Prevalence and characterisation of Staphylococcus aureus causing community-acquired skin and soft tissue infections on Java and Bali, Indonesia.

OBJECTIVES: To define the role of Staphylococcus aureus in community settings among patients with skin and soft tissue infections (SSTI) in Indonesia. METHODS: Staphylococcus aureus were cultured from anterior nares, throat and wounds of 567 ambulatory patients presenting with SSTI. The mecA gene and genes encoding Panton-Valentine leukocidin (PVL; lukF-PV and lukS-PV) and exfoliative toxin (ET; eta and etb) were determined by PCR. Clonal relatedness among methicillin-resistant S. aureus (MRSA) and PVL-positive S. aureus was analysed using multilocus variable-number tandem-repeat analysis (MLVA) typing, and multilocus sequence typing (MLST) for a subset of isolates. Staphylococcal cassette chromosome mec (SCCmec) was determined for all MRSA isolates. Moreover, determinants for S. aureus SSTI, and PVL/ET-positive vs PVL/ET-negative S. aureus were assessed. RESULTS: Staphylococcus aureus were isolated from SSTI wounds of 257 (45.3%) patients, eight (3.1%) of these were MRSA. Genes encoding PVL and ETs were detected in 21.8% and 17.5% of methicillin-susceptible S. aureus (MSSA), respectively. PVL-positive MRSA was not detected. Nasopharyngeal S. aureus carriage was an independent determinant for S. aureus SSTI (odds ratio [OR] 1.8). Primary skin infection (OR 5.4) and previous antibiotic therapy (OR 3.5) were associated with PVL-positive MSSA. Primary skin infection (OR 2.2) was the only factor associated with ET-positive MSSA. MLVA typing revealed two more prevalent MSSA clusters. One ST1-MRSA-SCCmec type IV isolate and a cluster of ST239-MRSA-SCCmec type III were found. CONCLUSIONS: Community-acquired SSTI in Indonesia was frequently caused by PVL-positive MSSA, and the hospital-associated ST239-MRSA may have spread from the hospital into the community.

Cochlear implantation and clinical features in patients with Noonan syndrome and Noonan syndrome with multiple lentigines caused by a mutation in PTPN11.

Existing literature only reports a few patients with Noonan syndrome (NS) and Noonan syndrome with multiple lentigines (NSML) who underwent cochlear implantation (CI). The present study describes four NS patients and one NSML patient with a PTPN11 mutation. They all had severe to profound hearing loss, and they received a CI. The age at which the CI surgery occurred ranged from 1 to 13 years old, and the audiological results in all five patients improved after the CI. Otological and audiological examinations in NS and NSML are important, and for those with severe hearing loss, the CI surgery improved the audiological outcome regardless of age.

Cochlear Implantation in Patients With Usher Syndrome Type IIa Increases Performance and Quality of Life.

OBJECTIVES: Usher syndrome type IIa (USH2a) is characterized by congenital moderate to severe hearing impairment and retinitis pigmentosa. Hearing rehabilitation starts in early childhood with the application of hearing aids. In some patients with USH2a, severe progression of hearing impairment leads to insufficient speech intelligibility with hearing aids and issues with adequate communication and safety. Cochlear implantation (CI) is the next step in rehabilitation of such patients. This study evaluates the performance and benefit of CI in patients with USH2a. DESIGN: Retrospective case-control study to evaluate the performance and benefit of CI in 16 postlingually deaf adults (eight patients with USH2a and eight matched controls). Performance and benefit were evaluated by a speech intelligibility test and three quality-of-life questionnaires. RESULTS: Patients with USH2a with a mean age of 59 years at implantation exhibited good performance after CI. The phoneme scores improved significantly from 41 to 87% in patients with USH2a (p = 0.02) and from 30 to 86% in the control group (p = 0.001). The results of the questionnaire survey demonstrated a clear benefit from CI. There were no differences in performance or benefit between patients with USH2a and control patients before and after CI. CONCLUSIONS: CI increases speech intelligibility and improves quality of life in patients with USH2a.

