Luis Vitetta

Interventions that can Reduce Inappropriate Prescribing in the Elderly A Systematic Review

Inappropriate prescribing of medicines may lead to a significant risk of an adverse drug-related event. In particular, prescribing may be regarded as inappropriate when alternative therapy that is either more effective or associated with a lower risk exists to treat the same condition. This review aims to identify interventions and strategies that can significantly reduce inappropriate prescribing in the elderly. The review is based on a search of electronic databases using synonyms of keywords such as ‘elderly’, ‘interventions’, ‘optimized prescribing’ and ‘inappropriate prescribing’ to identify reported interventions intended to improve inappropriate prescribing in the elderly. A total of 711 articles published in English were retrieved and considered. Of these, 24 original studies, involving 56 to 124802 participants, met the inclusion criteria and were included in the systematic review. In 16 studies, the statistical power used to assess the impact of the intervention was >90% at a significance level of α=0.05.Various interventions were included in this study, such as educational interventions, medication reviews, geriatricians’ services, multidisciplinary teams, computerized support systems, regulatory policies and multi-faceted approaches. Because of variability in assessment methodologies, mixed responses were found for education interventions aimed at improving inappropriate prescribing. For example, some studies did not assess what data were required to define whether a given level of intervention would be adequate, and others did not consider how many participants would be needed to demonstrate that a significant difference existed.Each of the three computerized support system interventions reported produced a significant enhancement in both prescribing and dispensing practices. Pharmacist interventions in community and hospital settings were evaluated in seven studies. However, variable criteria were used, with two studies using the Medication Appropriateness Index, another two studies using self-designed criteria for inappropriate prescribing, and the remaining three studies using Beers’ criteria. A difficulty in assessing studies involving nursing home residents is that both consultant pharmacists and onsite pharmacist services may be involved, and, in one of the studies, only the role of the consultant pharmacist was considered. One of the most effective interventions appeared to be multidisciplinary case conferences involving a geriatrician, which resulted in a number of examples of reduced inappropriate prescribing in both community and hospital settings. As the effect of regulatory policies as an intervention is dependent on the target population involved, the effectiveness of this type of intervention was variable.Different strategies may be useful in reducing inappropriate prescribing in the elderly. It is not clear whether combined strategies undertaken simultaneously have a synergistic effect.

Alcohol consumption and the etiology of colorectal cancer: A review of the scientific evidence from 1957 to 1991

The relationship between alcohol consumption and colorectal cancer in humans has been examined in 52 major studies in the past 35 years. An association was found in five of the seven correlational studies. An elevated risk was found in about half of the 31 case-control studies and, of these, in 9 of the 10 studies using community controls but in only 5 of the 17 studies using hospital controls (p = 0.008), suggesting that the absence of association when hospital controls are used is due to a high prevalence of alcohol consumption/alcohol-related illness in the hospital controls. Of the 14 cohort studies, an association with alcohol was found in 10, while in 3 of the 4 cohort studies in which an association was not found the alcohol data obtained were somewhat restricted. A positive dose-response effect was found in two of three cohort studies and in all four case-control studies with community controls in which this effect was examined. In both case-control and cohort studies, the association was found for females and males and for colon and rectal cancer. When the type of alcohol consumed was examined separately, beer was the principal type of at-risk alcoholic beverage, with much less risk for spirits and least risk for wine. Statistically significant elevations of risk were more often found in males than in females and slightly more frequently for rectal than for colon cancer and were related almost entirely to beer, rather than to wine or spirit, consumption. The alcohol risk was independent of the dietary risk in those studies that controlled for this factor. There was some confirmatory evidence for alcohol augmentation in rodent models of chemically induced carcinogenesis in six of nine studies. The hypotheses of alcohol as a direct and specific colorectal carcinogen include increased mucosal cell proliferation, the activation of intestinal procarcinogens, and the role of unabsorbed carcinogens, particularly in beer. Also, five of six other human studies showed an association between alcohol/beer consumption and adenomatous polyps, consistent with the hypothesis that alcohol stimulates the colorectal mucosa. General or indirect carcinogenic effects of alcohol include immunodepression, activation of liver procarcinogens, and changes in bile composition, as well as nitrosamine content of alcoholic beverages and increased tissue nitrosamine levels. With alcohol/beer consumption, the overall conclusion on present evidence is that alcohol, particularly beer consumption, is an etiologic factor for colon and rectal cancer for females and males.(ABSTRACT TRUNCATED AT 400 WORDS)

Muscarinic and nicotinic receptors synergistically modulate working memory and attention in humans

