Apixaban versus no anticoagulation for the prevention of venous thromboembolism in children with newly diagnosed acute lymphoblastic leukaemia or lymphoma (PREVAPIX-ALL): a phase 3, open-label, randomised, controlled trial.

BACKGROUND: Paediatric patients with acute lymphoblastic leukaemia or lymphoma are at increased risk of venous thromboembolism resulting in increased mortality and morbidity. We hypothesised that apixaban, a direct oral anticoagulant, would safely reduce venous thromboembolism in this patient population. METHODS: PREVAPIX-ALL was a phase 3, open-label, randomised, controlled trial conducted in 74 paediatric hospitals in 9 countries. Participants aged 1 year or older to younger than 18 years with newly diagnosed acute lymphoblastic leukaemia (pre-B cell or T cell) or lymphoblastic lymphoma (B cell or T cell immunophenotype) and a central venous line in place throughout induction were randomly assigned 1:1 to standard of care (SOC, ie, no systemic anticoagulation) or weight-adjusted twice-daily apixaban during induction. Randomisation was performed centrally and stratified by age (those <10 years or those ≥10 years). Participants weighing 35 kg or less were administered 2·5 mg twice daily of apixaban as a 2·5 mg tablet, 0·5 mg tablets, or 0·4 mg/mL oral solution, while those weighing more than 35 kg were administered weight-adjusted prophylactic doses using 0·5 mg tablets or the 0·4 mg/mL oral solution twice daily. Primary outcomes were assessed by a blinded central adjudication committee. The primary efficacy outcome for the intention to treat population was the composite of symptomatic or clinically unsuspected venous thromboembolism, the primary safety outcome was major bleeding, and secondary safety outcomes included clinically relevant non-major (CRNM) bleeding. Patients were screened for venous thromboembolism by ultrasound and echocardiogram at the end of induction. The trial was registered with ClinicalTrials.gov (NCT02369653) and is now complete. FINDINGS: Between Oct 22, 2015, and June 4, 2021, 512 participants were randomly assigned and included in analyses (222 [43%] female and 290 [57%] male; 388 [76%] White, 52 [10%] Asian, 24 [5%] Black or African American, and 48 [9%] other races; and 122 [24%] Hispanic or Latino ethnicity). During a median follow-up period of 27 days (IQR 26-28), 31 (12%) of 256 patients on apixaban had a composite venous thromboembolism compared with 45 (18%) of 256 participants receiving SOC (relative risk [RR] 0·69, 95% CI 0·45-1·05; p=0·080). Two major bleeding events occurred in each group (RR 1·0, 95% CI 0·14-7·01; p=1·0). A higher incidence of CRNM bleeding, primarily grade 1 or 2 epistaxis, occurred in the apixaban group (11 [4%] of 256 participants) compared with the SOC group (3 [1%] of 256; RR 3·67, 95% CI 1·04-12·97, p=0·030). The most frequent grade 3-5 adverse events in both groups were thrombocytopenia (n=28 for the apixaban group and n=20 for the SOC group) or platelet count decreased (n=49 and n=45), anaemia (n=77 and n=74), febrile neutropenia (n=27 and n=20), and neutropenia (n=16 and n=17) or neutrophil count decreased (n=22 and n=25). Five deaths occurred, which were due to infection (n=3 in the SOC group), cardiac arrest (n=1 in apixaban group), and haemorrhagic cerebral sinus vein thrombosis (n=1 in the SOC group). There was one apixaban-related death (coagulopathy and haemorrhage after cardiac arrest of unknown cause). INTERPRETATION: PREVAPIX-ALL is, to our knowledge, the first trial assessing primary thromboprophylaxis using a direct oral anticoagulant in paediatric patients with acute lymphoblastic leukaemia or lymphoma. No statistically significant treatment benefit was identified in participants receiving apixaban. Major and CRNM bleeding were infrequent overall, but a higher incidence of CRNM bleeding (primarily epistaxis in younger children) occurred in participants receiving apixaban. For patients deemed to be at particularly high risk of thrombosis, PREVAPIX-ALL provides encouraging safety data for the use of apixaban in clinical settings in which the potential benefits are thought to outweigh the risk of bleeding. FUNDING: Bristol Myers Squibb-Pfizer Alliance.

