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Hypoxia-inducible factor 1α (HIF-1α) plays an essential role in the adaptive response of cells to hypoxia. The cyclin-dependent kinase inhibitor p27(Kip1) is highly expressed in the normal endometrium but is lost during endometrial carcinogenesis. However, in high-grade cancers, p27 re-expression is observed. We analysed the role of HIF-1α in hypoxia-induced expression of p27 in vitro and in vivo in endometrial cancer. Paraffin-embedded specimens from endometrioid endometrial carcinoma ( n = 39) were stained immunohistochemically for HIF-1α, p27, and Ki67. HEC1B, an endometrial carcinoma cell line, was cultured under normoxic or hypoxic conditions in the presence or absence of transiently expressed short hairpin RNAs targeting HIF-1α. Protein expression of p27 and HIF-1α was assessed by western blotting. Immunohistochemical staining revealed perinecrotic HIF-1α expression in 67% of the cases and p27 staining centrally in the tumour islands, mostly around necrosis, in 46% of the cases. In 50% of the tumours with perinecrotic HIF-1α expression, p27 and HIF-1α perinecrotic/central co-localization was observed. In these tumour sections, hypoxia-associated p27 expression showed less proliferation around necrosis. Analysis of cultured endometrial carcinoma cells demonstrated that p27 protein expression is induced by hypoxia. This induction was abrogated by transient knockdown of HIF-1α using RNAi. Furthermore, hypoxia induced cell cycle arrest in HEC1B cells. We conclude that, in endometrioid endometrial carcinoma, p27 re-expression by hypoxia is HIF-1α-dependent and leads to cell cycle arrest. This may contribute to the survival of cancer cells in hypoxic parts of the tumour. Copyright © 2007 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A decision aid for the surgical treatment of early breast cancer was evaluated in a randomized controlled trial. The decision aid, a tape and workbook, includes explicit presentation of probabilities, photographs and graphics, and a values clarification exercise. Community surgeons were randomized to use the decision aid or a control pamphlet. Patients completed a questionnaire prior to using the decision aid, after reviewing it but prior to surgery, and 6 months after enrollment. There was no difference in anxiety, knowledge, or decisional regret across the 2 groups. There was a nonsignificant trend toward lower decisional conflict in the decision aid group. A subgroup of women who were initially leaning toward mastectomy or were unsure had lower decisional conflict. Although the decision aid had minimal impact on the main study outcomes, a subgroup may have benefited. Such subgroups should be identified, and appropriate decision support interventions should be developed and evaluated. [ABSTRACT FROM AUTHOR]

Disability associated with chronic obstructive pulmonary disease has led to the development of rehabilitation programmes that aim to increase exercise tolerance and improve quality of life. Many reports of the benefits of rehabilitation have been from uncontrolled trials and unsupervised programmes. In view of the commitment asked of patients, their families, and health-care professionals, rehabilitation should be justified by a demonstration of sustained improvement over conventional treatment. We undertook a prospective randomised controlled trial of respiratory rehabilitation in 89 subjects (44 men, 45 women) aged 66 (SD 7) years with severe but stable chronic obstructive pulmonary disease who received rehabilitation or conventional community care. The treatment group were rehabilitated as inpatients for 8 weeks and supervised as outpatients for 16 weeks. Primary outcome measures of exercise tolerance and quality of life were made at baseline and repeated at 12, 18, and 24 weeks. The difference between baseline and last follow-up was significant for 6 min walk distance (37.9 m [95% CI 10.8-65.0], p = 0.0067) and submaximal cycle time (4.7 min [2.1-7.3]). There were also significant differences in questionnaire assessment of dyspnoea (p = 0.0061), emotional function (p = 0.0150), mastery (p = 0.0002), and dyspnoea index (p = 0.0053). Improvements in exercise tolerance and quality of life can be achieved and sustained for 6 months in patients undergoing respiratory rehabilitation compared with those receiving conventional care. [ABSTRACT FROM AUTHOR]

