Effect of maternal and infant covariates on sibship correlation in birth weight

Birth weight on 12,644 singleton infants from 6,196 sibships born in Maryland between 1980 and 1984 were used to estimate the effects of nine maternal and infant covariates on the sibship correlation in birth weight. Assuming a homogeneous correlation across all families, the estimated intraclass correlation was 0.4664 (+/- 0.0099). This high sibship correlation makes it possible to predict, with reasonable accuracy, the birth weight of a child given information on previous sibs, as well as covariates on the mother and/or infant pertinent to a given pregnancy. The reduction in variance associated with incorporating information on the nine covariates used here was approximately equal to that obtained by conditioning on a single previous sib. Testing for heterogeneity in correlation among different groups of families showed that a crude measure of parity (first live birth vs. other), time between births, mother's marital status, and maternal age at the birth of the last child significantly influenced the sibship correlation in birth weight.     

Retrospective review of pemetrexed with or without platinum in malignant mesothelioma: The Australian 'Special Access Scheme' experience

Background: Pemetrexed and cisplatin have recently been shown to significantly improve survival compared with cisplatin alone. However, there are only limited data reflecting teaching hospital experience outside a clinical trial. Pemetrexed has only been available in Australia on a restricted basis since 2002. We reviewed our experience of patients treated on the Australian ‘Special Access Scheme’ at three major thoracic oncology units. Methods: Charts were reviewed for all patients enrolled on the scheme. Data was extracted on age, World Health Organization (WHO) performance status, histology, prior therapy, time from diagnosis to starting pemetrexed, chemotherapy (pemetrexed alone or with a platinum), cycle number, response rate, actuarial progression‐free and overall survival. Doses were cisplatin 75 mg/m² or carboplatin AUC = 5 and pemetrexed 500 mg/m² every 21 days. Results: 52 patients (32 male and 20 female) were reviewed. Median age was 58 years and 88% were WHO 0–1. Histology included 54% epithelial, 17% biphasic (epithelial and sarcomatoid) and 21% undefined. The median time from diagnosis to administration of pemetrexed was 145 days. Sixty‐five percent had minimal surgical intervention with video assisted thoracoscopy, pleurodesis and biopsy, while 19% had received prior palliative radiation. Seventy‐one percent were chemotherapy naïve, the remaining 29% having received previous platinum and/or gemcitabine regimens. Twenty‐three percent had pemetrexed alone, 35% in combination with carboplatin and 42% with cisplatin. The median number of cycles was 4 (range 1–13). The response rate was 33%. No toxicity was observed in 20% grade 3–4 toxicity in 10% (majority nausea/vomiting). The median progression‐free and overall survival times from starting pemetrexed were 184 days and 298 days, respectively. Conclusions: Pemetrexed‐based regimens are safe and effective in a community setting in malignant mesothelioma.     

Fluconazole dosing in continuous veno-venous haemofiltration (CVVHF): need for a high daily dose of 800 mg

To cover intermediate sensitive Candida glabrata in ICU patients,fluconazole plasma peak levels at least in the range of 16–32µg/ml appear necessary for treatment. Previous studiesdid not reach these fluconazole levels under continuous veno-venoushaemofiltration (CVVHF) with dosages of 200–600 mg fluconzoledaily. In the present study, nine patients simultaneously requiringCVVHF for treatment of acute oligoanuric renal failure and antimycotictherapy of Candida septicemia received fluconazole 800 mg/day.Fluconazole plasma levels were determined to evaluate whetherthis dosage is adequate to reach the advised fluconazole levels.Patients were dialysed on two consecutive days with an ultrafiltrationrate (UF) of 1000 ml/h or 2000 ml/h, respectively, in a randomizedorder. The predilution was 800 ml/h and 1800 ml/h, respectively.The treatment was tolerated without adverse effects. All patientsreached plasma fluconazole concentrations between 16 and 32µg/ml, remaining in this range for a minimum of 1 up to24 h with a mean of 9.6 h and a UF rate of 2000 ml/h, and 15.7h with a UF rate of 1000 ml/h. So far, there are no in vivodata on the fluconazole plasma concentrations required for effectivetreatment. However, our data demonstrate, that at least thefluconazole concentrations desirable on the basis of in vitrosusceptibility testing can be reached in critically ill patientson CVVHF in an ICU setting. However, in these patients, 800mg fluconazole/day are necessary to achieve fungicidal drugconcentrations.     

