Short-term changes in drug agglomeration within interactive mixtures following blending.

The objective was to investigate the nature and extent of short-term dynamic changes to dissolution within specific interactive mixtures following blending. Two micronized drugs, nitrazepam and flunitrazepam, were formulated into lactose-based interactive mixtures containing a micronized surfactant. The dissolution rate of the drugs decreased significantly over a period of days after preparation. The dissolution was modelled using a multi-exponential equation, allowing estimation of agglomeration and dissolution rate. From this model, decreasing dissolution rates were consistent with increasing agglomeration. Particle-sizing studies provided evidence of an increase in drug agglomerates over the same timescale. This is the first study to report short-term dissolution changes immediately following secondary processing. Several hypotheses are proposed for increases in agglomeration, which potentially relate to changes in surface charge, particle rearrangements, recrystallisation at surfaces and the role of moisture, although the role of mechanical processing on agglomerate behaviour remains poorly understood. The observations from this study may have wider implications, for dissolution and for other powder-based drug delivery systems which include interactive mixtures with fine powders. This study emphasizes the need for improved understanding if we are to implement a "Quality by Design" ethos to improve control and risk management over the performance and stability of these systems.

Effect of supervised surgical training on outcomes after resection of colorectal cancer.

BACKGROUND: The process of training surgeons in technique for resection of colorectal cancer should not compromise patient care or outcomes. The aim of this study was to compare morbidity, mortality and survival rates after resection performed by trainees with those for a consultant surgeon. METHODS: Outcomes for 150 patients operated on by a single colorectal surgeon at a private hospital were compared with those of 344 patients admitted under the same surgeon and operated on by closely supervised trainee surgeons in a public teaching hospital between 1995 and 2002. RESULTS: Co-morbidity was significantly more common in patients operated on by trainees; their American Society of Anesthesiologists grades were higher and tumours were more advanced. Of 16 postoperative complications evaluated, only respiratory and cardiac problems were significantly more common in patients operated on by trainees. There was no difference in operative mortality, local recurrence or 2-year survival rate after adjustment for age and tumour stage. CONCLUSION: Outcomes after resection for colorectal cancer did not differ between the consultant and trainees in the context of a closely supervised training programme.

Assessment of the accuracy of transrectal ultrasonography in anorectal neoplasia.

BACKGROUND: Accurate preoperative staging of anorectal neoplasia is required to identify patients for whom local excision or adjuvant therapy may be appropriate. The objectives of this study were to review the accuracy of endoluminal transrectal ultrasonography (TRUS) in the staging of rectal cancers and to determine the learning curve before optimal staging accuracy can be achieved. METHODS: The results of all TRUS examinations for the assessment of anorectal neoplasia performed by two colorectal surgeons at two teaching hospitals of the University of Sydney from 1991 to 2001 were collected prospectively. RESULTS: Of the 433 patients examined by TRUS, 356 were included, of whom 263 (73.9 per cent) had nodal status assessed histologically. Of the 77 patients excluded, 50 had undergone radiotherapy before operation. TRUS achieved excellent accuracy when compared with histopathology reports using kappa statistics for standard Union Internacional Contra la Cancrum (UICC) staging (kappa = 0.89), tumour wall penetration (kappa = 0.70), lymph node detection (kappa = 0.66) and a proposed new staging system (kappa = 0.94). In addition, the increase in TRUS accuracy with operator experience demonstrates the need to perform 50 or more procedures before optimal accuracy is achieved. CONCLUSION: TRUS provides an appropriate investigation with which to select patients with T1 tumours for local excision, and patients with T3 or T4 tumours for preoperative radiotherapy. The relative inaccuracy of staging T2 tumours by TRUS has led to a proposed alternative ultrasonographic staging system.

An internship for college students in physical medicine and rehabilitation: effects on awareness, career choice, and disability perceptions.

