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PubMed2006

Harm and benefits of short-term pre-operative radiotherapy in patients with resectable rectal carcinomas.

AIM: To weigh the harms and benefits of short-term pre-operative radiotherapy in the treatment of resectable rectal cancer. METHODS: The benefits (reduction of local recurrence) and harm (increase of short-term complications) of short-term pre-operative radiotherapy are balanced using a model which classifies patients in one of five outcome combinations; 1-benefit without additional harm, 2-benefit with additional harm, 3-no benefit, no additional harm, 4-no benefit but additional harm, 5-mortality due to combined treatment. The results of four randomised clinical trials (RCT) which study the addition of short-term pre-operative radiotherapy in rectal cancer were classified according to this model. RESULTS: Five to thirteen percent of the patients have benefit without additional harm of pre-operative radiotherapy, while 0-2% have benefit with additional harm; 74-87% has neither benefit nor additional harm and 6-11% have no benefit but additional harm. A small percentage of patients (1-6%) dies post-operatively as a result of the addition of radiotherapy. CONCLUSION: This model provides a transparent appreciation of the harmful and beneficial effects of any treatment modality investigated by means of a randomised clinical trial. As for short-term pre-operative radiotherapy in resectable rectal cancer is shown, a small percentage of patients benefits from such treatment. Most patients have neither benefit nor additional harm, while a small percentage suffers from additional harm while not receiving any benefit.

Carcinoma↗
PubMed1992

Is there a J curve distribution for diastolic blood pressure?

The question whether there is a level of diastolic pressure during treatment below which further reduction of pressure may be harmful rather than beneficial is of great interest. If, as the proponents of this hypothesis maintain, death from CHD among treated hypertensives becomes more rather than less common at very low diastolic pressure, this might explain at least in part why most primary prevention trials of hypertension have failed to show a reduction in CHD mortality. However, as the sceptics have pointed out, the evidence that drug induced lowering of blood pressure is harmful is not of the highest quality, and alternative explanations for excess cardiovascular mortality at low diastolic pressure exist. In the following review of this hotly contested debate it is concluded that both proponents and sceptics may be correct, but that the presence of a J curve should not divert attention from the main benefit of treating hypertension which is a reduction in the risk of fatal and non fatal stroke.

Blood Pressure↗
PubMedDate not supplied

Pro-oxidative vs antioxidative properties of ascorbic acid in chromium(VI)-induced damage: an in vivo and in vitro approach.

The effect of antioxidant ascorbic acid (vitamin C) pretreatment on chromium(VI)-induced damage was investigated using the yeast Saccharomyces cerevisiae as a model organism. The objective of this study was to pretreat yeast cells with the antioxidant ascorbic acid in an effort to increase cell tolerance against reactive chromium intermediates and reactive oxygen species formed during chromium(VI) reduction. Intracellular oxidation was estimated using the fluorescence indicators dihidro-2,7-dichlorofluorescein, dihydroethidium and dihydrorhodamine 123. The role of ascorbic acid pretreatment on chromium(VI) toxicity was determined by measuring mitotic gene conversion, reverse mutations, 8-OHdG, hydroxyl radical, superoxide anion and chromium(V) formation. The chromium content in the biomass was determined by flame atomic absorption spectrometry. In the absence of chromium, ascorbic acid effectively protected the cells against endogenous reactive oxygen species formed during normal cellular metabolism. In vitro measurements employing EPR and the results of supercoiled DNA cleavage revealed that the pro-oxidative action of ascorbic acid during Cr(VI) reduction was concentration-dependent and that harmful hydroxyl radical and Cr(V) had formed following Cr(VI) reduction. However, the in vivo results highlighted the important role of increased cytosol reduction capacity related to modification of Cr(V) formation, increased chromium accumulation, better scavenging ability of superoxide anions and hydrogen peroxide, and consequently decreased cytotoxicity and genotoxicity in ascorbic acid pretreated cells. Ascorbic acid influenced Cr(VI) toxicity both as a reducing agent, by decreasing Cr(V) persistence, and as an antioxidant, by decreasing intracellular superoxide anion and hydrogen peroxide formation and by quenching free radicals formed during Cr(VI) to Cr(III) reduction. Increased 8-OHdG and decreased reduced glutathione in ascorbic acid-treated cells might induce an endogenous antioxidant defense system and thus increase cell tolerance against subsequent Cr-induced stress.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Drug policy in Canada--the way forward.