Chirurgisches Konzept und Ergebnisse bei nekrotisierender Fasziitis

BACKGROUND: Necrotizing fasciitis (NF) is still a source of high morbidity and mortality. These difficult cases are increasingly referred to burn centers due to special wound and critical care issues. Here we examine our institution's recent experience with a large series of NF. METHOD: We performed a retrospective chart review of 32 consecutive patients over a 10-year period with NF who required radical surgical debridement and surface reconstruction. RESULTS: Overall survival was 85%, with average length of stay of 74.0+/-7.5 days for survivors (S) and 68.8+/-6.3 days for nonsurvivors (NS) (P>0.05). Time until first operation was 5.2 days in S and 3.4 days in NS (P<0.05). Patient age averaged 51.1+/-11.2 years for S and 57.0+/-12.0 years for NS (P<0.05). Survivors averaged 1.6 relevant comorbidities and NS averaged 3.6 (P<0.05). Affected total body surface (TBS) per patient averaged 6.8+/-3.3% for S and 10.2+/-5.1% for NS (P<0.05). All NS had affection of the trunk, and none of the patients with exclusive affection of extremities died. CONCLUSIONS: There were frequent delays in diagnosis and referrals to our institution, and progress can be made in educating the medical community to identify these patients. Not only the affected TBS and location but also comorbidities, age, and immediate surgical treatment are important prognostic factors. Referral to a specialized facility such as a burn center is urgently recommended for optimal surgical intervention, wound care, and critical care management.     

FEASIBILITY OF CONDUCTING CARDIOVASCULAR OUTCOME RESEARCH IN AUSTRALIAN GENERAL PRACTICE: RESULTS FROM THE ANBP2 PILOT STUDY

1. The present study aimed to determine the feasibility of conducting a 5 year cardiovascular outcome trial of the treatment of 6000 elderly hypertensive patients in Australian general practices. 2. General practitioners (GPs) were invited to participate by mail and personal follow-up. Patient records were reviewed to identify subjects for a blood pressure (BP) screening programme. Blood pressure was measured on three occasions and eligible subjects were included if the average BP was 160 mmHg systolic or 90 mmHg diastolic if systolic BP was 140 mmHg. 3. Seven hundred and forty-one GPs were approached and 89 were enrolled in the study (12% of mail invites and 75% of those receiving a personal contact). In 16 practices where screening was completed, 82 000 records were reviewed to identify 4% patients eligible for screening. Twenty-two per cent of eligible subjects attended screening. Of 1938 subjects screened, 180 (9%) had BP 5=160/90 mmHg. Forty-seven percent of subjects (n = 916) were receiving antihypertensive therapy and 184 (20%) were withdrawn from therapy. One hundred and sixteen (63%) of these subjects had BP return to study entry levels within 6 weeks. Fifty-seven newly diagnosed and 81 previously treated subjects were randomized (7% of the screened population). 4. Based on the high participation rate of GPs, the response rate of patients to attend a BP screening programme and the 7% randomization to screening ratio for entry into the study, the ANBP2 pilot study has demonstrated that it is feasible to recruit subjects from Australian general practices to a cardiovascular outcome trial.     

Hyperthermic therapy procedures for supplementing radiotherapy of malignant intraocular tumors

Since more than a century ago, temperatures above 40 degrees C have been known to be effective in cancer treatment. Since that time numerous studies have documented that hyperthermia alone causes tumor regression and that the therapeutic effect depends on the amount and duration of heat delivered to a malignant tumor. However, after it was shown that heat combined with irradiation or chemotherapy potentiates the effect of hyperthermia, both thermoradiotherapy and thermochemotherapy were applied in experimental and clinical studies in several medical specialties. In ophthalmic oncology both retinoblastoma and uveal melanoma are treated by irradiation combined with local hyperthermia. In the present paper the use of ultrasound and microwave energy as locally applicable heat sources in intraocular malignancies is described and their suitability discussed. As is the case with malignant skin tumors and malignant tumors of the gastrointestinal and urogenital systems, malignant ocular tumors are accessible to externally applied heat and can thus be treated well by ultrasound and microwave hyperthermia. On the basis of experimental and clinical results gained with both ultrasound and microwave energy the advantages and drawbacks of these two technical modalities in intraocular tumor therapy are pointed out.