Objective: To provide clinical guidelines for primary care physicians who are dealing with domestic abuse and who have both the abused woman and her partner as patients.Participants: A 15-member expert panel with members having experience in family practice, gynecology, emergency medicine, medical ethics, nursing, psychology, law, and social work; an 11-member consulting group with members representing medicine, consumers, police, psychology, social work, and nursing; and participants from focus groups including 48 previously abused women and 10 previously abusive men. Members of the expert panel and the consulting group were recruited by the research team. Focus group members were recruited through the agencies from which they were receiving services.Evidence: Available research information, and opinions of the expert panel, the consulting group, and the focus group participants.Consensus Process: Scoring of 144 clinical scenarios was performed by the expert panel using a modified Delphi technique involving 4 iterations. Scenarios were rated in terms of best practice for primary care physicians dealing with suspected and confirmed cases of physical abuse. Consulting group members and focus group participants then commented on the panel's results. Final guidelines were approved by the panel and the consulting group, with comments reserved in the guidelines for information from focus group participants.Conclusions: It is not a conflict of interest for the physician to deal with abuse of the female partner when both partners are patients. Both patients have a right to autonomy, confidentiality, honesty, and quality care. Patients should be dealt with independently, thereby facilitating assessment of the magnitude and severity of the victim's injuries. Physicians should not discuss the possibility of domestic abuse with the male partner without the prior consent of the abused female partner. Joint counseling is generally inadvisable and should be attempted only when the violence has ended, provided both partners give independent consent and the physician has adequate training and skills to deal with the situation without escalating the violence. If the physician feels unable to deal effectively with either patient because of the dual relationship, referral to another qualified physician is preferred. [ABSTRACT FROM AUTHOR]

Intracardiac tumors, though uncommon, necessitate a swift and accurate diagnosis for personalized treatment and prognosis estimation. While multi-modality imaging often determines the etiology of these cardiac masses, histological confirmation remains essential for definitive diagnosis and its specific treatment. Since cardiac tumors are often found in high-risk locations (ventricular free wall or atria), precision biopsy is paramount. The least invasive strategy would be to achieve this by means of endomyocardial biopsy (EMB); however real-time additional imaging is essential to reduce the risk of perforation/tamponade and to minimize sampling error. Intracardiac echocardiography (ICE) emerges as an excellent tool to achieve this goal preventing procedural complications and reducing the likelihood of sampling errors obtaining a definitive histopathological diagnosis in all cases. This paper outlines our diagnostic algorithm for optimal patient selection, details three illustrative cases, and elucidates the steps to acquire histopathology via percutaneous transvenous biopsy with ICE guidance in patients with right-sided cardiac tumors. Given the rarity of intracardiac tumors, we advocate these patients be managed by a dedicated multidisciplinary cardio-oncology team including an interventional cardiologist., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Background: Patients with advanced cancer who no longer have standard treatment options available may decide to participate in early phase clinical trials (i.e. experimental treatments with uncertain outcomes). Shared decision-making (SDM) models help to understand considerations that influence patients' decision. Discussion of patient values is essential to SDM, but such communication is often limited in this context and may require new interventions. The OnVaCT intervention, consisting of a preparatory online value clarification tool (OnVaCT) for patients and communication training for oncologists, was previously developed to support SDM. This study aimed to qualitatively explore associations between patient values that are discussed between patients and oncologists during consultations about potential participation in early phase clinical trials before and after implementation of the OnVaCT intervention., Methods: This study is part of a prospective multicentre nonrandomized controlled clinical trial and had a between-subjects design: pre-intervention patients received usual care, while post-intervention patients additionally received the OnVaCT. Oncologists participated in the communication training between study phases. Patients' initial consultation on potential early phase clinical trial participation was recorded and transcribed verbatim. Applying a directed approach, two independent coders analysed the transcripts using an initial codebook based on previous studies. Steps of continuous evaluation and revision were repeated until data saturation was reached., Results: Data saturation was reached after 32 patient-oncologist consultations (i.e. 17 pre-intervention and 15 post-intervention). The analysis revealed the values: hope, perseverance, quality or quantity of life, risk tolerance, trust in the healthcare system/professionals, autonomy, social adherence, altruism, corporeality, acceptance of one's fate, and humanity. Patients in the pre-intervention phase tended to express values briefly and spontaneously. Oncologists acknowledged the importance of patients' values, but generally only gave 'contrasting' examples of why some accept and others refuse to participate in trials. In the post-intervention phase, many oncologists referred to the OnVaCT and/or asked follow-up questions, while patients used longer phrases that combined multiple values, sometimes clearly indicating their weighing., Conclusions: While all values were recognized in both study phases, our results have highlighted the different communication patterns around patient values in SDM for potential early phase clinical trial participation before and after implementation of the OnVaCT intervention. This study therefore provides a first (qualitative) indication that the OnVaCT intervention may support patients and oncologists in discussing their values., Trial Registration: Netherlands Trial Registry: NL7335, registered on July 17, 2018., (© 2024. The Author(s).)

