Longitudinal assessment of health-related quality of life in osteoporosis: data from the population-based Canadian Multicentre Osteoporosis Study.

Little is known about the association between health-related quality of life (HRQOL) and osteoporosis in the absence of fracture, and how HRQOL may change over time. This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. INTRODUCTION: Fragility fractures have a detrimental effect on the health-related quality of life (HRQOL) of those with osteoporosis. Less is known about the association between HRQOL and osteoporosis in the absence of fracture. METHODS: Canadian Multicentre Osteoporosis Study participants completed the SF-36, a detailed health questionnaire and measures of bone mineral density (BMD) at baseline and follow-up. We report the results of participants ≥ 50 years with 10-year follow-up. Self-reported osteoporosis at baseline and BMD-based osteoporosis at follow-up were ascertained. Multivariable linear regression models were developed for baseline SF-36 domains, component summaries, and change over time, adjusting for relevant baseline information. RESULTS: Baseline data were available for 5266 women and 2112 men. Women in the osteoporosis group had substantially lower SF-36 baseline scores, particularly in the physically oriented domains, than those without osteoporosis. A similar but attenuated pattern was evident for the men. After 10-year follow-up (2797 women and 1023 men), most domain scores dropped for women and men regardless of osteoporosis status, with the exception of mentally-oriented ones. In general, a fragility fracture was associated with lower SF-36 scores and larger declines over time. CONCLUSIONS: This study provides evidence of substantially reduced HRQOL in women and men with self-reported and/or BMD-confirmed osteoporosis, even in the absence of fragility fracture. HRQOL should be thoroughly investigated even prior to fracture, to develop appropriate interventions for all stages of the disease.

Do Contemporary Randomized Controlled Trials Meet ESMO Thresholds for Meaningful Clinical Benefit?

Background: The European Society for Medical Oncology (ESMO) recently released a magnitude of clinical benefit scale (ESMO-MCBS) for systemic therapies for solid cancers. Here, we evaluate contemporary randomized controlled trials (RCTs) against the proposed ESMO thresholds for meaningful clinical benefit. Methods: RCTs evaluating systemic therapy for breast cancer, nonsmall cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic cancer published 2011-2015 were reviewed. Data were abstracted regarding trial characteristics and outcomes, and these were applied to the ESMO-MCBS. We also determined whether RCTs were designed to detect an effect that would meet clinical benefit as defined by the ESMO-MCBS. Results: About 277 eligible RCTs were included (40% breast, 31% NSCLC, 22% CRC, 6% pancreas). Median sample size was 532 and 83% were funded by industry. Among all 277 RCTs, the experimental therapy was statistically superior to the control arm in 138 (50%) trials: results of only 31% (43/138) of these trials met the ESMO-MCBS clinical benefit threshold. RCTs with curative intent were more likely to meet clinically meaningful thresholds than those with palliative intent [61% (19/31) versus 22% (24/107), P < 0.001]. Among the 226 RCTs for which the ESMO-MCBS could be applied, 31% (70/226) were designed to detect an effect size that could meet ESMO-MCBS thresholds. Conclusion: Less than one-third of contemporary RCTs with statistically significant results meet ESMO thresholds for meaningful clinical benefit, and this represents only 15% of all published trials. Investigators, funding agencies, regulatory agencies, and industry should adopt more stringent thresholds for meaningful benefit in the design of future RCTs.

Shifting practice in definitive chemoradiation for localized esophageal cancer.

