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PubMed2006

What price do we pay to prevent alcohol-related harms in Aboriginal communities? The Alice Springs trial of liquor licensing restrictions.

This paper analyses the trial of alcohol restrictions that was implemented in Alice Springs in the Northern Territory from April 2002 to June 2003. The trial included a ban on alcohol in containers greater than 2 litres and reduced take-away trading hours. The history of the trial, its findings, and the different interpretations placed on trial data is discussed. Particular emphasis is placed on evidence indicating a link between alcohol price and consumption. Data from the evaluations of the Alice Springs trial are reviewed. The trials adds substantial new evidence to the strength of the relationship between alcohol price, consumption and harm as the restrictions led to a 1000% increase in the sale of the cheapest form of alcohol-2-litre port. Recent proposals for supply reduction strategies such as a tiered volumetric tax on alcohol and a trial of alcohol restrictions based on a minimum price benchmark demand further consideration by policy makers, especially in regions marked by a excessive alcohol consumption and a high burden of alcohol-related harms such as Alice Springs.

Alcoholic Beverages↗
PubMed2002

Reduction of cytokine-induced expression and activity of MMP-1 and MMP-13 by mechanical strain in MH7A rheumatoid synovial cells.

Excessive mechanical load induces harmful outcomes for joint diseases, such as osteoarthritis and rheumatoid arthritis, but physical stimuli at appropriate intensity are essential for growth and maintenance of bone and articular cartilage. Using a fibroblast-like synoviocyte cell line derived from a patient with rheumatoid arthritis, we examined the effects of gentle cyclic strain, focusing on the expression and activity of matrix metalloproteinase-1 (MMP-1) and MMP-13. Synovial cells were cultured on a collagen-coated agar block and exposed to 2% cyclic strain at 6 rev./min for 1 h. Expression of MMP-1 and MMP-13 was assayed using semi-quantitative and real-time PCR, as well as immunoblotting. Their activity was measured using spectrofluorometry and zymography. The results showed that the cyclic strain reduced the mRNA and protein levels of MMP-1 and MMP-13, and that both collagenase and gelatinase activity was decreased under the strain. The reduction in MMP activity by the cyclic strain was not achieved by the transcriptional inhibitor, actinomycin D. In the presence of proinflammatory cytokines, such as IL-1 beta and TNF-alpha, the strain reduced the cytokine-induced expression and activities of MMPs. Interestingly, the strain elevated the mRNA level of tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2. These results support a potential role of mechanical strain in down-regulating the cytokine-mediated proteolytic processes in synoviocytes.

Arthritis, Rheumatoid↗
PubMed2003

Reduction of oral acetaldehyde levels using a controlled-release chlorhexidine chip as a prevention strategy against upper digestive tract cancer.

Increasing evidence indicates a strong relationship exists between harmful habits like smoking and alcohol drinking and upper digestive tract cancer. In addition, smokers and alcohol drinkers also exhibit high salivary levels of carcinogenic acetaldehyde, the first metabolite of alcohol. This compound has been indicated as a major cancer causing factor in the upper digestive tract, especially among alcohol drinkers. Interestingly, acetaldehyde is produced from alcohol present in the epithelia by mucosal alcohol dehydrogenases (ADH) in the upper digestive tract. However, much higher levels derive from the bacterial oxidation of alcohol by the oral microflora. In this respect, the reduction of oral microbes can become a fundamental factor in diminishing the risk of cancer. In this article, we hypothesize that the antimicrobial agent chlorhexidine, formulated as controlled-release chip, and fixed by a dental device, (i.e., a modified orthodontic bracket), may be the most rational strategy for reducing acetaldehyde production by microflora.

Acetaldehyde↗
PubMed2000

Anticonvulsants for preventing mortality and morbidity in full term newborns with perinatal asphyxia.