Purpose: Patients with rare cancers (incidence less than 6 cases per 100,000 persons per year) commonly have less treatment opportunities and are understudied at the level of genomic targets. We hypothesized that patients with rare cancer benefit from approved anticancer drugs outside their label similar to common cancers., Experimental Design: In the Drug Rediscovery Protocol (DRUP), patients with therapy-refractory metastatic cancers harboring an actionable molecular profile are matched to FDA/European Medicines Agency-approved targeted therapy or immunotherapy. Patients are enrolled in parallel cohorts based on the histologic tumor type, molecular profile and study drug. Primary endpoint is clinical benefit (complete response, partial response, stable disease ≥ 16 weeks)., Results: Of 1,145 submitted cases, 500 patients, including 164 patients with rare cancers, started one of the 25 available drugs and were evaluable for treatment outcome. The overall clinical benefit rate was 33% in both the rare cancer and nonrare cancer subgroup. Inactivating alterations of CDKN2A and activating BRAF aberrations were overrepresented in patients with rare cancer compared with nonrare cancers, resulting in more matches to CDK4/6 inhibitors (14% vs. 4%; P ≤ 0.001) or BRAF inhibitors (9% vs. 1%; P ≤ 0.001). Patients with rare cancer treated with small-molecule inhibitors targeting BRAF experienced higher rates of clinical benefit (75%) than the nonrare cancer subgroup., Conclusions: Comprehensive molecular testing in patients with rare cancers may identify treatment opportunities and clinical benefit similar to patients with common cancers. Our findings highlight the importance of access to broad molecular diagnostics to ensure equal treatment opportunities for all patients with cancer., (©2022 The Authors; Published by the American Association for Cancer Research.)

When standard treatment options are not available anymore, patients with advanced cancer may participate in early phase clinical trials. Improving this complex decision-making process may improve their quality of life. Therefore, this prospective multicenter study with questionnaires untangles several contributing factors to decisional conflict (which reflects the quality of decision-making) in patients with advanced cancer who recently decided upon early phase clinical trial participation (phase I or I/II). We hypothesized that health-related quality of life, health literacy, sense of hope, satisfaction with the consultation, timing of the decision, and the decision explain decisional conflict. Mean decisional conflict in 116 patients was 30.0 (SD = 16.9). Multivariate regression analysis showed that less decisional conflict was reported by patients with better global health status (β = −0.185, p = 0.018), higher satisfaction (β = −0.246, p = 0.002), and who made the decision before (β = −0.543, p < 0.001) or within a week after the consultation (β = −0.427, p < 0.001). These variables explained 37% of the variance in decisional conflict. Healthcare professionals should realize that patients with lower global health status and who need more time to decide may require additional support. Although altering such patient intrinsic characteristics is difficult, oncologists can impact the satisfaction with the consultation. Future research should verify whether effective patient-centered communication could prevent decisional conflict.

Cancer therapy-related cardiac dysfunction (CTRCD) is one of the most concerning cardiovascular side effects of cancer treatment. Important reviews within the field of cardio-oncology have described various agents to be associated with a high risk of CTRCD, including mitomycin C, ifosfamide, vincristine, cyclophosphamide, and clofarabine. The aim of this study was to provide insight into the data on which these incidence rates are based. We observed that the reported cardiotoxicity of mitomycin C and ifosfamide is based on studies in which most patients received anthracyclines, complicating the interpretation of their association with CTRCD. The high incidence of vincristine-induced cardiotoxicity is based on an incorrect interpretation of a single study. Incidence rates of clofarabine remain uncertain due to a lack of cardiac screening in clinical trials. The administration of high-dose cyclophosphamide (>1.5 g/m 2 /day) is associated with a high incidence of CTRCD. Based on our findings, a critical re-evaluation of the cardiotoxicity of these agents is warranted., (© 2019 The Authors.)

