Emerging drug therapies for frailty

The metaphor of a frail older person as a car running out of petrol seems to have resonance in the lay media. Though it may be an over simplistic representation of a complex and dynamic process, it does facilitate discussion with patients and their relatives about the appropriateness of interventions, such as whether or not there is enough fuel (physiological reserves) to get up a really steep hill (undergo a coronary bypass graft). It can also be used as a way to emphasise what can be done to help. For example, in some longitudinal studies, 5% of older patients are less frail after 5 years follow up, suggesting there are things that can still be done to “fill up the tank”. This review will consider whether drug therapies can fulfil this role.Frail older people are often prescribed long lists of medications but it is debatable whether current treatments actually address the causes or consequences of frailty itself. Here, we explore the associations between frailty and co-morbidity and evaluate whether the management of chronic disease may impact frailty development or progression. We consider how the management of hypertension may have an important role in the prevention of frailty, mediated by reduction of cerebrovascular disease, but why aggressive management of hypertension may have negative consequences for those who are already frail. We also summarise the evidence linking immunosenescence, inflammation and endocrine changes to frailty and investigate whether targeted drug therapy has the potential to influence frailty pathophysiology.     

Emotion Coaching Intervention for Chinese Mothers of Preschoolers: A Randomized Controlled Trial

Child Psychiatry & Human Development - Preschoolers’ emotional development typically hinges on the family emotional climate and their interactions with caregivers. This study used a...     

Diabetes impairs hypothalamo-pituitary-adrenal (HPA) responses to hypoglycemia,and insulin treatment normalizes HPA but not epinephrine responses

We recently established that in addition to plasma adrenocorticotrophic hormone (ACTH) and corticosterone, hypothalamic corticotrophin-releasing hormone (CRH) mRNA and hippocampal type 1 glucocorticoid receptor (GR1) mRNA were also upregulated in uncontrolled streptozotocin-induced diabetes. In the current study, control, diabetic, and insulin-treated diabetic rats underwent a hyperinsulinemic-hypoglycemic glucose clamp to evaluate central mechanisms of hypothalamo-pituitary-adrenal (HPA) and counterregulatory responses to insulin-induced hypoglycemia. Increases in plasma ACTH, corticosterone, and epinephrine were significantly lower in diabetic rats versus controls. Insulin treatment restored ACTH and corticosterone but not epinephrine responses to hypoglycemia in diabetic rats. Glucagon and norepinephrine responses to hypoglycemia were not affected by diabetes or insulin treatment. In response to hypoglycemia, hypothalamic CRH mRNA and pituitary proopiomelanocortin mRNA expression increased in control and insulin-treated but not in untreated diabetic rats. Arginine vasopressin mRNA was unaltered by hypoglycemia in all groups. Interestingly, hypoglycemia decreased hippocampal GR1 mRNA expression in control and insulin-treated diabetic rats but not in diabetic rats. In contrast, type 2 glucocortoid receptor (GR2) mRNA was not altered by hypoglycemia. In conclusion, despite increased basal HPA activity, HPA responses to hypoglycemia were markedly reduced in uncontrolled diabetes. We speculate that the defect in CRH response could be related to the defective GR1 response. It is intriguing that insulin treatment restored the HPA response to hypoglycemia but, surprisingly, not the deficient epinephrine response. This is important because during severe hypoglycemia, epinephrine is an important counterregulatory hormone.     

Serum Uric Acid to Creatinine Ratio in Patients with Chronic Obstructive Pulmonary Disease

Serum uric acid (UA), the final product of purine degradation, has been shown to be increased in the hypoxic state. We assessed whether the presence of higher values of serum UA and serum UA to creatinine ratio is associated with clinical or functional characteristics in patients with chronic obstructive pulmonary disease (COPD). Fifty-nine consecutive stable patients with COPD, without comorbid conditions, were included. Clinical and functional characteristics were compared between patients with levels below and above the median values of serum UA and serum UA to creatinine ratio. Patients with serum UA levels above the median value differed significantly from the group with levels below this value only in FVC (p = 0.04), and serum UA did not correlate significantly with the parameters analyzed. Patients with the serum UA to creatinine ratio above the median value had lower FVC (63 ± 18 vs. 73 ± 15 percentage of predicted, p = 0.028), lower FEV₁ (43 ± 19 vs. 55 ± 18 percentage of predicted, p = 0.019), and a higher level of dyspnea (MRC scale, 1.5 ± 1.1 vs. 0.8 ± 1.0, p = 0.011). The serum UA to creatinine ratio correlated with FVC (r = −0.27), with FEV₁ (r = −0.31), and with dyspnea (r = 0.29). In view of these results, we consider that the serum UA to creatinine ratio warrants evaluation as an additional parameter for predicting outcome in COPD.     

Bupreorphine:a new pharmacotherapy for opioid addictions treatment

The federal Drug Abuse Treatment Act 2000 (DATA) opened a window of opportunity for patients with the disease of addiction by providing increased access to options for treatment. Previously, only methadone maintenance, approved for use only through specially regulated clinics, was available to treat opioid addiction. DATA allows any physician choosing to take a short specialty training course and become certified to prescribe buprenorphine. Buprenorphine and buprenorphine/ naloxone (Subutex, Suboxone) can be prescribed by certified physicians in a traditional office setting to treat patients with opioid dependence. Clinical studies indicate buprenorphine maintenance is as effective as methadone maintenance in retaining patients in substance abuse treatment and reducing illicit opioid use. Sublingual buprenorphine is more effective than clonidine or clonidine/naltrexone in short-term opioid detoxification treatment. Buprenorphine provides an additional tool to treat opioid addiction and improve the quality of lives of these patients. More physicians are needed to treat patients with addiction. DATA facilitates this by removing existing barriers and increasing access to treatment.