BACKGROUND: The efficacy of carboplatin-paclitaxel in the trimodality setting was demonstrated in the cross trial. Because of better tolerance, that regimen has been adopted as an alternative for patients receiving definitive chemoradiation (dcrt). The purpose of our study was to compare outcomes in patients with localized esophageal and gastroesophageal junction (gej) cancer who received dcrt using either platinum-5-fluorouracil (5fu) or carboplatin-paclitaxel. METHODS: Medical records and outcomes for all patients diagnosed with localized carcinoma of the esophagus and gej at our centre between 2008 and 2015 were reviewed. All patients who underwent dcrt using cisplatin-5fu, carboplatin-5fu, or carboplatin-paclitaxel were included. RESULTS: The 73 identified patients (34 cisplatin-5fu, 13 carboplatin-5fu, 26 carboplatin-paclitaxel) were all prescribed concomitant radiotherapy of 50 Gy in 25 daily fractions. The diagnosis was adenocarcinoma in 64% and squamous cell carcinoma in 36%. Median overall survival (os) duration for the cisplatin-5fu group was 28 months [95% confidence interval (ci): 19 to 41 months], with a 3-year os rate of 44%, in contrast to the 15 months (95% ci: 11 to 17 months) and 15% in the carboplatin-paclitaxel group (log-rank p = 0.0047). Median os duration for the carboplatin-5fu group was 17 months (95% ci: 11 to 68 months) with a 3-year os rate of 31%. Adjusting for patient and disease factors, better os durations and rates were associated with cisplatin-5fu (hazard ratio: 0.34; p = 0.0016) and carboplatin-5fu (hazard ratio: 0.55; p = 0.20) than with carboplatin-paclitaxel. CONCLUSIONS: In a dcrt regimen, a better os is associated with cisplatin-5fu than with carboplatin-paclitaxel. Clinical trials to determine optimal chemotherapy regimens are warranted for patients who are not suitable for surgery.

Toward improved goals-of-care documentation in advanced cancer: report on the development of a quality improvement initiative.

BACKGROUND: Documentation of advance care planning for patients with terminal cancer is known to be poor. Here, we describe a quality improvement initiative. METHODS: Patients receiving palliative chemotherapy for metastatic lung, pancreatic, colorectal, and breast cancer during 2010-2015 at the Cancer Centre of Southeastern Ontario were identified from electronic pharmacy records. Clinical notes were reviewed to identify documentation of care plans in the event of acute deterioration. After establishing baseline practice, we sought to improve documentation of goals of care and referral rates to palliative care. Using quality improvement methodology, we developed a guideline, a standardized documentation system, and a process to facilitate early referral to palliative care. RESULTS: During 2010-2015, 456 patients were included in the baseline cohort: 63% with lung cancer, 16% with colorectal cancer, 13% with pancreatic cancer, and 7% with breast cancer. Care goals in the event of an acute illness were documented by medical oncologists in 6% of cases (26 of 456). Of the 456 patients, 47% (n = 214) were seen by palliative care; care goals were documented by palliative care in 48% of the patients seen (103 of 214). With those baseline data in hand, a local practice guideline and process was developed to facilitate the identification of patients for whom advance care planning and early palliative care referral should be considered. A system was also established so that goals-of-care documentation will be supported with a written framework and broadly accessible in the electronic medical record. CONCLUSIONS: Low rates of documentation of advance care planning and referral to palliative care persist and have stimulated a local quality improvement initiative.

Evaluation of the utility of the ISTH-BAT in haemophilia carriers: a multinational study.

INTRODUCTION: There has been increasing recognition in recent years that female carriers of haemophilia manifest abnormal bleeding; however, data on the use of bleeding assessment tools in this population are lacking. AIM: Our objective was to validate the ISTH-BAT in haemophilia carriers to describe bleeding symptoms and allow for comparisons with factor levels and other patient groups. METHODS: This was a prospective, observational, cross-sectional study performed by members of Global Emerging HEmostasis Panel (GEHEP). Unselected consecutive haemophilia carriers were recruited and a CRF and the ISTH-BAT were completed by study personnel. RESULTS: A total of 168 haemophilia carriers were enrolled: 155 haemophilia A and 13 haemophilia B. The mean age was 40 years (range: 20-82). Carriers had higher mean bleeding scores (BS) compared with age-matched controls (n = 46; 5.7 vs. 1.43; P < 0.0001) and Type 3 VWD OC (n = 32; 3.0; P = 0.009), but lower BS compared with women with Type 1 VWD (n = 83; 8.7; P < 0.0001). Fifteen carriers reported haemarthrosis, and of those six had normal FVIII/FIX levels. There was a significant but weak negative correlation between BS and factor level (Spearman's r2  = -0.36, P < 0.001). CONCLUSION: Our results show that haemophilia carriers experience abnormal bleeding, including haemarthrosis. Overall, BS in women with Type 1 VWD > haemophilia carriers > Type 3 VWD OC > controls. Understanding the performance of the ISTH-BAT in this population is a critical step in future research aimed at investigating the underlying pathophysiology of abnormal bleeding, with the ultimate goal of optimizing treatment.