This article is one of a series commissioned to mark the tenth anniversary of the Canadian HIV/AIDS Legal Network, discussing past developments and future directions in areas of policy and law related to HIV/AIDS. It takes a critical look at Canada's drug policy. Despite calls for a balanced approach focused on reducing drug-related harm, Canada's method of dealing with problems of illicit drug use has remained prohibitionist in nature, and by far the greatest part of federal funding is devoted to supply-reduction initiatives. Considerable changes in policy and law are needed to significantly reduce the harms associated with injection drug use in Canada. These include developing a comprehensive and integrated strategy, exploring alternative legal frameworks, piloting innovative approaches to reducing injection-related harms, and investing in broad social policies that address the determinants of injection drug use.

Canada↗
PubMed2006

Combined chemotherapy and radiotherapy (without surgery) compared with radiotherapy alone in localized carcinoma of the esophagus.

BACKGROUND: Esophageal carcinoma can be managed primarily with either a surgical or non-surgical radiotherapeutic approach. Combination chemotherapy (CT) and radiotherapy (RT) has been incorporated into clinical practice and applied increasingly, especially in North America. OBJECTIVES: To evaluate combined CT and RT (CTRT) versus RT alone in patients with localized esophageal carcinoma. Outcomes included overall survival, cause-specific survival, local recurrence, dysphagia relief, quality of life, acute and chronic toxicities. SEARCH STRATEGY: The Cochrane strategy for identifying randomized trials was combined with relevant MeSH headings. The Cochrane Library, MEDLINE, CancerLIT and EMBASE were last searched in April 2005. References from relevant articles and personal files were included. SELECTION CRITERIA: Randomized controlled trials in patients with localized esophageal cancer comparing RT alone with combined CTRT were included. Studies comparing non-chemotherapy agents such as pure radiotherapy sensitisers, immunostimulants, planned esophagectomy, were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data independently. Trial quality was assessed using the Jadad scale and Detsky checklist. Sensitivity analyses were planned to examine the effect of concomitant versus sequential treatment, study quality, radiotherapy dose, and whether the drug regimen contained cisplatin or 5-fluorouracil were performed. MAIN RESULTS: Nineteen randomized trials were included, with eleven concomitant and eight sequential RTCT studies. Concomitant RTCT provided significant reduction in mortality with a harms ratio (HR) of 0.73 (95% confidence interval (CI) 0.64 to 0.84). Using an estimated mortality rate for the control group of 62% at year one and 83% at year two, the absolute survival benefit for RTCT was 9% (95% CI 5 to 12%) and 4% (95% CI 3 to 6%]) respectively. There was an absolute reduction of local recurrence rate of 12% (95% CI 3 to 22%), number needed to treat (NNT) of 9, when the local recurrence rate for the RT alone arm was 68%. This was associated with a significant risk of severe and life-threatening toxicities (number needed to harm (NNH)of 6). Sensitivity analyses did not identify any factors that interacted with the results. The results from sequential RTCT studies showed no significant benefit in survival or local control but significant toxicities. AUTHORS' CONCLUSIONS: Based on the available data, when a non-operative approach is selected then concomitant RTCT is superior to RT alone for patients with localized esophageal cancer but with significant toxicities. In patients who are in good general condition, and the risk benefit has been thoroughly discussed with the patient, concomitant RTCT should be considered for the management of esophageal cancer compared with radiotherapy alone.

