Who will need long-term care? Creation and validation of an instrument that identifies older people at risk.

The aim of this study was to create and measure the predictive validity of a screening instrument that identifies older people who are at risk for developing a need for long-term care within a year. This was an observational study, with participants allocated to either a derivation cohort or a validation cohort, in the United States. A nationally representative sample of older community-dwelling Medicare beneficiaries (n = 6,538) participated in the Medicare Current Beneficiary Survey. Questions addressed sociodemographic, functional, health-related, and utilization characteristics in 1991 and 1992, linked to records of Medicare payments for health services during 1991-1992. In the derivation cohort, 14 self-reported characteristics were significant predictors of developing a need for long-term care within 1 year. In the validation cohort, these 14 characteristics identified a high-risk subgroup (18%) that, during the following year, developed a need for long-term care at six times the rate of the low-risk majority. This brief survey instrument identifies a high-risk minority of older people that will, during the following year, develop a need for long-term care at six times the rate of the low-risk majority. This instrument may be useful for targeting at-risk subgroups of older populations to receive interventions designed to preserve functional independence and avert the need for long-term care.     

What do pediatric primary care providers think are important research questions? A perspective from PROS providers.

OBJECTIVE: To describe what pediatric primary care providers involved in the Pediatric Research in Office Settings (PROS) research network think are important yet inadequately addressed questions in pediatric primary care research. METHODS: A total of 1785 pediatric primary care providers in the PROS network were asked what they thought were important yet inadequately addressed areas of primary care research. We used a single, open-ended question in a mail survey. Written answers to this question were analyzed by qualitative methods to determine the main themes of interest to pediatric primary care providers. RESULTS: Overall survey response rate was 48.7%; the open-ended question yielded 1109 individual answers. Six lines of inquiry were identified as being important to these providers: (1) effective counseling techniques to use in anticipatory guidance; (2) strategies to prevent and treat obesity; (3) the effectiveness of well-child care; (4) ongoing management of patients with attention-deficit/hyperactivity disorder; (5) the role of the primary care provider in caring for children with mental health needs; and (6) optimal organization of office practices. CONCLUSIONS: The translation of research into practice may be improved by a better understanding of the needs and interests of those who see pediatric patients in the primary care setting.     

Phase I and pharmacologic study of the human DNA methyltransferase antisense oligodeoxynucleotide MG98 given as a 21-day continuous infusion every 4 weeks

Purpose: MG98 is a second generation phosphorothioate antisense oligodeoxynucleotide which is a highly specific inhibitor of translation of the mRNA for human DNA MeTase I (DNMT 1). This phase I study examined the toxicity and pharmacologic profile of MG98 administered as a continuous 21-day intravenous infusion every 4 weeks. Patients and methods: Fourteen patients with solid cancers received a total of 25 cycles of MG98 at doses ranging from 40 to 240 mg/m²/day. Steady-state concentrations of MG98 were measured as were several pharmacodynamic assessments including mRNA of the target gene, DNMT1, in PBMC. In addition, other potential surrogate markers of drug effects were explored, including hemoglobin F, Vimentin and GADD45. Results: Dose limiting effects were drug-related reversible transaminase elevation and fatigue seen at doses of 240, 200 and 160 mg/m²/day. The dose level of 80 mg/m²/day was felt to be safe and tolerable when delivered on this schedule. No evidence of antitumor activity was observed. Although pharmacokinetic analysis revealed that at the higher dose levels, mean Css values of MG98 were approximately 10-fold times the IC₅₀ values associated with target inhibition in vitro, the extent of MG98 penetration into target tumors in this trial was not determined. No consistent, dose-related changes in correlative markers including DNMT1 mRNA, hemoglobin F, Vimentin and GADD45, were observed. Conclusions: This schedule of MG98 given as a 21-day continuous intravenous infusion every 4 weeks was poorly tolerated in the highest doses; therefore, further disease-site specific evaluation of the efficacy of this agent will utilize a more favorable, intermittent dosing schedule. Pharmacodynamic evaluations undertaken in an attempt to explore and validate the biological mechanisms of MG98 did not show dose-related effects.     

Angiotensin-converting enzyme genotype and outcome in pediatric IgA nephropathy

Angiotensin-converting enzyme (ACE) I/D polymorphism has been implicated as a genetic marker for progression of glomerular disease. Studies of ACE genotypes in adults with IgA nephropathy (IgAN) have yielded conflicting results. We performed ACE genotyping on 79 patients with IgAN diagnosed prior to age 18 years who had either progressed to end-stage renal disease (ESRD) or are now more than 5 years post biopsy. Mean follow-up was 14.8 years for those with normal renal function. Forty-three (54.4%) subjects had normal renal function and a normal urinalysis at last evaluation. Sixteen (20%) progressed to ESRD and 1 has chronic renal insufficiency. Kaplan-Meier survival curves for progression to ESRD did not differ significantly for the ACE DD, ID, and II genotype groups (P=0.095, log-rank test). By univariate analysis, presence of hypertension and degree of proteinuria at diagnosis, and unfavorable histology but not ACE genotype, was significantly associated with progression to ESRD. In the Cox proportional hazards model that included grade of proteinuria, the ACE D allele was a significant independent predictor of outcome with a hazard ratio of 2.37 (P=0.031). Our data, while inconclusive, suggest that the ACE D allele may associate with poor outcome in pediatric IgAN.     