A retrospective study on the role of diabetes and metformin in colorectal cancer disease survival.

BACKGROUND: Recent studies have suggested an effect of metformin on mortality for patients with both diabetes and colorectal cancer (crc). However, the literature is contradictory, with both positive and negative effects being identified. We set out to determine the effect of metformin with respect to prognosis in crc patients. METHODS: After a retrospective chart review of crc patients treated at the Cancer Centre of Southeastern Ontario, Kaplan-Meier analyses and Cox proportional hazards regression models were used to compare overall survival (os) in patients with and without diabetes. RESULTS: We identified 1304 crc patients treated at the centre. No significant differences between the diabetic and nondiabetic groups were observed with respect to tumour pathology, extent of metastatic disease, time or toxicity of chemotherapy, and the os rate (1-year os: 85.6% vs. 86.4%, p = 0.695; 2-year os: 73.6% vs. 77.0%, p = 0.265). In subgroup analysis, diabetic patients taking metformin survived significantly longer than their counterparts taking other diabetes treatments (os for the metformin group: 91% at 1 year; 80.5% at 2 years; os for the group taking other treatments, including diet control: 80.6% at 1 year, 67.4% at 2 years). Multivariate analysis suggests that patients with diabetes taking treatments other than metformin experience worse survival (p = 0.025). CONCLUSIONS: Our results suggest that crc patients with diabetes, excluding those taking metformin, might have a worse crc prognosis. Taking metformin appears to have a positive association with prognosis. The protective nature of metformin needs further evaluation in prospective analyses.

A retrospective analysis of the role of proton pump inhibitors in colorectal cancer disease survival.

BACKGROUND: Proton pump inhibitors (ppis) are a commonly used medication. A limited number of studies have identified a weak-to-moderate association between ppi use and colorectal cancer (crc) risk, but none to date have identified an effect of ppi use on crc survival. We therefore postulated that an association between ppi use and crc survival might potentially exist. METHODS: We performed a retrospective chart review of 1304 crc patients diagnosed from January 2005 to December 2011 and treated at the Cancer Centre of Southeastern Ontario. Kaplan-Meier analysis and Cox proportional hazards regression models were used to evaluate overall survival (os). RESULTS: We identified 117 patients (9.0%) who were taking ppis at the time of oncology consult. Those taking a ppi were also more often taking asa or statins (or both) and had a statistically significantly increased rate of cardiac disease. No identifiable difference in tumour characteristics was evident in the two groups, including tumour location, differentiation, lymph node status, and stage. Univariate analysis identified a statistically nonsignificant difference in survival, with those taking a ppi experiencing lesser 1-year (82.1% vs. 86.7%, p = 0.161), 2-year (70.1% vs. 76.8%, p = 0.111), and 5-year os (55.2% vs. 62.9%, p = 0.165). When controlling for patient demographics and tumour characteristics, multivariate Cox regression analysis identified a statistically significant effect of ppi in our patient population (hazard ratio: 1.343; 95% confidence interval: 1.011 to 1.785; p = 0.042). CONCLUSIONS: Our results suggest a potential adverse effect of ppi use on os in crc patients. These results need further evaluation in prospective analyses.

Generation and optimization of the self-administered bleeding assessment tool and its validation as a screening test for von Willebrand disease.