Combined Modality Therapy↗
PubMed2004

Oral health and reduction in respiratory capacity in a cohort of community-dwelling elderly people: a population-based 5-year follow-up study.

OBJECTIVES: Several anaerobic bacteria originating in periodontal pockets have been isolated from infected lungs and pharyngeal microflora. Increased bacterial load in lungs is known to be a risk factor for decline in forced expiratory volume during the first second. The aim was to evaluate both cross-sectionally and longitudinally the association between oral health status and forced expiratory volume during the first second (FEV1) in older residents of the city of Jyväskylä, Finland. DESIGN: Cross-sectional and prospective cohort study over a 5-year follow-up. SETTING: Research laboratory of the University of Jyväskylä. PARTICIPANTS: In 1990 dental status and FEV1 were examined in 203 80-year-old people, of whom 88 survivors were retested 5 years later. MAIN OUTCOME MEASURES: Primary: dental status and FEV1. Secondary: existence of pulmonary diseases, height, handgrip strength, smoking, and length of education. RESULTS: Participants were regrouped into three categories according to their baseline oral health status. At baseline, men with complete prostheses had the lowest FEV1. Five years later the greatest reduction in FEV1 was seen in subjects with poor periodontal status or complete prostheses (-9.4%) while those with healthy periodontal status showed no reduction in FEV1 values (+1.0%, p = 0.006). CONCLUSIONS: Periodontal infections and complete prostheses may be reservoirs for pathogens which may be harmful and partly explain the observed reduction in FEV1 during ageing.

Aged↗
PubMed1977

Halothane hepatotoxicity and the reduced derivative, 1,1,1-trifluoro-2-chloroethane.

Halothane (1,1,1-trifluoro-2-bromo-2-chloroethane) is a safe, clinically useful inhalation anesthetic. Rare, unpredictable cases of liver necrosis have been reported following its use. Although the mechanism of this reaction in man is unknown the most plausible is biotransformation to reactive intermediates compounds. The oxidative metabolism of halothane appears to be benign. There is early evidence that reductive (nonoxygen dependent) may be harmful. Since the bromine atom of halothane appears to possess weak bond energy, the reduced, debrominated derivative of halothane, 1,1,1-trifluoro-2-chloroethane, was synthesized and tested for hepatotoxicity in the rat. The derivative is unstable and thus was prepared anaerobically and trapped in propylene glycol solvent. Injection of small amounts of this compound into the portal vein of rats produces extensive liver necrosis. It is postulated that biotransformation of halothane via a reductive pathway could produce this reactive intermediate metabolite.

Animals↗
PubMed1994

Periodic health examination, 1994 update: 1. Obesity in childhood. Canadian Task Force on the Periodic Health Examination.

OBJECTIVE: To update the 1979 Canadian Task Force on the Periodic Health Examination recommendation on screening for childhood obesity by reviewing any new evidence concerning health risks in childhood and adulthood, and effective preventive or therapeutic interventions. OPTIONS: Detection: routine measurement of height and weight, use of skinfold thickness measurements, calculation of body mass index (BMI). INTERVENTION: diet, exercise, behaviour modification and comprehensive family-based weight-reduction programs. Components of these interventions could be offered routinely or reserved for children and families who perceive obesity to be a present or potential problem. OUTCOMES: The task force reviewed the probability of obese children become obese adults as a risk factor for adult heart disease and overall related illness and death in adult life as well as obesity as a risk factor for physical and psychologic illness in childhood. EVIDENCE: A MEDLINE search for relevant articles published between January 1981 and February 1991 was undertaken. VALUES: The task force's evidence-based rules for recommendations were used. BENEFITS, HARMS AND COSTS: If weight reduction in childhood were shown to prevent physical or psychologic illness in childhood, or illness and death in adult life, screening and treatment should be recommended. Screening for obesity may cause anxiety on the part of the child and family; malnutrition in children as a result of parents becoming overly anxious about the health risks of obesity has been reported. Most weight reduction programs have limited long-term effectiveness and can be costly. RECOMMENDATIONS: There is insufficient evidence of short-term or long-term benefits from screening for or treatment of childhood obesity to recommend such screening or recommend against it. There is fair evidence to recommend against very-low-kilojoule diets for preadolescents. There is insufficient evidence to recommend for or against exercise programs or intensive family-based programs for most obese children. VALIDATION: These recommendations are similar to those of the American Academy of Pediatrics and the US Preventive Services Task Force. SPONSOR: These guidelines were developed and endorsed by the Canadian task force, which is funded by Health Canada.