Apixaban for Prevention of Thromboembolism in Pediatric Heart Disease.

BACKGROUND: Children with heart disease frequently require anticoagulation for thromboprophylaxis. Current standard of care (SOC), vitamin K antagonists or low-molecular-weight heparin, has significant disadvantages. OBJECTIVES: The authors sought to describe safety, pharmacokinetics (PK), pharmacodynamics, and efficacy of apixaban, an oral, direct factor Xa inhibitor, for prevention of thromboembolism in children with congenital or acquired heart disease. METHODS: Phase 2, open-label trial in children (ages, 28 days to <18 years) with heart disease requiring thromboprophylaxis. Randomization 2:1 apixaban or SOC for 1 year with intention-to-treat analysis. PRIMARY ENDPOINT: a composite of adjudicated major or clinically relevant nonmajor bleeding. Secondary endpoints: PK, pharmacodynamics, quality of life, and exploration of efficacy. RESULTS: From 2017 to 2021, 192 participants were randomized, 129 apixaban and 63 SOC. Diagnoses included single ventricle (74%), Kawasaki disease (14%), and other heart disease (12%). One apixaban participant (0.8%) and 3 with SOC (4.8%) had major or clinically relevant nonmajor bleeding (% difference -4.0 [95% CI: -12.8 to 0.8]). Apixaban incidence rate for all bleeding events was nearly twice the rate of SOC (100.0 vs 58.2 per 100 person-years), driven by 12 participants with ≥4 minor bleeding events. No thromboembolic events or deaths occurred in either arm. Apixaban pediatric PK steady-state exposures were consistent with adult levels. CONCLUSIONS: In this pediatric multinational, randomized trial, bleeding and thromboembolism were infrequent on apixaban and SOC. Apixaban PK data correlated well with adult trials that demonstrated efficacy. These results support the use of apixaban as an alternative to SOC for thromboprophylaxis in pediatric heart disease. (A Study of the Safety and Pharmacokinetics of Apixaban Versus Vitamin K Antagonist [VKA] or Low Molecular Weight Heparin [LMWH] in Pediatric Subjects With Congenital or Acquired Heart Disease Requiring Anticoagulation; NCT02981472).

ReducinG stroke by screening for UndiAgnosed atRial fibrillation in elderly inDividuals (GUARD-AF): Rationale and design of the GUARD-AF randomized trial of screening for atrial fibrillation with a 14-day patch-based continuous ECG monitor.

BACKGROUND: Screening for atrial fibrillation (AF) is attractive because AF independently raises the risk of ischemic stroke, this risk is largely reversible by long-term oral anticoagulant therapy (OAC), and many patients with AF remain undiagnosed and untreated. Recent trials of one-time brief screening for AF have not produced a significant increase in the proportion of patients diagnosed with AF. Trials of longer-term screening have demonstrated an increase in AF diagnoses, primarily paroxysmal AF. To date, however, no trials have demonstrated that screening for AF results in lower rates of stroke. Clinical practice guidelines conflict in their level of support for screening for AF. METHODS: The GUARD-AF individually randomized trial is designed to test whether screening for AF in individuals age 70 years or greater using a 2-week single-lead electrocardiographic patch monitor can identify patients with undiagnosed AF and lead to treatment with OAC, resulting in a reduced rate of stroke in the screened population. The trial's efficacy end point is hospitalization for stroke (either ischemic or hemorrhagic) and the trial's safety end point is hospitalization for a bleeding event. End points will be ascertained via Medicare claims or electronic health records at 2.5 years after study start. Enrollment is based in primary care practices and the OAC decision for screen-detected cases is left to the patient and their physician. The initial planned target sample size was 52,000, with 26,000 allocated to either screening or to usual care. RESULTS: Trial enrollment was severely hampered by the novel coronavirus disease 2019 (COVID-19) pandemic and stopped at a total enrollment of 11,931 participants. Of 5,965 randomized to the screening arm, 5,713 patients (96%) returned monitors with analyzable results. Incidence of screen-detected and clinically detected AF and associated stroke and bleeding outcomes will be ascertained. CONCLUSIONS: GUARD-AF is the largest AF screening randomized trial using a longer-term patch-based continuous electrocardiographic monitor. The results will contribute important information on the yield of patch-based AF screening, the "burden" of AF detected (percent time in AF, longest episode), and physicians' OAC decisions as a function of AF burden. GUARD-AF's stroke and bleed results will contribute to pooled trial analyses of AF screening, thereby informing future studies and guidelines.

