In clinical epidemiology, experimental studies usually take the form of randomized controlled clinical trials (RCTs). The data analysis of an RCT can be performed by using two complementary strategies, that is according to the intention to treat (ITT) principle and the per protocol (PP) analysis. By using the ITT approach, investigators aim to assess the effect of assigning a drug whereas by adopting the PP analysis, researchers investigate the effect of receiving the assigned treatment, as specified in the protocol. Both ITT and PP analyses are essentially valid but they have different scopes and interpretations dependent on the context.

In March–April 2020, the Corona Virus Disease 19 (COVID-19) pandemic suddenly hit Italian healthcare facilities and in some of them many staff members became infected. In this work 595 health care workers from a public company were tested for Severe acute respiratory syndrome coronavirus 2 (82 positive) and asked to complete a questionnaire on early COVID-19 symptoms. Respiratory symptoms were present in 56.1% of cases. Anosmia and dysgeusia in COVID-19 cases were found to have an odds ratio (OR) = 100.7 (95% Confidence Interval [CI] = 26.5–382.6) and an OR = 51.8 (95%CI 16.6–161.9), respectively. About one in three of the cases (29.3%) never manifested symptoms. Anxiety was reported by 16.6% of COVID-19 cases and depression by 20.3%, with a significant increase in the estimated risk (OR = 4.3; 95%CI = 2.4–7.4 for anxiety, OR = 3.5; 95%CI = 2.0–6.0 for depression). In cases, sleep was a significant moderating factor in the relationship between occupational stress, or organizational justice, and anxiety. The early diagnosis of COVID-19 in health care workers, must consider, in addition to respiratory disorders and fever, anosmia, dysgeusia, exhaustion, myalgias and enteric disorders. The frequency of anxiety and depression disorders in the population examined was not higher than that commonly recorded in the same company during periodic checks in the years preceding the epidemic. In COVID-19 cases there was a significant risk of anxiety, especially in those who had low sleep quality. Mental health support and improvement interventions must mainly concern workers with positive tests and should also tend to improve sleep quality.

Chronic kidney disease (CKD) is a condition characterized by the gradual loss of kidney function over time and it is a worldwide health issue. The estimated frequency of CKD is 10% of the world’s population, but it varies greatly on a global scale. In absolute terms, the staggering number of subjects affected by various degrees of CKD is 850,000,000, and 85% of them are in low- to middle-income countries. The most important risk factors for chronic kidney disease are age, arterial hypertension, diabetes, obesity, proteinuria, dyslipidemia, and environmental risk factors such as dietary salt intake and a more recently investigated agent: pollution. In this narrative review, we will focus by choice just on some risk factors such as age, which is the most important non-modifiable risk factor, and among modifiable risk factors, we will focus on hypertension, salt intake, obesity, and sympathetic overactivity.

Alkaline phosphatase (ALP) is an evolutionary conserved enzyme and widely used biomarker in clinical practice. Tissue-nonspecific alkaline phosphatase (TNALP) is one of four human isozymes that are expressed as distinct TNALP isoforms after posttranslational modifications, mainly in bone, liver, and kidney tissues. Beyond the well-known effects on bone mineralization, the bone ALP (BALP) isoforms (B/I, B1, B1x, and B2) are also involved in the pathogenesis of ectopic calcification. This narrative review summarizes the recent clinical investigations and mechanisms that link ALP and BALP to inflammation, metabolic syndrome, vascular calcification, endothelial dysfunction, fibrosis, cardiovascular disease, and mortality. The association between ALP, vitamin K, bone metabolism, and fracture risk in patients with chronic kidney disease (CKD) is also discussed. Recent advances in different pharmacological strategies are highlighted, with the potential to modulate the expression of ALP directly and indirectly in CKD–mineral and bone disorder (CKD-MBD), e.g., epigenetic modulation, phosphate binders, calcimimetics, vitamin D, and other anti-fracture treatments. We conclude that the significant evidence for ALP as a pathogenic factor and risk marker in CKD-MBD supports the inclusion of concrete treatment targets for ALP in clinical guidelines. While a target value below 120 U/L is associated with improved survival, further experimental and clinical research should explore interventional strategies with optimal risk–benefit profiles. The future holds great promise for novel drug therapies modulating ALP.

Vitamin K acts as a coenzyme of carboxylase, catalyzing the carboxylation of several vitamin K dependent proteins. Beyond its well-known effects on blood coagulation, it also exerts relevant effects on bone and the vascular system. In this review, we point out the relevance of an adequate vitamin K intake to obtain sufficient levels of carboxylated (active form) vitamin K dependent proteins (such as Osteocalcin and matrix Gla protein) to prevent bone health. Another bone-related action of Vitamin K is being a ligand of the nuclear steroid and xenobiotic receptor (SXR). We also discuss the recommended intake, deficiency, and assessment of vitamin K. Furthermore, we review the few available studies that have as pre-specified outcome bone fractures, indicating that we need more clinical studies to confirm that vitamin K is a potential therapeutic agent for bone fractures.

It is well known from observational studies that sedentary lifestyle and reduced physical activity are common in dialysis and chronic kidney disease (CKD) patients and associate with an increased risk of morbidity and mortality in this patient population. Epidemiological studies indicate that CKD patients undergo physical activity ~9 days/month and 43.9% of dialysis patients report not exercising at all. On the basis of awareness about the strong link between sedentary lifestyle and adverse clinical outcomes, the National Kidney Foundation and Kidney Disease: Improving Global Outcomes have provided specific recommendations for physical activity in patients with kidney disease. Given the fact that CKD is a public health problem and it is still debated which type of exercise should be prescribed in these patients, this review focuses on the most robust evidence accumulated so far on the beneficial effect of various types of physical exercise on clinical outcomes in CKD and dialysis patients. This review does not treat this very important topic in another CKD category of patients, such as kidney-transplanted patients, for whom a special issue should be dedicated.