Development of a core outcome set for research and audit studies in reconstructive breast surgery.

BACKGROUND: Appropriate outcome selection is essential if research is to guide decision-making and inform policy. Systematic reviews of the clinical, cosmetic and patient-reported outcomes of reconstructive breast surgery, however, have demonstrated marked heterogeneity, and results from individual studies cannot be compared or combined. Use of a core outcome set may improve the situation. The BRAVO study developed a core outcome set for reconstructive breast surgery. METHODS: A long list of outcomes identified from systematic reviews and stakeholder interviews was used to inform a questionnaire survey. Key stakeholders defined as individuals involved in decision-making for reconstructive breast surgery, including patients, breast and plastic surgeons, specialist nurses and psychologists, were sampled purposively and sent the questionnaire (round 1). This asked them to rate the importance of each outcome on a 9-point Likert scale from 1 (not important) to 9 (extremely important). The proportion of respondents rating each item as very important (score 7-9) was calculated. This was fed back to participants in a second questionnaire (round 2). Respondents were asked to reprioritize outcomes based on the feedback received. Items considered very important after round 2 were discussed at consensus meetings, where the core outcome set was agreed. RESULTS: A total of 148 items were combined into 34 domains within six categories. Some 303 participants (51·4 per cent) (215 (49·5 per cent) of 434 patients; 88 (56·4 per cent) of 156 professionals) completed and returned the round 1 questionnaire, and 259 (85·5 per cent) reprioritized outcomes in round 2. Fifteen items were excluded based on questionnaire scores and 19 were carried forward to the consensus meetings, where a core outcome set containing 11 key outcomes was agreed. CONCLUSION: The BRAVO study has used robust consensus methodology to develop a core outcome set for reconstructive breast surgery. Widespread adoption by the reconstructive community will improve the quality of outcome assessment in effectiveness studies. Future work will evaluate how these key outcomes should best be measured.

The relationship between eosinophilia and airway remodelling in mild asthma.

BACKGROUND: Eosinophilia is a marker of corticosteroid responsiveness and risk of exacerbation in asthma; although it has been linked to submucosal matrix deposition, its relationship with other features of airway remodelling is less clear. OBJECTIVE: The aim of this study was to investigate the relationship between airway eosinophilia and airway remodelling. METHODS: Bronchial biopsies from subjects (n = 20 in each group) with mild steroid-naïve asthma, with either low (0-0.45 mm(-2)) ) or high submucosal eosinophil (23.43-46.28 mm(-2) ) counts and healthy controls were assessed for in vivo epithelial damage (using epidermal growth factor receptor staining), mucin expression, airway smooth muscle (ASM) hypertrophy and inflammatory cells within ASM. RESULTS: The proportion of in vivo damaged epithelium was significantly greater (P = 0.02) in the high-eosinophil (27.37%) than the low-eosinophil (4.14%) group. Mucin expression and goblet cell numbers were similar in the two eosinophil groups; however, MUC-2 expression was increased (P = 0.002) in the high-eosinophil group compared with controls. The proportion of submucosa occupied by ASM was higher in both asthma groups (P = 0.021 and P = 0.046) compared with controls. In the ASM, eosinophil and T-lymphocyte numbers were higher (P < 0.05) in the high-eosinophil group than both the low-eosinophil group and the controls, whereas the numbers of mast cells were increased in the high-eosinophil group (P = 0.01) compared with controls. CONCLUSION: Submucosal eosinophilia is a marker (and possibly a cause) of epithelial damage and is related to infiltration of ASM with eosinophils and T lymphocytes, but is unrelated to mucus metaplasia or smooth muscle hypertrophy.

Improving mortality outcomes of Stevens Johnson syndrome/toxic epidermal necrolysis: A regional burns centre experience.