Adolescent↗
PubMed1996

An evidence-based approach to prescribing NSAIDs in musculoskeletal disease: a Canadian consensus. Canadian NSAID Consensus Participants.

OBJECTIVE: To make recommendations for the long-term use of nonsteroidal anti-inflammatory drugs (NSAIDs) in primary care practice, particularly for patients at high risk for NSAID-induced complications. OPTIONS: The use of misoprostol to prevent gastrointestinal ulceration and other unwanted NSAIDs effects was considered. The role of cyclooxygenase-2 (COX-2) versus COX-1 inhibiting agents was also examined. OUTCOMES: Reduction of complications associated with long-term use of NSAIDs. EVIDENCE: Evidence was gathered in late 1995 from published research studies and reviews. Position papers were prepared by faculty and advisory board members and discussed at the Canadian NSAID Consensus Symposium in Cambridge, Ont., Jan. 26 and 27, 1996. VALUES: Recommendations were based on randomized, placebo-controlled clinical trials (level I evidence) and case-control studies (level II evidence) involving NSAID use when such evidence was available. When the scientific literature was incomplete or inconsistent in a particular area, recommendations reflect the consensus of the participants at the symposium (level III evidence). Physicians were recruited from across Canada for their expertise in rheumatology, gastroenterology, epidemiology, gerontology, family practice, and clinical and basic scientific research. BENEFITS, HARMS AND COSTS: Although a reduction in complications due to inappropriate NSAID use should reduce costs of additional investigations, admissions to hospital and time lost from work, definitive cost analysis studies are not yet available. RECOMMENDATIONS: Currently, no NSAID is available that lacks potential for serious toxicity; therefore, long-term use of NSAIDs should be avoided whenever possible, particularly in high-risk patients (e.g., those who are elderly, suffer from hypertension, congestive heart failure, renal or hepatic impairment or volume depletion, take certain concomitant medications or have a history of peptic ulcer disease) (level I evidence). If NSAIDs are to be used in patients with gastric or nephrotoxic risk factors, the lowest effective dose of NSAID should be used (level III evidence); NSAIDs that are weak COX-1 inhibitors may be preferred (level II evidence). In addition, concomitant administration of misoprostol is recommended in patients at increased risk for upper gastrointestinal complications (level I evidence). However, the clinical judgement of the practising clinician must always be part of any therapeutic decision. VALIDATION: These recommendations are based on the consensus of Canadian experts in rheumatology, gastroenterology and epidemiology, and have been subjected to external peer review.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1995

The risk of harm to oneself from drinking, Canada 1989.

In a national sample of 11,634 Canadians aged 15 years and above, risk curves for harm to six life-areas from one's own drinking and for assault by another drinker rose steadily with the respondent's volume of alcohol consumption. While drinking five or more drinks on an occasion at least once a month substantially raised the risk at a given volume of drinking, the risk rose with volume even among those not regularly drinking five or more drinks. These relationships remained in logistic regressions which controlled for gender, age and educational level. Younger respondents, those without higher education and men reported more harm for a given level of their own drinking although differences by gender disappeared above one-third of one drink per day. Three sets of guidelines for low-risk drinking--two from Canada, and one generally used in Britain--were compared in terms of the proportions of respondents reporting harm from their own drinking among those who had kept within the guideline in the previous 7 days' drinking. More restrictiveness in the guidelines was associated with substantial reductions in reported drinking-related harm.

