Alcohol use, drunkenness and tobacco smoking in rural western Kenya.

OBJECTIVES: To describe the prevalence of smoking and alcohol use and abuse in an impoverished rural region of western Kenya. METHODS: Picked from a population-based longitudinal database of demographic and health census data, 72 292 adults (≥18 years) were asked to self-report their recent (within the past 30 days) and lifetime use of tobacco and alcohol and frequency of recent 'drunkenness'. RESULTS: Overall prevalence of ever smoking was 11.2% (11.0-11.5) and of ever drinking, 20.7% (20.4-21.0). The prevalence of current smoking was 6.3% (6.1-6.5); 5.7% (5.5-5.9) smoked daily. 7.3% (7.1-7.5) reported drinking alcohol within the past 30 days. Of these, 60.3% (58.9-61.6) reported being drunk on half or more of all drinking occasions. The percentage of current smokers rose with the number of drinking days in a month (P < 0.0001). Tobacco and alcohol use increased with decreasing socio-economic status and amongst women in the oldest age group (P < 0.0001). CONCLUSIONS: Tobacco and alcohol use are prevalent in this rural region of Kenya. Abuse of alcohol is common and likely influenced by the availability of cheap, home-manufactured alcohol. Appropriate evidence-based policies to reduce alcohol and tobacco use should be widely implemented and complemented by public health efforts to increase awareness of their harmful effects.

Access to HIV community services by vulnerable populations: evidence from an enhanced HIV/AIDS surveillance system.

HIV disproportionately affects vulnerable populations such as black and minority ethnic groups, men who have sex with men (MSM) and migrants, in many countries including those in the UK. Community organisations in the UK are charitable non-governmental organisations with a proportion of the workforce who volunteer, and provide invaluable additional support for people living with HIV (PLWHIV). Information on their contribution to HIV care in vulnerable groups is relatively sparse. Data generated from an enhanced HIV surveillance system in North West England, UK, was utilised for this study. We aimed to determine the characteristics of individuals who chose to access community services in addition to clinical services (1375 out of 4195 records of PLWHIV in clinical services). Demographic information, risk factors including residency status, uniquely gathered in this region, and deprivation scores were examined. Multivariate logistic regression modelling was conducted to predict the relative effect of patient characteristics on attendance at community services. Attendance at community services was highest in those living in the most, compared with least, deprived areas (p<0.001), and was most evident in MSM and heterosexuals. Compared to white UK nationals attendance was significantly higher in non-UK nationals of uncertain residency status (Adjusted odds ratio [AOR] = 21.91, 95% confidence interval [CI] 10.48-45.83; p<0.001), refugees (AOR = 5.75, 95% CI 3.3-10.03; p<0.001), migrant workers (AOR = 5.48, 95% CI 2.22-13.51; p<0.001) and temporary visitors (AOR = 3.44, 95% CI 1.68-7.05; p<0.001). Community services, initially established predominantly to support MSM, have responded to the changing demography of HIV and reach the most vulnerable members of society. Consequent to their support of migrant populations, community services are vital for the management of HIV in black and minority groups. Paradoxically, this coincides with increasing funding pressures on these services.

Acute presentations of HIV are still missed in low prevalence areas.

OBJECTIVES: To evaluate missed opportunities and delays in the diagnosis of HIV in a low prevalence setting over a 24 year period. METHODS: Patients with acute presentations of HIV were included in a retrospective note based review. Data were compared from acute presentations in 1985-2001 (88/241 new patients) with 2005-2007 (99/136 new patients). The number of recorded clinical and laboratory clues to infection and subsequent time delays to diagnosis of HIV were evaluated. RESULTS: The findings reflect the shifting demographics of HIV in the UK over the past two decades, exemplified by an eightfold increase in tuberculosis at presentation. Despite recording clinical stigmata of HIV (clues) in the notes, the number of missed clues increased, and many clinicians failed to request HIV testing. The median delay between presentation and diagnosis reduced from 5 to 1 day (p<0.001), and mortality dropped from 14% to 4% among patients presenting with acute symptoms. However, there was still a delay of more than 30 days before diagnosis for almost one in five patients. CONCLUSIONS: Despite some improvement and better awareness, there are still significant delays before hospital doctors consider the diagnosis of HIV for patients in low prevalence areas, even among some patient groups with high risk. Hospitals should consider moving to opt-out routine HIV testing of all medical admissions.