INTRODUCTION: Stevens Johnson Syndrome/toxic epidermal necrolysis (SJS/TEN) are rare, potentially fatal desquamative disorders characterised by large areas of partial thickness skin and mucosal loss. The degree of epidermal detachment that occurs has led to SJS/TEN being described as a burn-like condition. These patients benefit from judicious critical care, early debridement and meticulous wound care. This is best undertaken within a multidisciplinary setting led by clinicians experienced in the management of massive skin loss and its sequelae. In this study, we examined the clinical outcomes of SJS/TEN overlap & TEN patients managed by our regional burns service over a 12-year period. We present our treatment model for other burn centres treating SJS/TEN patients. METHODS: A retrospective case review was performed for all patients with a clinical diagnosis of TEN or SJS/TEN overlap admitted to our paediatric and adult burns centre between June 2004 and December 2016. Patient demographics, percentage total body surface area (%TBSA), mucosal involvement, causation, severity of illness score (SCORTEN), length of stay and survival were appraised with appropriate statistical analysis performed using Graph Pad Prism 7.02 Software. RESULTS: During the study period, 42 patients (M26; F: 16) with TEN (n=32) and SJS/TEN overlap (n=10) were managed within our burns service. Mean %TBSA of cutaneous involvement was 57% (range 10-100%) and mean length of stay (LOS) was 27 days (range 1-144 days). We observed 4 deaths in our series compared to 16 predicted by SCORTEN giving a standardised mortality ratio (SMR) of 24%. CONCLUSION: Management in our burns service with an aggressive wound care protocol involving debridement of blistered epidermis and wound closure with synthetic and biological dressings seems to have produced benefits in mortality when compared to predicted outcomes.

Protection of spermatogenesis in rats from the cytotoxic procarbazine by the depot formulation of Zoladex, a gonadotropin-releasing hormone agonist.

The hypothesis that adjuvant treatment designed to produce testicular atrophy would preserve fertility in males receiving cancer chemotherapy was examined in the rat. Testicular atrophy was induced by a depot formulation of Zoladex [D-Ser(Bu(t))6-Aza-Gly10-GnRH], a gonadotropin-releasing hormone (GnRH) analogue. The experiments were conducted in albino Wistar as well as in the piebald variegated rat. Rats received the depot Zoladex formulation 2 weeks before and immediately prior to being treated with four weekly doses of procarbazine (200 mg/kg). Testicular function was evaluated 50 and 90 days after the last procarbazine dose. Procarbazine induced testicular atrophy concomitant with marked germinal cell aplasia in both strains of rat. In the Wistar rat adjuvant treatment with Zoladex caused slight but not significant alleviation of the testicular toxicity of procarbazine. The testicular toxicity of procarbazine was more extensive in the piebald variegated rat, and 50 days after the last procarbazine treatment the testes were small, sperm were absent, and the stem cell index was close to zero. Serum luteinizing hormone (LH) concentrations were raised and testicular LH receptor binding was low in the presence of normal serum and testicular testosterone concentrations, indicating compensated Leydig cell failure. Testicular weight and sperm content, as well as LH receptor binding, were still decreased in rats which received both Zoladex and procarbazine, suggesting that the analogue offered no protection. However, the stem cell index of the seminiferous tubules in the procarbazine-Zoladex-treated rats was not significantly different from vehicle-treated rats, which suggested that recovery from the effects of procarbazine was in progress. Ninety days after the end of procarbazine treatment alone the testes of rats were still atrophied and there was little evidence of active spermatogenesis. Leydig cell failure appeared to have progressed as, in addition to the low testicular LH receptor content and raised serum LH concentration, the prostate and seminal vehicle weights were decreased. The combination of Zoladex treatment with procarbazine was successful in preserving testicular function in the piebald variegated rats as virtually all the functional and morphological parameters of both the seminiferous tubule and the Leydig cell were not significantly different from those of vehicle-treated rats. This study demonstrates for the first time that effective gonadal protection from the toxic effects of procarbazine chemotherapy can be achieved by administration of the depot formulation of the gonadotropin-releasing hormone analogue Zoladex. The results show clearly that complete suppression of spermatogenesis is not a prerequisite for the successful outcome of treatments designed to protect the gonad from cytotoxic chemotherapy.

Effect of hyperoxia on phosphatidylcholine synthesis, secretion, uptake and stability in the newborn rabbit lung.

