Nasopharyngeal carriage and macrolide resistance in Indigenous children with bronchiectasis randomized to long-term azithromycin or placebo.

Although long-term azithromycin decreases exacerbation frequency in bronchiectasis, increased macrolide resistance is concerning. We investigated macrolide resistance determinants in a secondary analysis of a multicenter randomized controlled trial. Indigenous Australian children living in remote regions and urban New Zealand Maori and Pacific Islander children with bronchiectasis were randomized to weekly azithromycin (30 mg/kg) or placebo for up to 24 months and followed post-intervention for up to 12 months. Nurses administered and recorded medications given and collected nasopharyngeal swabs 3-6 monthly for culture and antimicrobial susceptibility testing. Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups, while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher. Australian children, compared to New Zealand children, had higher carriage overall, significantly higher carriage of macrolide-resistant bacteria at baseline (16/38 versus 2/40 children) and during the intervention (69/152 versus 22/239 swabs), and lower mean adherence to study medication (63 % versus 92 %). Adherence ≥70 % (versus <70 %) in the Australian azithromycin group was associated with lower carriage of any pathogen [odds ratio (OR) 0.19, 95 % confidence interval (CI) 0.07-0.53] and fewer macrolide-resistant pathogens (OR 0.34, 95 % CI 0.14-0.81). Post-intervention (median 6 months), macrolide resistance in S. pneumoniae declined significantly in the azithromycin group, from 79 % (11/14) to 7 % (1/14) of positive swabs, but S. aureus strains remained 100 % macrolide resistant. Azithromycin treatment, the Australian remote setting, and adherence <70 % were significant independent determinants of macrolide resistance in children with bronchiectasis. Adherence to treatment may limit macrolide resistance by suppressing carriage.

Respiratory health outcomes 1 year after admission with severe lower respiratory tract infection.

Severe lower respiratory infection (LRI) is believed to be one precursor of protracted bacterial bronchitis, chronic moist cough (CMC), and chronic suppurative lung disease. The aim of this study was to determine and to describe the presence of respiratory morbidity in young children 1 year after being hospitalized with a severe LRI. Children aged less than 2 years admitted from August 1, 2007 to December 23, 2007 already enrolled in a prospective epidemiology study (n = 394) were included in this second study only if they had a diagnosis of severe bronchiolitis or of pneumonia with no co-morbidities (n = 237). Funding allowed 164 to be identified chronologically, 131 were able to be contacted, and 94 agreed to be assessed by a paediatrician 1 year post index admission. Demographic information, medical history and a respiratory questionnaire was recorded, examination, pulse oximetry, and chest X-ray (CXR) were performed. The predetermined primary endpoints were; (i) history of CMC for at least 3 months, (ii) the presence of moist cough and/or crackles on examination in clinic, and (iii) an abnormal CXR when seen at a time of stability. Each CXR was read by two pediatric radiologists blind to the individuals' current health. Results showed 30% had a history of CMC, 32% had a moist cough and/or crackles on examination in clinic, and in 62% of those with a CXR it was abnormal. Of the 81 children with a readable follow-up X-ray, 11% had all three abnormal outcomes, and 74% had one or more abnormal outcomes. Three children had developed bronchiectasis on HRCT. The majority of children with a hospital admission at <2 years of age for severe bronchiolitis or pneumonia continued to have respiratory morbidity 1 year later when seen at a time of stability, with a small number already having sustained significant lung disease.

Diagnosing and preventing chronic suppurative lung disease (CSLD) and bronchiectasis.

Current diagnostic labelling of childhood bronchiectasis by radiology has substantial limitations. These include the requirement for two high resolution computerised tomography [HRCT] scans (with associated adversity of radiation) if criteria is adhered to, adoption of radiological criteria for children from adult data, relatively high occurrence of false negative, and to a smaller extent false positive, in conventional HRCT scans when compared to multi-detector CT scans, determination of irreversible airway dilatation, and absence of normative data on broncho-arterial ratio in children. A paradigm presenting a spectrum related to airway bacteria, with associated degradation and inflammation products causing airway damage if untreated, entails protracted bacterial bronchitis (at the mild end) to irreversible airway dilatation with cystic formation as determined by HRCT (at the severe end of the spectrum). Increasing evidence suggests that progression of airway damage can be limited by intensive treatment, even in those predestined to have bronchiectasis (eg immune deficiency). Treatment is aimed at achieving a cure in those at the milder end of the spectrum to limiting further deterioration in those with severe 'irreversible' radiological bronchiectasis.