Progression of stunting and its predictors among school-aged children in western Kenya.

OBJECTIVE: The objectives of this study were (1) to assess whether a cohort of school-aged children experiences progression of stunting over a 2-y-period of observation and (2) to identify baseline nutritional and body composition risk factors for the progression of stunting. METHODS: As part of a large-scale, randomized controlled trial assessing the impact of insecticide-treated bednets (ITNs) on nutritional status, we longitudinally followed a cohort of school-aged children over a 2-y-period in western Kenya. Anthropometric measurements were made at four time points from which Z-scores for height-for-age (HAZ), weight-for-age (WAZ), and body mass index (BMIZ) were calculated. Two measures of body composition, upper arm fat area and upper arm muscle area, were derived from mid-upper arm circumference (MUAC) and triceps skinfold thickness. RESULTS: Subjects experienced a mean change in HAZ from baseline to 9 months of -0.16 [-0.19, -0.13], from baseline to 16 months of -0.18 [-0.22, -0.15], and from baseline to 24 months of -0.36 [-0.41, -0.31]. Thus, the average individual's change in HAZ at the three follow-up time points is significantly less than zero, meaning that, on average, the cohort is deviating further from NCHS reference medians over time. The baseline nutritional measure that explained the greatest amount of variance in the progression of stunting was the upper arm muscle area Z-score (F=8.1; P=0.005). CONCLUSIONS: This longitudinal study provides further evidence from a distinct ecological setting regarding the progression of undernutrition during middle childhood in the developing world. It suggests that school-aged children in the developing world do not experience catch-up growth or remain stable. Rather, they continue to deviate from NCHS standards, accruing greater height deficits with age. In addition, absolute lean body mass explained the most variability in the progression of stunting, which supports cross-sectional findings from other studies.

Recognition of pallor associated with severe anaemia by primary caregivers in western Kenya.

OBJECTIVES: To explore which pallor signs and symptoms of severe anaemia could be recognized by primary caregivers following minimal instructions. METHODS: Data from three community-based cross-sectional surveys were used. Test characteristics to predict haemoglobin (Hb) concentrations < 5 and < 7 g/dl were compared for different combinations of pallor signs (eyelid, tongue, palmar and nailbed) and symptoms. RESULTS: Pallor signs and haemoglobin levels were available for 3782 children under 5 years of age from 2609 households. Comparisons of the sensitivity and specificity at a range of haemoglobin cut-offs showed that Hb < 5 g/dl was associated with the greatest combined sensitivity and specificity for pallor at any anatomical site (sensitivity = 75.6%, specificity = 63.0%, Youden index = 38.6). Higher or lower haemoglobin cut-offs resulted in more children being misclassified. Similar results were obtained for all individual pallor sites. Combining a history of soil eating with pallor at any site improved the sensitivity (87.8%) to detect Hb < 5 g/dl with a smaller reduction in specificity (53.3%; Youden index 41.1). Other combinations including respiratory signs or poor feeding resulted in lower accuracy. CONCLUSION: Primary caregivers can recognize severe anaemia (Hb < 5 g/dl) in their children, but only with moderate accuracy. Soil eating should be considered as an additional indicator of severe anaemia. The effect of training caretakers to improve recognition of severe anaemia and care-seeking behaviour at the household level should be assessed in prospective community-based studies.

All-cause mortality among young children in western Kenya. VI: the Asembo Bay Cohort Project.