OBJECTIVE: To show the impact that an internship program in Physical Medicine and Rehabilitation (PM&R) for college students has on their knowledge about the field, career choice, and perceptions about people with disabilities. DESIGN: Twelve students were selected to participate in the study. Students observed patient therapies and followed faculty and physiatry resident physicians. Students also participated in research studies in rehabilitation research. Group discussions regarding specific projects, research methods, career choice, and perceptions about disability were part of a didactic curriculum. Surveys about PM&R knowledge, attitudes toward people with disabilities, demographics, and course evaluations were administered. RESULTS: Results showed that the program increased knowledge about PM&R (P < 0.008). Premedical students missed significantly fewer questions (8.2 vs. 11.7; P = 0.04) on this survey than did other participants. Results also showed that this program affected their attitudes toward people with disabilities and student choice to pursue a career in health care. CONCLUSIONS: This type of internship experience provides an educational environment for college students to become acquainted with PM&R, interact positively with people with disabilities, and influence career choice in the allied health professions.

Characterisation of adhesional properties of lactose carriers using atomic force microscopy.

The atomic force microscopy (AFM) colloid probe technique was investigated as a method for the characterisation of adhesional properties of pharmaceutical powder surfaces. Lactose carriers used in dry powder inhaler (DPI) formulations were chosen for investigation since adhesion between the carrier surface and drug particles has been proposed to affect the dispersion of drug particles. Individual adhesion forces were determined by measuring the detachment forces in air between the colloid probe and the lactose particle surface. The colloid probe consisted of a silica sphere (10 microm diameter) attached to a V-shaped silicon nitride cantilever (spring constant, k=0.42 N/m). Adhesion forces were calculated from individual force-distance curves using Hooke's Law. Individual forces measured at various adhesion sites were observed to be reproducible and stable over 10 min (coefficient of variation, CV below 5%). The adhesion force distribution determined from measurements at multiple sites (n>50) on each sample followed a log-normal relationship (regression coefficient, r(2) ranged between 0.95 and 0.99). This enabled characterisation in terms of the geometric mean adhesion force and a geometric standard deviation (GSD). Significant differences (P<0.001) in adhesion force were observed between samples, ranging from 37.47+/-1.95 to 117.48+/-2.20 nN. This study demonstrates the suitability of AFM as sensitive technique for the characterisation of adhesional properties of pharmaceutical particles.

Reducing the preterm birth rate: a population health strategy.

The rate of preterm birth has been increasing in Canada and the United States. Efforts to prevent preterm birth have been largely ineffective. A population health strategy that integrates disease prevention and health promotion is needed. In this article, the five categories of health determinants proposed by the Federal, Provincial and Territorial Advisory Committee on Population Health are used as a framework to discuss risk factors and propose policies and interventions to reduce the preterm birth rate.

Female spirit cults as a window on gender relations in the highlands of Papua New Guinea.

Early writings on male cults in the highlands of Papua New Guinea tended to stress the exclusion of women and the collective agency of men. Looking at a subset of these cults from the Western and Southern Highlands Provinces, centering on Female Spirit figures, the authors argue that in these cases the cults are better understood as expressions of a collaborative model, in which gendered cooperation, both in practice and in terms of ritual symbolism, is activated in order to produce fertility and wealth. Positive collaboration is involved as well as structural complementarity. The collaborative model is therefore suggested as an alternative to the model of "male exclusivity" in the analysis of certain cult practices in these parts of the New Guinea highlands region.

Education of women about the prevention of preterm birth.

OBJECTIVES: To describe: 1) The education of pregnant women by health care professionals about the prevention of preterm birth; and 2) professionals' views about future initiatives. BACKGROUND: A population survey of health professionals was conducted in Eastern Ontario. The response rate was 73% (608/835). RESULTS: Education materials for women receiving prenatal care about the prevention of preterm birth were available from 10% (12/115) of family physicians, 40% (23/58) of obstetricians, 19% (57/306) of labour room nurses and 76% (94/124) of the prenatal teachers. Only one third of physicians routinely discussed the signs and symptoms of preterm labour prior to 20 weeks. Practitioners' future priorities were smoking cessation programs for pregnant women and increased attendance at early prenatal classes. CONCLUSIONS: Most women are not being educated by anyone in the health care team about the prevention of preterm birth. There is a need for multidisciplinary guidelines about the timing and type of information for women about risk reduction and the early identification and treatment of preterm labour.