The effects of breathing greater than 95% oxygen from birth for 48 h of life on surfactant phosphatidylcholine synthesis and secretion, as well as uptake and stability of exogenous phosphatidylcholine were studied using rabbit lung tissue slices. Lung slices from animals breathing greater than 95% oxygen for 48 h exhibited a decreased rate of [14C]phosphatidylcholine release (30%) in comparison to lung slices from air-exposed controls. In vitro incorporation of [14C]choline into phosphatidylcholine was decreased by a similar amount in lung slices from pups exposed to greater than 95% oxygen. Uptake of exogenous [14C]phosphatidylcholine by lung slices from hyperoxic-exposed and control groups was not different, and the stability of extracellular phosphatidylcholine was likewise unaffected by hyperoxia. Turnover of labelled phosphatidylcholine taken up by tissue slices from medium was apparently decreased in association with hyperoxic exposure. These results are consistent with multiple sites of effect of hyperoxia on the pulmonary surfactant system in the newborn. These effects of hyperoxia on the lung surfactant system occur at a time of critical adaption to extrauterine life, and thus may have major consequences on lung function and ultimate survival of the premature infant with respiratory distress syndrome.

Suturing of lacerations of skeletal muscle.

Our aim was to compare the biomechanical properties of suturing methods to determine a better method for the repair of lacerated skeletal muscle. We tested Kessler stitches and the combination of Mason-Allen and perimeter stitches. Individual stitches were placed in the muscle belly of quadriceps femoris from a pig cadaver and were tensioned mechanically. The maximum loads and strains were measured and failure modes recorded. The mean load and strain for the Kessler stitches were significantly less than those for combination stitches. All five Kessler stitches tore out longitudinally from the muscle. All five combination stitches did not fail but successfully elongated. Our study has shown that the better method of repair for suturing muscle is the use of combination stitches.

Cancer Information Service utilization by selected U.S. ethnic groups.

The Cancer Information Service (CIS) has responded to information requests of more than 5 million people since 1976. Of interest to staff has been program coverage--in particular, patterns of use by audiences identified as being at high risk for cancer. This paper presents an introductory analysis of the use of the CIS between 1983 and 1990 by ethnic and racial groups. Data analysis, although affected by demographic data-collection restrictions, confirms suspected underutilization by racial and ethnic minorities. Although members of minority audiences call the CIS less frequently, they use the CIS for information about cancer-prevention topics more often than they do for treatment information, and their calls tend to be longer than calls from Whites. Television is demonstrated to be the most effective medium to stimulate use of the CIS among all audience groups. The authors conclude that expanding program coverage is important to reach target audiences, as is a more rigorous data-collection plan to assess utilization patterns. They also suggest the use of program funds to buy air time on a regular basis to stimulate use of the CIS by high-risk audiences and the general public.

Information-management technology in the Cancer Information Service.

This paper identifies the potential applications of information-management technology in the Cancer Information Service national network and describes some innovations of individual network offices in each area. New applications are explored and recommendations are made for coordinating these efforts nationally.

Physiologic, health and lifestyle factors associated with femoral neck bone density in older women.

Three hundred eleven women aged between 60 and 91 years (mean age 72.2) who were randomly recruited from the community underwent bone density assessments of the femoral neck. Two complementary multivariate techniques were used to assess the relationships between femoral neck bone density and a range of anthropometric, health, and lifestyle measures. Stepwise multiple linear regression analysis revealed age, weight, height, quadriceps strength, and lifelong smoking to be variables that independently and significantly explained part of the variance in femoral neck bone density within the group. Multiple logistic regression revealed that after adjusting for established predictors of bone mineral density, age, height, and weight, reduced quadriceps strength, lifelong smoking, and little childhood activity were significantly associated with low bone density (< 0.70 g/cm2), whereas superior quadriceps strength, nonsmoking, and high levels of current physical activity were significantly associated with high bone density (> 0.84 g/cm2). In contrast, current calcium intake was not significantly associated with bone density. The study findings highlight possible public health initiatives for minimizing age-related femoral neck bone loss in older women.

The effect of a 12-month exercise trial on balance, strength, and falls in older women: a randomized controlled trial.