Although all-cause mortality has been used as an indicator of the health status of childhood populations, such data are sparse for most rural areas of sub-Saharan Africa, particularly community-based estimates of infant mortality rates. The longitudinal follow-up of more than 1,500 children enrolled at birth into the Asembo Bay Cohort Project (ABCP) in western Kenya between 1992 and 1996 has provided a fixed birth cohort for estimating all-cause mortality over the first 5 yr of life. We surveyed mothers and guardians of cohort children in early 1999 to determine survival status. A total of 1,260 households were surveyed to determine the survival status of 1,556 live births (99.2% of original cohort, n = 1,570). Most mothers (66%) still resided but 27.5% had migrated, and 5.5% had died. In early 1999, the overall cumulative incidence of all-cause mortality for the entire 1992-1996 birth cohort was 26.5% (95% confidence interval, 24.1-28.9%). Neonatal and infant mortality were 32 and 176 per 1,000 live births, respectively. These community-based estimates of mortality in the ABCP area are substantially higher than for Kenya overall (nationally, infant mortality is 75 per 1,000 live births). The results provide a baseline description of all-cause mortality among children in an area with intense Plasmodium falciparum transmission and will be useful in future efforts to monitor changes in death rates attributable to control programs for specific diseases (e.g., malaria and HIV/AIDS) in Africa.

New recommendations from the 1999 American College of Cardiology/American Heart Association acute myocardial infarction guidelines.

OBJECTIVE: To review literature relating to significant changes in drug therapy recommendations in the 1999 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for treating patients with acute myocardial infarction (AMI). DATA SOURCES: 1999 ACC/AHA AMI guidelines, English-language clinical trials, reviews, and editorials researching the role of drug therapy and primary angioplasty for AMI that were referenced in the guidelines were included. Additional data published in 2000 or unpublished were also included if relevant to interpretation of the guidelines. STUDY SELECTION: The articles selected influence AMI treatment recommendations. DATA SYNTHESIS: Many clinicians and health systems use the ACC/AHA AMI guidelines to develop treatment plans for AMI patients. This review highlights important changes in AMI drug therapy recommendations by reviewing the results of recent clinical trials. Insights into evolving drug therapy strategies that may impact future guideline development are also described. CONCLUSIONS: Several changes in drug therapy recommendations were included in the 1999 AMI ACC/AHA guidelines. There is emphasis on administering fibrin-specific thrombolytics secondary to enhanced efficacy. Selection between fibrin-specific agents is unclear at this time. Low response rates to thrombolytics have been noted in the elderly, women, patients with heart failure, and those showing left bundle-branch block on the electrocardiogram. These patient groups should be targeted for improved utilization programs. The use of glycoprotein (GP) IIb/IIIa receptor inhibitors in non-ST-segment elevation MI was emphasized. Small trials combining reduced doses of thrombolytics with GP IIb/IIIa receptor inhibitors have shown promise by increasing reperfusion rates without increasing bleeding risk, but firm conclusions cannot be made until the results of larger trials are known. Primary percutaneous coronary intervention (PCI) trials suggest lower mortality rates for primary PCI when compared with thrombolysis alone. However, primary PCI, including coronary angioplasty, is only available at approximately 13% of US hospitals, making thrombolysis the preferred strategy for most patients. Clopidogrel has supplanted ticlopidine as the recommended antiplatelet agent for patients with aspirin allergy or intolerance following reports of a better safety profile. The recommended dose of unfractionated heparin is lower than previously recommended, necessitating a separate nomogram for patients with acute coronary syndromes. Routine use of warfarin, either alone or in combination with aspirin, is not supported by clinical trials; however, warfarin remains a choice for antithrombotic therapy in patients intolerant to aspirin. Beta-adrenergic receptor blockers continue to be recommended, and emphasis is placed on improving rates of early administration (during hospitalization), even in patients with moderate left ventricular dysfunction. New recommendations for drug treatment of post-AMI patients with low high-density lipoprotein cholesterol and/or elevated triglycerides are included, with either niacin or gemfibrozil recommended as an option. Supplementary antioxidants are not recommended for either primary or secondary prevention of AMI, with new data demonstrating lack of efficacy vitamin E in primary prevention. Estrogen replacement therapy or hormonal replacement therapy should not be initiated solely for prevention of cardiovascular disease, but can be continued in cardiovascular patients already taking long-term therapy for other reasons. Bupropion has been added as a new treatment option for smoking cessation. As drug therapy continues to evolve in treating AMI, more frequent updates of therapy guidelines will be necessary.

