A feasibility study of microwave therapy for precancerous actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a common premalignant skin lesion that can progress to cutaneous squamous cell carcinoma (cSCC). Microwave therapy is an established cancer treatment and has been used for plantar viral warts. OBJECTIVES: To evaluate the efficacy and feasibility of microwave as a treatment for AK. METHODS: Stage I was a dose-setting study, in which seven participants had the dielectric properties of 12 thick and 22 thin AKs assessed for optimization of the microwave dose used for treatment in Stage II. Stage II was a randomized, internally controlled trial evaluating 179 AKs in 11 patients (93 treated, 86 untreated controls) on the scalp/forehead or dorsal hand. Participants received one treatment initially and a repeat treatment to unresolved AKs at week 4. The response was assessed at six visits over 4 months. The primary outcome was partial or complete resolution of the treated AKs. RESULTS: A significantly higher proportion of treated AK areas responded than untreated (90% vs. 15%; P < 0·001). Thin AKs were more responsive than thick AKs. The site did not affect efficacy. Pain was severe, but brief (80% reported pain lasting 'a few seconds only'). Adverse effects were minimal (erythema, n = 6; flaking, n = 3; itch, n = 3). All participants who would chose microwave therapy over their current treatment cited the shorter discomfort period. CONCLUSIONS: Microwave therapy is a portable, safe and effective treatment for AK. An easy-to-deliver, acceptable therapy for AK is attractive as a prevention strategy. While these results are promising, a larger randomized controlled trial is needed against an effective comparator to confirm clinical efficacy and patient acceptability. What is already known about this topic? Actinic keratoses (AKs) are common precancerous skin lesions. Successful treatment of AK can prevent cutaneous squamous cell carcinoma (cSCC). Most topical therapies for AK require repeated application over weeks and drive local skin inflammation, leading to poor compliance. An easy-to-deliver and effective treatment for AK, suitable for use in primary care, could reduce cSCC. What does this study add? Microwave therapy is a feasible, effective treatment for AK. Ninety per cent of treated AKs showed full or partial resolution at 120 days post-treatment. Microwave therapy was painful, but the pain was short-lived (seconds) and this short discomfort period was cited as the main reason that microwave was preferred to their current treatment.

Are we assuming too much with our statistical assumptions? Lessons learned from the ALTTO trial.

BACKGROUND: Design, conduct, and analysis of randomized clinical trials (RCTs) with time to event end points rely on a variety of assumptions regarding event rates (hazard rates), proportionality of treatment effects (proportional hazards), and differences in intensity and type of events over time and between subgroups. DESIGN AND METHODS: In this article, we use the experience of the recently reported Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization (ALTTO) RCT, which enrolled 8381 patients with human epidermal growth factor 2-positive early breast cancer between June 2007 and July 2011, to highlight how routinely applied statistical assumptions can impact RCT result reporting. RESULTS AND CONCLUSIONS: We conclude that (i) futility stopping rules are important to protect patient safety, but stopping early for efficacy can be misleading as short-term results may not imply long-term efficacy, (ii) biologically important differences between subgroups may drive clinically different treatment effects and should be taken into account, e.g. by pre-specifying primary subgroup analyses and restricting end points to events which are known to be affected by the targeted therapies, (iii) the usual focus on the Cox model may be misleading if we do not carefully consider non-proportionality of the hazards. The results of the accelerated failure time model illustrate that giving more weight to later events (as in the log rank test) can affect conclusions, (iv) the assumption that accruing additional events will always ensure gain in power needs to be challenged. Changes in hazard rates and hazard ratios over time should be considered, and (v) required family-wise control of type 1 error ≤ 5% in clinical trials with multiple experimental arms discourages investigations designed to answer more than one question. TRIAL REGISTRATION: clinicaltrials.gov Identifier NCT00490139.

The North West Diabetic Pregnancy Audit: a practical system for multi-centre diabetic pregnancy audit.

AIMS: Improving care for women with pre-gestational diabetic pregnancy is a core objective of the St Vincent Declaration and the Diabetes National Service Framework. The aim was to develop a practicable collaborative audit methodology for pre-gestational diabetic pregnancy. METHODS: In 1999, care professionals in the north-west of England agreed standards and a simple monthly data collection system. Annual reports are compiled to summarize compliance with the standards. Each hospital receives an individualized report comprising tables and funnel plots that allow between-hospital comparisons. RESULTS: Data on pre-gestational diabetic pregnancies are collated from 30 maternity units. Funnel plots and tables presented in the annual reports highlight any large differences between hospitals in booking and outcome measures for diabetic pregnancies. CONCLUSIONS: The annual audit reports allow the assessment of current management and outcomes for diabetic pregnancies at a regional and local level. These reports help to identify areas where diabetic pregnancy care requires further attention.

A survey of vaccine coverage and antibiotic prophylaxis in splenectomised patients in Scotland.