Sugar-Sweetened Beverage Consumption and Caries Prevalence in Underserved Black Adolescents.

Purpose: The purpose of this study was to examine the association between sugar-sweetened beverage (SSB) consumption and dental caries prevalence among underserved Black adolescents. Methods: This was a cross-sectional study of 545 Black adolescents, ages 12 to 17 years, who participated in the Howard Meharry Adolescent Caries Study (HMACS). The outcome was dental caries prevalence, measured using the decayed, missing, and filled permanent tooth surfaces (DMFS) index. Participants were recruited from middle and high schools in Washington, D.C., USA, and Nashville, Tenn., USA. Questionnaires were used to assess beverage intake, demographic, and health-related behavioral characteristics. The multivariable analysis used marginalized zero-inflated Poisson regression (MZIP) stratified by toothbrushing frequency to estimate adjusted mean caries ratios (MRs), adjusted odds ratios (ORs), and 95 percent confidence intervals (95 percent CIs). Results: The mean age of the participants was 14.1 years. Participants in the highest quartile for SSB consumption had a higher caries ratio than those in the lowest quartile [MR equals (=) 1.59, 95 percent CI equals 1.15 to 2.20] and a lower odds of not being at risk for caries (OR = 0.24, 95 percent CI = 0.09 to 0.61). These findings were only observed among those brushing once a day or less (n =202). Conclusions: Among Black adolescents in this study who brushed once a day or less, high levels of sugar-sweetened beverage consumption were associated with greater caries prevalence and a reduced likelihood of remaining caries-free than those with lower levels of SSB consumption. Future studies will focus on interventions to reduce SSB consumption.

Food Insecurity, Meal Behaviors, Beverage Intake, and Body Mass Index in Underserved Adolescents.

OBJECTIVE: Associations between food insecurity, meal patterns, beverage intake, and body mass index (BMI) were investigated using data from the Howard Meharry Adolescent Caries Study. METHODS: Secondary analyses of food security status used the Wilcoxon rank sum, chi-square, and Fisher's exact tests. RESULTS: The group of adolescents (n=627) was 42.1% male, 14.2±1.9 years, 86.9% African American, and 19.9% food-insecure. Meal frequency, meal structure, most beverage intake, and BMI did not differ by food-security status. Adolescents from Washington, DC were more likely to be food insecure than adolescents from Nashville, TN (P=0.003). Most had unstructured meal patterns and irregular breakfast intake. Median milk intake was below and sugar-sweetened beverage intake above dietary recommendations. CONCLUSIONS: This study extends our knowledge concerning food insecurity in urban African American adolescents and suggests public health initiatives designed to encourage meal structure, increase milk intake, and reduce sugar-sweetened beverage intake can improve diet quality of underserved youth.

A Case of Cheilitis Granulomatosa/Orofacial Granulomatosis.