Warfarin for stroke prevention in octogenarians with atrial fibrillation.

The authors examined warfarin use in elderly patients with atrial fibrillation. Medical records were abstracted from a random sample of Medicare beneficiaries with atrial fibrillation who were discharged from Kansas hospitals. Data were analyzed for warfarin and aspirin use and risk factors for stroke or bleeding in patients 65-79 years of age or 80 years and older. Stroke risk factors other than age and atrial fibrillation were seen in 98% of 142 patients less than 80 years of age and 100% of 141 octogenarians. Warfarin use was similar in the younger and older age groups (50% vs. 45%, respectively; p = ns) and was not associated with the number of stroke or bleeding risk factors. Compared to patients less than 80 years of age, octogenarians were less likely to receive aspirin (38% vs. 27%, respectively; p < 0.05). Anticoagulation rates for high-risk patients with atrial fibrillation were low and poorly explained by stroke or bleeding risks.

Aggressive diuresis for severe heart failure in the elderly.

STUDY OBJECTIVE: To determine the efficacy, safety, and economic benefit of continuous IV infusion of furosemide as a treatment modality for elderly patients with class IV heart failure. DESIGN: Prospective trial of consecutively admitted elderly patients > 65 years old with class IV heart failure. SETTING: A single cardiovascular service in a university medical center. PATIENTS: Seventeen male and female patients > 65 years old consecutively admitted to a cardiovascular service. RESULTS: High-dose, continuous IV infusion of furosemide was successful in providing a 9- to 20-L diuresis in an average of 3.5 days without causing clinical complications or aberrations in blood chemistry. The length of stay was 2.3 days shorter than a contemporary group of class III and class IV elderly patients with heart failure managed on other medical services. The Medicare reimbursement for heart failure was $6,047. Patients receiving IV bolus diuretic therapy incurred billing charges of $10,193, or a loss of $4,146 per patient to the hospital. Patients receiving diuretic infusion therapy incurred billing charges of $4,944. This was a difference of $5,249 per patient treated by continuous IV infusion compared to bolus therapy and a profit per Medicare patient of $1,103. Therefore, a $4,146 billing loss was converted to $1,103 profit. CONCLUSION: IV furosemide infusion therapy for class IV heart failure in the elderly is a safe, effective, and economic mode of therapy.

Optimizing beta-blocker use after myocardial infarction.

Although beta-adrenergic blockers can significantly reduce mortality after a myocardial infarction, these agents are prescribed to only a minority of patients. Underutilization of beta blockers may be attributed, in part, to fear of adverse effects, especially in the elderly and in patients with concomitant disorders such as diabetes or heart failure. However, studies have shown that such patients are precisely the ones who derive the greatest benefit from beta blockade. Advancing age or the presence of potentially complicating disease states is usually not a justification for withholding beta-blocker therapy. With use of cardioselective agents and through careful dosing and monitoring, the benefits of beta blockers after myocardial infarction far outweigh the potential risks in most patients.

Maintenance and sustained use of insecticide-treated bednets and curtains three years after a controlled trial in western Kenya.