OBJECTIVES: To assess the benefits and harm of administering anticonvulsants to infants of 37 weeks gestation or more following perinatal asphyxia with the primary aims of prevention of death or subsequent severe neurodevelopmental disability and/or the prevention of seizures. SEARCH STRATEGY: Relevant randomised controlled trials were identified using a combination of electronic database searches (MEDLINE), hand searches and a search of the Neonatal Review Group trials register. SELECTION CRITERIA: All randomised, or quasi-randomised, controlled clinical trials with reported data comparing the following outcomes: mortality, neurodevelopmental disability, neonatal seizures and adverse events, following anticonvulsant therapy in term infants (37 weeks or more), compared to controls with or without placebo, following perinatal asphyxia. DATA COLLECTION AND ANALYSIS: Methodological quality and validity of studies were assessed without consideration of the results. Data relevant to the outcome were extracted and analysed. MAIN RESULTS: Five randomised or quasi-randomised controlled trials which met the selection criteria were identified. No studies were of sufficient methodological quality and size to demonstrate a valid, clinically significant change in the risk of mortality or severe neurodevelopmental disability. A meta-analysis combining three studies comparing barbiturates with conventional therapy following perinatal asphyxia demonstrated no difference in risks of death, severe neurodevelopmental disability, or death or severe neurodevelopmental disability. REVIEWER'S CONCLUSIONS: At the present time, anticonvulsant therapy to term infants in the immediate period following perinatal asphyxia cannot be recommended for routine clinical practice, other than in the treatment of prolonged or frequent clinical seizures. Any future studies should be of high quality: randomised control trials with allocation concealment, performance and outcome assessment blinding. Such studies should be of sufficient size, with minimal attrition, to have the power to detect clinically important reductions in mortality and severe neurodevelopmental disability, as the primary outcome measures.

Anticonvulsants↗
PubMed2005

A fresh look at the benefits and costs of the US acid rain program.

The US Acid Rain Program (Title IV of the 1990 Clean Air Act Amendments) has achieved substantial reductions in emissions of sulfur dioxide (SO2) and nitrogen oxides (NOx) from power plants in the United States. We compare new estimates of the benefits and costs of Title IV to those made in 1990. Important changes in our understanding of and ability to quantify the benefits of Title IV have occurred. Benefits to human health now take a much higher profile because the contribution of SO2 and NOx emissions to the formation of fine particulate (PM2.5) is substantial, and evidence of the harmful human health effects of PM2.5 has emerged in the last 15 years. New estimates of the health benefits of PM2.5 reductions are the largest category of quantified health and environmental benefits and total over 100 billion US dollars annually for 2010 when the program is expected to be fully implemented. Although important uncertainties exist in any specific estimate of the benefits, even if the estimates were calculated using more limiting assumptions and interpretations of the literature they would still substantially exceed the costs. Estimates of annualized costs for 2010 are about 3 billion US dollars, which is less than half of what was estimated in 1990. Research since 1990 also suggests that environmental problems associated with acid deposition and nitrogen deposition are more challenging to resolve than originally thought and will require larger reductions in emissions to reverse. The greater than expected benefits to human health, the greater vulnerability of natural resources and ecosystems, and the lower than expected costs all point to the conclusion that further reductions in SO2 and NOx emissions from power plants beyond those currently required by Title IV are warranted.

Acid Rain↗
PubMed2002

Error reduction in the New World. How we can improve the level of safety for everyone in our operating rooms.

In order to do no harm, ask yourself and your colleagues the following questions: Is our environment safe? Does staff follow all safety measures? Do physicians and visitors follow safety rules? Is every staff member aware of their role in safety for all? Is there an effective staff/leader safety inspection team in place and functioning effectively? Are all reasonable recommendations implemented? Have the errors been reviewed in detail? If so, what were the results and what changes were made? Is self-reporting encouraged without repercussions? Do you know what your error rates are, what the root causes were, which systems were lacking, and how they have been modified? Needless to say we have a great deal of work to do and many challenges to overcome if we are to decrease our risk of error. But where to start? Do a critical analysis of the current system and, on a daily basis, focus on improving some small piece of the safety network that will have a lasting impact. The commitment and participation of staff, strong visible leadership, and accountable, well-trained individuals and teams will all be major contributors to a safe environment.

Humans↗
PubMed2001

Regulation of nicotine replacement therapies (NRT): a critique of current practice.

Nicotine replacement therapy (NRT) describes a group of products delivering nicotine that are licensed for the relief of withdrawal as an aid to smoking cessation. This paper examines areas where public health considerations suggest changes should be made to the current indications and characteristics for NRT products. It is argued that the current regulatory framework restricts access to NRT without adequately considering that the likely consequence is continued dependent use of a far more harmful and widely available version of the same drug: tobacco. The paper argues that minors, pregnant smokers and smokers with cardiovascular disease (CVD) be allowed to use NRT. NRT use for smoking reduction, to support temporary abstinence, for long-term use should also be enabled and NRT products should be made as widely available as cigarettes. This paper also recommends that regulators encourage the development of less harmful forms of nicotine delivery devices to compete with cigarettes. Although this paper is written largely with reference to the UK medicines regulatory framework, these issues also apply to many other countries.

Adolescent↗
PubMed2007

Preventing postmarketing changes in recommended doses and marketing withdrawals.

