The presence of even mild diabetic complications has a significant impact on patients' quality of life. Early diagnosis and treatment is essential to help prevent deterioration of HRQOL in these patients.

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Between 1983 and 1995, 546 Blalock-Taussig shunt procedures were performed in 472 patients: 128 (23-0%) were classical shunts, 90 of them on the same side as to the aortic arch, and 418 (77.0%) were modified shunts, 182 on the same side of the arch. At the time of surgery, 78 patients were aged below one week, 270 from one week to 12 months, and 198 patients were over one year of age. The mean pre-operative arterial saturation (71.7%± 16.5%) was significantly increased to 83%±17.9% immediately after the procedure (p=0.017). The overall hospital mortality rate was 2.9% (16/546), with rates of 2.3% (3/128) for the classical, and 3.1% (13/418) for the modified shunts (p= not significant). The rate was significantly higher, however, for classical shunts when the pulmonary arterial diameter was less than 4 mm (15.4% versus zero; p=0.047), though this relationship was reversed for modified shunts (zero versus 3-6%; p=0.338). Early mortality was significantly influenced by the age at surgery, 5/78 (6.4%) in patients aged below 1 week, 3.7% between 1 week and 1 year, and 0.5% over 1 year (p=0.019). Early mortality was also significantly increased in patients weighing 3kg or less, 8/156 (5.1%), versus 3/303 (1.0%), p=O.O37. Overall, 51 shunts failed (9.3%), 10 early and 41 late. Early failure was significantly increased in patients weighing 3kg or less, 8/156 (5.1%) versus 3/303 (1.0%), p=0.0l6. The overall early failure rate was 1.4% (3/215) when heparin was administered intra-operatively and for 48 hours postoperatively, in contrast to an early failure rate of 3.4% (7/203) when heparin was not used (p = 0.294). Overall rates of failure during follow-up were 9-1% (17/188) in heparinized patients versusl3-6% (24/177), (p=0.173) in non-heparinized patients. Failure of classical shunts was 10.2% (13/128), compared with 6.7% (28/418) for modified shunts (p=0.195). Failure was more common overall if the pulmonary arterial diameter was less than 4 mm, 14.7% (9/61), as opposed to 8.7% (26/300) when the diameter was 4 mm or greater, (p=0.l44). Administration of aspirin during follow-up after the modified shunt procedure reduced failure from 11 % (18/163) to 6.7% (10/150), p=0.176. Classical or modified Blalock-Taussig shunts, either on the same side or opposite to the aortic arch, can be performed on patients of any age with minimum postoperative complications and low operative mortality. The use of intra-and post-operative heparin appears to reduce the overall rate of failure, and the administration of aspirin during follow-up appears to reduce failure of modified Blalock-Taussig shunts.

BackgroundIndividual randomized trials of first-line antiretroviral treatment do not consistently show an association between higher baseline HIV-1 RNA and lower efficacy. MethodsA MEDLINE search identified 21 HIV clinical trials with published analyses of antiretroviral efficacy by baseline HIV-1 RNA, using a standardized efficacy endpoint of HIV-1 RNA suppression <50 copies/mL at week 48. ResultsAmong 21 clinical trials identified, eight evaluated only nonnucleoside reverse transcriptase inhibitor (NNRTI)-based combinations, eight evaluated only protease inhibitor-based regimens and five compared different treatment classes. Ten of the trials included tenofovir (TDF)/emtricitabine (FTC) as only nucleoside reverse transcriptase inhibitor (NRTI) backbone, in addition but not restricted to abacavir (ABC)/lamivudine (3TC) (n = 7), zidovudine (ZDV)/3TC (n = 4) and stavudine (d4T)/3TC (n = 1). Across trials, the mean percentage of patients achieving HIV-1 RNA < 50 copies/mL at week 48 was 81.5% (5322 of 6814) for patients with baseline HIV-1 RNA < 100 000, vs. 72.6% (3949 of 5556) for patients with HIV-1 RNA > 100 000 copies/mL. In the meta-analysis, the absolute difference in efficacy between low and high HIV-1 RNA subgroups was 7.4% [95% confidence interval (CI) 5.9-8.9%; P < 0.001]. This difference was consistent in trials of NNRTI-based treatments (difference = 6.9%; 95% CI 4.3-9.6%), protease inhibitor-based treatments (difference = 8.4%; 95% CI 6.0-10.8%) and integrase or chemokine (C-C motif) receptor 5 (CCR5)-based treatments (difference = 6.0%; 95% CI 2.1-9.9%) and for trials using TDF/FTC (difference = 8.4%; 95% CI 6.0-10.8%); there was no evidence for heterogeneity of this difference between trials (Cochran's Q test; not significant). ConclusionsIn this meta-analysis of 21 first-line clinical trials, rates of HIV-1 RNA suppression at week 48 were significantly lower for patients w ith baseline HIV-1 RNA > 100 000 copies/mL (P < 0.001). This difference in efficacy was consistent across trials of different treatment classes and NRTI backbones.

Despite the equivalent efficacy and more favorable resistance implications of PI- versus NNRTI-based first line therapy, widespread use of PI-based first-line therapy is not warranted at this time, due to resource limitations and predicted increased risk of resistance-related failure of NNRTI/NRTI second-line regimens. PI-based first-line therapy could be reconsidered when antiretroviral agents from other classes become available for second-line regimens in resource-limited settings.