Autologous breast reconstruction: the Vanderbilt experience (1998 to 2005) of independent predictors of displeasing outcomes

BACKGROUND: Optimal surgical outcomes are dependent on an appreciation of comorbid conditions that may handicap results. The purpose of this retrospective analysis was to delineate risk factors for complications after autologous breast reconstruction. STUDY DESIGN: An institutional database was constructed of patients who underwent autologous breast reconstruction from 1998 to 2005. Variables captured included age, diabetes and smoking status, prereconstruction radiation therapy, concomitant breast resection, preoperative albumin, flap type, and body mass index (BMI; based on World Health Organization classifications: BMI>25, overweight; >30, obese). The primary outcome was noninfectious wound complications (NIWC), a novel classification based on the extent of tissue derangement and need for operative intervention. Secondary outcomes were wound infection, hematoma, hernia, and fat necrosis. Statistical analysis was performed using chi-square tests and multiple logistic regression. RESULTS: The analysis included 200 flaps (transverse rectus abdominis myocutaneous [TRAM]=171; latissimus dorsi=29) in 180 patients. There were 19 infections (9.5%), 3 total flap losses (1.5%), 14 hematomas (7%), and 11 donor-site hernias (6%). The incidences of fat necrosis and any NIWC were 18% and 36%, respectively. Mean followup was 13.1 months (range 1.1 to 51.7 months). Multiple logistic regression demonstrated that obesity (BMI>30) is a statistically significant independent risk factor for any NIWC (hazards ratio=6.58; 95% CI, 2.85 to 15.18; p < 0.01) and for NIWC requiring operative treatment (NIWC>or=3; hazard ratio=6.23; 95% CI 2.15 to 18.05; p < 0.01). Increased BMI predicts NIWC, NIWC requiring operative intervention, and wound infection (p < 0.01). CONCLUSIONS: These data suggest that obesity is a strong predictor of simple and complex NIWC and of wound infection after autologous breast reconstruction. Obese patients should be counseled about their significantly increased risk of experiencing these unwanted outcomes.     

How does prosthesis head size affect vibration transmission in ossiculoplasty?

OBJECTIVES: The transmission of vibrations from the tympanic membrane to the stapes footplate by an ossicular reconstruction prosthesis is affected by the size of the prosthesis head. We sought to determine if augmenting or reducing the head size of prosthesis had a systematic effect on transmission of vibrations to the stapes. STUDY DESIGN: We conducted a fresh cadaveric temporal bone middle ear study. METHODS: The incus was replaced with a prosthesis using a tympanic membrane to stapes head (TASH)-type hydroxyapatite prosthesis in nine fresh cadaveric temporal bones. Three prosthesis head sizes were created: unaltered, reduced, and augmented. Stapes vibrations were measured with a laser Doppler vibrometer in response to acoustic frequency chirps at 90 dB SPL. RESULTS: All three head size prostheses resulted in smaller stapes vibrations than the intact ear. There was no difference in the vibration transmission between the three different head sizes. All prostheses showed a vibration loss of 10 to 15 dB compared to the intact ear. CONCLUSIONS AND SIGNIFICANCE: Within the range of sizes tested, prosthesis head size had little impact on vibration transmission to the stapes footplate.     

Consensus guidelines for the management of atopic dermatitis: An Asia–Pacific perspective

Atopic dermatitis (AD) is a relatively common disease in patients in the Asia–Pacific region. It presents a particular clinical challenge and requires careful clinical management. The chronic nature of AD characterized by flares, exacerbations and periods of quiescence requires a multipronged approach aimed at reducing itch, inflammation and the appearance of secondary lesions. In addition, varying levels of maintenance therapy may be required to avoid exacerbations. Survey data from the region indicate that there is significant variation across the Asia–Pacific with regard to current treatment practices. The management of AD may also be influenced by differing health‐care systems, variable climate, access to medical care and cultural diversity. The current consensus guidelines have been developed to provide up‐to‐date and concise evidence‐ and experience‐based recommendations directed towards general practitioners and general dermatologists in the Asia–Pacific region on the management of pediatric and adult AD.     

Epidermal Growth Factor Receptors in Genetically Induced Hyperproliferative Skin Disorders

The presence and morphologic distribution of epidermal growth factor receptor (EGF-R) were investigated in a variety of genetic disorders that affect human epidermis. These diseases included various forms of ichthyoses as well as restrictive dermopathy and the CHILD syndrome (congenital hemidysplasia-ichthyosiform erythroderma-limb defects). The distribution of EGF-R was detected by immunohistochemical techniques. Increased staining of immunoreactive EGF-R was frequently, but not always, seen in lesions with experimental or clinical evidence of hyperproliferation, suggesting an increased potential to respond to endogenous levels of either transforming growth factor-alpha or EGF. The finding that EGF-R levels are not always increased in congenital epidermal disorders indicated that the presence of this receptor pathway is not simply a marker for aberrant epidermis.