In large experimental trials throughout Africa, insecticide-treated bednets and curtains have reduced child mortality in malaria-endemic communities by 15%-30%. While few questions remain about the efficacy of this intervention, operational issues around how to implement and sustain insecticide-treated materials (ITM) projects need attention. We revisited the site of a small-scale ITM intervention trial, 3 years after the project ended, to assess how local attitudes and practices had changed. Qualitative and quantitative methods, including 16 focus group discussions and a household survey (n = 60), were employed to assess use, maintenance, retreatment and perceptions of ITM and the insecticide in former study communities. Families that had been issued bednets were more likely to have kept and maintained them and valued bednets more highly than those who had been issued curtains. While most households retained their original bednets, none had treated them with insecticide since the intervention trial was completed 3 years earlier. Most of those who had been issued bednets repaired them, but none acquired new or replacement nets. In contrast, households that had been issued insecticide-treated curtains often removed them. Three (15%) of the households issued curtains had purchased one or more bednets since the study ended. In households where bednets had been issued, children 10 years of age and younger were a third as likely to sleep under a net as were adults (relative risk (RR) = 0. 32; 95% confidence interval (95%CI) = 0.19, 0.53). Understanding how and why optimal ITM use declined following this small-scale intervention trial can suggest measures that may improve the sustainability of current and future ITM efforts.

Transmission of epidemic Vibrio cholerae O1 in rural western Kenya associated with drinking water from Lake Victoria: an environmental reservoir for cholera?

Sub-Saharan Africa has the highest reported cholera incidence and mortality rates in the world. In 1997, a cholera epidemic occurred in western Kenya. Between June 1997 and March 1998, 14,275 cholera admissions to hospitals in Nyanza Province in western Kenya were reported. There were 547 deaths (case fatality rate = 4%). Of 31 Vibrio cholerae O1 isolates tested, all but one were sensitive to tetracycline. We performed a case-control study among 61 cholera patients and age-, sex-, and clinic-matched controls. Multivariate analysis showed that risk factors for cholera were drinking water from Lake Victoria or from a stream, sharing food with a person with watery diarrhea, and attending funeral feasts. Compared with other diarrheal pathogens, cholera was more common among persons living in a village bordering Lake Victoria. Cholera has become an important public health concern in western Kenya, and may become an endemic pathogen in the region.

Ibutilide: an antiarrhythmic agent for the treatment of atrial fibrillation or flutter.

OBJECTIVE: To discuss the clinical pharmacology of the antiarrhythmic drug ibutilide in patients with atrial fibrillation (AF) or atrial flutter (AFl). DATA SOURCES: A MEDLINE search (January 1983-December 1997) was used to identify pertinent English-language articles on ibutilide. Key search terms included ibutilide, AF, AFl, cardioversion, and sinus rhythm. The MEDLINE search was supplemented by references included in the bibliographies of comprehensive review articles and studies. STUDY SELECTION: Studies and review articles describing the chemistry, pharmacology, and pharmacokinetics of ibutilide were selected. All abstracts and published clinical trials evaluating the efficacy and safety were reviewed. DATA EXTRACTION: Pertinent information on the pharmacology and mechanism of action of ibutilide was summarized. Data were extracted from the clinical trials describing trial design, patient population, interventions, methods of evaluation, outcomes, and statistical significance. DATA SYNTHESIS: Ibutilide is a Vaughan-Williams class III antiarrhythmic agent approved for intravenous use for the rapid termination of recent-onset AF or AFl. The drug is extensively metabolized by the liver, has a volume of distribution of 11-15 L/kg, is 40% protein bound, and has an elimination half-life of 6 hours (range 2-12). Data from two placebo-controlled trials demonstrated the efficacy of ibutilide for converting AF or AFl of short duration (< or = 90 d) to normal sinus rhythm. A third placebo-controlled trial demonstrated efficacy in patients who developed AF or AFl following cardiac surgery. Comparative trials with procainamide and sotalol have shown at least similar and perhaps superior efficacy with ibutilide. There are no comparative trials with other antiarrhythmic drugs or with direct current cardioversion (DCC). In 586 clinical trial patients receiving ibutilide, the most significant adverse effect was the development of torsade de pointes in 25 patients (4.3%) including 10 cases (1.7%) in which the rhythm was sustained. All cases of torsade de pointes were terminated electrically and none resulted in death or severe morbidity. No prospective cost-effectiveness studies are available; however, results from two decision models suggest that ibutilide may have advantages over other drugs and first-line electrical cardioversion. CONCLUSIONS: Ibutilide appears to be an effective alternative method for rapid conversion of recent-onset AF or AFl. The drug may be particularly useful in patients who have undergone recent cardiac surgery or those who are not ideal candidates for DCC. Although studies suggest that the risk of proarrhythmia and in particular torsade de pointes is relatively low, caution is advised until additional experience is gained in clinical practice.