OBJECTIVE: To determine whether a 12-month program of regular exercise can improve balance, reaction time, neuromuscular control, and muscle strength and reduce the rate of falling in older women. DESIGN: A randomized, controlled trial of 12 months duration. SETTING: Conducted as part of the Randwick Falls and Fractures Study in Sydney, Australia. PARTICIPANTS: One hundred ninety-seven women aged 60 to 85 years (mean age 71.6, SD = 5.4) who were randomly recruited from the community. OUTCOME MEASURES: Accidental falls, postural sway, reaction time, neuromuscular control, and lower limb muscle strength. MAIN RESULTS: Exercise and control subjects were tested before, midway through, and at the end of the trial. At initial testing, exercisers and controls performed similarly in all tests and were well matched in relevant health and lifestyle factors. The mean number of classes attended for the 75 exercise subjects who completed the program was 60.0 (range 26-82). At the end of the trial, the exercise subjects showed improved performance in all five strength measures, in reaction time, neuromuscular control, body sway on a firm surface with the eyes open, and body sway on a compliant surface with the eyes open and closed. In contrast, there were no significant improvements in any of the test measures in the controls. In one test measure, hip flexion strength, the exercisers showed continued improvement throughout the study year. There was no significant difference in the proportion of fallers between the exercise and control subjects. Interesting trends were evident, however, between falls frequency and adherence to the exercise program. CONCLUSIONS: These findings show that exercise can produce long-term benefits with regard to improving sensorimotor function in older persons. The findings also suggest that high compliance to an exercise program may reduce falls frequency, although further studies are required to conclusively demonstrate that exercise offers an effective means of preventing falls.

Physiological factors associated with falls in older community-dwelling women.

OBJECTIVE: To determine the prevalence of impaired vision, peripheral sensation, lower limb muscle strength, reaction time, and balance in a large community-dwelling population of women aged 65 years and over, and to determine whether impaired performances in these tests are associated with falls. DESIGN: One-year prospective study. SETTING: Conducted as part of the Randwick Falls and Fractures Study, in Sydney, Australia. PARTICIPANTS: Four hundred fourteen women aged 65 to 99 years (mean age 73.7 years, SD = 6.3) were randomly selected from the community; 341 of these women were included in the 1-year prospective study. MAIN RESULTS: The prevalence of impairment in all tests increased with age. In the year following assessment, 207 subjects (60.7%) experienced no falls, 63 subjects (18.5%) fell one time only, and 71 subjects (20.8%) fell on two or more occasions. After controlling for age, multiple falling was associated with low contrast visual acuity and contrast sensitivity, poor vibration sense and proprioception, reduced lower limb strength, slow reaction time, and impaired balance, as indicated by four sway tests and two clinical stability measures. Discriminant function analysis identified visual contrast sensitivity, proprioception in the lower limbs, quadriceps strength, reaction time, and sway on a compliant (foam rubber) surface with the eyes open as the variables that significantly discriminated between subjects who experienced multiple falls and subjects who experienced no falls or one fall only (Wilks' lambda = 0.73 (P < 0.001), canonical correlation = 0.52). This procedure correctly classified 75% of subjects into multiple faller or nonmultiple faller groups. CONCLUSIONS: These findings support previous results conducted in retirement village and institutional setting and indicate that the test procedure aids in the identification of older community-dwelling women at risk of falls.

Cervical cone margins as a predictor for residual dysplasia in post-cone hysterectomy specimens.

OBJECTIVE: To determine the relation between dysplasia at cervical cone margins and the presence or absence of residual dysplasia in post-cone hysterectomy specimens. METHODS: We performed a 6-year retrospective, multicenter study and reviewed 250 cases in which the patient had a cold-knife cervical cone biopsy followed by a hysterectomy within 6 months. Pathology reports from 23 institutions described the margins in conization specimens and the subsequent status of residual dysplasia in the hysterectomy specimens. RESULTS: There was a statistically significant difference in the prevalence of residual dysplasia in hysterectomy specimens between patients with positive margins on cone biopsy (47%) and those with negative margins (23%) (P < .01). The positive predictive value for residual dysplasia given positive cone margins was 47%, and the negative predictive value was 77%. The grade of post-cone residual dysplasia increased commensurately with the grade of dysplasia in the conization specimen. CONCLUSIONS: The presence of dysplasia at the cervical cone margin relates significantly with the presence of residual dysplasia in the post-cone hysterectomy specimen. The grade of residual dysplasia in the post-cone hysterectomy specimen increased as the grade of dysplasia in the conization specimen increased. Free margins on a cone biopsy specimen with dysplasia offer reassurance that invasive cancer is not present in the remaining uterus.