Background: Patients with advanced cancer for whom standard systemic treatment is no longer available may be offered participation in early phase clinical trials. In the decision making process, both medical-technical information and patient values and preferences are important. Since patients report decisional conflict after deciding on participation in these trials, improving the decision making process is essential. We aim to develop and evaluate an Online Value Clarification Tool (OnVaCT) to assist patients in clarifying their values around this end-of-life decision. This improved sharing of values is hypothesized to support medical oncologists in tailoring their information to individual patients' needs and, consequently, to support patients in taking decisions in line with their values and reduce decisional conflict., Methods: In the first part, patients' values and preferences and medical oncologists' views hereupon will be explored in interviews and focus groups to build a first prototype OnVaCT using digital communication (serious gaming). Next, we will test feasibility during think aloud sessions, to deliver a ready-to-implement OnVaCT. In the second part, the OnVaCT, with accompanied training module, will be evaluated in a pre-test (12-18 months before implementation) post-test (12-18 months after implementation) study in three major Dutch cancer centres. We will include 276 patients (> 18 years) with advanced cancer for whom standard systemic therapy is no longer available, and who are referred for participation in early phase clinical trials. The first consultation will be recorded to analyse patient-physician communication regarding the discussion of patients' values and the decision making process. Three weeks afterwards, decisional conflict will be measured., Discussion: This project aims to support the discussion of patient values when considering participation in early phase clinical trials. By including patients before their first appointment with the medical oncologist and recording that consultation, we are able to link decisional conflict to the decision making process, e.g. the communication during consultation. The study faces challenges such as timely including patients within the short period between referral and first consultation. Furthermore, with new treatments being developed rapidly, molecular stratification may affect the patient populations included in the pre-test and post-test periods., Trial Registration: Netherlands Trial Registry number: NTR7551 (prospective; July 17, 2018).

TWIST1, an antiapoptotic and prometastatic transcription factor, is overexpressed in many epithelial cancers including breast. Only little is known regarding the regulation of TWIST1 in these cancers. Recently, an increase in the TWIST1 promoter methylation has been shown in breast cancers. To correlate the percentage of TWIST1 promoter methylation to the protein levels, we analyzed simultaneously the methylation status as well as the mRNA and the percentage of cells expressing TWIST1 in normal breast tissue and 76 invasive breast cancers. We found that TWIST1 promoter methylation is significantly more prevalent in malignant compared with healthy breast tissue. Furthermore, the percentage of cells expressing TWIST1 was greater in breast malignancy compared with matched healthy tissue from the same patients. There was no correlation, however, between TWIST1 promoter methylation and TWIST1 protein or RNA expression. This indicates that although TWIST1 CpG methylation is useful as a biomarker in breast cancer diagnosis, there is no direct correlation with TWIST1 expression.

Hypoxia-inducible factors (HIFs) are highly conserved transcription factors that play a crucial role in oxygen homeostasis. Intratumoral hypoxia and genetic alterations lead to HIF activity, which is a hallmark of solid cancer and is associated with poor clinical outcome. HIF activity is regulated by an evolutionary conserved mechanism involving oxygen-dependent HIFalpha protein degradation. To identify novel components of the HIF pathway, we performed a genome-wide RNA interference screen in Caenorhabditis elegans, to suppress HIF-dependent phenotypes, like egg-laying defects and hypoxia survival. In addition to hif-1 (HIFalpha) and aha-1 (HIFbeta), we identified hlh-8, gska-3 and spe-8. The hlh-8 gene is homologous to the human oncogene TWIST1. We show that TWIST1 expression in human cancer cells is enhanced by hypoxia in a HIF-2alpha-dependent manner. Furthermore, intronic hypoxia response elements of TWIST1 are regulated by HIF-2alpha, but not HIF-1alpha. These results identify TWIST1 as a direct target gene of HIF-2alpha, which may provide insight into the acquired metastatic capacity of hypoxic tumors.

Metastases formation is a major factor in disease progression and accounts for the majority of cancer deaths. The molecular mechanisms controlling invasion, dissemination to blood or lymphatic systems and spread of tumor cells to distant organs are still poorly understood. Recent observations indicate that the meta-static phenotype may already be present during the angiogenic switch of tumors. Intratumoral hypoxia correlates with poor prognosis and enhanced metastases formation. The Hypoxia Inducible Factors (HIFs) are key molecules in the hypoxic response and play critical roles during tumor cell expansion by regulating energy metabolism and the induction of angiogenesis. Increasing evidence implicates HIF function in metastatic cell characteristics, like epithelial to mesenchymal transition, cell detachment, invasion and tumor cell seeding. Here, we review the link between tumor cell hypoxia and the acquisition of metastatic behavior. We hypothesize that polyclonal tumor selection by hypoxia enhances metastatic capacity by transcriptional control of key regulators of metastasis. This polyclonal hypoxic gene profile potentially develops into a metastatic profile, driving metastasis formation. The hypoxic gene profile in primary tumors may therefore provide a prognostic indicator in clinical decision-making.