Functional abnormalities in muscarinic and nicotinic receptors are associated with a number of disorders including Alzheimers disease and schizophrenia. While the contribution of muscarinic receptors in modulating cognition is well established in humans, the effects of nicotinic receptors and the interactions and possible synergistic effects between muscarinic and nicotinic receptors have not been well characterized in humans. The current study examined the effects of selective and simultaneous muscarinic and nicotinic receptor antagonism on a range of cognitive processes. The study was a double-blind, placebo-controlled, repeated measures design in which 12 healthy, young volunteers completed cognitive testing under four acute treatment conditions: placebo (P); mecamylamine (15 mg) (M); scopolamine (0.4 mg i.m.) (S); mecamylamine (15 mg)/scopolamine (0.4 mg i.m.) (MS). Muscarinic receptor antagonism with scopolamine resulted in deficits in working memory, declarative memory, sustained visual attention and psychomotor speed. Nicotinic antagonism with mecamylamine had no effect on any of the cognitive processes examined. Simultaneous antagonism of both muscarinic and nicotinic receptors with mecamylamine and scopolamine impaired all cognitive processes impaired by scopolamine and produced greater deficits than either muscarinic or nicotinic blockade alone, particularly on working memory, visual attention and psychomotor speed. These findings suggest that muscarinic and nicotinic receptors may interact functionally to have synergistic effects particularly on working memory and attention and suggests that therapeutic strategies targeting both receptor systems may be useful in improving selective cognitive processes in a number of disorders.

Diet, alcohol, smoking, serum β‐carotene, and vitamin A in male nonmelanocytic skin cancer patients and controls

A case-control study was conducted in Melbourne, Australia of 88 consecutive males admitted for the surgical removal of a nonmelanocytic skin cancer (histologically confirmed basal cell carcinoma and squamous cell carcinoma) and of 88 male control patients admitted for small elective surgical procedures. In both cases and controls, previous diet, alcohol consumption, and smoking habit were investigated and serum beta-carotene and vitamin A levels were measured. A statistically significant inverse relationship was found between the risk of skin cancer and a high intake of fish (p = 0.05); vegetables in general (p < 0.001); beans, lentils, or peas (p < 0.001), carrots, silverbeet (Swiss chard), or pumpkin (p < 0.001); cruciferous vegetables (cabbage, brussel sprouts, or broccoli) (p < 0.001); and beta-carotene- and vitamin C-containing foods (p = 0.004). Cases had a lower mean serum level of beta-carotene (p < 0.001) and vitamin A (p = 0.02) than controls. The incidence of skin cancer in the study was inversely related to the level of serum beta-carotene (p < 0.0001). The correlation coefficient between dietary beta-carotene/vitamin C and serum beta-carotene was 0.22 (p = 0.04). Smoking and alcohol consumption showed no statistically significant association with the risk of nonmelanocytic skin cancer. The results were similar for both cell types. A high intake of vegetables including cruciferous vegetables, beta-carotene- and vitamin C-containing foods, and fish appears to be protective for nonmelanocytic skin cancer, and this deserves further study, as does the possible etiologic relevance of the low serum levels of beta-carotene and vitamin A.

Healthy aging: regulation of the metabolome by cellular redox modulation and prooxidant signaling systems: the essential roles of superoxide anion and hydrogen peroxide

The production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) has long been proposed as leading to random deleterious modification of macromolecules with an associated progressive development of age associated systemic disease. ROS and RNS formation has been posited as a major contributor to the aging process. On the contrary, this review presents evidence that superoxide anion (and hydrogen peroxide) and nitric oxide (and peroxynitrite) constitute regulated prooxidant second messenger systems, with specific sub-cellular locales of production and are essential for normal metabolome and physiological function. The role of these second messengers in the regulation of the metabolome is discussed in terms of radical formation as an essential contributor to the physiologically normal regulation of sub-cellular bioenergy systems; proteolysis regulation; transcription activation; enzyme activation; mitochondrial DNA changes; redox regulation of metabolism and cell differentiation; the concept that orally administered small molecule antioxidant therapy is a chimera. The formation of superoxide anion/hydrogen peroxide and nitric oxide do not conditionally lead to random macromolecular damage; under normal physiological conditions their production is actually regulated consistent with their second messenger roles.

Mind‐Body Medicine: Stress and Its Impact on Overall Health and Longevity

The belief that adverse life stressors and the emotional states that can lead to major negative impacts on an individuals body functions and hence health has been held since antiquity. Adverse health outcomes such as coronary heart disease, gastrointestinal distress, and cancer have been linked to unresolved lifestyle stresses that can be expressed as a negative impact on human survival and ultimately a decrease of the human life span. Psychological modulation of immune function is now a well‐established phenomenon, with much of the relevant literature published within the last 50 years. Psychoneuroimmunology and psychoneuroendocrinology embrace the scientific evidence of research of the mind with that of endocrinology, neurology and immunology, whereby the brain and body communicate with each other in a multidirectional flow of information that consists of hormones, neurotransmitters/neuropeptides, and cytokines. Advances in mind‐body medicine research together with healthy nutrition and lifestyle choices can have a significant impact on health maintenance and disease prevention and hence the prolongation of the human life span.