Adolescent↗
PubMed2006

Preliminary outcomes of a trial to reduce conflict and containment on acute psychiatric wards: City Nurses.

Acute psychiatric wards experience high levels of conflict behaviours (violence, absconding, self-harm, rule breaking and medication refusal) by patients. These events cause stress and injury to staff and patients. Their management through containment methods (e.g. sedation, restraint, seclusion) is contentious, and nurses are ambivalent about their use. The aim of this study was to reduce conflict and containment on two acute psychiatric wards through changes in nurses' beliefs, attitudes and practices. Two 'City Nurses' were employed to work with two acute wards for 1 year, assisting with the implementation of changes according to a working model of conflict and containment generation, itself based on previous research. Evaluation was via before-and-after measures. Statistically and clinically significant decreases in conflict occurred, with falls in aggression, absconding and self-harm. Ward atmosphere improved and nurse-patient interaction rates increased. There was no significant change in containment method use. Significant reductions in aggression, absconding and self-harm can be achieved on acute psychiatric wards. However, it does not appear that containment can be reduced, even through large reductions in conflict.

Attitude of Health Personnel↗
PubMedDate not supplied

[The place of statins in acute coronary accidents].

Statin therapy significantly decreases the rate of clinical events in secondary prevention, however their use in patients with the acute phase of acute coronary syndromes remains controversial. Their pleiotropic effects on thrombosis, inflammation, and endothelial dysfunction, might improve vascular healing. Although numerous observational studies have shown a significant reduction in mortality, one trial suggested that the statins may have a potentially harmful effect in patients with low cholesterol. However, randomised controlled trials have not demonstrated harmful effects. Of these trials, the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study is the only trial with adequate statistical power to show a significant reduction in ischemic events at 16 weeks with a high dose of once daily atorvastatin 80 mg.

Acute Disease↗
PubMed2003

Aspirin for the prevention of cardiovascular disease: calculating benefit and harm in the individual patient.

AIMS: To estimate the absolute reduction in the risk of cardiovascular events and absolute increase in gastrointestinal haemorrhage associated with aspirin for individuals with different baseline risks. METHODS: Calculation of absolute treatment effects from estimates of: (i) baseline risks for cardiovascular event and gastrointestinal haemorrhage; and (ii) relative risks of these events with treatment. Baseline cardiovascular risks were derived from existing risk scores, and baseline risk of gastrointestinal haemorrhage from an observational cohort study. Changes in relative risks were obtained from clinical trial data. The effects of aspirin treatment were calculated in examples of two individuals with very different baseline risks. RESULTS: Treatment of a healthy 74-year-old man (blood pressure 144/88 mm Hg and no history of gastrointestinal disorder) would reduce his annual risk of a cardiovascular event from 2% to 1.74% (absolute risk reduction 0.26%, number needed to treat 385), but increase the gastrointestinal haemorrhage risk from 0.3% to 0.51% (absolute risk increase 0.21%, number needed to harm 476). In a 66-year-old obese man, following a transient ischaemic attack, and with a history of hospital treatment for a peptic ulcer, the annual risk of a cardiovascular event would be reduced from 5% to 4.35% (absolute risk reduction 0.65%, number needed to treat 153), but the risk of gastrointestinal haemorrhage would increase from 1.08% to 1.83% (absolute risk increase 0.75%, number needed to harm 133). CONCLUSIONS: Estimating benefit and harm by taking into account the baseline risks in each individual allows patients and doctors to judge for themselves the magnitude of the trade-offs involved in taking aspirin.

Aged↗
PubMed1989

Salutary effects of modest fluid replacement in the treatment of adults with diabetic ketoacidosis. Use in patients without extreme volume deficit.

