Cardiovascular Risk and Mild Thyroid Hormone Deficiency: Are there some Differences in the Elderly?

Subclinical hypothyroidism (sHT) is a clinical condition defined as serum TSH concentration above the upper limit of the reference range in the face of normal free T4 (FT4) and free T3 (FT3) levels. Subclinical hypothyroidism, the prevalence of which increases with age, especially among women, up to almost 20%, encompasses several pathological entities, mainly represented by chronic autoimmune thyroiditis [1,2]. sHT is often associated to symptoms that resembles those of overt hypothyroidism, although to a lesser extent thus, the expression ‘mild thyroid impairment’ or ‘mild thyroid hormone deficiency’ would be more appropriate for defining such a condition [1]. Nonetheless, the term sHT is recognized worldwide and will be utilized in the present editorial. Since 90s, a relationship between sHT and increased cardio-vascular (CV) risk (both heart failure and coronary heart disease events) has been reported, although some experiences suggest that the risk may depend on the degree of TSH elevation [1,3-5]. Moreover, several reports from elderly population (>65 years old) showed that this relationship seems no longer evident in such individuals especially in the oldest old (>85 years old) [6-9]

The Use of Antipsychotic Drugs for Treating Behavioral Symptoms in Alzheimer’s Disease

According to the World Alzheimer’s report, dementia was estimated to affect 50 million worldwide in 2018, number expected to increase to more than 150 million within 30 years. Alzheimer’s disease is the most common type of dementia, accounting on its own for 2/3 of all dementia cases. The initial signs and symptoms of Alzheimer’s disease relate to progressive cognitive decline, inexorably progressing until the loss of independence. Neuropsychiatric and behavioral symptoms may occur during the progression of the disease; around 20% of patients without any behavioral symptoms at the diagnosis will experience some of them within 2 years. Consequences are early institutionalization, lower quality of life, of both patients and carers, and more severe cognitive impairment. Treatment options for behavioral symptoms include pharmacological and nonpharmacological approaches. The latter are usually preferred, since antipsychotic therapy is not free from several, and often serious, adverse events. However, behavioral symptoms are not always controllable with non-pharmacological intervention. The psychotropic class of medication more frequently prescribed for behavioral symptoms are atypical antipsychotics; among them, risperidone is the only one licensed for the treatment of aggression, in Europe but not in the USA. On that regard, the use of antipsychotic drugs should be limited, due to the increased risk of mortality, stroke, hallucination, and higher risk of relapse after discontinuation. Some new agents are under evaluation, such as pimavanserin and lumateperone. In this review, we are evaluating the current available pharmacological options to treat behavioral symptoms as well as the forthcoming new agents

Clarithromycin-induced rhabdomyolysis: a case report

Rhabdomyolysis is a clinical and laboratory syndrome that is caused by various etiologies, involving the skeletal muscle. Clarithromycin, like other macrolides, is an inhibitor of CYP450 3A4, the major enzyme responsible for the metabolism of several drugs, in particular some statins. Rhabdomyolysis related to macrolide–statin interaction has previously been described. To date, rhabdomyolysis induced by clarithromycin has been described in only one previous report. We describe the case of a 90-year-old Caucasian male, admitted to the University Hospital of Pisa for dyspnea, who developed rhabdomyolysis associated with clarithromycin administration

Mild Thyroid Deficiency in the Elderly

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Potential drug–drug interactions in alzheimer patients with behavioral symptoms