Guiding parents' use of the Internet for newborn education.

Shorter hospital stays have had an impact on the traditional role of mother-baby nurses in providing education on parenting to their patients. In recent years, there has been a proliferation of consumer health information available on the Internet related to parenting. Publication of information on the Internet, however, is not monitored and reviewed in the way that traditional print sources are; therefore, there is no guarantee that the information is current, unbiased, or accurate. As more consumers search the World Wide Web for parenting information, nurses need to learn more about this technology so they can assist parents in identifying how to locate information they can trust.

Guidelines for stroke prevention in patients with atrial fibrillation.

Atrial fibrillation (AF) is a major independent risk factor for stroke. AF is most commonly associated with nonvalvular cardiovascular disease and is especially frequent among the elderly. The annual risk for stroke in patients with AF is approximately 5% with a wide range depending on the presence of additional risk factors. For patients who cannot successfully be converted and maintained in normal sinus rhythm (NSR), antithrombotic therapy is an effective method for preventing stroke. The 2 drugs which are indicated for stroke prophylaxis in patients with AF are warfarin and aspirin. For primary prevention, warfarin reduces the risk of stroke approximately 68%. Aspirin therapy is less effective, resulting in a 20 to 30% risk reduction. Combination therapy with aspirin and low intensity warfarin adjusted to an International Normalised Ratio (INR) of 1.2 to 1.5 has not been shown to be superior to standard intensity warfarin with a target INR of 2.0 to 3.0. In patients with AF and a prior history of stroke or transient ischaemic attack (TIA), the absolute risk reduction with warfarin is even greater because of the high risk of stroke in this population. In contrast, aspirin has not been shown to significantly reduce the risk of stroke in patients with AF when used for secondary prevention. When appropriately managed, warfarin is associated with a low risk of major bleeding. In controlled trials of highly selected patients, the annual rate of intracranial haemorrhage (ICH) with warfarin was approximately 0.3%. Studies have shown that specialty anticoagulation clinics can achieve similar low rates of major bleeding. However, these results cannot be extrapolated to the general population. Factors which have been identified as predictors of bleeding include advanced age, number of medications and most importantly, the intensity of anticoagulation. INR values above 4.0 have been associated with an increased risk of major bleeding while values below 2.0 have been associated with thrombosis. Slow careful dosage titration, regular laboratory monitoring and patient education can substantially reduce the risk of complications. In patients with AF, antithrombotic therapy has been shown to be cost effective. For high risk patients, warfarin is the most cost-effective therapy, provided the risks for bleeding are minimised. In contrast, aspirin is the most cost-effective agent for low risk patients. Current practice guidelines for stroke prophylaxis recommend warfarin (target INR 2.5: range 2.0 to 3.0) for AF patients at high risk for stroke including those over 75 years of age or younger patients with additional risk factors. Aspirin should be reserved for low risk patients or those unable to take warfarin. Although these recommendations are strongly supported by the clinical trial evidence, studies show that many patients are not receiving appropriate antithrombotic therapy. In particular, warfarin is underutilised in high risk elderly patients. Additional studies are needed to identify barriers that prevent implementation of the clinical trial findings into clinical practice.