Bacterial Infections in Terminally Ill Hospice Patients

Terminally ill patients are very susceptible to infections, which are the result of disease-related processes and/or therapy-induced mechanisms. These patients are already subject to multiple severe symptoms and associated comorbid conditions, with much resultant distress. Infection increases this symptom burden and further reduces quality of life. We have retrospectively investigated the prevalence of infection and clinical course in 102 consecutive patients who died after admission to a tertiary palliative care unit and assessed the site-specific frequency of infection, pathogenic organisms involved, and the pattern of antibiotic agents used. The prevalence of symptoms and comorbid conditions on admission and during the progress phase of care were noted. Median overall survival of the total cohort was 12 days. The median survival of patients with infections was 22 days. Thirty-seven patients (36.3%) were diagnosed with 42 separate infections. The sites of infections were the urinary tract (42.5%), the respiratory tract (22.9%), blood (12.5%), skin and subcutaneous tissues (12.5%), and the eyes (10.0%). There were 20 separate positive cultures isolated from specimens obtained from 13 individual patients. Three isolates were obtained from 1 patient, 2 isolates obtained from 5 patients, and 1 isolate was obtained from each of the 7 remaining patients. Escherichia coli was the most common pathogen isolated. Eleven patients with infections (31.4%) were diagnosed on admission, and antibiotic treatment was commenced within 48 hours of admission in 21 patients (60%). Overall antibiotic response and symptom control of infections was observed to be a minimum of 40%. Psychological distress was common in this group of patients (P = 0.001) as were disabling symptoms on admission, such as pain, immobility, and weakness. Symptoms indicating poor survival, such as severe pain and dyspnea, were not significantly associated with infection. Decreased patient survival in this cohort was not significantly associated with the presence of bacterial infection (P = 0.07), irrespective of whether or not a positive culture isolate was obtained. We conclude that appropriate management of infection resulted in enhanced palliative symptom control.

Improved cognitive performance after dietary supplementation with a Pinus radiata bark extract formulation.

Dietary interventions may have the potential to counter age‐related cognitive decline. Studies have demonstrated an improvement in age‐related cognitive impairment in animals after supplementation with plant extracts containing flavonoids but there are few human studies. This double‐blind, controlled study examined the effects on cognitive performance of a 5 week supplementation with Enzogenol® Pinus radiata bark extract containing flavonoids, in 42 males aged 50–65 years, with a body mass index >25. Participants were supplemented for 5 weeks either with Enzogenol® plus vitamin C, or with vitamin C only. A battery of computerized cognitive tests was administered, and cardiovascular and haematological parameters were assessed prior to and following supplementation. The speed of response for the spatial working memory and immediate recognition tasks improved after supplementation with Enzogenol® plus vitamin C, whereas vitamin C alone showed no improvements. A trend in a reduction of systolic blood pressure was observed with Enzogenol® plus vitamin C, but not with vitamin C alone. The blood safety parameters were unchanged. The findings suggest a beneficial effect of supplementation with Enzogenol® on cognition in older individuals. Larger studies are needed to ascertain its potential as a preventive treatment for age‐related cognitive decline. Copyright

A population survey on the use of 24 common medicinal herbs in Australia.

Herbal medicine use is common in Australia but little is known about the use of individual herbs.

Ginger (Zingiber officinale) and chemotherapy-induced nausea and vomiting: a systematic literature review

Chemotherapy-induced nausea and vomiting (CINV) is a common side-effect of cytotoxic treatment. It continues to affect a significant proportion of patients despite the widespread use of antiemetic medication. In traditional medicine, ginger (Zingiber officinale) has been used to prevent and treat nausea in many cultures for thousands of years. However, its use has not been confirmed in the chemotherapy context. To determine the potential use of ginger as a prophylactic or treatment for CINV, a systematic literature review was conducted. Reviewed studies comprised randomized controlled trials or crossover trials that investigated the anti-CINV effect of ginger as the sole independent variable in chemotherapy patients. Seven studies met the inclusion criteria. All studies were assessed on methodological quality and their limitations were identified. Studies were mixed in their support of ginger as an anti-CINV treatment in patients receiving chemotherapy, with three demonstrating a positive effect, two in favor but with caveats, and two showing no effect on measures of CINV. Future studies are required to address the limitations identified before clinical use can be recommended.