A case of a 19-year-old female patient is presented to a private practice dental clinician with swelling of the lower lip and inflammation of the anterior dorsal tongue. The patient presented with moderate oral pain as well as abdominal pain. The lesions were biopsied and noted for a granulomatous histopathologic appearance. The patient reported a history of using cinnamon as a flavoring agent. The lesions resolved within two weeks after the biopsy procedures and topical steroid therapy. The lesions were diagnosed as cheilitis granulomatosa/orofacial granulomatosis. The patient has remained lesion free as of the three-year follow-up. Etiologic, diagnostic and therapeutic issues related to this relatively rare condition of cheilitis granulomatosa/orofacial granulomatosis are discussed.

An Approach to Engaging Schools In Oral Health Initiatives: The Howard Meharry Adolescent Caries Study (HMACS).

Use of community-based participatory research (CBPR) principles can help identify strategies for development and implementation of studies that can address oral health disparities disfavoring African American youth. This paper summarizes approaches of the Howard Meharry Adolescent Caries Study (HMACS) to provide sustained oral health services beyond the life of a research study.

Staff perceptions of the emergency department working environment: An international cross-sectional survey.

OBJECTIVES: The aims of this study were to describe clinical staff perceptions of their ED working environment and to explore associations between staff demographics, coping styles and the work environment. METHODS: A cross-sectional study was conducted in one Swedish ED and two Australian EDs in 2015-2016. Descriptive statistics were used to explore stressors, coping styles and aspects of the working environment for the combined cohort and the cohort split by age, sex, professional role, years of employment in the ED and country. Regression analyses examined the impact of coping style and demographic characteristics on staff perceptions of the working environment. RESULTS: Two hundred and six ED staff completed the survey (response rate: 64%). Factors most stressful for ED staff included death or sexual abuse of a child, heavy workload and poor skill mix. Staff perceptions of the working environment differed based on age, sex, country, tenure and job role. Regression analysis of perceptions of the work environment on demographics and coping strategies revealed that negative coping strategies were associated with low self-realisation, high workload, high conflict and high nervousness. Active coping and positive thinking were associated with increased self-realisation. Positive thinking was associated with lower levels of conflict. CONCLUSIONS: Employees engaging in positive coping strategies had more positive perceptions of the work environment, while those engaging in maladaptive coping strategies reported negative perceptions of the work environment. These data suggest that strategies that promote the use of active coping and positive thinking should be encouraged and warrant further research in the ED.

Reducing Dental Plaque Scores in Long-term Care Facilities Using a Checklist and Random Inspections: A Pilot Study.

The development and use of tailored interventions in overcoming barriers to optimum health in long-term care facility residents is of the highest importance. One successful approach to improving health outcomes is the use of a checklist by health care providers. Despite the evidence of the success of such checklists in nursing and medicine, there is little evidence on their use in improving dental outcomes. This study investigated whether an intervention comprising the daily use of a checklist for oral care by nursing staff supplemented by random inspections by a charge nurse resulted in lower dental plaque scores in patient participants at a long-term care facility (n=19) as compared with in those at another long-term care facility that did not receive the intervention (n=13). All participants received a dental cleaning at baseline. At a follow-up examination at 6 to 8 weeks post-baseline, significant differences were observed in the plaque scores between the participants at each location, with the median plaque scores in those undergoing the intervention being less than half of those in the patients that did not (20.8% vs. 52.8%, p<0.001). After adjusting for age in a linear regression model, this difference remained significant. The use of a daily checklist for oral care supplemented by random inspections by a charge nurse was associated with lower plaque scores (p<0.001). These results warrant further research, including prospective studies aimed at establishing how use of both clinical supervision and a checklist for oral health may influence plaque scores in geriatric patients in long-term care facilities over time.

Morale, stress and coping strategies of staff working in the emergency department: A comparison of two different-sized departments.