Hypoxia-inducible factor 1alpha (HIF-1alpha) plays an essential role in the adaptive response of cells to hypoxia. The cyclin-dependent kinase inhibitor p27(Kip1) is highly expressed in the normal endometrium but is lost during endometrial carcinogenesis. However, in high-grade cancers, p27 re-expression is observed. We analysed the role of HIF-1alpha in hypoxia-induced expression of p27 in vitro and in vivo in endometrial cancer. Paraffin-embedded specimens from endometrioid endometrial carcinoma (n = 39) were stained immunohistochemically for HIF-1alpha, p27, and Ki67. HEC1B, an endometrial carcinoma cell line, was cultured under normoxic or hypoxic conditions in the presence or absence of transiently expressed short hairpin RNAs targeting HIF-1alpha. Protein expression of p27 and HIF-1alpha was assessed by western blotting. Immunohistochemical staining revealed perinecrotic HIF-1alpha expression in 67% of the cases and p27 staining centrally in the tumour islands, mostly around necrosis, in 46% of the cases. In 50% of the tumours with perinecrotic HIF-1alpha expression, p27 and HIF-1alpha perinecrotic/central co-localization was observed. In these tumour sections, hypoxia-associated p27 expression showed less proliferation around necrosis. Analysis of cultured endometrial carcinoma cells demonstrated that p27 protein expression is induced by hypoxia. This induction was abrogated by transient knockdown of HIF-1alpha using RNAi. Furthermore, hypoxia induced cell cycle arrest in HEC1B cells. We conclude that, in endometrioid endometrial carcinoma, p27 re-expression by hypoxia is HIF-1alpha-dependent and leads to cell cycle arrest. This may contribute to the survival of cancer cells in hypoxic parts of the tumour.

Hypoxia is a hallmark of solid cancers and triggers the transcription of genes responsible for cell survival. The transcription factor Hypoxia-Inducible Factor 1 (HIF-1) is a key regulator in this response and frequently activated in human cancer. HIF-1 activation is associated with tumor aggressiveness and poor clinical outcome and, therefore, may provide an attractive therapeutic target. Here we provide a novel approach for HIF-1 targeted therapy using single-domain llama antibodies directed against the HIF-1alpha oxygen dependent degradation domain which encompass the N-terminal transactivation domain. Conditional expression of HIF intrabodies in mammalian cells interfered with binding to pVHL and inhibited hypoxia induced activation of endogenous target genes. Inducible intrabody targeting is a highly specific strategy for temporal protein inactivation and may have applications for disease treatment.

Hypoxia-inducible factor-1 alpha (HIF-1alpha) is the regulatory subunit of the heterodimeric transcription factor HIF-1 and the key factor in cellular response to low oxygen tension. Expression of HIF-1alpha protein is associated with poor patient survival and therapy resistance in many types of solid tumors. Insight into HIF-1alpha regulation in solid tumors is important for therapeutic strategies. In this study, we determined the pathophysiological relevance of HIF-1alpha regulation by the oncogenic phosphatidylinositol 3'-kinase (PI 3-kinase)/Akt signaling pathway. We modeled the physiology of hypoxic tumor regions by culturing carcinoma cells under low oxygen tension in the absence of serum. We observed that hypoxic induction of HIF-1alpha protein was decreased by serum deprivation. Overexpression of dominant-active Akt1 restored HIF-1alpha expression, whereas inhibition of PI 3-kinase activity reduced hypoxic HIF-1alpha protein levels to a similar extent as serum deprivation. Immunohistochemical analysis of 95 human breast cancers revealed that lack of Akt1 phosphorylation correlates with low HIF-1alpha levels. To our knowledge, this is the first reported comparison between HIF-1alpha expression and Akt phosphorylation in human carcinomas. We conclude that Akt activity is physiologically relevant for HIF-1alpha expression in breast cancer. This implies that HIF-1alpha function might be therapeutically targeted by inhibition of the PI 3-kinase/Akt pathway.