Paediatric Cochlear Implantation in Patients with Waardenburg Syndrome.

OBJECTIVE: To analyse the benefit of cochlear implantation in young deaf children with Waardenburg syndrome (WS) compared to a reference group of young deaf children without additional disabilities. METHOD: A retrospective study was conducted on children with WS who underwent cochlear implantation at the age of 2 years or younger. The post-operative results for speech perception (phonetically balanced standard Dutch consonant-vocal-consonant word lists) and language comprehension (the Reynell Developmental Language Scales, RDLS), expressed as a language quotient (LQ), were compared between the WS group and the reference group by using multiple linear regression analysis. RESULTS: A total of 14 children were diagnosed with WS, and 6 of them had additional disabilities. The WS children were implanted at a mean age of 1.6 years and the 48 children of the reference group at a mean age of 1.3 years. The WS children had a mean phoneme score of 80% and a mean LQ of 0.74 at 3 years post-implantation, and these results were comparable to those of the reference group. Only the factor additional disabilities had a significant negative influence on auditory perception and language comprehension. CONCLUSIONS: Children with WS performed similarly to the reference group in the present study, and these outcomes are in line with the previous literature. Although good counselling about additional disabilities concomitant to the syndrome is relevant, cochlear implantation is a good rehabilitation method for children with WS.

Allelic Mutations of KITLG, Encoding KIT Ligand, Cause Asymmetric and Unilateral Hearing Loss and Waardenburg Syndrome Type 2.

Linkage analysis combined with whole-exome sequencing in a large family with congenital and stable non-syndromic unilateral and asymmetric hearing loss (NS-UHL/AHL) revealed a heterozygous truncating mutation, c.286_303delinsT (p.Ser96Ter), in KITLG. This mutation co-segregated with NS-UHL/AHL as a dominant trait with reduced penetrance. By screening a panel of probands with NS-UHL/AHL, we found an additional mutation, c.200_202del (p.His67_Cys68delinsArg). In vitro studies revealed that the p.His67_Cys68delinsArg transmembrane isoform of KITLG is not detectable at the cell membrane, supporting pathogenicity. KITLG encodes a ligand for the KIT receptor. Also, KITLG-KIT signaling and MITF are suggested to mutually interact in melanocyte development. Because mutations in MITF are causative of Waardenburg syndrome type 2 (WS2), we screened KITLG in suspected WS2-affected probands. A heterozygous missense mutation, c.310C>G (p.Leu104Val), that segregated with WS2 was identified in a small family. In vitro studies revealed that the p.Leu104Val transmembrane isoform of KITLG is located at the cell membrane, as is wild-type KITLG. However, in culture media of transfected cells, the p.Leu104Val soluble isoform of KITLG was reduced, and no soluble p.His67_Cys68delinsArg and p.Ser96Ter KITLG could be detected. These data suggest that mutations in KITLG associated with NS-UHL/AHL have a loss-of-function effect. We speculate that the mechanism of the mutation underlying WS2 and leading to membrane incorporation and reduced secretion of KITLG occurs via a dominant-negative or gain-of-function effect. Our study unveils different phenotypes associated with KITLG, previously associated with pigmentation abnormalities, and will thereby improve the genetic counseling given to individuals with KITLG variants.

Long-term outcome after statin treatment in routine clinical practice: results from a prospective PCI cohort study.