OBJECTIVE: Clinical staff in EDs are subject to a range of stressors. The objective of this study was to describe and compare clinical staff perceptions of their ED's working environment across two different Australian EDs. METHODS: This was a cross-sectional, descriptive, research design that included distribution of three survey tools to clinical staff in two Australian EDs in 2016. Descriptive statistics were reported to characterise workplace stressors, coping styles and the ED environment. These data were compared by hospital and the employee's clinical role (nurse or physician). RESULTS: In total, 146 ED nurses and doctors completed the survey (response rate: 67%). Despite geographical variation, the staff at the two locations had similar demographic profiles in terms of age, sex and years of experience. Staff reported moderate levels of workload and self-realisation but low levels of conflict or nervousness in the workplace. Nurses and physicians reported similar perceptions of the work environment, although nurses reported slightly higher median levels of workload. Staff rated the death or sexual abuse of a child as most stressful, followed by workplace violence and heavy workload. Staff used a large range of coping strategies, and these were similar across both sites. CONCLUSION: These findings are the first multi-site and multidisciplinary examinations of Australian ED staff perceptions, improving our understanding of staff stressors and coping strategies and highlighting similarities across different EDs. These data support the development and implementation of strategies to improve ED working environments to help ensure professional longevity of ED staff.

Effective admissions practices to achieve greater student diversity in dental schools.

In this chapter we describe the institutional and policy-level strategies that dental schools in the Pipeline, Profession, and Practice: Community-Based Dental Education program used to modify their admissions practices to increase the diversity of their student bodies. Schools developed and used clear statements recognizing the value of diversity. They incorporated recent U.S. Supreme Court rulings regarding educational diversity into their revised admissions practices; these rulings cited diversity as both a "compelling interest" and its use in only "narrowly tailored" circumstances. We make a case for admissions decisions based on a comprehensive evaluation that balances the quantitative and qualitative qualities of a candidate. It refutes the practice of overreliance on standardized tests by detailing the whole-file review process to measure merit and professional promise. Also described is a range of noncognitive variables (e.g., leadership, ability to sustain academic achievement with competing priorities, volunteerism, communication, social background, and disadvantaged status) that schools can take into consideration in admissions decisions. Admissions committees can tie this comprehensive review of candidates into the case for promoting cross-cultural understanding and enhanced competence to provide care to patients from diverse backgrounds. In addition, the chapter reviews the challenges schools face in developing admissions policies and procedures that reflect the university's mission for diversity. It addresses the importance of a diverse composition of the admissions committee. It also describes how tailored workshops and technical assistance for admissions committees can help schools improve their student diversity and how admissions committees can engage in a process of periodic review of their diversity objectives in relationship to the school's mission.

Comparative outcomes study of metformin intervention versus conventional approach the COSMIC Approach Study.

OBJECTIVE: Metformin was approved by the Food and Drug Administration in 1995 subject to the conduct of a randomized trial to evaluate the risk of lactic acidosis or other serious adverse events (SAEs) with this agent, under usual care conditions. RESEARCH DESIGN AND METHODS: The Comparative Outcomes Study of Metformin Intervention versus Conventional (COSMIC) Approach Study was a randomized, open-label, active-comparator, parallel-group, 1-year trial in type 2 diabetic patients suboptimally controlled on diet or sulfonylurea. Patients received metformin (n = 7,227) or other usual care treatments (n = 1,505). The primary end point was the incidence of SAEs, death, and hospitalization. RESULTS: SAEs occurred in 10.3% (95% CI 9.6-11.1%) of the metformin group and in 11.0% (9.5-12.7%) of the usual care group (P = 0.431). Lactic acidosis did not occur. All-cause mortality (1.1% [0.9-1.4%] vs. 1.3% [0.8-2.0%], P = 0.596) and hospitalization (9.4% [8.8-10.1%] vs. 10.4% [8.9-12.1%], P = 0.229) were similar between groups. CONCLUSIONS: The incidence of SAEs was similar between groups. Lactic acidosis was not observed. Metformin may be safely prescribed for type 2 diabetes if contraindications and warnings are respected. This study demonstrates the utility of large, simple trials for risk evaluation of treatments for common diseases.

Gastrointestinal tolerability of extended-release metformin tablets compared to immediate-release metformin tablets: results of a retrospective cohort study.