AIMS: To determine the coverage of vaccine and antibiotic prophylaxis in splenectomised patients in Scotland. METHODS: Patients who had undergone splenectomy between 1 January 1988 and 31 December 1998 were identified. A questionnaire was sent to general practitioners to validate vaccine and antibiotic status for these patients. RESULTS: A total of 974 living splenectomised patients were identified during the study period. Information on vaccine and antibiotic status was available for 708 (73%) and 770 (79%) of living patients, respectively. Coverage of pneumococcal vaccine (88%) was higher than that of Haemophilus influenza type b (Hib) conjugate vaccine (70%) or meningococcal vaccine (51%). Only 47% of patients received all three vaccines. A higher coverage was also documented for pneumococcal vaccine (28%) than Hib (19%) and meningococcal vaccine (14%) before elective splenectomy. Only 13% received all three vaccines before splenectomy. Coverage of influenza vaccine increased significantly, from 76% in the 1997/1998 season to 96% in the 2000/2001 season. Antibiotic prophylaxis was received by 67% of all patients. The current recommendation, comprising pneumococcal and Hib vaccination and antibiotic prophylaxis, was received by only 52% of the patients. There was no association between the coverage of vaccine and socioeconomic status. CONCLUSION: Further improvement in coverage of recommended vaccines and antibiotic prophylaxis is still needed to reduce the risk of serious infection in this high risk group.

In situ characterization of Helicobacter pylori arginase.

The properties of Helicobacter pylori arginase activity in metabolically competent cells and lysates were investigated with the aim of obtaining a better understanding of the nitrogen metabolism of the bacterium. One-dimensional 1H- and 13C-nuclear magnetic resonance spectroscopy, spectrophotometry, radio tracer analysis and protein purification techniques were employed to characterize in situ the first step in the utilization of l-arginine by the bacterium. Arginase activity was associated with the cell-envelope fraction obtained by centrifugation of lysates. A Km of 22+/-3 mM was determined for the enzyme activity, and differences of Vmax were observed between strains. Divalent cations stimulated arginase activity, and the most potent activators were Co2+>Ni2+>Mn2+. The activity was highly specific for l-arginine and did not catabolize analogs recognized by other arginases of prokaryote and eukaryote origin. The Ki of several inhibitors was measured and served also to characterize the enzyme activity. The presence of bicarbonate enhanced the hydrolysis of l-arginine in cell suspensions, but not in lysates or semi-purified enzyme preparations. Amino acid sequence analyses revealed important differences between the deduced structures of H. pylori arginase and those of other organisms. This finding was consistent with experimental data which showed that H. pylori arginase has unique properties.

Analysis of 16S rRNA and methane monooxygenase gene sequences reveals a novel group of thermotolerant and thermophilic methanotrophs, Methylocaldum gen. nov.

Two methanotrophic bacteria with optimum growth temperatures above 40 degrees C were isolated. Thermotolerant strain LK6 was isolated from agricultural soil, and the moderately thermophilic strain OR2 was isolated from the effluent of an underground hot spring. When compared to the described thermophilic methanotrophs Methylococcus capsulatus and Methylococcus thermophilus, these strains are phenotypically similar to Methylococcus thermophilus. However, their 16S rRNA gene sequences are markedly different from the sequence of Methylococcus thermophilus ( approximately 8% divergence) and, together with Methylomonas gracilis, they form a distinct, new genus within the gamma-subgroup of the Proteobacteria related to extant Type I methanotrophs. Further phenotypic characterisation showed that the isolates possess particulate methane monooxygenase (pMMO) but do not contain soluble methane monooxygenase. The nucleotide sequence of a gene encoding pMMO (pmoA) was determined for both isolates and for Methylomonas gracilis. PmoA sequence comparisons confirmed the monophyletic nature of this newly recognised group of thermophilic methanotrophs and their relationship to previously described Type I methanotrophs. We propose that strains OR2 and LK6, together with the misclassified thermophilic strains Methylomonas gracilis VKM-14LT and Methylococcus thermophilus IMV-B3122, comprise a new genus of thermophilic methanotrophs, Methylocaldum gen. nov., containing three new species: Methylocaldum szegediense, Methylocaldum tepidum and Methylocaldum gracile.

A comparison of emergency medical helicopter accident rates in the United States and the Federal Republic of Germany.

The purpose of this study was to compare accident rates of helicopter emergency medical services (USA-HEMS) to domestic air taxi service (USA-Taxi) and helicopter emergency medical services in the Federal Republic of Germany (FRG-HEMS). Contingency tables compared the total hours flown to the number of fatal and non-fatal accidents for USA-HEMS (1982-7) vs. USA-Taxi (1980-5) and USA-HEMS (1982-7) vs. FRG-HEMS (1982-7). The overall accident rate for USA-HEMS was 11.7/100,000 h, with the fatal accident rate being 4.7/100,000 h. This was significantly different from the USA-Taxi overall accident rate of 6.7/100,000 h and the fatal accident rate of 1.6/100,000 h (chi 2 = 20.441, p = 0.0001). The USA-HEMS overall and fatal accident rates were not significantly different than the FRG-HEMS overall (10.9/100,000 h) and fatal (4.1/100,000 h) accident rate (chi 2 = 0.061, p = 0.97). These data suggest that emergency air transport is inherently more risky than routine air taxi services.

