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PubMed1997

[Effect of enalapril on restrictive type diastolic filling disorder in severe congestive heart failure].

Authors investigated the effect of enalapril (10-20 mg daily) on twenty-nine patients with chronic heart failure in NYHA III-IV stadium who's ejection fraction value was under 40% and had restrictive type of diastolic filling abnormality. Parameters of left ventricular function were measured by echocardiography and the basal data were compared to data detected at the time of 3 and 6 months control. A beneficial effect of enalapril was found on functional cardiac status (reduction in NYHA score), on systolic function (augmentation in ejection fraction and mean mitral anulus motion amplitude). Parallel with the previous parameters in the severity of restrictive diastolic filling alterations (reducing the value of pathologically high E/A ratio and an increasing in deceleration time of early diastolic filling wave) a countable decrease was observed. Authors emphasize the favourable effect of angiotensin converting enzyme inhibitors on chronic heart failure caused by different reasons independently of its severity. The source of drug action is reduction of the preload and afterload as well as keeping under control the harmful ventricular remodelling based on impediment of myocardial angiotensin system.

Adolescent↗
PubMed2006

Evidence base for practice: reduction of restraint and seclusion use during child and adolescent psychiatric inpatient treatment.

BACKGROUND: Restraint and seclusion of children has great potential for harm. Since the mid-1980s, psychiatric inpatient personnel for children and adolescents have put considerable energy in reducing the use of extreme measures of aggression management. While the use of restraints is a particular problem in the United States, aggression management and means of control in psychiatric settings is an international issue. APPROACH: The core question of this review was: What is the current state of the evidence supporting restraint reduction efforts with children and adolescents? Studies were reviewed and critiqued that related to programs of restraint reduction, restraint reduction methods, and aggression management. Internationally, there seems to be more emphasis on reducing coercive measures by understanding the context of their use. Thus, studies exploring staff perceptions and decisions concerning coercive measures were also examined. FINDINGS: The evidence supporting restraint reduction methods in the United States comes mainly from case study reports of clinical sites' quality improvement projects. Consequently, a collection of studies is accumulating that supports a multi-strategy approach to restraint reduction. Limited evidence exists for aggression management measures and training in de-escalation techniques. Controversial aggression management techniques such as the use of pro re nata medication and holding continue to be used with very little support for their efficacy. RECOMMENDATIONS: Recommendations include taking a view of restraint and seclusion as emergency measures to address dangerous aggression, not interventions examined in controlled studies. As such it is suggested that sites pool data on restraint use and reduction efforts to create a database for benchmarking and studying variations among hospitals. Furthermore, attention should also be given to developing additional means for addressing aggressive behaviors.

Adolescent↗
PubMed2004

Therapeutic options and results following fixed atlantoaxial rotatory dislocations.

Atlantoaxial rotatory dislocation (AARD) represents a rare pathological condition of the upper cervical spine that is frequently misdiagnosed, leading to a delay in therapy. In a long-term assessment of clinical and radiological results, three different therapeutic options with regard to the length of the dislocation-therapy interval (DTI) were evaluated. Twenty-six patients were treated for AARD from December 1988 until April 2000. Proper diagnosis was established after an average interval of 15 months. Three different therapeutical protocols were followed in order to reduce the dislocation: (1) closed transoral reposition under general anesthesia; (2) temporary transoral fixation utilizing the Harms T-plate; (3) definitive transoral fusion. The eight patients treated by closed reduction had the best pain relief. The average visual analogue scale (VAS) score was 96.6 points, while the rotatory motion of the upper cervical spine, as assessed by dynamic MRI, was 25.3 degrees to each side. The length of the dislocation-therapy-interval (DTI) averaged 1.4 months. A mean VAS Score of 92.3 points was recorded in the ten patients treated with a temporary fixation of C1/C2. In this subgroup the DTI had an average length of 5.3 months. The mean rotation to each side was 13.9 degrees . In the eight patients who underwent definitive fusion the mean VAS score was 60.6 points, while the average length of the DTI was 40.5 months. In conclusion, the clinical outcome and the subjective well-being following AARD deteriorates with increasing length of the dislocation-therapy interval.

Adolescent↗
PubMed2003

The effects of LDL reduction and HDL augmentation on physiologic and inflammatory markers.