The use of multi drug regimens among the elderly population has increased tremendously over the last decade although the benefits of medications are always accompanied by potential harm, even when prescribed at recommended doses. The elderly populations are particularly at an increased risk of adverse drug reactions considering comorbidity, poly-therapy, physiological changes affecting the pharmacokinetics and pharmacodynamics of many drugs and, in some cases, poor compliance due to cognitive impairment and/or depression. In this setting, drug-drug interaction may represent a serious and even life-threatening clinical condition. Moreover, the inability to distinguish drug-induced symptoms from a definitive medical diagnosis often results in addition of yet another drug to treat the symptoms, which in turn increases drug-drug interactions. Cognitive enhancers, including acetylcholinesterase inhibitors and memantine, are the most widely prescribed agents for Alzheimer's disease (AD) patients. Behavioral and psychological symptoms of dementia, including psychotic symptoms and behavioral disorders, represent noncognitive disturbances frequently observed in AD patients. Antipsychotic drugs are at high risk of adverse events, even at modest doses, and may interfere with the progression of cognitive impairment and interact with several drugs including anti-arrhythmics and acetylcholinesterase inhibitors. Other medications often used in AD patients are represented by anxiolytic, like benzodiazepine, or antidepressant agents. These agents also might interfere with other concomitant drugs through both pharmacokinetic and pharmacodynamic mechanisms. In this review we focus on the most frequent drug-drug interactions, potentially harmful, in AD patients with behavioral symptoms considering both physiological and pathological changes in AD patients, and potential pharmacodynamic/pharmacokinetic drug interaction mechanisms

Subclinical Hypothyroidism: behavioral and psychophysiological characteristics.A pilot study

Background: Clinical hypothyroidism affects various aspects of cognitive and affective brain function. The most severe hypothyroidism may also mimic a picture of melancholic depression and dementia. Subclinical hypothyroidism (SHT) is characterized by elevated TSH levels despite normal thyroid hormone concentrations. The aim of this research is to verify the presence of a typical psychophysiological pattern in SHT patients. Methods: Since 1998 fifty patients who underwent surgeries at the Department of Endocrinology, University of Pisa, diagnosed with SHT, were subsequently recruited. Subjects underwent an inspection of the reported symptoms using the Crown & Crisp Experiential Index, and a psychophysiological assessment with a simultaneous recording of the parameters Skin Conductance Level/ Response (SCL/SCR), Surface Frontal Electromyogram (EMG), Peripheral Temperature (PT), Heart Rate (HR). As a control group, fifty subjects without endocrine disorders were subsequently recruited. Results: Data shows little difference in levels in hormonal assays except for TSH. There is also a significant elevation of some of the CCEI subscales: Anxiety, Depression, and Somatic Complaints. At the autonomic level, there is a general pattern of excessive arousal with significant differences in SCL/SCR, HR, and PT. Conclusions: A first data interpretation is that in sub-clinical hypothyroidism, the body tries to support and integrate the general lack of energy with an acceleration of the autonomic activity. This condition of initial arousal could be a useful indicator in order to monitor the treatment course and its effectiveness on the pathological evolution

Review of the clinical evidence for interferon β 1a (Rebif®) in the treatment of multiple sclerosis

Interferon (INF) β 1a 22 or 44 μg (Rebif®) administered s.c. 3 times a week (t.i.w) is a well established immunomodulating treatment for relapsing remitting multiple sclerosis (RRMS). This review focuses on its mechanisms of action, evidence of efficacy, safety, and tolerability. Several pharmacodynamic properties explain the immunomodulatory actions of INF β 1a 22 or 44 μg s.c. t.i.w. Pivotal trials and post-marketing studies proved that the drug is effective in reducing disease activity and likely in slowing disease progression. Head-to-head comparative studies with other marketed INFs β in RRMS suggested a better therapeutic response associated with higher doses and frequency of administration of Rebif®. Additional evidence indicated a beneficial effect of INF β 1a in patients with clinically isolated syndromes (CIS) suggestive of MS, as treatment reduced time to conversion to clinically definite (CD) disease. Further, although the drug did not prove to slow time to progression there were benefits on relapse- and MRI-related secondary outcome measures in secondary progressive (SP) MS. Pivotal trials, their cross-over extensions, and post-marketing studies consistently showed that INF β 1a 22 or 44 μg s.c. t.i.w. is safe and well tolerated, as adverse drug reactions are usually mild and manageable

Acute portal vein thrombosis precipitated by indomethacin in a HCV-positive elderly patient