Longitudinal pulmonary function of childhood bronchiectasis and comparison with cystic fibrosis.

BACKGROUND: Little has been published on the progression of non-cystic fibrosis bronchiectasis (BX), especially in childhood. Data are needed for prognosis and evaluation of the effectiveness of treatments. A study was undertaken to evaluate the change in lung function over time in children with BX, and to consider covariates and compare them with the local cystic fibrosis (CF) population. METHODS: Children with BX or CF and > or =3 calendar years of lung function data were identified from hospital clinics. Diagnosis was made by high resolution CT scans, sweat tests, and genetic studies. Lung function performed on a single plethysmograph between 6 and 15 years of age and > or =6 weeks after diagnosis was analysed longitudinally (linear mixed model). The impact of reference equation and "best annual" versus "all data" approaches were evaluated. RESULTS: There were 44 children in each of the BX and CF groups with an overall mean 5.7 calendar years follow up data. The estimated forced expiratory volume in 1 second (FEV(1)) in the BX group had an intercept of 68% predicted (Polgar) at 10 years of age which fell at a rate of 1.9% per annum using "best annual" data compared with 63% and 0.9% using "all data". Those with post-infectious BX or chronic Haemophilus influenzae infection had more severe disease. In CF the FEV(1) ("best annual") intercept was 85% predicted with a slope of -2.9% per annum. The choice of reference equation affected the magnitude of the result but not the conclusions. CONCLUSION: Children with BX have significant airway obstruction which deteriorates over time, regardless of analysis strategy or reference. Effective interventions are needed to prevent significant morbidity and adult mortality.

Nitric oxide levels and ciliary beat frequency in indigenous New Zealand children.

New Zealand children's morbidity from respiratory disease is high. This study examines whether subclinical ciliary abnormalities underlie the increased prevalence of respiratory disease in indigenous New Zealand children. A prospective study enrolled a group of healthy children who were screened for respiratory disease by questionnaire and lung function. Skin-prick tests were performed to control for atopy. Exhaled and nasal NO was measured online by a single-breath technique using chemiluminescence. Ciliary specimens were obtained by nasal brushings for assessment of structure and function. The ciliary beat frequency (CBF) (median CBF, 12.5 Hz; range, 10.4-16.8 Hz) and NO values (median exhaled NO, 5.6 ppb; range, 2.3-87.7 ppb; median nasal NO, 403 ppb; range, 34-1,120 ppb) for healthy New Zealand European (n=58), Pacific Island (n=61), and Maori (n=16) children were comparable with levels reported internationally. No ethnic differences in NO, atopy, or CBF were demonstrated. Despite an apparently normal ciliary beat, the percentage of ciliary structural defects was 3 times higher than reported controls (9%; range, 3.6-31.3%), with no difference across ethnic groups. In conclusion, it is unlikely that subclinical ciliary abnormalities underlie the increased prevalence of respiratory disease in indigenous New Zealand children. The high percentage of secondary ciliary defects suggests ongoing environmental or infective damage.

Retrospective review of children presenting with non cystic fibrosis bronchiectasis: HRCT features and clinical relationships.

Non cystic fibrosis (CF) bronchiectasis in children presents with a spectrum of disease severity. Our aims were to document the extent and severity of disease in children with non-CF bronchiectasis, to review the inter- and intraobserver agreement for the high-resolution computed tomography (HRCT) features examined, and to assess correlations between HRCT features and clinical measures of severity. We performed a retrospective review of 56 children from the Starship Children's Hospital. HRCT scans were scored by a modified Bhalla system, and the chest X-rays using the Brasfield score. Scores were correlated with demographics, number of hospitalizations, disease duration, pulmonary function, clinical examination, and chronic sputum infection. The bronchiectasis seen was widespread and severe, particularly in Maori and Pacific Island children. The kappa coefficient for intraobserver agreement was better than that for interobserver agreement. Comparisons between HRCT scan and lung function parameters showed that the strongest relationships were between forced expiratory volume in 1 sec (FEV(1)) and forced expiratory flow between 25-75% of forced vital capacity (FEF(25-75)) with the extent of bronchiectasis, bronchial wall thickening, and air trapping. Children with digital clubbing and chest deformity showed significantly higher scores for extent of bronchiectasis, bronchial wall dilatation and thickness, and overall computed tomography (CT) score. No relationship was demonstrated between chronic sputum infection and CT score. The HRCT score demonstrated a stronger correlation between the extent and severity of bronchiectasis, and spirometry values, than the chest X-ray score. In conclusion, pediatric non-CF bronchiectasis in Auckland is extensive and severe. The good intraobserver ratings mean that consistency of scoring is possible on repeated scans. This study cannot comment on the relationships of CT and less severe disease.