Inhaled nitric oxide prevents left ventricular impairment during endotoxemia.

We evaluated the effect of long-term inhalation of nitric oxide (NO) on cardiac contractility after endotoxemia by using the end-systolic elastance of the left ventricle (LV) as a load-independent contractility index. Chronic instrumentation in 12 pigs included implantation of two pairs of endocardial dimension transducers to measure LV volume and a micromanometer to measure LV pressure. One week later, the animals were divided into a control group (n = 6) or a NO group (n = 6). All animals received intravenous Escherichia coli endotoxin (10 micrograms. kg-1. h-1) and equivalent lactated Ringer solution. NO inhalation (20 parts/million) was begun 30 min after the initiation of endotoxemia and was continued for 24 h. In both groups, tachycardia, pulmonary hypertension, and systemic hyperdynamic changes were noted. The end-systolic elastance in the control group was significantly decreased beyond 7 h. NO inhalation maintained the end-systolic elastance at baseline levels and prevented its impairment. These findings indicate that NO exerts a protective effect on LV contractility in this model of endotoxemia.

Poly(sodium 4-styrene sulfonate): evaluation of a topical microbicide gel against herpes simplex virus type 2 and Chlamydia trachomatis infections in mice.

OBJECTIVE: To investigate the in vivo activity of poly(sodium 4-styrene sulfonate) (T-PSS) gel formulations as topical microbicides. METHODS: The ability of the gel formulations to reduce the incidence of infection when applied prior to pathogen challenge was examined in mouse models of vaginal herpes simplex type 2 (HSV-2) and Chlamydia trachomatis infection, and rectal HSV-2 infection. RESULTS: In the vaginal HSV-2 challenge studies, 10% T-PSS gel provided significant protection against infection, even when administered 60 min prior to virus challenge (P < 0.0001). Both 5% and 10% T-PSS gel formulations significantly reduced the incidence of upper genital tract C. trachomatis infection in animals treated up to 5 min before challenge (P < 0.001). However, no protection against C. trachomatis infection was seen in animals treated 30 min before challenge. In mice challenged rectally with HSV-2, both the 5% and 10% T-PSS gels significantly reduced infection at 20 s (P < 0.01 for both). However, only the 10% gel provided significant protection when administered 5 min before challenge (P < 0.01). CONCLUSIONS: T-PSS gel formulations have promising in vivo activity as topical microbicides.

A survey of smoking cessation knowledge, training, and practice among U.S. Army general medical officers.

BACKGROUND: Historically, cigarette-smoking rates have been higher among military personnel than among civilians, although recently these rates have decreased. METHODS: In March 1997, a questionnaire assessing (1) training received on smoking cessation, (2) objective knowledge of smoking-cessation techniques, (3) frequency of practice habits, and (4) personal tobacco use among physicians, was successfully mailed to 232 of the total population of 279 Army general medical officers (GMOs). RESULTS: One-hundred-fifty (65%) GMOs returned questionnaires. Of these, 3.3% reported personal cigarette smoking, and 7.3% regularly used smokeless tobacco. During internship, few (13%) GMOs received smoking-cessation training. Primary care programs provided training more frequently than did surgery internship programs. The mean score on the objective knowledge portion was 72%. GMOs had a variable practice pattern in their use of smoking-cessation techniques (percent answering "usually" or "always"): helping patients set quit dates (35%), offering to prescribe the nicotine patch (59%), referring patients to a behavior-modification program (86%). Physicians who received training during internship were significantly more likely (p < 0.01) to help their patients set a quit date. Training did not result in a statistically increased frequency of other practice habits. CONCLUSIONS: GMOs received minimal training on smoking cessation during internship. GMOs refer patients to smoking-cessation classes, reflecting the strategy of the Army Health Promotion program. Strategies to increase the frequency that GMOs prescribe nicotine replacement and assist patients in setting a quit date are needed. Military smoking-cessation efforts may provide valuable lessons for the civilian community.