Cholesterol plays an important role in atherogenesis. Oxidized low-density lipoprotein cholesterol is harmful to arteries whereas high-density lipoprotein cholesterol appears to have beneficial properties on vascular function. There is increasing evidence that inflammation is also involved in the atherogenic process. Inflammation accelerates atherosclerosis and promotes thrombogenesis, and inflammatory biomarkers have been correlated with cardiovascular risk. There is now evidence that lowering low-density lipoprotein and raising high-density lipoprotein cholesterol have beneficial effects on inflammation that might contribute to the reduction in clinical cardiovascular events with currently available lipid-altering therapies. New therapeutic strategies are being designed to inhibit specific aspects of the inflammatory system that contribute to the initiation and progression of atherosclerosis.

Arteriosclerosis↗
PubMed1998

Nicotine replacement: a new approach to reducing tobacco-related harm.

Primary prevention is usually regarded as the most desirable goal in efforts to control tobacco-related diseases. However, this has not been very effective so far; moreover, it would take 30-40 yrs for primary prevention to translate into major health benefits. Modification of tobacco products and/or reduction of tobacco use may also have some impact on tobacco-related diseases. A tobacco dose-dependent risk has been observed in these diseases, including cancer, cardiovascular diseases, chronic nonspecific respiratory disorders, and problems during pregnancy. Reduced smoking (smoking fewer cigarettes, leading to a reduced intake of toxic substances) may be indicated in individuals who: 1) are failing in cessation attempts; 2) want to quit but are unable to do so; and 3) do not want to quit but want to reduce smoking. Studies have shown that nicotine replacement medications may be an untapped source in efforts to reduce smoking. Based on Austrian data, it is estimated that, approximately 10 yrs after implementation, a 1% reduction in smoking could save 14 male lung cancer deaths each year, and a 50% reduction would save 700 male lives. Inclusion of females and other tobacco-related diseases suggest that thousands of lives could be saved if smoking could be reduced by 50%. In the European Union, such a reduction in smoking could save > or = 100,000 lives annually. Even a 1% reduction would save 1,000 lives. In conclusion, reduced smoking should be explored as a valid method of reducing tobacco-related harm in those unwilling or unable to quit smoking.

Gingiva↗
PubMed2006

Beneficial effects of statins on perioperative cardiovascular outcome.

PURPOSE OF REVIEW: This review evaluates clinical and experimental articles that have recently been published on the cardioprotective effect of perioperative statin therapy. RECENT FINDINGS: Perioperative statin therapy improves short and long-term cardiac outcome following noncardiac surgery. This cardiovascular protection has been attributed to the so-called pleiotropic effects, which have a positive effect on plaque stability. With no clinical studies reporting an increased incidence of adverse effects of perioperative statin use, it appears to be a safe and helpful therapeutic option. SUMMARY: Perioperative statin therapy may stabilize coronary plaques due to pleiotropic effects and results in a reduction of perioperative cardiovascular complications.

Atherosclerosis↗
PubMed2002

Leptin protects the pancreas from damage induced by caerulein overstimulation by modulating cytokine production.

BACKGROUND: Recent identification of specific leptin receptors in the pancreas suggests that this peptide may also play some role in this gland. AIM: To examine the effect of intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of leptin in rats on caerulein-induced pancreatitis (CIP), pancreatic gene expression of leptin and inflammatory cytokine production. METHODS: Caerulein (25 micrograms/kg) was infused subcutaneously into conscious rats over 5 h to produce CIP. Leptin (1, 5, or 10 micrograms/kg) was injected i.p. or i.c.v. 30 min prior to the CIP induction. The plasma level of TNF alpha and IL-4 was determined by ELISA, while plasma leptin was measured by RIA and leptin gene expression in pancreas by RT-PCR. RESULTS: CIP was characterized by the usual pancreatic edema, reduction in pancreatic blood flow (PBF) and an increase in serum levels of amylase, TNF alpha and IL-4. Pretreatment with i.p. or i.c.v. leptin of the CIP rats partially reversed the harmful effects of CIP on the pancreas, and reduced pancreatic inflammation and the fall in PBF. This was accompanied by a dose-dependent reduction in serum levels of amylase and TNF alpha, while serum IL-4 in the CIP rats pretreated with leptin rose dose-dependently as compared to control rats with CIP alone. Pretreatment with leptin resulted in the dose-dependent rise in plasma leptin level over that observed in vehicle-treated controls. Leptin mRNA expression in the pancreas was dose-dependently increased after infusion of caerulein. Leptin content in isolated pancreatic acini was also increased dose-dependently by caerulein added to the incubation medium bathing these acini. CONCLUSIONS: (1) Exogenous leptin protects the pancreas against damage by CIP; (2) endogenous leptin seems to limit the extend of pancreatic damage, and (3) these protective effects of leptin could be attributed to the reduction in TNF alpha and to the increase in IL-4 production.