Paediatric bronchiectasis in the twenty-first century: experience of a tertiary children's hospital in New Zealand.

OBJECTIVE: Despite its decline in developed countries, bronchiectasis appeared to be a common diagnosis in Auckland, New Zealand children. The aims of this study were: to document the number of children in Auckland with bronchiectasis, their severity, clinical characteristics and possible aetiologies; to assess whether there was a relationship between ethnicity and poverty; and to estimate a crude bronchiectasis prevalence rate for New Zealand. METHODS: A retrospective review of the case histories of all children attending a tertiary children's hospital in Auckland with bronchiectasis diagnosed by high-resolution chest computed tomography (CT) scan, during the period 1998-2000 was undertaken. Data collected included patient demographics, number of hospitalizations pre- and post-diagnosis, lung function tests, radiology and investigations. The New Zealand deprivation 1996 index was applied to the data to obtain a measure of socio-economic status. RESULTS: Bronchiectasis was found to be common, with an estimated prevalence of approximately one in 6000 in the Auckland paediatric population. It was disproportionately more common in the Pacific Island and Maori children. In Pacific Island children, bronchiectasis not caused by cystic fibrosis was nearly twice as common in the general population than cystic fibrosis. Socio-economic deprivation and low immunization rates may be significant contributing factors. The bronchiectasis seen was extensive. Ninety-three percent had bilateral disease and 64% had involvement of four or more lobes on chest CT scan. A wide range of comorbidities and underlying aetiologies were evident. CONCLUSIONS: Paediatric bronchiectasis in Auckland, New Zealand, is common but underresourced. Only the most severe cases are being recognized, providing a significant challenge for paediatric health professionals.

Palivizumab prophylaxis of respiratory syncytial virus infection in high-risk infants.

Palivizumab prophylaxis significantly reduces hospitalization for respiratory syncytial virus (RSV) disease in preterm infants. However, palivizumab is very expensive. Data from a New Zealand cost-effectiveness analysis were considered by representatives of the Infectious Diseases and Immunisation, Fetus and Newborn, and Respiratory Committees of the Paediatric Society of New Zealand. Prophylaxis in all high-risk groups was associated with net cost. The consensus panel recommends that the priority for palivizumab be given to babies discharged on home oxygen with chronic lung disease, followed by babies born at 28 weeks or less gestation.

Addition of alendronate to ongoing hormone replacement therapy in the treatment of osteoporosis: a randomized, controlled clinical trial.

Alendronate and estrogen are effective therapies for postmenopausal osteoporosis, but their efficacy and safety as combined therapy are unknown. The objective of this study was to evaluate the addition of alendronate to ongoing hormone replacement therapy (HRT) in the treatment of postmenopausal women with osteoporosis. A total of 428 postmenopausal women with osteoporosis, who had been receiving HRT for at least 1 yr, were randomized to receive either alendronate (10 mg/day) or placebo. HRT was continued in both groups. Changes in bone mineral density (BMD) and biochemical markers of bone turnover were assessed. Compared with HRT alone, at 12 months, alendronate plus HRT produced significantly greater increases in BMD of the lumbar spine (3.6% vs. 1.0%, P < 0.001) and hip trochanter (2.7% vs. 0.5%, P < 0.001); however, the between-group difference in BMD at the femoral neck was not significant (1.7% vs. 0.8%, P = 0.072). Biochemical markers of bone turnover (serum bone-specific alkaline phosphatase and urine N-telopeptide) decreased significantly at 6 and 12 months with alendronate plus HRT, and they remained within premenopausal levels. Addition of alendronate to ongoing HRT was generally well tolerated, with no significant between-group differences in upper gastrointestinal adverse events or fractures. This study demonstrated that, in postmenopausal women with low bone density despite ongoing treatment with estrogen, alendronate added to HRT significantly increased bone mass at both spine and hip trochanter and was generally well tolerated.

Humidification difficulties in two tracheostomized children.