Epidemiological and control issues related to malaria in pregnancy.

Pregnant women infected with malarial parasites have an increased risk of maternal anaemia, abortion, stillbirth, prematurity, intra-uterine growth retardation, and infants of low birthweight. A 'state-of-the-art' symposium on malaria in pregnancy was convened in Kisumu, Kenya, in November 1997, to discuss the biological and clinical impact of malaria in pregnancy, and to identify antimalarial drugs and control strategies to protect pregnant women. The deleterious effects of malarial infection during pregnancy were shown to be associated both with Plasmodium falciparum and P. vivax infections, and to occur under a wide range of malaria transmission pressures. Control interventions, thus, need to be targeted at pregnant women in all endemic areas. Alternative antimalarial drugs to chloroquine have been tested and shown to be effective (and safe) against malaria in pregnancy. Delivery of cost-effective control interventions has been explored; investments are needed to facilitate the scaling-up of successful approaches to national-programme level. Several important research questions related to malaria in pregnancy were highlighted at the Kisumu meeting. Increased international and local commitment, to resource effective malaria control in pregnancy adequately, is a public-health priority.

Safety of mefloquine and other antimalarial agents in the first trimester of pregnancy.

BACKGROUND: Safe and effective antimalarials are required to protect pregnant women from the harmful effects of malaria. METHODS: Data were collected from two separate prospective cohorts to ascertain the safety of chloroquine-proguanil, sulfadoxine-pyrimethamine (SP), and mefloquine taken in the first trimester of pregnancy. RESULTS: In a traveler cohort of 236 pregnant women, spontaneous abortions were reported in 7.6% of 99 women taking chloroquine-proquanil, 0% of 19 taking sulfadoxine-pyrimethamine, and 9.1% of 118 women taking mefloquine. Anomalies were identified in 1.7%, 0% and 0% of the same cohort, respectively. Differences in rates of adverse outcomes between the three groups were not statistically significant. In a pharmaceutical database of 331 and 153 women exposed to mefloquine and SP, respectively, the overall rate of abnormal outcomes (spontaneous abortions plus fetal anomalies) was not significantly different (p=.29). Spontaneous abortions were significantly higher with mefloquine than SP (9.1% and 2.6%, respectively; p=.01), but the higher rate was comparable to background rates (7%-11%). Fetal anomalies in the mefloquine group (4.8%) were lower than the SP group (7.8%), but this was statistically not significant (p=.19), and was comparable with the background rate of 4.6% (p=.84). However, mefloquine exposure resulted in a significantly higher rate of therapeutically induced abortions, undertaken for perceived risk to the fetus, compared with SP (p<.0001). CONCLUSION: From the clinical data available, there is no indication that the risk of taking mefloquine in the first trimester of pregnancy is greater than that from any of the other antimalarials studied and the risk is considerably lower than that associated with falciparum malaria.

Primary stroke prevention in nonvalvular atrial fibrillation: implementing the clinical trial findings.