INTRODUCTION/AIM: Our aim was to generate, optimize and validate a self-administered bleeding assessment tool (self-BAT) for von Willebrand disease (VWD). METHODS: In Phase 1, medical terminology in the expert-administered International Society on Thrombosis and Haemostasis (ISTH)-BAT was converted into a Grade 4 reading level to produce the first version of the Self-BAT which was then optimized to ensure agreement with the ISTH-BAT. In Phase 2, the normal range of bleeding scores (BSs) was determined and test-retest reliability analysed. In Phase 3, the optimized Self-BAT was tested as a screening tool for first time referrals to the Haematology clinic. RESULTS: Bleeding score from the final optimized version of the Self-BAT showed an excellent intra-class correlation coefficient (ICC) of 0.87 with ISTH-BAT BS in Phase 1. In Phase 2, the normal range of BSs for the optimized Self-BAT was determined to be 0 to +5 for females and 0 to +3 for males and excellent test-retest reliability was shown (ICC = 0.95). In Phase 3, we showed that a positive Self-BAT BS (≥6 for females, ≥4 for males) has a sensitivity of 78%, specificity of 23%, positive predictive value (PPV) of 0.15 and negative predictive value (NPV) of 0.86 for VWD; these figures improved when just the females were analysed; sensitivity of 100%, specificity of 21%, PPV = 0.17 and NPV = 1.0. CONCLUSION: We show an optimized Self-BAT can generate comparable BS to the expert-administered ISTH-BAT and is a reliable, effective screening tool to incorporate into the assessment of individuals, particularly women, referred for a possible bleeding disorder.

Real-world impact of granulocyte-colony stimulating factor on febrile neutropenia.

BACKGROUND: Primary prophylaxis with granulocyte colony-stimulating factors (pp-g-csf) is recommended in patients undergoing chemotherapy carrying a febrile neutropenia (fn) risk of 20% or more. In the present study, we examined clinical practice patterns and the impact of pp-g-csf on fn incidence in women with early-stage breast cancer (ebc) treated with modern adjuvant chemotherapy (act). METHODS: This single-centre retrospective cohort study of women with ebc, who were identified from the pharmacy database and who received at least 1 cycle of modern act from January 2009 to December 2011, was conducted at the Cancer Centre of Southeastern Ontario. Data on patient demographics, pathology, stage distribution, chemotherapy, pp-g-csf use, dose reductions, chemotherapy delays, treatment discontinuation, relative dose intensity, and fn events were collected. Chi-square tests, t-tests, univariate and multivariate logistic regression analyses, and nonparametric Mann-Whitney U-tests were used for data analysis. RESULTS: Of the 239 women eligible for analysis, 145 (61%) received pp-g-csf, and 50 (21%) developed at least 1 episode of fn. Use of pp-g-csf was associated with a significantly lower rate of fn (14% vs. 31%, p = 0.002) and trends to fewer dose delays (17% vs. 27%, p = 0.060) and dose reductions (19% vs. 25%, p = 0.28). Among women receiving pp-g-csf, higher fn rates were associated with an age of 65 years or older, taxane-based chemotherapy, and prophylaxis with filgrastim. CONCLUSIONS: Clinical practice patterns at our institution showed that more than 50% of ebc patients treated with modern act received pp-g-csf, which led to fewer fn episodes and increased delivery of planned act. The observed high fn risk despite pp-g-csf was linked to older age, taxane-based chemotherapy, and filgrastim.

Industry Funding of Oncology Randomised Controlled Trials: Implications for Design, Results and Interpretation.

AIMS: Most randomised controlled trials (RCTs) in oncology are now funded by the pharmaceutical industry. We explore the extent to which RCT design, results and interpretation differ between industry-funded and non-industry-funded RCTs. MATERIALS AND METHODS: In this cross-sectional analysis, a structured literature search was used to identify all oncology RCTs published globally during 2014-2017. Industry funding was identified based on explicit statements in the publication. Descriptive statistics were used to compare elements of trial methodology and output between industry- and non-industry-funded RCTs. RESULTS: The study sample included 694 RCTs; 71% were funded by industry. Industry-funded trials were more likely to test systemic therapy (97% versus 62%; P < 0.001), palliative-intent therapy (71% versus 41%; P < 0.001) and study breast cancer (20% versus 12%; P < 0.001). Industry-funded trials were larger (median sample size 474 versus 375; P < 0.001) and more likely to meet their primary end point (49% versus 41%; P < 0.001). Among positive trials, there were no differences in the magnitude of benefit between industry- and non-industry-funded RCTs. Trials funded by industry were published in journals that had a significantly higher median impact factor (21, interquartile range 7, 28) than non-industry-funded trials (impact factor 12, interquartile range 5, 24; P = 0.005); this persisted when adjusted for whether a trial was positive or negative. CONCLUSIONS: The vast majority of oncology RCTs are now funded by industry. Industry-funded trials are larger, more likely to be positive, predominantly test systemic therapies in the palliative setting and are published in higher impact journals than trials without industry support.