Effective humidification is sometimes difficult to achieve in children when normal mechanisms are bypassed by having a tracheostomy in situ. The humidification options available in the paediatric population are heat and moisture exchangers (HMEs) and heated humidifiers, both of which are reviewed and discussed. In some circumstances the humidification achieved with HMEs is inadequate. We outline the hospital and subsequent home management of two infants, both with tracheostomies in situ, who unsuccessfully trialed HMEs and subsequently achieved effective humidification with heated humidifiers. We propose that heated humidifiers would help more tracheostomized infants who are suffering from similar problems.

Effect of measurement conditions on measured levels of peak exhaled nitric oxide.

BACKGROUND: It is possible to measure nitric oxide (NO) levels in exhaled air. The absolute concentrations of exhaled NO obtained by separate workers in similar patient groups and normal subjects with apparently similar techniques have been very different. A study was undertaken to determine whether changes in measurement conditions alter the concentration of exhaled NO. METHOD: NO concentrations measured by a chemiluminescence analyser (Dasibi Environmental Corporation) and carbon dioxide (CO2) measured by a Morgan capnograph were analysed in single exhalations from total lung capacity in healthy volunteers (mean age 35.9 years). Ten subjects performed five exhalations at four different expiratory flow rates, at four different expiratory mouth pressures, and before and after drinking hot (n = 5) or cold (n = 5) water. Three subjects performed five exhalations on a day of high background NO (mean NO level 134 ppb) before and after a set of five exhalations made while both the subject and analysers were sampling from a low NO/NO-free reservoir system. RESULTS: The mean peak concentration of NO decreased by 35 ppb (95% CI 25.7 to 43.4) from a mean (SE) of 79.0 (15.5) ppb at an expiratory flow rate of 250 ml/min to 54.1 (10.7) ppb at 1100 ml/min. The mean peak concentration of NO did not change significantly with change in mouth pressure. The mean (SE) peak NO concentration decreased from 94.4 (20.8) ppb to 70.8 (16.5) ppb (p = 0.002, 95% CI 12.9 to 33.1) with water consumption. The mean NO concentration with machine and subject sampling from the low NO reservoir was 123.1 (19.4) ppb, an increase from results obtained before (81.9 (10.2) ppb, p = 0.001, 95% CI -19.9 to -62.7) and after (94.2 (18.3) ppb, p = 0.017, 95% CI 6.0 to 51.8) sampling with high ambient NO. CONCLUSIONS: The measurement of exhaled NO must be performed in a carefully standardised manner to enable different teams of investigators to compare results.

Is nitric oxide in exhaled air produced at airway or alveolar level?

The aim of this study was to determine whether the nitric oxide (NO) measured in exhaled air is produced at airway or alveolar level. Exhaled NO was measured using a chemiluminescence analyser, and carbon dioxide (CO2 concentration using a Morgan capnograph in single exhalations in 12 healthy subjects (mean age 32 yrs; 6 males and 6 females). For each subject, five exhalations were made directly into the NO analyser and five were made through a T-piece system, which allowed measurement of expiratory flow rate. The peak NO levels measured via the T-piece system were 41.2 (SEM 10.8) parts per billion (ppb), significantly lower than direct levels 84.8 (14.0) ppb (p<0.001). The levels of NO tended to rise to an early peak and plateau, while the CO2 levels continued to rise to peak late in the exhalation. The mean times to reach peak NO levels were 32.2 s (direct) and 23.1 s (T-piece), which were significantly different from that of peak CO2 levels 50.5 s (direct) and 51.4 s (T-piece) (p<0.001). At peak NO level, the simultaneous CO2 level mean 4.9% (SEM 0.14)%, was significantly lower than the peak CO2 reached, 5.8 (0.21)% (p<0.001). We conclude that peak nitric oxide levels are dependent on measurement conditions. There are significant differences between the time to peak of carbon dioxide and nitric oxide. Therefore, most nitric oxide, unlike carbon dioxide, is produced in airways and not at alveolar level.

Efficacy and tolerability of finasteride in symptomatic benign prostatic hyperplasia: a primary care study. Primary Care Investigator Study Group.

