Optimal restricted two-stage designs

The fixed sample p value at the final stage of a group sequential design may be "significant" while the overall p value for the trial as designed may be "nonsignificant." This can lead to confusion in reporting and interpreting final stage results. Two-stage designs are presented that allow acceptance, rejection, or continuation at the first stage while retaining the fixed sample critical value at the second stage. The designs are optimized under this restriction to minimize the expected sample size under the null hypothesis, the expected sample size under a specific alternative hypothesis, or the maximum expected sample size. These restricted designs are almost fully efficient when compared to optimal unrestricted two-stage designs. Additionally, one can interpret the results of hypothesis tests at the final stage as though a fixed sample design had been used. Examples are given which illustrate the use of these restricted plans in the design and analysis of clinical trials.     

Documentation of care outcomes in an academic nursing clinic: an assessment

PURPOSE: To assess documentation of client data collected at an academic nursing clinic using the Wilson and Cleary Health Related Quality of Life (HRQOL) conceptual model as a framework. DATA SOURCES: A chart audit of 100 randomly selected active client records was conducted. CONCLUSIONS: Although several significant HRQOL variables were documented, data regarding general health perception and quality of life were not present. The HRQOL conceptual model provided an appropriate structure for evaluating the documentation. Further effort must be made to include key HRQOL dimensions in the clinic's documentation system. IMPLICATIONS FOR PRACTICE: Documenting the quality of care provided in nursing clinics is essential in order for other professionals and the public to recognize nursing professionals as accountable and credible. This project formed the basis for a computerized outcomes-based client record system.     

Temperature and the oxygen-hemoglobin dissociation curve of the harbor seal, Phoca vitulina

To determine the effect of temperature and pH on oxygen-hemoglobin affinity of the harbor seal, we measured 61 biotonometric oxygen-hemoglobin dissociation curves on blood from 5 seals at 3 temperatures and a range of pH values. The average (+/- SEM) hemoglobin concentration was 3.44 +/- 0.15 mM, nearly 50% greater than found in normal humans. At pH 7.4 the P50 (partial pressure of O2 at 50% hemoglobin saturation) +/- SEM values were 22.4 +/- 0.6,25.3 +/- 0.5, and 28.5 +/- 0.4 Torr at 33, 37 and 41 degrees C, respectively. The effect of temperature on oxygen-hemoglobin affinity, (delta log P50/delta T) was 0.014 +/- 0.001 at pH 7.4, significantly lower than that observed in human and dog blood. This low temperature sensitivity may facilitate oxygen off-loading from hemoglobin when temperature gradients exist within the animal or as tissue temperature decreases during a dive. Temperature did not significantly affect the Hill coefficient 'n' (shape) of the dissociation curve which averaged 2.43 +/- 0.04 at 37 degrees C. The fixed-acid Bohr coefficient (delta log P50/delta pH) was -0.606 +/- 0.032 at 37 degrees C and increased with temperature. This relatively large value for the Bohr coefficient was similar to those previously reported for the Northern Elephant, Bladdernose, and Weddell Seals, and may facilitate oxygen off-loading as acidosis develops during a dive.     

Enhancing patient autonomy with risk assessment and invasive diagnosis: an ethical solution to a clinical challenge

The purpose of this study was to describe a clinically based, ethically justified informed consent process for risk assessment and invasive genetic diagnosis that enhances patient autonomy. Appealing to the ethical principle of respect for the autonomy of pregnant women, we show that patients can exercise their autonomy meaningfully in the informed consent process in response to the offer of risk assessment (RA) and invasive diagnosis (ID) and in response to the results of risk assessment. All pregnant patients in the first trimester should be offered both RA and ID. Women will sort themselves, in response, into 4 groups; those who refuse both RA and ID, those who are uncertain about RA, those who accept RA, and those who accept ID. Women who proceed to RA will sort themselves, in response to its results, into 3 groups: women for whom the risk of aneuploidy is acceptable or unacceptable and women who are not certain whether such risk is acceptable. For this last group only, the informed consent process should present information about current controversies of first-trimester and second-trimester further testing to better assess risk. Clinical strategies are identified for the implementation of the varied responses of pregnant women to the offer of RA and ID. Autonomy-enhancing strategies for the evaluation of pregnancy provide the basis for solving the ethical challenge that is presented by the wide variety of evaluation techniques.     

Wound healing with “spray‐on” autologous skin grafting (ReCell) compared with standard care in patients with large diabetes‐related foot wounds: an open‐label randomised controlled trial

There is an urgent need for interventions that improve healing time, prevent amputations and recurrent ulceration in patients with diabetes‐related foot wounds. In this randomised, open‐label trial, participants were randomised to receive an application of non‐cultured autologous skin cells (“spray‐on” skin; ReCell) or standard care interventions for large (>6 cm²), adequately vascularised wounds. The primary outcome was complete healing at 6 months, determined by assessors blinded to the intervention. Forty‐nine eligible foot wounds in 45 participants were randomised. An evaluable primary outcome was available for all wounds. The median (interquartile range) wound area at baseline was 11.4 (8.8‐17.6) cm². A total of 32 (65.3%) index wounds were completely healed at 6 months, including 16 of 24 (66.7%) in the spray‐on skin group and 16 of 25 (64.0%) in the standard care group (unadjusted OR [95% CI]: 1.13 (0.35‐3.65), P = .845). Lower body mass index (P = .002) and non‐plantar wounds (P = .009) were the only patient‐ or wound‐related factors associated with complete healing at 6 months. Spray‐on skin resulted in high rates of complete healing at 6 months in patients with large diabetes‐related foot wounds, but was not significantly better than standard care (Australian New Zealand Clinical Trials Registry: ACTRN12618000511235).     