OBJECTIVE: To review the clinical trials evaluating warfarin for primary stroke prophylaxis in nonvalvular atrial fibrillation (NVAF), to discuss the relative benefits and risks of warfarin versus aspirin therapy, and to review the clinical practice guidelines and identify potential barriers to their implementation in clinical practice. DATA SOURCES: A MEDLINE literature search was performed to identify clinical trials of antithrombotic therapy for NVAF, clinical practice guidelines, studies evaluating physician practices and attitudes, cost-effectiveness studies, and pertinent review articles. Key search terms included atrial fibrillation, stroke, antithrombotic, warfarin, aspirin, and cost-effectiveness. DATA EXTRACTION: Prospective, randomized clinical trials were selected for analysis. Clinical practice guidelines from recognized panels of experts were reviewed. Comprehensive review articles were selected. DATA SYNTHESIS: NVAF is a common arrhythmia that is associated with a substantial risk for stroke. Seven prospective, randomized, clinical trials have conclusively demonstrated the efficacy of warfarin for stroke prevention. The greatest benefits are achieved in older patients and those with comorbidities that increase their risk for stroke. The potential benefits of preventing a devastating stroke, however, must be weighed against the potential for bleeding complications. Warfarin has been shown to be cost-effective in high-risk patients, provided the rate of complications is minimized. Nonetheless, many physicians remain hesitant to implement warfarin therapy in older, high-risk patients. The clinical data on aspirin are less consistent than those observed with warfarin. Aspirin appears to be most effective in younger individuals or those considered to be at low risk for stroke. CONCLUSIONS: In patients with NVAF, the personal, social, and economic consequences of stroke are often devastating. Clinical trials have provided definitive proof that the risks of stroke can be significantly reduced through the use of appropriate antithrombotic therapy. Despite this evidence and the recommendations of a number of clinical practice guidelines, variations in care exist that continue to place patients at risk. Additional outcomes research is needed to evaluate the impact of the clinical trial findings and practice guidelines on clinical practice and to develop methods for overcoming barriers to implementation.

Difficulty in removal of certain intramedullary nails.

Intramedullary nailing is the most common treatment for displaced diaphyseal fractures of the femur and tibia. Gerhard Küntscher introduced the technique of intramedullary nailing to clinical practice in the 1940s, and this method has been the focus of many authors with regard to indications, technique, complications, and outcome. The five cases presented here represent a complication not often reported in recent years: the difficulty in removing an intact intramedullary nail. Inspection of the interlocking nails in four of the cases presented reveals a specific design characteristic: the cross sectional design of the nail prevents the distal, unslotted end of the nail from being extracted from the medullary cavity. This problem is preventable by a change in nail design or the development of absorbable implants.

Severe musculoskeletal symptoms during continuous infusion of bumetanide.

BACKGROUND: The continuous infusion of the loop diuretic, bumetanide, has been shown to be effective in the treatment of severe refractory edema. Musculoskeletal symptoms have been reported with bumetanide following both oral and intermittent i.v. bolus therapy. It has been suggested that these adverse effects do not occur with continuous infusion. We describe, however, a series of patients with heart failure who developed severe disabling musculoskeletal symptoms during the continuous infusion of humetanide. OBJECTIVE: To evaluate the characteristics of bumetanide-induced musculoskeletal symptoms during continuous i.v. infusion in patients with severe heart failure. METHODS: Heart failure patients receiving continuous infusions of bumetanide were monitored for the development of musculoskeletal symptoms. For patients who experienced the adverse reaction, data were collected on demographics, medical diagnoses, concurrent medications, the diuretic regimen, symptoms, time course of the reaction, laboratory findings, alternative therapy, and outcomes. RESULTS: Of 34 patients who received continuous infusions of bumetanide, eight patients experienced a total of 11 episodes of severe musculoskeletal symptoms. All patients had severe congestive heart failure and refractory edema. The reaction was most severe at infusion rates of approximately 2 mg/h and was not associated with any specific laboratory abnormality. The symptoms resolved completely after discontinuing the bumetanide therapy. In two of the patients, the adverse reaction was precipitated again during rechallenge with the bumetanide infusion. Patients who were given an equivalent or higher dose of a continuous furosemide infusion, diuresed without experiencing musculoskeletal symptoms. CONCLUSIONS: The continuous i.v. infusion of the loop diuretic, bumetanide, may result in severe, disabling musculoskeletal symptoms. The reaction appears to be dose related, without specific risk factors, and is reversible on discontinuation of the infusion. Patients who experience this reaction may be successfully diuresed with equivalent doses of a furosemide infusion.