Clinical outcomes of patients with severe aortic stenosis at increased surgical risk according to treatment modality

Objectives The aim of this study was to assess the role of transcatheter aortic valve implantation (TAVI) compared with medical treatment (MT) and surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) at increased surgical risk. Background Elderly patients with comorbidities are at considerable risk for SAVR. Methods Since July 2007, 442 patients with severe AS (age: 81.7 ± 6.0 years, mean logistic European System for Cardiac Operative Risk Evaluation: 22.3 ± 14.6%) underwent treatment allocation to MT (n = 78), SAVR (n = 107), or TAVI (n = 257) on the basis of a comprehensive evaluation protocol as part of a prospective registry. Results Baseline clinical characteristics were similar among patients allocated to MT and TAVI, whereas patients allocated to SAVR were younger (p < 0.001) and had a lower predicted peri-operative risk (p < 0.001). Unadjusted rates of all-cause mortality at 30 months were lower for SAVR (22.4%) and TAVI (22.6%) compared with MT (61.5%, p < 0.001). Adjusted hazard ratios for death were 0.51 (95% confidence interval: 0.30 to 0.87) for SAVR compared with MT and 0.38 (95% confidence interval: 0.25 to 0.58) for TAVI compared with MT. Medical treatment (<0.001), older age (>80 years, p = 0.01), peripheral vascular disease (<0.001), and atrial fibrillation (p = 0.04) were significantly associated with all-cause mortality at 30 months in the multivariate analysis. At 1 year, more patients undergoing SAVR (92.3%) or TAVI (93.2%) had New York Heart Association functional class I/II as compared with patients with MT (70.8%, p = 0.003). Conclusions Among patients with severe AS with increased surgical risk, SAVR and TAVI improve survival and symptoms compared with MT. Clinical outcomes of TAVI and SAVR seem similar among carefully selected patients with severe symptomatic AS at increased risk.

Long-term clinical outcomes of biodegradable polymer biolimus-eluting stents versus durable polymer sirolimus-eluting stents in patients with coronary artery disease (LEADERS): 4 year follow-up of a randomised non-inferiority trial

Background The effectiveness of durable polymer drug-eluting stents comes at the expense of delayed arterial healing and subsequent late adverse events such as stent thrombosis (ST). We report the 4 year follow-up of an assessment of biodegradable polymer-based drug-eluting stents, which aim to improve safety by avoiding the persistent inflammatory stimulus of durable polymers. Methods We did a multicentre, assessor-masked, non-inferiority trial. Between Nov 27, 2006, and May 18, 2007, patients aged 18 years or older with coronary artery disease were randomly allocated with a computer-generated sequence to receive either biodegradable polymer biolimus-eluting stents (BES) or durable polymer sirolimus-eluting stents (SES; 1:1 ratio). The primary endpoint was a composite of cardiac death, myocardial infarction, or clinically-indicated target vessel revascularisation (TVR); patients were followed-up for 4 years. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00389220. Findings 1707 patients with 2472 lesions were randomly allocated to receive either biodegradable polymer BES (857 patients, 1257 lesions) or durable polymer SES (850 patients, 1215 lesions). At 4 years, biodegradable polymer BES were non-inferior to durable polymer SES for the primary endpoint: 160 (18·7%) patients versus 192 (22·6%) patients (rate ratios [RR] 0·81, 95% CI 0·66–1·00, p for non-inferiority <0·0001, p for superiority=0·050). The RR of definite ST was 0·62 (0·35–1·08, p=0·09), which was largely attributable to a lower risk of very late definite ST between years 1 and 4 in the BES group than in the SES group (RR 0·20, 95% CI 0·06–0·67, p=0·004). Conversely, the RR of definite ST during the first year was 0·99 (0·51–1·95; p=0·98) and the test for interaction between RR of definite ST and time was positive (pinteraction=0·017). We recorded an interaction with time for events associated with ST but not for other events. For primary endpoint events associated with ST, the RR was 0·86 (0·41–1·80) during the first year and 0·17 (0·04–0·78) during subsequent years (pinteraction=0·049). Interpretation Biodegradable polymer BES are non-inferior to durable polymer SES and, by reducing the risk of cardiac events associated with very late ST, might improve long-term clinical outcomes for up to 4 years compared with durable polymer SES. Funding Biosensors Europe SA, Switzerland.