Deaggregation during the dissolution of benzodiazepines in interactive mixtures.

The purpose of this research was to investigate the influence of surfactants on the dissolution of benzodiazepines in interactive mixtures. The dissolution of ternary interactive mixtures consisting of micronized drugs (oxazepam, nitrazepam, and flunitrazepam) and micronized surfactants (sodium lauryl sulfate and cetrimide) adhered onto the surface of a lactose carrier (250-355 microm) was studied using the USP/NF paddle method. Dissolution was considered to occur from dispersed particle and aggregate fractions of the drugs, and data were modeled using multiexponential equations. The initial concentrations of the aggregates and dissolution rate constants were estimated using a Marquardt-Levenberg nonlinear least squares algorithm. The marked increase in dissolution rate which occurred with increasing concentrations of sodium lauryl sulfate and cetrimide resulted both from deaggregation of the benzodiazepine particles and from increases in the dissolution rate constants of the dispersed particle and aggregate fractions probably associated with an increased intrinsic dissolution rate. The presence of 5% sodium lauryl sulfate in the interactive mixture reduced the initial percent of aggregates from about 85% in a binary mixture to less than 10% and about doubled the dispersed particle dissolution rate constant. The presence of the surfactant in the surface particulate matrix of the interactive mixture was essential for its deaggregation effect. Sodium lauryl sulfate was more effective than cetrimide in achieving drug deaggregation.

Are special investigations of value in the management of patients with fecal incontinence?

PURPOSE: The aim of this study was to determine whether special investigations significantly alter either the diagnosis or the management plan of patients with fecal incontinence assessed on the basis of a structured history and physical examination alone. METHODS: Fifty consecutive patients with fecal incontinence were prospectively studied in a tertiary referral clinic. Each patient was assessed by two clinicians who independently formulated a diagnosis and treatment plan based on the history and physical examination. The resulting 100 patient assessments were then compared with the final diagnosis and treatment plan formulated on completion of endoanal ultrasound, anal manometry, external sphincter electromyography, and defecating proctography. RESULTS: In the assessment of fecal incontinence, the addition of special investigations altered the diagnosis of the cause of incontinence based on history and examination alone in 19 percent of cases. The management plan was altered in 16 percent of cases. Special investigations were most useful in separating neuropathy from rectal wall disorders and in demonstrating the unexpected presence of internal sphincter defects and neuropathy. CONCLUSIONS: Even experienced colorectal surgeons will misdiagnose up to one-fifth of patients presenting with fecal incontinence if assessment is based on the history and physical examination alone. However surgically correctable causes of incontinence are rarely missed on clinical assessment.

Factors affecting survival after excision of the rectum for cancer: a multivariate analysis.

PURPOSE: The aim of this study was to identify and categorize the independent prognostic effects of patient, clinical, operative, and pathology variables on long-term survival after anterior resection or abdominoperineal excision of the rectum for cancer. METHODS: Proportional hazards regression analysis was used to analyze prospective data from 709 patients who underwent surgery at Concord Hospital during a 23-year period. No patient received adjuvant therapy. RESULTS AND CONCLUSIONS: After adjusting for age and clinicopathologic stage, significantly poorer survival was experienced by males, patients with extensive tumor adherent to other organ(s), those with a high-grade tumor or a tumor showing venous invasion, those who had a postoperative cardiovascular or respiratory complication, and those who did not undergo surgery by a colorectal surgeon specialist. The nature of the operation performed had no independent effect on survival.

Influence of the carrier on the intrinsic rate of dissolution of diazepam in interactive mixtures.