The optimal rate of fluid administration to correct the volume deficit associated with diabetic ketoacidosis remains undefined. Thus, this study evaluates prospectively in adult patients without extreme volume deficit two regimens of therapy that differed exclusively in the rate of fluid infusion. In protocol 1 (12 patients), normal saline was infused at 1000 mL/h (approximately 14 mL/kg per hour) in the initial 4 hours and 500 mL/h (approximately 7 mL/kg per hour) during the subsequent 4 hours. In protocol 2 (11 patients), normal saline was infused at half the rates of protocol 1. For plasma bicarbonate level, the increment from admission levels at 2, 4, 8, 16, and 24 hours after admission was greater with protocol 2 at all times, attaining a statistically significant difference at 4 hours (3.7 vs 0.7 mmol/L) and at 24 hours (13.2 vs 8.4 mmol/L). These data support cautious restraint in the volume of fluid replacement used in the therapy of diabetic ketoacidosis, since prompt recovery, lack of any harmful effects, and a significant reduction in the overall cost of medical therapy are achieved with lower rates of saline infusion.

Adult↗
PubMed2005

Standard additio--a way of improving quantification of banned azo dyes in leather.

An analytical procedure based on supercritical-fluid extraction and microwave-assisted extraction was applied on six different real leather samples for the determination of banned azo dyes. Determination of the dyes was performed indirectly by measuring their corresponding harmful aromatic amines, formed after reduction. A comparative study between external standard calibration and standard addition using both the dyes as well as the corresponding amines showed that the latter quantification method provided the highest accuracy.

Journal Article↗
PubMed1986

Perspectives on treating hypertension.

Lowering the blood pressure to levels for which the arterial system has been designed should reduce various complications in the coronary and cerebral arteries, the heart, and the kidney. However, the antihypertensive treatment itself should not produce any significant damage. It is very likely that early modes of antihypertensive treatment did cause some biologic harm, which prevented the expected reduction in the incidence of coronary artery disease. However, the inability of these early forms of treatment to greatly improve coronary artery disease does not necessarily apply to treatments of the future.

Adrenergic beta-Antagonists↗
PubMed2005

The Tridimensional Personality Questionnaire: changes during psychological treatment of social phobia.

Thirty-nine individuals completed 12 weekly group sessions of psychological therapy for social phobia (social anxiety disorder). Before and after treatment, participants filled out the Tridimensional Personality Questionnnaire (TPQ, [Cloninger C.R., 1987a. A systematic method for clinical description and classification of personality variants. Archives of General Psychiatry, 44, 573-58]) and measures of social anxiety and depression. Treatment led to a significant reduction in social anxiety, depression, harm avoidance, and reward dependence. However, only pre-post changes in harm avoidance and depression were significantly correlated with pre-post changes in social anxiety. These results suggest that harm avoidance shows state-dependent changes during the course of treatment for social phobia. The implications of these findings for the trait/state distinction of the TPQ scales are discussed.

Adult↗
PubMed2006

Differential diagnosis of adult asthma.

Although the term "all that wheezes is not asthma" is not new, and the long list of asthma masqueraders has remained essentially the same for several decades, the importance of knowing when to question the accuracy ofa diagnosis of asthma has remained critical for physicians who care for patients with respiratory symptoms. The concepts of "asthma control" and"asthma severity" are currently evolving, although the fundamental hall-marks that define the syndrome of asthma endure and should be mastered by asthma specialists. Asthma masqueraders, including several that may confound a correct diagnosis of asthma, are important to consider when either the presentation of asthma is atypical or the response of the patient to treatment is suboptimal. COPD and VCD head the list of diagnoses most likely to be confused with asthma in everyday practice. Correctly identifying the diagnosis of COPD enables implementation of an up-to-date treatment plan that differs from asthma management. VCD is a vastly under recognized syndrome whose existence is widely accepted but whose pathophysiology is poorly understood, and correctly identifying a VCD component to asthma symptoms enables both a reduction in costly and potentially harmful asthma medications and focus on specific VCD treatment, such as speech therapy. For less common and uncommon asthma masqueraders, it is important to be familiar with their typical clinical presentation and basic diagnostic approaches.

Adult↗