Recent market withdrawals of prescription drug products have brought attention to premarketing safety research. Less known but related to some drug withdrawals are postmarketing dosage changes of newly marketed drugs, including both dosage reductions and increases. These events have serious effects on patients, manufacturers, and regulatory authorities. Most of these harmful events could be avoided by intensive employment of targeted clinical pharmacology investigations to optimize dosage prior to phase III testing and regulatory approval. In this paper, the frequency and implications of postmarketing dosing changes and market withdrawals are considered in light of approaches to preventing them.

Adverse Drug Reaction Reporting Systems↗
PubMed2001

Update in pharmacologic treatment of hypertension.

Initial pharmacologic therapy for hypertension is low-dose thiazide diuretics, beta-blockers, and ACE inhibitors. Increasing data have confirmed that ACE inhibitors have specific benefit in patients with diabetes, atherosclerosis, left ventricular dysfunction, and renal insufficiency. CCBs are alternative agents for ISH in the elderly and appear to decrease stroke with perhaps less protection against progression of renal insufficiency and proteinuria, CAD mortality and new onset heart failure versus other initial agents, especially ACE inhibitors. ARBs are well tolerated and effective blood pressure lowering agents but have not been confirmed as effective as ACE inhibitors for reducing renal progression, clinical events, or mortality from heart failure. Effective pharmacologic antihypertensive therapy may avoid disabling and undetected cerebrovascular disease, cognitive dysfunction, and disturbing symptoms of elevated blood pressure. Vasopeptidase inhibitor, such as omapatrilat, and endothelin-1 antagonist, such as bosentan, may become future agents approved for the reduction of morbidity and mortality with hypertension. The ALLHAT trial continues to examine the potential benefits and harms of amlodipine versus chlorthalidone and lisinopril in a diverse high-risk population. Based on ALLHAT data, however, doxazosin is no longer an acceptable initial pharmacological agent. Intensive pharmacologic treatment with blood pressure lowering to less than 130/85 mm Hg is recommended with diabetes, renal insufficiency, and heart failure with additional goal of less than 125/75 mm Hg with renal failure and proteinuria greater than 1 g/24 h, based on multiple outcome studies.

Adrenergic beta-Antagonists↗
PubMed2003

Eating habits and appetite control in the elderly: the anorexia of aging.

Although a high prevalence of overweight is present in elderly people, the main concern in the elderly is the reported decline in food intake and the loss of the motivation to eat. This suggests the presence of problems associated with the regulation of energy balance and the control of food intake. A reduced energy intake causing body weight loss may be caused by social or physiological factors, or a combination of both. Poverty, loneliness, and social isolation are the predominant social factors that contribute to decreased food intake in the elderly. Depression, often associated with loss or deterioration of social networks, is a common psychological problem in the elderly and a significant cause of loss of appetite. The reduction in food intake may be due to the reduced drive to eat (hunger) resulting from a lower need state, or it arises because of more rapidly acting or more potent inhibitory (satiety) signals. The early satiation appears to be predominantly due to a decrease in adaptive relaxation of the stomach fundus resulting in early antral filling, while increased levels and effectiveness of cholecystokinin play a role in the anorexia of aging. The central feeding drive (both the opioid and the neuropeptide Y effects) appears to decline with age. Physical factors such as poor dentition and ill-fitting dentures or age-associated changes in taste and smell may influence food choice and limit the type and quantity of food eaten in older people. Common medical conditions in the elderly such as gastrointestinal disease, malabsorption syndromes, acute and chronic infections, and hypermetabolism often cause anorexia, micronutrient deficiencies, and increased energy and protein requirements. Furthermore, the elderly are major users of prescription medications, a number of which can cause malabsorption of nutrients, gastrointestinal symptoms, and loss of appetite. There is now good evidence that, although age-related reduction in energy intake is largely a physiologic effect of healthy aging, it may predispose to the harmful anorectic effects of psychological, social, and physical problems that become increasingly frequent with aging. Poor nutritional status has been implicated in the development and progression of chronic diseases commonly affecting the elderly. Protein-energy malnutrition is associated with impaired muscle function, decreased bone mass, immune dysfunction, anemia, reduced cognitive function, poor wound healing, delayed recovery from surgery, and ultimately increased morbidity and mortality. An increasing understanding of the factors that contribute to poor nutrition in the elderly should enable the development of appropriate preventive and treatment strategies and improve the health of older people.

Aged↗
PubMed2003

The potential role of computerisation and information technology in improving prescribing in hospitals.

For physicians, prescribing of drugs is one of the most common actions in daily practice. In the continuum prescribing, dispensing, administration and use of drugs, failures may occur and can lead to patient harm. The use of computerised physician order entry systems is subject to much discussion regarding medication error reduction. This commentary analyses the issues where such systems can contribute to improved care.

