Epidemiology and outcome of HIV infection in North-East Scotland (1985-1997).

OBJECTIVE: to assess the epidemiology of HIV infection in North-East Scotland. METHODS: retrospective casenote review of all HIV-infected patients who have had contact with the Infection Unit in Aberdeen. RESULTS: one hundred and forty-two HIV-infected patients were treated between April 1985 and December 1997. The risk behaviour related to the acquisition of the HIV infection was: 56 (39%) homosexually infected, 45 (32%) heterosexually-infected, 34 (24%) injecting drug users (IDUs), and seven (5%) blood products or not known. Sixteen of the 45 (36%) heterosexually-infected patients were native to Africa and 16 of the 34 (31%) IDUs were prisoners in Peterhead prison at the time of referral. Fifty-two (37%) of the cohort continue to attend the Infection Unit, 41 (29%) have relocated, 40 (28%) have died and nine (6%) have been lost to follow-up. The ratio of heterosexual:homosexual men:IDUs changed significantly between the first 7 years (12:21:25) and the second 6 years (33:35:9) of the review, with significantly more patients being infected through heterosexual contact and fewer infected by IDU in the second period-P<0.001. The median AIDS survival was 17 months. Survival was significantly longer in those patients who took anti-retroviral therapy (median = 20 months) than in the patients who opted not to take anti-retroviral therapy (median = 11 months)-P<0.01. CONCLUSIONS: Although homosexual contact represents the commonest risk group for HIV infection in this region, the number of heterosexually-infected patients has increased significantly in the last 5 years. Temporary residents account for one-third of the HIV-infected population cared for in NE Scotland. Almost half of those lost to follow-up have returned to Africa or been released from prison. The introduction of anti-retroviral therapy has resulted in a dramatic improvement in AIDS survival in our cohort as it has done elsewhere.     

Angiotensin converting enzyme inhibition and arterial endothelial function in adults with Type 1 diabetes mellitus.

AIMS: Arterial endothelial dysfunction is a key early event in atherogenesis, and occurs in asymptomatic adults with Type 1 diabetes mellitus (DM). As angiotensin converting enzyme (ACE) inhibitors have been reported to reverse microvascular endothelial dysfunction acutely, we assessed the longer term effect of ACE inhibition on large vessel endothelial physiology in a randomized, crossover double-blind controlled clinical trial. METHODS: Flow-mediated arterial dilatation (FMD), which is largely due to endothelial release of nitric oxide, was assessed by vascular ultrasound in 20 Type 1 DM subjects with known endothelial dysfunction. These subjects, aged 28+/-5 years, were studied before and after 12 weeks oral therapy with either the ACE inhibitor perindopril 4 mg daily or the diuretic hydrene (triamterene 50 mg with hydrochlorothiazide 25 mg) daily. RESULTS: Although perindopril lowered both systolic and diastolic blood pressure by 2.7/3.2 mmHg, respectively (F3,78 = 4.7, P= 0.006; F3,78 = 3.2, P = 0.03), there was no significant effect of either perindopril or hydrene on FMD (baseline FMD before perindopril 4.6+/-2.5%, after 4.1+/-3.4%, baseline FMD before hydrene 5.4+/-3.6%, after 6.0+/-3.3%; F3,78= 1.9, P=0.1). Glycaemic control deteriorated slightly on hydrene whilst lipid levels, heart rate, resting blood flow and the arterial responses to nitroglycerine, a smooth muscle dilator, were unaffected by the treatment given. CONCLUSION: ACE inhibitor therapy for 3 months did not improve arterial endothelial function in Type 1 DM subjects.     

Phosphodiesterase 5 inhibitor treatment and survival in interstitial lung disease pulmonary hypertension: A Bayesian retrospective observational cohort study

Background and Objective

Pulmonary hypertension is a life-limiting complication of interstitial lung disease (ILD-PH). We investigated whether treatment with phosphodiesterase 5 inhibitors (PDE5i) in patients with ILD-PH was associated with improved survival.

Methods

Consecutive incident patients with ILD-PH and right heart catheterisation, echocardiography and spirometry data were followed from diagnosis to death, transplantation or censoring with all follow-up and survival data modelled by Bayesian methods.

Results

The diagnoses in 128 patients were idiopathic pulmonary fibrosis (n = 74, 58%), hypersensitivity pneumonitis (n = 17, 13%), non-specific interstitial pneumonia (n = 12, 9%), undifferentiated ILD (n = 8, 6%) and other lung diseases (n = 17, 13%). Final outcomes were death (n = 106, 83%), transplantation (n = 9, 7%) and censoring (n = 13, 10%). Patients treated with PDE5i (n = 50, 39%) had higher mean pulmonary artery pressure (median 38 mm Hg [interquartile range, IQR: 34, 43] vs. 35 mm Hg [IQR: 31, 38], p = 0.07) and percentage predicted forced vital capacity (FVC; median 57% [IQR: 51, 73] vs. 52% [IQR: 45, 66], p=0.08) though differences did not reach significance. Patients treated with PDE5i survived longer than untreated patients (median 2.18 years [95% CI: 1.43, 3.04] vs. 0.94 years [0.69, 1.51], p = 0.003) independent of all other prognostic markers by Bayesian joint-modelling (HR 0.39, 95% CI: 0.23, 0.59, p < 0.001) and propensity-matched analyses (HR 0.38, 95% CI: 0.22, 0.58, p < 0.001). Survival difference with treatment was significantly larger if right ventricular function was normal, rather than abnormal, at presentation (+2.55 years, 95% CI: −0.03, +3.97 vs. +0.98 years, 95% CI: +0.47, +2.00, p = 0.04).

Conclusion

PDE5i treatment in ILD-PH should be investigated by a prospective randomized trial.     

Change in gait speed and adverse outcomes in patients with idiopathic pulmonary fibrosis: A prospective cohort study

Background and Objective

Gait speed is associated with survival in individuals with idiopathic pulmonary fibrosis (IPF). The extent to which four-metre gait speed (4MGS) decline predicts adverse outcome in IPF remains unclear. We aimed to examine longitudinal 4MGS change and identify a cut-point associated with adverse outcome.

Methods

In a prospective cohort study, we recruited 132 individuals newly diagnosed with IPF and measured 4MGS change over 6 months. Death/first hospitalization at 6 months were composite outcome events. Complete data (paired 4MGS plus index event) were available in 85 participants; missing 4MGS data were addressed using multiple imputation. Receiver-Operating Curve plots identified a 4MGS change cut-point. Cox proportional-hazard regression assessed the relationship between 4MGS change and time to event.

Results

4MGS declined over 6 months (mean [95% CI] change: −0.05 [−0.09 to −0.01] m/s; p = 0.02). A decline of 0.07 m/s or more in 4MGS over 6 months had better discrimination for the index event than change in 6-minute walk distance, forced vital capacity, Composite Physiologic Index or Gender Age Physiology index. Kaplan–Meier curves demonstrated a significant difference in time to event between 4MGS groups (substantial decline: >−0.07 m/s versus minor decline/improvers: ≤−0.07 m/s; p = 0.007). Those with substantial decline had an increased risk of hospitalization/death (adjusted hazard ratio [95% CI] 4.61 [1.23–15.83]). Similar results were observed in multiple imputation analysis.

Conclusion

In newly diagnosed IPF, a substantial 4MGS decline over 6 months is associated with shorter time to hospitalization/death at 6 months. 4MGS change has potential as a surrogate endpoint for interventions aimed at modifying hospitalization/death.