Because increasing numbers of men are seeking treatment for benign prostatic hyperplasia (BPH) from primary care physicians, we sought to assess the efficacy and tolerability of finasteride in a primary care setting. In this randomized, double-masked study, 2,112 men with symptomatic BPH received either finasteride (n = 1,589) or placebo (n = 523) for 1 year. At 3, 6, 9, and 12 months, urinary symptoms were measured using the American Urological Association Symptom Index (AUASI). Quality of life was assessed using the BPH Impact Index (BII), which assessed bother, worry, physical discomfort, and restriction in activities. Both patients and investigators assessed overall urologic status. Investigators assessed the effect of the drug on plasma lipids in a subset of patients. Patients treated with finasteride had a statistically significant mean decrease in AUASI scores compared with patients treated with placebo beginning at month 6 and continuing throughout the study. At month 12, adjusted mean decreases in AUASI scores were -4.96 for finasteride versus -3.71 for placebo. Statistically significant differences in favor of finasteride were also noted on BII at months 9 and 12. Patient and investigator overall assessments showed greater improvement in the finasteride group beginning at month 6. The incidence of drug-related sexual adverse experiences was significantly greater in finasteride-treated patients but led to withdrawal in only 2.2% of these patients. Overall lipid profile was not significantly altered in either group. Based on improvement in symptoms and quality of life, and on its favorable tolerability profile, finasteride should be considered by primary care physicians for management of symptomatic BPH.

Combined analysis of two multicenter studies of finasteride 5 mg in the treatment of symptomatic benign prostatic hyperplasia.

The purpose of this paper is to examine effects of finasteride 5 mg across different age groups in an ethnically diverse population of men with symptomatic benign prostatic hyperplasia (BPH) seen in community urology and primary care practices. Data were combined from two previous placebo-controlled randomised trials of finasteride that evaluated changes in urinary symptoms, blinded global assessments of urologic status, adverse experiences, and effects on dihydrotestosterone (DHT) and prostate-specific antigen (PSA) in over 4500 men. Finasteride showed a favourable efficacy and tolerability profile in this large ethnically diverse population and was similarly effective in middle-aged and older men with BPH and prostate gland enlargement.

Exhaled nitric oxide measurements in normal and asthmatic children.

The aim of this study was to determine whether we could measure exhaled nitric oxide (NO) levels in children, and whether the same pattern of exhaled NO concentrations was observed in asthmatic and normal children as had been seen in adults. Using a chemiluminescence NO analyzer, we measured NO in exhaled air both directly and through a T-piece allowing us to measure carbon dioxide (CO2), mouth pressure, and expiratory flows. In 39 normal children the mean peak exhaled NO was 49.6 parts per billion (ppb) (SD 37.4) when all expired gas passed directly through the NO analyzer, and 29.7 ppb (SD 27.1) when expiration occurred through a T-piece. The results were significantly higher in 15 asthmatic subjects on bronchodilator therapy only [126.1 ppb (SD 77.1) direct (P < 0.001), and 109.5 ppb (SD 106.8) via T-piece (P < 0.001)]. In 16 asthmatics on regular inhaled corticosteroids the mean peak exhaled levels were significantly lower 48.7 ppb (SD 43.3) direct (P < 0.001) and 45.2 ppb (SD 45.9) via T-piece (P < 0.01). There was no difference between the normal children and the asthmatic children on regular inhaled corticosteroids (P = 0.9 direct, P = 0.2 via T-piece). There were no significant differences in carbon dioxide levels, mouth pressure, duration of expiration and expiratory flows between the different groups, and no difference between carbon dioxide levels, mouth pressure and duration of expiration between the two methods (direct and T-piece). In 6 asthmatic children mean peak exhaled levels on NO fell from a median peak level of 124.5 ppb to 48.6 ppb when measured before and 2 weeks after commencement of inhaled corticosteroid treatment. The measurement of exhaled NO levels may be useful as a noninvasive means of monitoring children with asthma.

Measurement of expired nitric oxide levels in children.

Nitric oxide (NO) can be measured directly in expired air in adults. The purpose of our study was to measure NO levels in children and to compare these values with adults. Exhaled NO was measured in 39 normal prepubertal children (23 girls), aged 9-11 years (mean 9.9 years). Exhaled NO was measured by the chemiluminescence method that is sensitive in a range of 2 to 4,000 ppb of NO on an adapted analyzer (Dasibi Environmental). Wearing a nose clip. 5 measurements were recorded in each child with exhalation 1) directly into the NO analyzer (flow rate 240 mL/min) with measurements of NO, carbon dioxide, and mouth pressure; and 2) using a T-piece to allow measurements at a different flow rate. For all measurements, background NO levels were less than 10 ppb. The mean direct level was 49.6 ppb, SD 37.8 (range, 11.5-197.2 ppb) compared with T-piece levels of 29.2 ppb. SD 27.1 (range, 5.1-141.2 ppb). There was no significant difference between boys and girls for direct or T-piece recordings. Mean direct NO in boys was 43.1 ppb, SD 40.5 and in girls 55.2 ppb, SD 35.4; mean T-piece in boys was 25.6 ppb. SD 29.2 and in girls 33.8 ppb, SD 25.1. Mean NO levels in prepubertal children are lower than in adults and show no difference between males and females.