Computers↗
PubMed2002

Effect of oil pollution on euendolithic cyanobacteria of the Arabian Gulf.

Microbial euendoliths (true borer) cyanobacteria are carbonate-boring microorganisms found in modern and ancient marine environments. Modern euendoliths include a wide range of prokaryotes as well as eukaryotes, which have been reported world-wide. The importance of euendolithic cyanobacteria concerns their role in bio-erosion of calcium carbonate substrates and as ecological indicators of shallow, tropical and subtropical marine environments. Arabian Gulf ooids from four sites along the east coast of Saudi Arabia have been bored and inhabited by several species of euendolithic cyanobacteria. This assemblage of different species exists simultaneously within the same ooid grain. Comparisons of 1989 and 1992 data reveal a drastic reduction in active euendoliths, and the average numbers of colonies in these ooids. This study reveals the harmful effect of the 1991 oil spill on these unique microorganisms residing in these ooids.

Cyanobacteria↗
PubMed1994

Sexually compulsive men and inhibited sexual desire.

Sexually compulsive males report extremely high rates of desire involving paraphiliac activity. Desire and arousal in partner sex is usually low or unstable. Cognitive-behavioral strategies and techniques are presented based on four components in the assessment/intervention process: 1) eliminating or reducing paraphiliac arousal; 2) sex education, changing sexual attitudes, self-disclosure, sexual assertiveness, and reduction of guilt and shame; 3) confronting secrecy and cognitive distortions, increasing empathy for victims, awareness of harm to others, and commitment to abstain from compulsive, abusive behavior; and 4) developing a healthy sexual desire and arousal pattern that nurtures and maintains an intimate relationship. The motivated male (especially with a partner he is comfortable with, attracted to, and trusts) can develop a pleasurable, erotic sexual pattern that allows him to maintain desire during partner sex.

Adult↗
PubMed1998

Flexible sigmoidoscopy as a mass screening tool.

Endoscopic removal of premalignant adenomas from the distal bowels of the entire population, 3 to 5-yearly from age 50, is advocated in the US as a feasible method of reducing colorectal cancer mortality rates. In the UK, a single flexible sigmoidoscopy (FS) is regarded as a more cost-effective option. Although more acceptable than colonoscopy, FS and polypectomy are expensive and invasive procedures carrying a small risk of serious harm. We believe that, before implementing mass screening, precise estimates are required of the magnitude of the reduction in mortality and costs (financial, physical and emotional). Several randomized trials, including a large British study, are currently evaluating these aspects.

Adenoma↗
PubMed2005

Volume-based referral for cardiovascular procedures in the United States: a cross-sectional regression analysis.

BACKGROUND: We sought to estimate the numbers of patients affected and deaths avoided by adopting the Leapfrog Group's recommended hospital procedure volume minimums for coronary artery bypass graft (CABG) surgery and percutaneous coronary intervention (PCI). In addition to hospital risk-adjusted mortality standards, the Leapfrog Group recommends annual hospital procedure minimums of 450 for CABG and 400 for PCI to reduce procedure-associated mortality. METHODS: We conducted a retrospective analysis of a national hospital discharge database to evaluate in-hospital mortality among patients who underwent PCI (n = 2,500,796) or CABG (n = 1,496,937) between 1998 and 2001. We calculated the number of patients treated at low volume hospitals and simulated the number of deaths potentially averted by moving all patients to high volume hospitals under best-case conditions (i.e., assuming the full volume-associated reduction in mortality and the capacity to move all patients to high volume hospitals with no related harms). RESULTS: Multivariate adjusted odds of in-hospital mortality were higher for patients treated in low volume hospitals compared with high volume hospitals for CABG (OR 1.16, 95% CI 1.10-1.24) and PCI (OR 1.12, 95% CI 1.05-1.20). A policy of hospital volume minimums would have required moving 143,687 patients for CABG and 87,661 patients for PCI from low volume to high volume hospitals annually and prevented an estimated 619 CABG deaths and 109 PCI deaths. Thus, preventing a single death would have required moving 232 CABG patients or 805 PCI patients from low volume to high volume hospitals. CONCLUSION: Recommended hospital CABG and PCI volume minimums would prevent 728 deaths annually in the United States, fewer than previously estimated. It is unclear whether a policy requiring the movement of large numbers of patients to avoid relatively few deaths is feasible or effective.

Aged↗
PubMed2002

Ageism in rectal carcinoma? Treatment and outcome variations.