Animals↗
PubMed2002

Benefit and harm of low-dose aspirin in well-treated hypertensives at different baseline cardiovascular risk.

BACKGROUND: The effects of aspirin in subjects without cardiovascular disease are controversial. In the intensively treated patients of the Hypertension Optimal Treatment (HOT) Study, randomization to low-dose aspirin (75 mg daily) versus placebo significantly reduced cardiovascular events (-15%) and myocardial infarction (-36%), but increased major bleedings (+65%). The present analyses of HOT Study data aim at identifying subgroups of hypertensives with different benefit-to-harm ratios from aspirin, in order to provide recommendations about the use of aspirin in hypertension. METHODS: The 18 790 hypertensive patients (aspirin 9399, placebo 9391; average treatment duration 3.8 years) were stratified for global cardiovascular risk and for individual risk factors. Subgroup-treatment interaction analyses (end points: cardiovascular events, myocardial infarction, major bleedings) were performed by a Cox proportional hazard model. Relative and absolute benefits and harms were calculated. RESULTS: Interaction analyses indicated that of all subgroups, only patients with serum creatinine > 1.3 mg/dl had a significantly greater reduction of cardiovascular events and myocardial infarction (-13 and -7/1000 patient-years), while risk of bleeding was not significantly different between subgroups. In addition to patients with higher creatinine, a favourable balance between benefit and harm of aspirin was found in subgroups of patients at higher global baseline risk and baseline systolic pressure > or = 180 or diastolic pressure > or = 107 mmHg. CONCLUSIONS: Low-dose aspirin should be recommended to well-treated hypertensive patients with even moderate increase in serum creatinine. Aspirin may also be recommended in well-treated hypertensives at higher global cardiovascular risk or higher initial blood pressures.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

Red cell volume-related ion transport systems in hemoglobinopathies.

This review has examined the expression of ion transporters involved in cell volume regulation in erythrocytes of patients homozygous for hemoglobin S (Hb S) with SS cells, of patients homozygous for Hb C (CC cells), or from patients with SC disease whose red cells contain both Hb S and Hb C (SC cells). Transport proteins that control intracellular cation content and, hence, red cell volume, may have pathophysiologic implications for these hemoglobinopathies. Ion transporters involved in volume regulation are highly expressed in the young circulating cells of these hemoglobinopathies, which display large interindividual differences. In SS disease, there are a large number of circulating young cells that exhibit a very high activity of ion transporters involved in cell volume reduction such as K:Cl cotransport. The activation of this transport system leads to significant reduction in cell volume when cells encounter an acid or deoxygenated environment. This process is particularly harmful because it favors Hb S polymerization and cell sickling. Another transport process that can contribute to the deoxy-stimulated K+ efflux exhibited by SS red cells is the opening of Ca(++)-activated K+ channels. The use of charybdotoxin (a very specific inhibitor of these channels) can yield information about the number of channels and the contribution of this pathway to the generation of dense and irreversibly sickled cells. Lastly, studies of ion transporters leading to cell volume increases indicate that Na+/H+ exchange activity (which is very high in young AA, SS, and SC red cells and persists after reticulocyte maturation) may counteract the volume reduction effects of K:Cl cotransport. The physiologic role of this antiporter in human red cells has not yet been studied.

Anemia, Sickle Cell↗
PubMed2000

Psychosocial versus pharmacological treatments for deliberate self harm.