Outcomes of antiretroviral treatment programs in rural Southern Africa

Data on outcomes of antiretroviral treatment (ART) programs in rural sub-Saharan African are scarce. We describe early losses and long-term outcomes in 6 rural programs in Southern Africa with limited access to viral load monitoring and second-line ART.

Outcomes of antiretroviral treatment in programmes with and without routine viral load monitoring in Southern Africa

Objectives: To compare outcomes of antiretroviral therapy (ART) in South Africa, where viral load monitoring is routine, with those in Malawi and Zambia, where monitoring is based on CD4 cell counts. Methods: We included 18 706 adult patients starting ART in South Africa and 80 937 patients in Zambia or Malawi. We examined CD4 responses in models for repeated measures and the probability of switching to second-line regimens, mortality and loss to follow-up in multistate models, measuring time from 6 months. Results: In South Africa, 9.8% [95% confidence interval (CI) 9.1–10.5] had switched at 3 years, 1.3% (95% CI 0.9–1.6) remained on failing first-line regimens, 9.2% (95% CI 8.5–9.8) were lost to follow-up and 4.3% (95% CI 3.9–4.8) had died. In Malawi and Zambia, more patients were on a failing first-line regimen [3.7% (95% CI 3.6–3.9], fewer patients had switched [2.1% (95% CI 2.0–2.3)] and more patients were lost to follow-up [15.3% (95% CI 15.0–15.6)] or had died [6.3% (95% CI 6.0–6.5)]. Median CD4 cell counts were lower in South Africa at the start of ART (93 vs. 132 cells/μl; P < 0.001) but higher after 3 years (425 vs. 383 cells/μl; P < 0.001). The hazard ratio comparing South Africa with Malawi and Zambia after adjusting for age, sex, first-line regimen and CD4 cell count was 0.58 (0.50–0.66) for death and 0.53 (0.48–0.58) for loss to follow-up. Conclusion: Over 3 years of ART mortality was lower in South Africa than in Malawi or Zambia. The more favourable outcome in South Africa might be explained by viral load monitoring leading to earlier detection of treatment failure, adherence counselling and timelier switching to second-line ART.

Outcomes of antiretroviral therapy in the Swiss HIV Cohort Study: latent class analysis

An in-depth understanding of the different groups that make up the HIV-infected population should inform prevention and care. Using latent class analysis (LCA) we identified seven groups with similar socio-demographic and behavioral characteristics at enrolment in the Swiss HIV Cohort Study: older gay men, younger gay men, older heterosexual men, injection drug users, single migrants, migrant women in partnerships and heterosexual men and women. Outcomes of combination antiretroviral therapy (ART) were analyzed in 1,633 patients starting ART. Compared to older gay men, the probability of a virologic response to ART was reduced in single migrants, in older heterosexual men and in IDUs. Loss to follow-up was higher in single migrants and IDUs, and mortality was increased in older heterosexual men and IDUs. Socio-behavioral groups identified by LCA allow insights above what can be gleaned from traditional transmission groups, and may identify patients who could benefit from targeted interventions.

Long-term clinical and angiographic outcomes of diabetic patients after revascularization with early generation drug-eluting stents

Early generation drug-eluting stents (DESs) reduce restenosis and repeat revascularization procedures. However, the long-term safety and efficacy of early generation DES according to diabetic status are poorly established.

Thrombophilia and outcomes of assisted reproduction technologies: a systematic review and meta-analysis

Thrombophilia has been associated with pregnancy complications and recurrent miscarriage. The aim of this systematic review was to evaluate the controversial association between thrombophilia and failures of assisted reproduction technology (ART). A systematic search of the literature for studies reporting on thrombophilia in women undergoing ART up to April 2011 yielded 33 studies (23 evaluating anti-phospholipid antibodies, 5 inherited thrombophilia, and 5 both) involving 6092 patients. Overall, methodologic quality of the studies was poor. Combined results from case-control studies showed that factor V Leiden was significantly more prevalent among women with ART failure compared with fertile parous women or those achieving pregnancy after ART (odds ratio = 3.08; 95% confidence interval, 1.77-5.36). The prothrombin mutation, methylenetetrahydrofolate reductase mutation, deficiency of protein S, protein C, or anti-thrombin were all not associated with ART failure. Women with ART failure tested more frequently positive for anti-phospholipids antibodies (odds ratio = 3.33; 95% confidence interval, 1.77-6.26) with evidence of high degree of between-study heterogeneity (I(2) = 75%; P < .00001). Prospective cohort studies did not show significant associations between thrombophilia and ART outcomes. Although case-control studies suggest that women experiencing ART failures are more frequently positive for factor V Leiden and anti-phospholipid antibodies, the evidence is inconclusive and not supported by cohort studies.