OBJECTIVE: Metformin, a biguanide antihyperglycemic medication, lowers blood glucose in patients with type 2 diabetes with minimal risk of hypoglycemia. Most common side effects include diarrhea, nausea and vomiting. Extended-release metformin (Glucophage XR)*, a once-daily tablet using the patented GelShield Diffusion System release mechanism, may be better tolerated than immediate-release metformin (Glucophage). This retrospective chart review examined the overall gastrointestinal (GI) tolerability of both formulations. RESEARCH DESIGN AND METHODS: Patient charts were reviewed and data were collected from October 2001 to May 2002. Adult patients with type 2 diabetes started on extended-release metformin (metformin-XR) or switched from immediate-release metformin to metformin-XR within the previous 2 years were eligible for inclusion in the metformin-XR cohort. Patients started on immediate-release metformin within the previous 2 years were eligible for inclusion in the immediate-release metformin cohort. Previous experience of GI side effects while taking immediate-release metformin did not prevent inclusion in either cohort, though patients with significant underlying GI disease or moderate to severe hepatic or renal impairment were excluded. GI tolerability was assessed during the first year of treatment with immediate-release metformin or metformin-XR. Primary endpoints were overall GI tolerability and frequency of diarrhea during the first year of treatment. RESULTS: A total of 471 patients' charts were reviewed and data were collected from four diabetes clinics; 310 (metformin-XR) and 158 (immediate-release metformin) eligible patients were included. Patients were, on average, 56 years old, and overweight (mean body mass index 33 kg/m2). The majority of patients were Caucasian (50%), Hispanic (24%) or Black (19%). Mean daily doses were 1258 mg (range 500-2500 mg) for metformin-XR and 1282 mg (range 500-2550 mg) for immediate-release metformin. About 25% of the metformin-XR cohort had been switched from immediate-release metformin due to a history of GI adverse events (AE). Despite this, the frequency of any GI AE was similar between metformin-XR and immediate release metformin (11.94 vs. 11.39%, p = 0.86). The incidence of individual GI AE also did not differ significantly between cohorts. In a cohort of 205 patients started on immediate-release metformin and switched to metformin-XR, the frequency of any GI AE was 26.34% (while taking immediate release metformin; n = 205) vs. 11.71% (after switching to metformin-XR; n = 205) (p = 0.0006) and the frequency of diarrhea was 18.05% (while taking immediate-release metformin) vs. 8.29% (after switching to metformin-XR) (p = 0.0084). CONCLUSIONS: In this retrospective chart review, patients switched from immediate-release metformin to metformin-XR experienced fewer GI side effects on comparable doses of the extended-release metformin.

Familial and cultural perceptions and beliefs of oral hygiene and dietary practices among ethnically and socio-economicall diverse groups.

UNLABELLED: OBJECTIVE; The aim of this international study was to develop a valid and reliable psychometric measure to examine the extent to which parents' attitudes about engaging in twice-daily tooth brushing and controlling sugar snacking predict these respective behaviours in their children. A supplementary objective was to assess whether ethnic group, culture, level of deprivation or children's caries experience impact upon the relationships between oral health related behaviours, attitudes to these respective behaviours and to dental caries. CLINICAL SETTING: Nurseries, health centres and dental clinics in 17 countries. PARTICIPANTS: 2822 children aged 3 to 4 years and their parents. MAIN OUTCOME MEASURES: Dental examination of children and questionnaire to parents. RESULTS: Factor analysis identified 8 coherent attitudes towards toothbrushing, sugar snacking and childhood caries. Attitudes were significantly different in families from deprived and non-deprived backgrounds and in families of children with and without caries. Parents perception of their ability to control their children's toothbrushing and sugar snacking habits were the most significant predictor of whether or not favourable habits were reported. Some differences were found by site and ethnic group. CONCLUSIONS: This study supports the hypothesis that parental attitudes significantly impact on the establishment of habits favourable to oral health. An appreciation of the impact of cultural and ethnic diversity is important in understanding how parental attitudes to oral health vary. Further research should examine in a prospective intervention whether enhancing parenting skills is an effective route to preventing childhood caries.