The impact of an air ambulance system on an established trauma center.

Hospital competition for air ambulance business has resulted in implementation of a helicopter service before the medical staff can prepare for the increased patient load. We reviewed the effect of an air ambulance on an already established trauma center (TC) by analyzing the impact of the helicopter trauma patient load during the initial year of operation. The helicopter carried a three-member flight crew consisting of a pilot, paramedic, and critical care nurse. Admission data of all flights from February 1982 through February 1983 were reviewed. Of the 325 air missions launched, 192 (59%) were for the transport of trauma victims. One hundred forty (73.6%) patients were transported from local hospitals, the remaining 52 (26.4%) from the accident scene. Ninety per cent of the injuries were due to motor vehicle accidents. Forty-nine per cent of the flights occurred on weekends and 68.8% were launched between 7:00 P.M. and 3:00 A.M. The average flight times from hospital and accident scenes were 37 min 30 sec and 13 min 30 sec, respectively. Of all trauma missions flown, 126 (65.8%) were considered new or 'captured' by the air ambulance system and brought to the TC. Thirty-seven (19.3%) patients died in flight, were DOA, or died within 1 hour of TC arrival. Eighty per cent of the deaths were from massive head injuries. The average injury severity score was 35.58 (all patients), 32.9 (survivors), and 45.80 (deaths).(ABSTRACT TRUNCATED AT 250 WORDS)

The freeze-fractured median eminence. II. Developmental changes in the neurohemal contact zone of the median eminence of the rat.

The neurohemal contact area of the median eminence was examined in adult, young, neonatal, and fetal rats in freeze-fracture preparations. While no specializations of the membranes of axonic terminals abutting on the perivascular space was observed, adjacent areas of the same membranes are rich in signs of hormone release. Signs of exocytosis are defined in the manner of Theodosis et al. (1978). Exocytotic pits with a single dense granule as a core are identified on P-faces along with mounds on corresponding E faces. These features appear near the time of birth, are especially numerous at 3 days, 3 weeks, and 5 weeks, and continue in lesser numbers into adulthood. Even more numerous and appearing even earlier, by the last day of fetal life, were P-face clusters of large particles usually in a pit, and pits without particles. These fall into 2 significantly different categories distinguished by the size of the pit. E face counterparts are large and small protuberances, respectively. Fenestrae of adult size and distribution are observed along the endothelium of portal vessels from the 20th day of fetal life on. Their frequency correlates well with other structural manifestations of a median eminence ready for the onset of functional activity at about the time of birth (Monroe and Paull 1974).

The freeze-fractured median eminence. I. Development of intercellular junctions in the ependyma of the 3rd ventricle of the rat.

Ependymal junctions in both the ventro-lateral wall and infundibular floor of the 3rd ventricle were examined in adult, young, neonatal, and fetal rats in freeze-fracture preparations. During late fetal and early postnatal life, tight junctions developed in both ventro-lateral and floor ependyma with, first, the appearance of an area of waffle-like or honeycomb texture in the membrane where tight junctions will appear; second, the decoration of P-face crests of this honeycomb with individual particles; and lastly, fusion of these particles into smooth strands. In adults, tight junctions were rare in the lateral ependyma, but persisted on the floor as a loose network. Many small ependymal gap junctions were already present at the earliest fetal stage (17 days) examined. They occupied significantly larger proportions of the membranes on the ventro-lateral wall than on the floor throughout the time course due to an increase in their size but not in their numbers. The smallest gap junctions were regarded as the newest in a process of renewal throughout life. The development of both junctional types parallels what is known on the onset of neuroendocrine functions in the median eminence. In the rat, this is apparently just before, at, or just after birth.

Reduction of acute anterior shoulder dislocations using the Milch technique: a study of ski injuries.

During the 1977-78, 1978-79, and 1979-80 ski seasons, 76 acute anterior shoulder dislocations were treated by one of three Orthopedic Surgeons at the Rutland Vermont Hospital Emergency Room: 68 (89.4%) were reduced on first attempt using the Milch technique of abduction and external rotation. Four (5.2%) required general anesthesia and four were reduced using meperidine hydrochloride (Demerol, Winthrop) and diazepam (Valium, Roche) and a traction-countertraction technique. Of the 68 shoulders reduced with the Milch technique, 47 (69.1%) required no analgesics or muscle relaxants. There were no complications attributable to the technique itself. Males were injured more frequently than females in a 4.4:1 ratio. Left shoulder injuries were as common as right. Recurrent dislocations occurred more frequently in younger individuals. Fractures of the greater tuberosity were associated injuries in five (6.6%) of all dislocations. These all occurred in individuals older than age 39 years and were coincident with primary dislocations.