Treatment outcomes of an integrated residential programme for patients with schizophrenia and substance use disorder

About half of all schizophrenic patients have a co-occurring substance use disorder, leading to poorer social and functional outcomes than obtained in non-abusing patients. To improve outcomes, integrated treatments have been designed that address the two conditions simultaneously. Results are, however, conflicting because the available effect studies are hampered by various methodological issues, among which are heterogeneous patient samples.

Anti-infective therapy of peri-implantitis with adjunctive local drug delivery or photodynamic therapy: six-month outcomes of a prospective randomized clinical trial

To compare the adjunctive clinical effects in the non-surgical treatment of peri-implantitis with either local drug delivery (LDD) or photodynamic therapy (PDT).

Clinical outcomes of patients with estimated low or intermediate surgical risk undergoing transcatheter aortic valve implantation

AimsTranscatheter aortic valve implantation (TAVI) is an established treatment alternative to surgical aortic valve replacement in high-risk and inoperable patients and outcomes among patients with estimated low or intermediate risk remain to be determined. The aim of this study was to assess clinical outcomes among patients with estimated low or intermediate surgical risk undergoing TAVI.Methods and resultsBetween August 2007 and October 2011, 389 consecutive patients underwent TAVI and were categorized according to the Society of Thoracic Surgeons (STS) score into low (STS < 3%; n = 41, 10.5%), intermediate (STS ≥3% and ≤8%, n = 254, 65.3%), and high-risk (STS > 8%; n = 94, 24.2%) groups for the purpose of this study. Significant differences were found between the groups (low risk vs. intermediate risk vs. high risk) for age (78.2 ± 6.7 vs. 82.7 ± 5.7 vs. 83.7 ± 4.9, P < 0.001), body mass index (28.1 ± 6.1 vs. 26.5 ± 4.9 vs. 24.4 ± 4.6, P < 0.001), chronic renal failure (34 vs. 67 vs. 90%, P < 0.001), all-cause mortality at 30 days (2.4 vs. 3.9 vs. 14.9%, P = 0.001), and all-cause mortality at 1 year (10.1 vs. 16.1 vs. 34.5%, P = 0.0003). No differences were observed with regards to cerebrovascular accidents and myocardial infarction during 1-year follow-up.ConclusionIn contemporary practice, TAVI is not limited to inoperable or STS-defined high-risk patients and should be guided by the decision of an interdisciplinary Heart Team. Compared with patients at calculated high risk, well-selected patients with STS-defined intermediate or low risk appear to have favourable clinical outcomes.

Clinicopathologic features and long-term outcomes of NUT midline carcinoma

NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer characterized by rearrangement of the NUT gene. Research advances have provided opportunities for targeted therapy in NMC, yet the clinical features of this rare disease have not been systematically characterized. We report on a large population of such patients to identify the disease characteristics and treatments, correlate them with outcome, and to consider clinical recommendations.

Microbial colonization patterns predict the outcomes of surgical treatment of intrabony defects

AIM: To explore the impact of bacterial load and microbial colonization patterns on the clinical outcomes of periodontal surgery at deep intrabony defects. MATERIALS AND METHODS: One hundred and twenty-two patients with advanced chronic periodontitis and at least one intrabony defect of >3 mm were recruited in 10 centres. Before recruitment, the infection control phase of periodontal therapy was completed. After surgical access and debridement, the regenerative material was applied in the test subjects, and omitted in the controls. At baseline and 1 year following the interventions, clinical attachment levels (CAL), pocket probing depths (PPD), recession (REC), full-mouth plaque scores and full-mouth bleeding scores were assessed. Microbial colonization of the defect-associated pocket was assessed using a DNA-DNA checkerboard analysis. RESULTS: Total bacterial load and counts of red complex bacteria were negatively associated with CAL gains 1 year following treatment. The probability of achieving above median CAL gains (>3 mm) was significantly decreased by higher total bacterial counts, higher red complex and T. forsythensis counts immediately before surgery. CONCLUSIONS: Presence of high bacterial load and specific periodontal pathogen complexes in deep periodontal pockets associated with intrabony defects had a significant negative impact on the 1 year outcome of surgical/regenerative treatment.