A multi-country comparison of caries-associated microflora in demographically diverse children.

OBJECTIVE: The aim of this formative international collaborative research on childhood dental caries was to undertake an initial investigation comparing the dental plaque of young children from diverse ethnic and socioeconomic backgrounds with and without dental caries. BASIC RESEARCH DESIGN: The following four null hypotheses were investigated. There were no differences in numbers of individual taxa when comparing plaque samples from: 1) caries-free children from deprived and non-deprived backgrounds; 2) children from deprived and non-deprived backgrounds with at least 3 decayed teeth; 3) children from non-deprived backgrounds who are caries free with those from similar backgrounds with at least 3 decayed teeth; and, 4) children from deprived backgrounds who are caries free with those from similar backgrounds with at least 3 decayed teeth. PARTICIPANTS: 277 children aged 3-4 years from 5 countries. MAIN OUTCOME MEASURES: A sample of interproximal plaque from anterior teeth was collected using sterile dental floss, and cultured according to accepted international standards. RESULTS: Analysis of the data found that the first null hypothesis was accepted and that the fourth was rejected. Unexpectedly, the second null hypothesis was rejected as the children with caries from deprived and non-deprived backgrounds had a different caries-associated flora. In particular, children living in deprivation harbored more caries-associated bacteria [mutans streptococci and lactobacilli]. This greater microbial challenge was associated with a higher level of cavitated carious lesions and with more frequent consumption of confectionery. Conclusions Children from deprived backgrounds with caries may be further disadvantaged by having higher levels of caries-associated microflora.

A Comparison of the Cough Profile of Fosinopril and Enalapril in Hypertensive Patients with a History of ACE Inhibitor-Associated Cough.

OBJECTIVE: Cough frequency and severity with fosinopril and enalapril were assessed in hypertensive patients with previous angiotensin-converting enzyme inhibitor (ACEI)-associated cough. DESIGN: Prospective, multicenter, randomized, 8-week double-blind treatment. PATIENTS: One hundred seventy-nine patients (mild-to-moderate hypertension, nonsmokers, mean age 58 years; 55% females; 72% Caucasian, 6% black, 19% Hispanic) were studied. Patients with other cough etiologies, significant co-morbidity, or confounding medications were excluded. INTERVENTIONS: Patients were randomized to fosinopril 10 mg (n = 85) or enalapril 5 mg (n = 94) once daily. Dosage could be doubled for blood pressure control after 4 weeks. Outcome measurements: The primary end point was all-cough frequency based on patient daily diary ratings; a cumulative cough frequency score was calculated. Secondary end points included cough severity, nonproductive cough frequency, night awakenings, cough time of day, and spontaneously reported cough. RESULTS: Fosinopril and enalapril demonstrated similar blood pressure control. Significant cough profile differences were observed in favor of fosinopril: all-cough frequency was 40.6 plus minus 3.8 (mean plus minus SE) versus 52.8 plus minus 3.6 (p = 0.02); nonproductive cough frequency was 26.7 plus minus 3.5 versus 40.3 plus minus 3.4 (p less-than-or-equal 0.01); and cough time of day was 49.2 plus minus 5.2 versus 66.0 plus minus 5.0 (p = 0.02), for fosinopril and enalapril, respectively. Subgroup analysis revealed all-cough frequency was 33.5 plus minus 6.3 versus 56.6 plus minus 5.3 (p = 0.006) for fosinopril and enalapril, respectively, in patients who previously had cough on one of these two ACEI (predominantly enalapril). Ten (12%) fosinopril and 25 (27%) enelapril patients spontaneously reported cough (p = 0.01). CONCLUSIONS: Hypertensive patients with previous ACEI-associated cough reported less frequent cough with fosinopril compared to enalapril, based on cumulative patient diary scores and spontaneously reported cough. This difference was most apparent in the subgroup of patients who previously experienced cough associated with enalapril therapy. Patients with prior ACEI-associated cough may experience less frequent with fosinopril.