Severity of bulimia: Relationship with depression and other psychopathology

There were 53 women (35 bulimics and 18 normal controls) who were compared on the Minnesota Multiphasic Personality inventory, the Symptom Checklist-90R, and the Beck Depression Inventory. The bulimics were separated into two groups, high (N = 18) and low (N = 17) frequency purgers, based upon a median split self-monitored purging data. Bulimics who purged less than 3 times per week (M = 1.71) were classified as low frequency purgers, and those who purged more than 3 times per week (M = 9.94) were classified as high frequency purgers. Comparisons of the three groups showed that both groups of bulimics differed from normals on measures of depression, but on other measres, i. e., anxiety interpersonal sensitivity and sociopathic trait, only the high frequency purgers differed from normals. Correlational analyses indicated that these same variables, and especially depression, were positively correlated with purging, suggesting that severity of bulimia may be associated with additional psychopathology. These findings were discussed in terms of the existing literature concerning the psychopathology of bulimia.     

HELPING BANGLADESHI FAMILIES: Tower Hamlets Parent Adviser Scheme

This paper describes the problem facing Bangladeshi families of children with mental handicaps in the East End of London. It illustrates how comprehensive help has been provided by employing a full-time Bangladeshi worker as a Parent Adviser, who was trained in counselling and child management skills before beginning regular home-visiting. The enormous benefits that have occurred as a result of this work are documented with reference to one family.     

Aortic wall metabolism in relation to susceptibility and resistance to experimental atherosclerosis

Different segments of the aorta and its branches show differing susceptibilities to atherosclerosis. To identify metabolic features that may account for plaque formation and sparing, we studied aortic wall respiration and glycolysis proximal and distal to an aortic coarctation in 30 rabbits fed a standard or atherogenic diet. Three months after coarctation, blood pressure in the proximal aorta was elevated, and plaque occupied 98% +/- 28% of the intimal surface compared with 57% +/- 26% for control animals (p less than 0.05). Aortic pressure distal to the stenosis remained normal, but plaque formation was markedly decreased (5% +/- 4%) compared with controls (30% +/- 27%, p less than 0.05). Metabolic studies included measurement of oxygen consumption of proximal and distal aortic walls, lactic acid production, and 2-deoxyglucose uptake. Elevated pressure or hyperlipidemia increased respiration (22.6 +/- 4.0 or 16.3 +/- 6.0 pmol oxygen consumed/min/microgram deoxyribonucleic acid [DNA] vs 5.8 +/- 5.2 for controls; p values less than 0.05) without increasing glycolytic metabolism. The coexistence of hypertension and hyperlipidemia resulted in maximal plaque formation and a sevenfold increase in both oxidative metabolism (46.6 +/- 27.2 pmol oxygen consumed/min/microgram DNA vs 5.8 +/- 5.2 for controls, p less than 0.004) and glycolytic metabolism (44 +/- 10 ng lactic acid produced/90 min/microgram DNA vs 6 +/- 3 for controls, p less than 0.004). In the spared aortic segment distal to coarctation, glycolytic metabolism was increased (10 +/- 8 ng lactic acid produced/90 min/microgram DNA vs 2 +/- 1 for controls, p less than 0.05) but oxidative metabolism remained normal.(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of splenectomy on survival rate of patients with colorectal cancer

Between 1966 and 1980, 68 patients were identified who had a splenectomy before or concurrent with resection of a colorectal adenocarcinoma. Control subjects with concurrent disease were then matched with each study patient for age, sex, stage of disease, and date of operation. Follow-up was complete. Between splenectomy patients and control subjects, there was no difference in the site of primary disease (rectum versus colon), the number of patients receiving adjuvant therapy, the technique of resection (cure versus palliation), or the extent of regional disease. Overwhelming sepsis occurred in only one splenectomy patient. Splenectomy was associated with a significant decrease in survival at 5 years in patients with regional (stage C) disease but not in patients with localized (stage B) disease. More splenectomy patients received blood transfusions than control subjects, but an independent effect on survival could not be demonstrated. The mechanism responsible for this adverse impact of splenectomy is undefined. However, splenectomy should be considered a possible factor in the survival of patients operated on for regional colorectal cancer.     

The effect of linear interpolation of the filtered projections on image noise in x-ray computed tomography

Measured values for image noise variance in x-ray computed tomography were found to be less than half of the values predicted by published formulas. This phenomenon had previously been attributed qualitatively to the use of linear interpolation of the filtered projections in the back projection process. An analysis of the reconstruction process has allowed the derivation of a formula for image noise variance which incorporates the effect of this interpolation, giving results which are less than 50% of the previously predicted values. This formula has been tested with images of a perspex rod produced by an x-ray microtomography scanner and with a similar image derived from mathematically modeled projection data. The predicted noise variance was within 1% of the measured values for both the simulated and the experimental data.