The use of interactive mixtures of drugs adhering to the surface of carriers can promote drug dissolution. The mechanism of dissolution of such mixtures has been studied using the rotating-disc method under conditions eliminating secondary influences such as carrier surface characteristics and drug particle aggregation. Levich plots were used to characterize the dissolution behaviour. Diazepam-compactrol interactive mixtures had initial dissolution rates similar to that of pure diazepam owing to the deposition of a continuous layer of diazepam on the disc surface from the interactive mixture. Linear Levich plots were produced at all drug loadings and the presence of compactrol in the disc slightly enhanced dissolution rates. Dissolution rates for diazepam-emcompress interactive mixtures were lower than those of pure diazepam. The Levich plots for these systems were non-linear with increasing negative curvature as the diazepam loading decreased. The rate of dissolution of diazepam in the lactose interactive mixture was markedly higher than that of pure diazepam, but high diazepam loadings in the lactose mixtures inhibited diazepam dissolution. Rapid carrier dissolution caused surface retraction of the disc, enhancing the dissolution rate. The Levich plots showed an upward curvature due to turbulence. Linear Levich plots for diazepam and other benzodiazepines and for diazepam-compactrol interactive mixtures showed that their dissolution in pH 5 phosphate buffer was diffusion-controlled. The Levich plots for diazepam-emcompress interactive mixtures were indicative of some interfacial control during dissolution, but the hypothesis of common ion precipitation of dissolved carrier, calcium phosphate, onto the disc surface did not fully explain this effect.

Change in smoking prevalence among pregnant women 1982-93.

Maternal smoking is the most prevalent risk factor for low birthweight in Canada. This study compared the prevalence of maternal smoking before and during pregnancy from 1983 to 1992. Population-based surveys of 3,296 women during six months in 1983 and 7,940 women during 12 months in 1992 were conducted in Ottawa-Carleton using a self-administered questionnaire completed in the hospital postpartum period. The proportion of women smoking after the first trimester of pregnancy decreased from 28.5% in 1983 to 18.7% in 1992. This difference was due mainly to a reduction in the proportion of women who smoked before pregnancy (37.4% to 26.4%). Another factor was that more women stopped smoking early in pregnancy (23.9% to 29.2%). Gradients in levels of smoking by age, education, marital status and poverty level still exist; however, this is true for the general population. Programs to decrease smoking in pregnancy should continue to focus on reducing smoking among women in general and among those in the preconception and early stages of pregnancy in particular.

Body composition in anorexia nervosa - changes with treatment, determinants and techniques.

Body fat, total body water and totally body nitrogen were estimated twice before and after refeeding in 32 patients with anorexia nervosa. Body composition was estimated once in 29 normal controls using the techniques of anthropometry, impedance and IVNCA. The influence of weight gain and other variables, ie psychological status, biochemical parameters, exercise and dietary composition, on protein repletion was examined. Methods of assessment of body composition were compared. The results demonstrated that in anorexia nervosa patients, protein was more completely replenished than fat when patients had reached 85% of average body weight for height and age. Weight gain was the only determinant of protein gain. There was no correlation with psychological, biochemical or exercise status nor with dietary composition. Direct methods, ie deuterium dilution and IVNCA, were shown to be preferable in determination of body composition in anorexia nervosa.

The need for a community-wide approach to promote healthy babies and prevent low birth weight.

A community-wide approach offers a potentially more effective way to promote healthy babies in healthy families and to prevent low birth weight. It can address the many factors associated with preterm birth and intrauterine growth restriction, the need to include all members of the community in effecting meaningful change in the incidence rate of adverse outcomes and the development of an effective mechanism to plan and coordinate the delivery of programs. Physicians have an essential role to play in this approach. The evaluation of such a program would complement current biomedical research on the prevention of preterm birth and intrauterine growth restriction. The work for this paper was supported by the Community Health Research Unit, funded by the Ontario Ministry of Health.

Intra-operative ultrasound for the detection of hepatic metastases from colorectal cancer.

The aim of this study was to compare the accuracy of intra-operative ultrasound (IOUS) with other imaging modalities and with surgical palpation in detecting liver metastases from colorectal cancer (CRC). Intra-operative ultrasound was performed in 100 patients undergoing surgery for CRC. All patients had pre-operative liver function tests, transcutaneous ultrasound and computerized tomography (CT) scan of the liver. The liver was palpated intra-operatively by a surgeon who was unaware of the pre-operative findings. The liver was then assessed by IOUS. Intra-operative ultrasound detected more patients with metastases than either CT scan, transcutaneous ultrasound or surgical palpation. It also detected a greater number of smaller metastases in these patients and allowed better anatomical definition compared with pre-operative investigations.