adverse impacts on the cardiovascular and other systems of the body. The mechanisms underlying cardiovascular DDI may involve the formation of a complex pharmacointeractome, including the absorption, distribution, metabolism, and elimination of drugs, which affect their respective bioavailability, efficacy, and/or harmful metabolites. The pharmacointeractome of cardiovascular drugs is likely operated with endogenous rhythms controlled by circadian clock genes. Basic and clinical investigations have improved the knowledge and understanding of cardiovascular pharmacogenomics and pharmacointeractomes, and additionally they have presented new evidence that the staging of deterministic circadian rhythms, according to the dosing time of drugs, e.g., upon awakening vs. at bedtime, cannot only differentially impact their pharmacokinetics and pharmacodynamics but also mediate agonistic/synergetic or antagonistic DDI. To properly manage CVD patients and avoid DDI, it is important that clinicians have sufficient knowledge of their multiple risk factors, i.e., age, gender, and life style elements (like diet, smoking, psychological stress, and alcohol consumption), and comorbidities, such as diabetes, hypertension, dyslipidemia, and depression, and the potential interactions between genetic or epigenetic background of their prescribed therapeutics

Sleep disorders, medical conditions, and road accident risk

Sleep disorders and various common acute and chronic medical conditions directly or indirectly affect the quality and quantity of one’s sleep or otherwise cause excessive daytime fatigue. This article reviews the potential contribution of several prevalent medical conditions – allergic rhinitis, asthma, chronic obstructive pulmonary disease, rheumatoid arthritis/osteoarthritis – and chronic fatigue syndrome and clinical sleep disorders – insomnia, obstructive sleep apnea, narcolepsy, periodic limb movement of sleep, and restless legs syndrome – to the risk for drowsy-driving road crashes. It also explores the literature on the cost-benefit of preventive interventions, using obstructive sleep apnea as an example. Although numerous investigations have addressed the impact of sleep and medical disorders on quality of life, few have specifically addressed their potential deleterious effect on driving performance and road incidents. Moreover, since past studies have focused on the survivors of driver crashes, they may be biased. Representative population-based prospective multidisciplinary studies are urgently required to clarify the role of the fatigue associated with common ailments and medications on traffic crash risk of both commercial and non-commercial drivers and to comprehensively assess the cost-effectiveness of intervention strategies

Circadian disruption: New clinical perspective of disease pathology and basis for chronotherapeutic intervention

Biological processes are organized in time as innate rhythms defined by the period (τ), phase (peak [Φ] and trough time), amplitude (A, peak-trough difference) and mean level. The human time structure in its entirety is comprised of ultradian (τ τ 28 h) bioperiodicities. The circadian time structure (CTS) of human beings, which is more complicated than in lower animals, is orchestrated and staged by a brain central multioscillator system that includes a prominent pacemaker – the suprachiasmatic nuclei of the hypothalamus. Additional pacemaker activities are provided by the pineal hormone melatonin, which circulates during the nighttime, and the left and right cerebral cortices. Under ordinary circumstances this system coordinates the τ and Φ of rhythms driven by subservient peripheral cell, tissue and organ clock networks. Cyclic environmental, feeding and social time cues synchronize the endogenous 24 h clocks and rhythms. Accordingly, processes and functions of the internal environment are integrated in time for maximum biological efficiency, and they are also organized and synchronized in time to the external environment to ensure optimal performance and response to challenge. Artificial light at night (ALAN) exposure can alter the CTS as can night work, which, like rapid transmeridian displacement by air travel, necessitates realignment of the Φ of the multitude of 24 h rhythms. In 2001, Stevens and Rea coined the phrase “circadian disruption” (CD) to label the CTS misalignment induced by ALAN and shift work (SW) as a potential pathologic mechanism of the increased risk for cancer and other medical conditions. Current concerns relating to the effects of ALAN exposure on the CTS motivated us to renew our long-standing interest in the possible role of CD in the etiopathology of common human diseases and patient care. A surprisingly large number of medical conditions involve CD: adrenal insufficiency; nocturia; sleep-time non-dipping and rising blood pressure 24 h patterns (nocturnal hypertension); delayed sleep phase syndrome, non-24 h sleep/wake disorder; recurrent hypersomnia; SW intolerance; delirium; peptic ulcer disease; kidney failure; depression; mania; bipolar disorder; Parkinson’s disease; Smith–Magenis syndrome; fatal familial insomnia syndrome; autism spectrum disorder; asthma; byssinosis; cancers; hand, foot and mouth disease; post-operative state; and ICU outcome. Poorly conceived medical interventions, for example nighttime dosing of synthetic corticosteroids and certain β-antagonists and cyclic nocturnal enteral or parenteral nutrition, plus lifestyle habits, including atypical eating times and chronic alcohol consumption, also can be causal of CD. Just as surprisingly are the many proven chronotherapeutic strategies available today to manage the CD of several of these medical conditions. In clinical medicine, CD seems to be a common, yet mostly unrecognized, pathologic mechanism of human disease as are the many effective chronotherapeutic interventions to remedy it