OBJECTIVES: To identify and synthesise the findings from all randomised controlled trials that have examined the effectiveness of treatments of patients who have deliberately harmed themselves. SEARCH STRATEGY: Electronic databases screened: MEDLINE (from 1966-February 1999); PsycLit (from 1974-March 1999); Embase (from 1980-January 1999); The Cochrane Controlled Trials Register (CCTR) No.1 1999. Ten journals in the field of psychiatry and psychology were hand searched for the first version of this review. We have updated the hand search of three specialist journals in the field of suicidal research until the end of 1998. Reference lists of papers were checked and trialists contacted. SELECTION CRITERIA: All RCTs of psychosocial and/or psychopharmacological treatment versus standard or less intensive types of aftercare for patients who shortly before entering a study engaged in any type of deliberately initiated self-poisoning or self-injury, both of which are generally subsumed under the term deliberate self-harm. DATA COLLECTION AND ANALYSIS: Data were extracted from the original reports independently by two reviewers. Studies were categorized according to type of treatment. The outcome measure used to assess the efficacy of treatment interventions for deliberate self-harm was the rate of repeated suicidal behaviour. We have been unable to examine other outcome measures as originally planned (e.g. compliance with treatment, depression, hopelessness, suicidal ideation/thoughts, change in problems/problem resolution). MAIN RESULTS: A total of 23 trials were identified in which repetition of deliberate self-harm was reported as an outcome variable. The trials were classified into 11 categories. The summary odds ratio indicated a trend towards reduced repetition of deliberate self-harm for problem-solving therapy compared with standard aftercare (0.70; 0.45 to 1.11) and for provision of an emergency contact card in addition to standard care compared with standard aftercare alone (0.45; 0.19 to 1.07). The summary odds ratio for trials of intensive aftercare plus outreach compared with standard aftercare was 0.83 (0.61 to 1.14), and for antidepressant treatment compared with placebo was 0.83 (0. 47 to 1.48). The remainder of the comparisons were in single small trials. Significantly reduced rates of further self-harm were observed for depot flupenthixol vs. placebo in multiple repeaters (0. 09; 0.02 to 0.50), and for dialectical behaviour therapy vs. standard aftercare (0.24; 0.06 to 0.93). REVIEWER'S CONCLUSIONS: There still remains considerable uncertainty about which forms of psychosocial and physical treatments of self-harm patients are most effective, inclusion of insufficient numbers of patients in trials being the main limiting factor. There is a need for larger trials of treatments associated with trends towards reduced rates of repetition of deliberate self-harm. The results of small single trials which have been associated with statistically significant reductions in repetition must be interpreted with caution and it is desirable that such trials are also replicated.

Cognitive Behavioral Therapy↗
PubMed1979

Effect on paroxysmal re-entrant supraventricular tachycardia of a drug affecting calcium transport (Ro 11-1781).

The effect of Ro 11-1781, a drug that affects calcium transport, in 10 patients with paroxysmal supraventricular tachycardia (PSVT), was studied by intracardiac recording and stimulation. The re-entry circuit involved an accessory pathway that conducted only in the ventriculo-atrial direction in 5 patients, and was confined to the A-V node in 5 cases. Prior to administration of Ro 11-1781 tachycardia could be initiated in all patients. An intravenous bolus of 2 mg/kg during PSVT terminated the tachycardia in all cases by blockade in the A-V node. Ro 11-1781 lengthened the A-V nodal conduction time as well as the functional and effective refractory period of the A-V node. The effective refractory period of the "fast" pathway was variably changed. After Ro 11-1781 the tachycardia zone was abolished in 3 cases, reduced in 3, increased in 3 and was converted to an echo zone in 1. The ability to sustain the PSVT was lost in one subject. The heart rate during PSVT was slowed following Ro 11-1781. Ro 11-1781 appears to be useful for the termination of PSVT, but its ability to prevent PSVT varies. Beneficial effects include abolition or narrowing of the tachycardia zone, loss of the ability to sustain PSVT and a reduction in heart rate during PSVT. The widening of the tachycardia zone may be harmful.

Adult↗
PubMed1994

Beta-blocker therapy in the Cardiac Arrhythmia Suppression Trial. CAST Investigators.