Hypoxia triggers the transcription of genes responsible for cell survival via the key player transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha). Overexpression of this protein has been implicated in cardiovascular disorders, carcinogenesis and cancer progression. For functional and diagnostic studies on the HIF-1alpha protein, we have identified single-domain antibody fragments directed against this protein by using a llama-derived nonimmune phage display library. This library displays the variable domains of the heavy-chain antibody subclass, found in these animals. Phage display selection with six recombinant HIF-1alpha proteins yielded five different antibody fragments. By epitope-mapping, we show that all five antibody fragments bind within the functionally important oxygen-dependent degradation domain of the HIF-1alpha protein. Two of these antibody fragments were engineered into bivalent antibodies that were able to detect human HIF-1alpha by immunohistochemistry, Western blotting and immunoprecipitation, and mouse HIF-1alpha by immunofluorescence and immunoprecipitation. These are the first single-domain antibody fragments that may be used in exploration of HIF-1alpha as a possible therapeutic target through molecular applications.

Background and Objectives: This study determined which clinical factors influence Canadian primary care physicians' management decisions in cases of female partner abuse., Methods: We used a cross-sectional survey design and randomly sampled (n = 2,014) English-speaking Canadian physicians with a primary interest in family or general practice who were practicing in any of the 12 provinces and territories in Canada and who were active in private practice and registered to prescribe. Respondents completed a questionnaire that required them to score management decision plans in response to case scenarios illustrating typical office-based situations that might involve domestic violence., Results: The response rate was 50.7% (n = 1,022). Using forward stepwise regression analysis, the strongest predictor of whether a physician endorsed a management plan in response to violence was whether the woman acknowledged or revealed the abuse. Male physicians were more likely than females to endorse talking with the suspected abuser if he was known to them, regardless of the quality of this patient-physician relationship with the abuser., Conclusions: Decisions about whether to deal with the abuse or the selection of a management plan are not dependent on the severity of the physical abuse and the emotional consequences. Whether a woman acknowledges or reveals the abuse, as well as whether both the male and female patients are in the physician's practice, are predictive of whether a physician's response to a case scenario involves dealing with spousal abuse and how he/she will address it.

Objectives: To determine the makes, models and prices of the implants provided by Ontario hospitals for hip and knee replacements and the policies and procedures governing purchases., Design: A questionnaire survey of hospitals with telephone follow-up., Study Population: Seventy-nine public hospitals in Ontario in which 10 or more hip or knee replacements were carried out in the fiscal year 1993/94. SURVEY RESPONSE: Seventy-six hospitals returned questionnaires (96% response rate), reporting on 4950 primary hip and 5107 primary knee implants. Sixty-two hospitals reported volumes and prices for 19 models used in 2961 hip implants. Information on price but not makes and models was available for 1989 hip implants. Model and price information was missing for 340 hip prostheses. Fifty-seven hospitals identified the models and prices for 3460 knee implants. Twenty-five hospitals provided prices but not specific models names for 1647 knee implants and hybrids., Outcome Measure: The prices paid for prostheses., Results: The average price of hip implants was Can$2141 (range from Can$650 to Can$3559). The average price for knee implants was Can$2412 (range from Can$1178 to Can$3777). The averages and ranges were about the same for specified and unspecified models and hybrids. The variations were unrelated to hospital policies about the numbers of procedures to be provided or the procedures for making purchases from suppliers., Conclusions: Savings of Can$13.7 million could have been made in Ontario during the fiscal year 1993/94 had the lowest prices been paid for the implants. Although it may be neither desirable nor possible to use the least expensive model and price in every hospital, the potential for cost reductions in the purchase of implants is substantial.