BACKGROUND: An increased risk of venous thromboembolism has been reported in patients treated with non-steroidal anti-inflammatory drugs (NSAIDs). We describe a case of acute portal vein thrombosis (PVT) in a hepatitis C virus (HCV)-positive elderly patient following administration of indomethacin. CASE PRESENTATION: A 79-year-old HCV-positive man was hospitalized for severe abdominal pain, nausea and vomiting, 15 days after starting indomethacin for back pain. Clinical signs and imaging evaluations disclosed a picture of PVT. Indomethacin was discontinued, and the patient was started on fondaparinux and antithrombin. He was discharged 15 days later due to improvement of his clinical conditions. Thirty days later, a follow-up ultrasound did not show appreciable signs of PVT. The time elapsing between the start of analgesic therapy and PVT onset suggests a role of indomethacin as the triggering agent. Indomethacin could have precipitated PVT by a combination of at least two detrimental mechanisms: 1) direct action on liver vascular endothelium by inhibition of prostacyclin biosynthesis; 2) damage to the intestinal mucosa, followed by inflammatory and pro-coagulant activation of portal endothelium upon exposure to bacterial endotoxins. CONCLUSIONS: This case can be of interest to physicians, who should exert caution when prescribing NSAIDs for inflammatory pain in patients with background inflammatory dysfunctions of the portal vein endothelium

Exploring Cost-Effectiveness of the Comprehensive Geriatric Assessment in Geriatric Oncology: A Narrative Review

: The Comprehensive Geriatric Assessment (CGA) and the corresponding geriatric interventions are beneficial for community-dwelling older persons in terms of reduced mortality, disability, institutionalisation and healthcare utilisation. However, the value of CGA in the management of older cancer patients both in terms of clinical outcomes and in cost-effectiveness remains to be fully established, and CGA is still far from being routinely implemented in geriatric oncology. This narrative review aims to analyse the available evidence on the cost-effectiveness of CGA adopted in geriatric oncology, identify the relevant parameters used in the literature and provide recommendations for future research. The review was conducted using the PubMed and Cochrane databases, covering published studies without selection by the publication year. The extracted data were categorised according to the study design, participants and measures of cost-effectiveness, and the results are summarised to state the levels of evidence. The review conforms to the SANRA guidelines for quality assessment. Twenty-nine studies out of the thirty-seven assessed for eligibility met the inclusion criteria. Although there is a large heterogeneity, the overall evidence is consistent with the measurable benefits of CGA in terms of reducing the in-hospital length of stay and treatment toxicity, leaning toward a positive cost-effectiveness of the interventions and supporting CGA implementation in geriatric oncology clinical practice. More research employing full economic evaluations is needed to confirm this evidence and should focus on CGA implications both from patient-centred and healthcare system perspectives

Hypothyroidism in the Elderly: Who Should Be Treated and How?

Hypothyroidism is among the most frequent chronic diseases in the elderly, and levothyroxine (l-T4) is worldwide within the 10 drugs more prescribed in the general population. Hypothyroidism is defined by increased serum thyroid-stimulating hormone (TSH) values and reduced circulating free thyroid hormones, whereas subclinical hypothyroidism (sHT) is characterized by free hormone fractions within the normal ranges and has been divided into two classes, depending on circulating TSH levels (above or below 10 mIU/L). Given that during aging, a natural trend toward higher values of circulating TSH has been reported, it is necessary to verify carefully the diagnosis of sHT to tailor an appropriate follow-up and ad hoc therapy, avoiding unnecessary or excessive treatment. In the current review, we evaluate the state of the art on hypothyroidism in the elderly with special focus on the effect of sHT on cognition and the cardiovascular system function. We also summarize the recommendations for a correct diagnostic workup and therapeutic approach to older people with an elevated TSH value, with special attention to the presence of frailty, comorbidities, and poly therapy. In conclusion, personalized therapy is crucial in good clinical practice, and in the management of older patients with sHT, multiple factors must be considered, including age-dependent TSH cutoffs, thyroid autoimmunity, the burden of comorbidities, and the possible presence of frailty. l-T4 is the drug of choice for the treatment of hypothyroid older people, but the risk of overtreatment, potential adverse drug reactions, and patient compliance should always be considered and thyroid status periodically reassessed