The Cardiac Arrhythmia Suppression Trial (CAST) showed antiarrhythmic drug suppression of asymptomatic or mildly symptomatic ventricular arrhythmias in survivors of myocardial infarction to be harmful. This study retrospectively searched the CAST results for evidence of mortality and morbidity reduction in patients receiving optional beta-blocker therapy. All enrolled (n = 2,611) and suppressed main study (n = 1,735) CAST patients with an ejection fraction of < or = 40% were examined using univariate analysis, Kaplan-Meier curves, and a Cox proportional-hazards multivariate analysis with respect to optional beta-blocker therapy prescribed at baseline. CAST patients receiving beta-blocker therapy had significantly enhanced survival at 30 days, and at 1 and 2 years of follow-up against all-cause and arrhythmic death or nonfatal cardiac arrest. Multivariate analysis showed beta-blocker therapy to be independently associated with a one-third reduction in arrhythmic death or cardiac arrest (p = 0.036). In CAST patients with a history of congestive heart failure, beta-blocker therapy was independently associated with longer time to occurrence of new or worsened congestive heart failure (p = 0.015). This study supports the secondary preventive benefit of beta-blocker therapy in high-risk post-myocardial infarction patients, and calls attention to the possible preventive benefit of beta-blocker therapy against proarrhythmic events experienced in the CAST.

Adrenergic beta-Antagonists↗
PubMed2001

Number needed to treat: caveat emptor.

Number needed to treat (NNT)-the inverse of the absolute risk reduction resulting from an intervention-was introduced as a yardstick to describe the harm as well as the benefit of therapeutic maneuvers. Analysis using NNT works well when comparing two or more interventions that have their impact over the same period of time in similar populations or patients. Under other conditions, however, analysis based on NNT can produce results that diverge widely from the impact that the interventions can be expected to have on risk of death. This can happen either for entire populations or for an individual when comparing NNTs for interventions which have their effects on different subsets of the population or when comparing interventions which have their effects over different periods of time. We demonstrate how this can occur by comparing the NNTs and effect of intervention on deaths in a population for automatic implantable cardioverter defibrillators (AICDs), heart transplantation, and cholesterol lowering through nutritional intervention with plant stanol ester.

Bias↗
PubMed1998

Educating young people about drugs: a systematic review.

AIMS: To assess the effectiveness of interventions directed at the prevention or reduction of use of illicit substances by young people or those directed at reducing harm caused by continuing use. DESIGN: A systematic review was conducted. Reports were identified through electronic and hand searching and contact with known workers in the area. Studies were included if they reported evaluations of interventions targeting illicit drug use and provided sufficient detail of the intervention and design of the evaluation to allow judgements to be made of their methodological soundness. Meta-analyses were conducted combining the data of the methodologically sound studies. PARTICIPANTS AND SETTINGS TARGETED BY INTERVENTIONS: Evaluations of interventions were included if their targeted audience included young people aged between 8 and 25 years. Identified evaluations were delivered in a range of settings including: schools and colleges; community settings; the family; medical/therapeutic settings; mass media. MEASUREMENTS: Data extracted from each report included details of design, content and theoretical orientation of intervention, setting of the intervention, target audience, methods, population size, subject refusal rates, rates of attrition, outcome measures, length of follow-up and findings, including statistical power. FINDINGS: The majority of studies identified were evaluations of interventions introduced in schools and targeting alcohol, tobacco and marijuana simultaneously. These studies were methodologically stronger than interventions targeting other drugs and implemented outside schools. Meta-analyses showed that the impact of evaluated interventions was small with dissipation of programme gains over time. Interventions targeting hard to reach groups have not been evaluated adequately. CONCLUSIONS: Effort needs to be directed towards the development of improved evaluative solutions to the problems posed by these groups. There is still insufficient evidence to assess the effectiveness of the range of approaches to drugs education; more methodologically sound evaluations are required. There is also a need to target interventions to reflect the specific needs and experiences of recipients.

Adolescent↗
PubMed1986

Determination of "heavy" organotin pollution of water and shellfish by a modified hydride atomic absorption procedure.