Efficacy, tolerability, and effect on health-related quality of life of finasteride versus placebo in men with symptomatic benign prostatic hyperplasia: a community based study. CUSP Investigators. Community based study of Proscar.

This study sought to assess the efficacy, tolerability, and effect of finasteride on health-related quality of life (HRQL) in a diverse population of men with moderate-to-severe symptomatic benign prostatic hyperplasia (BPH). This double-blind study evaluated finasteride and placebo for 12 months in 2342 men with BPH (16.2% black, 14.5% Hispanic, 69.3% Caucasian/other) in a community-based setting. At 3-month intervals, urinary symptoms were measured by use of the American Urologic Association symptom index. HRQL was assessed by use of the BPH impact index (BII), which evaluated degree of bother, worry, physical discomfort, and restriction in activities as a result of urinary symptoms. Additional questions regarding activities of living were administered, and global assessments of change in urologic status were performed by both patients and investigators. Compared with placebo, patients treated with finasteride had a statistically significant decrease in symptom scores when first measured at month 3. Symptom scores continued to improve in finasteride-treated patients throughout the study; at month 12, the mean decrease in symptom scores in the finasteride-treated patients was -4.8 compared with -3.4 for placebo patients ( P = 0.0001). Statistically significant differences in favor of finasteride also were noted at month 12 on the BII (P = 0.0465), and finasteride-treated patients experienced less interference with activities of living (P = 0.0518). Patient and investigator global assessments of urologic status showed that significantly more patients in the finasteride group considered themselves improved and were considered improved by investigators at month 12 (P = 0.000). Finasteride was generally well tolerated. The incidence of drug-related sexual adverse experiences was significantly higher in the finasteride group (P = 0.000), but led to withdrawal in only 1.5% of patients. The demonstrated efficacy and tolerability of finasteride in reducing symptoms and improving quality of life confirm observations of previous trials and make finasteride a highly desirable treatment option for many men with symptomatic BPH.

Efficacy and tolerability of a combination of enalapril and hydrochlorothiazide in the treatment of hypertension measured manually and with an ambulatory blood pressure monitor.

The efficacy and tolerability of an enalapril maleate-hydrochlorothiazide combination (EM-HCTZ) were evaluated in a prospective, open-label study in 26 patients with uncomplicated essential hypertension (mean baseline sitting systolic/diastolic blood pressure: 153/103 mmHg) requiring two agents to reduce sitting diastolic blood pressure (SDBP) below 90 mmHg. Their mean age was 52 years. Patients received enalapril 5 mg daily, which was increased to 10 mg if SDBP was not reduced to < 90 mmHg during a 5-week titration period following washout. If blood pressure did not reach that goal, 25 mg hydrochlorothiazide was added. Only patients who required enalapril 10 mg and hydrochlorothiazide 25 mg for control (SDBP < 90 mmHg) at the end of titration received open-label EM-HCTZ as maintenance therapy for 6 weeks. The SDBP of 19 of the 26 patients (73%) who began titration was controlled at the end of titration, and they received maintenance therapy. During maintenance, the mean SDBP decreased from baseline 13.2 mmHg at week 2, 13.3 mmHg at week 4, and 10.1 mmHg at week 6. All changes from baseline were significant. At the end of the maintenance period, SDBP was controlled in 8 (42%) of 19 patients enrolled. One patient was withdrawn from the study because blood pressure was poorly controlled. Ambulatory blood pressure (ABP) was monitored, average outcome was computed for each patient during the 24-hour interval, and with a paired comparison, baseline and follow-up data were compared with the data measured manually. The mean baseline ABP was 9 mmHg lower than the baseline SDBP measured manually (r = 0.58, P = 0.01). Following treatment with EM-HCTZ, mean diastolic blood pressure fell 10 mmHg and mean systolic blood pressure fell 15 mmHg. In summary, EM-HCTZ was highly effective and generally well-tolerated in a substantial proportion of participants whose SDBP remained > 90 mmHg on enalapril 10 mg. Important differences between blood pressure measured manually and with a monitor were also demonstrated.