AIMS: We aim to investigate the association between different types of statins, in particular simvastatin and atorvastatin, and long-term mortality after percutaneous coronary intervention (PCI). METHODS AND RESULTS: Between 2000 and 2005, a prospective cohort was constituted of 5,647 patients who underwent PCI. Type and doses of statin use were collected after the PCI procedure. Survival status was obtained from municipal civil registries. The primary endpoint was all-cause mortality. Secondary endpoints were cardiac and cancer mortality. Median follow-up was 5.0 years (range three to nine years). During follow-up 738 patients (13.1%) died. In total, 4,970 patients (88%) were on statin therapy four weeks after PCI of whom the majority used either atorvastatin (34%) or simvastatin (29%). Cumulative survival rates at eight years in the atorvastatin group were 83%, and 79% in the simvastatin group (log-rank, p=0.004). After adjustment, statin use was associated with a 50% mortality reduction (HR 0.49, 95% CI 0.40-0.59) and atorvastatin use was associated with lower total mortality than simvastatin use (adjusted HR 0.77, 95% CI 0.61-0.97). This was largely driven by cancer mortality (adjusted HR 0.59, 95% CI 0.38-0.91). CONCLUSIONS: In patients undergoing PCI the use of statins is associated with reduced mortality during prolonged follow-up. Patients using atorvastatin had a 23% lower mortality than those using simvastatin.

Health-related quality of life and long-term mortality in patients treated with percutaneous coronary intervention.

BACKGROUND: Health status has become increasingly important as an outcome measure in patients with cardiovascular disease. Poor patient-rated health status has been shown to predict mortality in patients with coronary artery disease and heart failure. In patients treated with percutaneous coronary intervention (PCI), we examined whether poor health status predicts 6-year mortality and whether a decline in health status is associated with adverse clinical outcome. METHODS: Consecutive patients (N = 872) treated with PCI as part of the RESEARCH registry, completed the 36-item Short-Form Health Survey (SF-36) at 1 and 12 months post-PCI. RESULTS: The SF-36 domains physical functioning (hazard ratio [HR] 2.59, 95% CI 1.61-4.16), social functioning (HR 2.76, 95% CI 1.74-4.37), role limitations due to physical functioning (HR 2.45, CI 1.52-3.92), mental health (HR 2.12, 95% CI 1.35-3.31), vitality (HR 1.73, 95% CI 1.09-2.74), bodily pain (HR 2.25, 95% CI 1.43-3.54), and general health (HR 2.46, 95% CI 1.57-3.87) were associated with 6-year mortality. A decline in health status was not related with higher 6-year mortality. CONCLUSIONS: Health status domains as measured with the SF-36 predicted death at 6-year follow-up in PCI patients treated with drug-eluting stenting, independent of demographic and clinical characteristics. In contrast, a decline in health status between 1 and 12 months post index procedure, as measured with the SF-36, was not associated with 6-year mortality in PCI patients treated with drug-eluting stenting.

Negative and positive affect are independently associated with patient-reported health status following percutaneous coronary intervention.

PURPOSE: We examined the association between negative and positive affect and 12-month health status in patients treated with percutaneous coronary intervention (PCI) with drug-eluting stents. METHODS: Consecutive PCI patients (n = 562) completed the Global Mood Scale at baseline to assess affect and the EuroQoL-5D (EQ-5D) at baseline and 12-month follow-up to assess health status. RESULTS: Negative affect [F(1, 522) = 17.14, P < .001] and positive affect [F(1, 522) = 5.11, P = .02] at baseline were independent associates of overall health status at 12-month follow-up, adjusting for demographic and clinical factors. Moreover, there was a significant interaction for negative by positive affect [F(1, 522) = 6.11, P = .01]. In domain-specific analyses, high negative affect was associated with problems in mobility, self-care, usual activities, pain/discomfort, and anxiety/depression with the risk being two to fivefold. Low positive affect was only associated with problems in self-care (OR: 8.14; 95% CI: 1.85-35.9; P = .006) and usual activities (OR: 1.87; 95% CI: 1.17-3.00; P = .009). CONCLUSIONS: Baseline negative and positive affect contribute independently to patient-reported health status 12 months post PCI. Positive affect moderated the detrimental effects of negative affect on overall health status. Enhancing positive affect might be an important target to improve patient-centered outcomes in coronary artery disease.