Is Percoll safe for in vivo use?

Fourteen virgin female rabbits were injected with 60% Percoll solution in the right ovary and uterine horn and sperm prepared with Percoll in the left ovary and uterine horn. Histologic examination after 4 weeks showed no inflammatory cell infiltration in either uterine horns or ovaries.

Prolonged suppression of rat testis function by a depot formulation of Zoladex, a GnRH agonist.

A sustained-release formulation of a potent gonadotropin-releasing hormone (GnRH) agonist, Zoladex (D-Ser(But),6 Aza Gly10-GnRH; ICI 118,630; goserelin), was administered subcutaneously (3.6 mg/depot) to male rats once every 28 days for 2-24 wk to determine the extent to which pituitary-testis function could be suppressed and whether suppression was maintained throughout the period of treatment. Administration of Zoladex resulted in sustained decreases in weight of the testis, epididymis, seminal vesicles and prostate gland. The decreases were apparent within 2 wk of initiating treatment. Patchy degeneration of the seminiferous tubules and atrophy of the Leydig cells were observed, but did not progress beyond the degree observed after 1 month of treatment. Serum and testis testosterone were markedly depressed after 2 wk of treatment, as was testis [125I]hCG binding. Serum gonadotropins were also reduced by treatment. Serum androgen binding protein (ABP) was elevated, testis ABP content remained unchanged, and epididymal ABP content was reduced. The changes are consistent with the hypothesis that this compound affects both the anterior pituitary gland and the testis. These findings indicate that depot delivery systems are a convenient way to administer GnRH analogs for sustained treatment schedules.

Should antioxidant vitamins be routinely recommended for older people?

The hypothesis that oxidative damage due to free radicals is an important cause of aging is the subject of much research and even more interest among the public and lay media. An increasing number of older people are asking whether they should be taking antioxidant vitamins, despite their considerable cost. Epidemiological and laboratory evidence indicates that oxidative damage caused by oxygen free radicals is important in many of the major diseases of older age. It is also clear that a diet high in antioxidants protects against these diseases, including many cancers and ischaemic heart disease. However, it has not been proven whether antioxidant vitamins, taken as dietary supplements, provide the same level of protection as a diet that is rich in fruit and vegetables. Although there appears to be no reason to discourage older people from taking vitamin E (tocopherols) and ascorbic acid (vitamin C), the best advice to give them is to reduce their intake of xenobiotics, to drink tea instead of coffee, and to eat liberal amounts of fruit, vegetables, nuts, soya beans and lentils. The use of beta-carotene as a dietary supplement should be discouraged.

Strain-dependency of procarbazine-induced testicular toxicity.

Three strains of rat were used to examine strain-dependency of procarbazine-induced testicular toxicity. CCFHB and CCFY1 outbred albino rats and inbred PVG piebald variegated rats were treated weekly with procarbazine (200 mg/kg/dose x 4). Fifty-six days later, the rats were killed and reproductive parameters evaluated. Strain-related differences in body, testis, prostate, seminal vesicle weights, testis sperm, intratesticular testosterone, and [125I]hCG binding to testicular LH receptors were observed. Although treatment with procarbazine affected testis function in all strains, significant interactions occurred between treatment and strain. LH receptor binding and stem-cell survival were more severely affected in the inbred strain than in outbred strains. Serum testosterone increased in the outbred strain but decreased in the inbred strain, generating an interaction that obscured possible main effects. Significant strain-related differences in within-group variances demonstrated that measurements were more variable in the outbred strains than in the inbred strain. Testes of the inbred strain appeared to be more sensitive to the effects of procarbazine than those of the outbred strains. These data illustrate two important toxicologic phenomena: differences in response variability and differences in target-organ sensitivity, both of which were explained by genetic variability.