Tin speciation in aquatic environment is very complex. To the natural SnIV and methylated compounds, human activities add mainly butylated, octylated, phenylated or even methylated derivatives. The most environmentally significant, due to their high toxicity and direct introduction in water through biocidal use, are the trisubstituted ones. Several sophisticated speciation procedures have been proposed, they are not susceptible of common use. We propose a simple and fast procedure allowing routine global distinction of "heavy" tin species that are most susceptible of exerting harmful effects. This AA method use the differences in volatility of stannanes generated by reduction with NaBH4. SnIV and the methylated species have very close response coefficients whereas "heavy" compounds respond very slightly at room temperature and are eliminated in a -40 degrees C cold trap. "Heavy" tin determination in water is thus obtained by the difference between two hydride AA experiments, one performed on the untreated sample ("light tin") and the other on a UV mineralised subsample (total tin). (The mineralisation of organotins is realised by UV irradiation-2 hours--in a quartz container--yields 95-100%.) The analysis of shellfish tissue relies also on two experiments. Total tin is measured on a mineralised sample and "light tin" is obtained on a subsample "solubilised" with an Ultra Turrax homogeneizer in a diluted HCl solution.

Animals↗
PubMed1978

Treatment of obesity: cost-benefit assessment of behavioral therapy, placebo, and two anorectic drugs.

Mazindol, diethylpropion, and a placebo were compared with behavioral therapy for effectiveness in producing weight reduction in an outpatient obesity clinic. Each method was also compared in cost and harmful side effects. The patients were recruited from the middle and lower socioeconomic groups. Of the 120 patients beginning treatment, only 33 completed the entire 14-week study. There was no statistically significant difference in the weight loss among the treatment groups. The program of behavioral therapy was administered by a dietitian who as experienced in the techniques of behavior modification; the drug treatment groups were seen by physicians. We conclude that behavioral therapy may be the treatment of choice in an outpatient obese population since it requires little physician time, is less expensive, and avoids the side effects of anorectic drugs.

Appetite Depressants↗
PubMed2003

Can we see more outpatients without more doctors?

A reduction in the number of return patients attending general cardiology clinics, if achievable without harm, would improve access for newly referred patients. Outpatient clinic letters (525) sent to general practitioners over a three-month period were reviewed. Simultaneously, physicians' opinions were collected by questionnaire. A subset of 30 clinic patients who attended three local general practitioners were studied to identify how many were assessed in primary care, and how often, in a six-month period. The hospital records of these patients were reviewed to determine whether information about these visits to the general practitioner was documented in the hospital notes. From the outpatient clinics the discharge rates were only 26% and the reason for further clinic review was often not clear. The fact that many patients had no intervention or treatment change performed at the clinic (42%) indicates that patients are reviewed to assess symptom change rather than to receive further interventions. The use of fixed times for review appointment (six months or 1 year) suggests that the intervals are determined by habit rather than clinical indication. A high proportion of patients (28/30) were reviewed at least once in primary care by general practitioners between hospital clinic visits and 20/30 were seen three or more times. There was poor documentation of these consultations in the hospital case notes, and so hospital physicians may be unaware that symptoms are under regular review in primary care. This study suggests that a substantial proportion of current cardiology return outpatients do not require regular outpatient review. However, alternative management demands good communication and exchange of information between secondary and primary care, development of formal written discharge planning in outpatient letters and other forms of follow-up.

Aged↗
PubMed1998

Oral splints: the crutches for temporomandibular disorders and bruxism?

Despite the extensive use of oral splints in the treatment of temporomandibular disorders (TMD) and bruxism, their mechanisms of action remain controversial Various hypotheses have been proposed to explain their apparent efficacy (i.e., true therapeutic value), including the repositioning of condyle and/or the articular disc, reduction in the electromyographic activity of the masticatory muscles, modification of the patient's "harmful" oral behavior, and changes in the patient's occlusion. Following a comprehensive review of the literature, it is concluded that any of these theories is either poor or inconsistent, while the issue of true efficacy for oral splints remains unsettled. However, the results of a controlled clinical trial lend support to the effectiveness (i.e., the patient's appreciation of the positive changes which are perceived to have occurred during the trial) of the stabilizing splint in the control of myofascial pain. In light of the data supporting their effectiveness but not their efficacy, oral splints should be used as an adjunct for pain management rather than a definitive treatment. For sleep bruxism, it is prudent to limit their use as a habit management aid and to prevent/limit dental damage potentially induced by the disorder. Future research should study the natural history and etiologies of TMD and bruxism, so that specific treatments for these disorders can be developed.

Behavior Therapy↗