PURPOSE: A patient decision aid for the surgical treatment of early stage breast cancer was developed and evaluated. The rationale for its development was the knowledge that breast conserving therapy (lumpectomy followed by breast radiation) and mastectomy produce equivalent outcomes, and the current general agreement that the decision for the type of surgery should rest with the patient. METHODS: A decision aid was developed and evaluated in sequential pilot studies of 18 and 10 women with newly diagnosed breast cancer who were facing a decision for breast conserving therapy or mastectomy. Both qualitative (general reaction, self-reported anxiety, clarity, satisfaction) and quantitative (knowledge and decisional conflict) measures were assessed. RESULTS: The decision aid consists of an audiotape and workbook and takes 36 min to complete. Based on qualitative comments and satisfaction ratings, 17 of 18 women reported a positive reaction to the decision aid, and all 18 reported that it helped clarify information given by the surgeon. Women did not report an increase in anxiety and 17 of 18 women were either satisfied or very satisfied with the decision aid. CONCLUSION: This pilot study supports the hypothesis that this decision aid may be a helpful adjunct in the decision for surgical management of early stage breast cancer. We are currently conducting a randomized trial of the decision aid versus a simple educational pamphlet to evaluate its efficacy as measured by knowledge, decisional conflict, anxiety and post-decisional regret.

Study Objective: We report on the incremental costs associated with improvements in health-related quality of life (HRQL) following 6 months of respiratory rehabilitation compared with conventional community care., Design: Prospective randomized controlled trial of rehabilitation., Setting: A respiratory rehabilitation unit., Participants: Eighty-four subjects who completed the rehabilitation trial., Intervention: Two months of inpatient rehabilitation followed by 4 months of outpatient supervision., Measurements and Results: All costs (hospitalization, medical care, medications, home care, assistive devices, transportation) were included. Simultaneous allocation was used to determine capital and direct and indirect hospitalization costs. The incremental cost of achieving improvements beyond the minimal clinically important difference in dyspnea, emotional function, and mastery was $11,597 (Canadian). More than 90% of this cost was attributable to the inpatient phase of the program. Of the nonphysician health-care professionals, nursing was identified as the largest cost center, followed by physical therapy and occupational therapy. The number of subjects needed to be treated (NNT) to improve one subject was 4.1 for dyspnea, 4.4 for fatigue, 3.3 for emotion, and 2.5 for mastery., Conclusion: Cost estimates of various approaches to rehabilitation should be combined with valid, reliable, and responsive measures of outcome to enable cost-effectiveness measures to be reported. Comparison studies with the same method are necessary to determine whether the improvements in HRQL that follow inpatient rehabilitation are cheap or expensive. Such information will be important in identifying the extent to which alternative approaches to rehabilitation can influence resource allocation. A consideration of cost-effectiveness from the perspective of NNT may be useful in the evaluation of health-care programs.

Although the number of users of home mechanical ventilation (HMV) is increasing, information regarding the users' perceptions of the impact of HMV on their lives is incomplete. We administered an open-ended questionnaire to 98 (48 male, 50 female) HMV users aged (mean +/- SD) 47.4 +/- 19.5 years with COPD (9%), thoracic restrictive disease (43%), and neuromuscular disease (48%). At the time of survey, subjects had received HMV for 59.5 +/- 58.3 months. Fifty-three percent were ventilated electively. Ventilator use was continuous (18%), at night only (37%), or at night with occasional daytime use (45%). Twenty-seven (28%) individuals identified themselves as being totally independent while 32 (33%) rated themselves as partially dependent on caregiver assistance for daily activities. Only 37 (38%) considered that they had made an informed choice when first starting HMV whereas 54 (55%) did not. The impact of using a mechanical ventilator was believed to be overwhelmingly positive (87%). Positive comments regarding the impact of the ventilator on lifestyle were grouped in the following categories: life sustaining, facilitating mobility, and improving physical symptoms. Negative comments were grouped in the following categories: limiting mobility, equipment issues, and social implications. HMV users with a tracheostomy volunteered significantly fewer positive statements than those ventilated noninvasively (p < 0.05). Whereas 52 (53%) of users indicated that they had experienced initial difficulties in coping with the ventilator, only 11 (11%) identified difficulties at the time of the survey.

It is said that we can learn as much about social processes from so-called 'deviant' institutions than from the more legitimate. 'Deviant' medical occupations have not attracted much attention from social scientists. Naturopathy is one of these nonconventional health occupations. It emerged in the 18th and 19th centuries and moved to Canada from the United States and Europe early in the 20th. The social history of naturopathy in Canada illustrates the importance of processes of occupational formation and organization as well as state recognition or legitimation. Furthermore, the development of naturopathy shows the importance of state-occupation and naturopathy-chiropractic relationships as well as the often noted relationships with the dominant health occupation of medicine. Incidentally noted are the changing relationships with the state and the dominance of the ideology of science.