BACKGROUND: Rectal cancer adjuvant and neo-adjuvant therapies are associated with improved survival and local control rates. Concerns regarding adverse treatment effects tend to reduce administration in the elderly-the very population this disease affects. PURPOSE: To determine the extent to which age alters rectal cancer treatment and its outcome. METHODS AND MATERIALS: Using the population based provincial cancer registry, patients with adenocarcinoma of the rectum diagnosed between 1991 and 1998 were identified. From this cohort, a random subsample of patients seen at the regional cancer center were selected for detailed analysis. Demographic and clinical data between the provincial cohort and the subsample were compared for homogeneity. Log rank tests and Kaplan-Meier survival estimates were carried out on the subsample. RESULTS: The population cohort (n = 1979) and the subsample (n = 259) were similar in age, sex, and treatment distributions. Elderly patients (>/=75 yr) made up 23% of the rectal cancer population in Alberta. Age had a highly significant (p = 0.001) impact on whether patients received surgery alone or had surgery plus chemoradiotherapy. This corresponded to a considerable survival advantage for those elderly patients who did receive multimodality therapy (p = 0.008). CONCLUSION: The advantage of multimodality therapy in rectal cancer is confirmed in this populationbased study. Although a significant number of elderly patients are fit enough to tolerate major surgery they are being denied adjuvant therapies, presumably on the basis of potentially high treatment-related complication rates, with a subsequent reduction in survival. Strategies must be developed to ensure that maximum treatment benefit is obtained without increased harm in the elderly rectal cancer patient.

Adult↗
PubMedDate not supplied

[A double-blind controlled study of the efficacy and acceptability of tianeptine in comparison with fluvoxamine in the treatment of depressed alcoholic patients].

AIM: The main objective of the study was the evaluation of therapeutic efficacy of tianeptine (T) (37.5 mg/day) in comparison with fluvoxamine (F) (100 mg/day) in depressed patients with alcohol dependence or harmful use who had abstained from alcohol, in a 6-week treatment period. The secondary objectives were the assessment of the acceptability of both drugs and analysis of the alcohol craving behaviour regarding both treatments. METHOD: Outpatients who met ICD-10 criteria for depression and alcohol dependence or harmful use were randomised to a double-blind 6-week comparative trail. Responders (50% or more reduction in baseline HDRS) were proposed to continue the same treatment up to 90 days. The antidepressant efficacy was assessed with the use of the HDRS (main criterion). Other scales used in the study were HARS, CGI and OCDS. Tolerance was evaluated by monitoring of adverse events. RESULTS: A total of 298 (150 in T group and 148 in F group) were randomized. Both drugs showed good efficacy in the treatment of depressive symptoms. In Full Analysis Set (FAS) mean HDRS score significantly decreased in both groups from 22.2 at baseline to 10.6 at end-point in T group and from 21.8 to 11.4 in F group. There was no statistical difference between groups. The number of patients found to be responders at end-point was 72.1% in the T group and 67.1% in the F group. There was significant improvement in both treatment groups in HARS and CGI. Also analysis of alcohol craving by the OCDS scale showed significant improvement in both groups. No significant difference between treatment groups regarding those scales was noted. In a 6-week treatment period, statistically significantly more patients continued the study in the T group. Tolerability of both drugs was good. 16.7% of the patients experienced at least one adverse event in the T group and 20.3% in the F group. CONCLUSION: Tianeptine and fluvoxamine are effective and safe in the treatment of depression in the group of patients with alcohol dependence.

Alcoholism↗
PubMed1985

Optimal elimination of leukemic T cells from human bone marrow with T101-ricin A-chain immunotoxin.

In view of bone marrow purging before autologous transplantation in T cell malignancies, an anti-human T cell immunotoxin (IT) has been prepared by coupling ricin A-chain to the monoclonal antibody T101 that binds the T1 differentiation antigen expressed by T lymphocytes as well as by T cell-derived hematologic malignancies. Using a sensitive and reliable clonogenic assay, optimal conditions were defined for the elimination of clonogenic human T leukemic cells among bone marrow cells. Maximal cytoreduction was obtained with IT at a dose of 2 micrograms/mL in the presence of 10 mmol/L NH4Cl. This treatment led to the reduction of more than six orders of magnitude of T101-positive clonogenic leukemic cells, with no harm to T101-negative cells. Moreover, we observed no toxicity of IT to human hematopoietic stem cells (CFU-GEMMT) derived from bone marrow of healthy volunteers. Thus, pretreatment of bone marrow samples with IT plus NH4Cl offers a safe, simple, reliable, and highly efficient means to eliminate undesirable leukemic T cells from the graft.

Ammonium Chloride↗