Variability of thromboelastographic responses following the administration of rFVIIa to haemophilia A dogs supports the individualization of therapy with a global test of haemostasis.

The efficacy of recombinant factor VIIa (rFVIIa) therapy in haemophilia A is challenged by the lack of a reliable monitoring tool for treatment response. This is further complicated by the significant inter-patient variability associated with this response. Thromboelastography (TEG), a real time global haemostatic test has shown superiority over conventional tests of haemostasis and has proven efficiency in the monitoring of bypass agents such as rFVIIa and FEIBA™. However, this evaluation has been limited to a few case studies or very small patient series. In this study, six severe haemophilia A dogs were treated with a clinically relevant single dose of rFVIIa, and therapy was monitored by thromboelastography predrug and at 15, 30 and 60 min postdrug administration using citrated whole blood samples activated with tissue factor and compared with non-tissue factor-activated samples. Despite the homogeneity of the tested dogs, a clear inter-individual variation was observed in the pre-and post-rFVIIa Thromboelastography analyzes. The improvement of global haemostatic parameters was seen as early as 15 min following drug administration, with a peak for factor VIIa activity in plasma at the same time. There is a significant correlation between plasma FVIIa and TEG parameters 15 min postinjection, and the baseline TEG profile influences the individual postdrug administration outcome. Together, these data support the value of TEG not only as an effective monitoring haemostatic test, but also as a tool for individualization of therapy to achieve the best haemostatic and cost effectiveness of rFVIIa therapy.

A prospective evaluation of the prevalence of symptomatic von Willebrand disease (VWD) in a pediatric primary care population.

The prevalence of von Willebrand disease (VWD) is reported as approximately 1%; however, these estimates were not based on individuals with significant symptoms. Four thousand five hundred ninety-two unselected parents/children were asked: "Does your child have a problem with bleeding/bruising?"; 223 (5%) answered yes, 41 of whom were administered the validated Pediatric Bleeding Questionnaire and had VWF testing. Five were diagnosed with VWD (three type 1, one type 2A, one type 2B). The prevalence of bleeding/bruising in a general pediatric population is 5%; the prevalence of symptomatic VWD at the level of pediatric primary care is at least 1 in 1,000.

Wait times for gastroenterology consultation in Canada: the patients' perspective.

Long wait times for health care have become a significant issue in Canada. As part of the Canadian Association of Gastroenterology's Human Resource initiative, a questionnaire was developed to survey patients regarding wait times for initial gastroenterology consultation and its impact. A total of 916 patients in six cities from across Canada completed the questionnaire at the time of initial consultation. Self-reported wait times varied widely, with 26.8% of respondents reporting waiting less than two weeks, 52.4% less than one month, 77.1% less than three months, 12.5% reported waiting longer than six months and 3.6% longer than one year. One-third of patients believed their wait time was too long, with 9% rating their wait time as 'far too long'; 96.4% believed that maximal wait time should be less than three months, 78.9% believed it should be less than one month and 40.3% believed it should be less than two weeks. Of those working or attending school, 22.6% reported missing at least one day of work or school because of their symptoms in the month before their appointment, and 9.0% reported missing five or more days in the preceding month. A total of 20.2% of respondents reported being very worried about having a serious disease (ie, scored 6 or higher on 7-point Likert scale), and 17.6% and 14.8%, respectively, reported that their symptoms caused major impairment of social functioning and with the activities of daily living. These data suggest that a significant proportion of Canadians with digestive problems are not satisfied with their wait time for gastroenterology consultation. Furthermore, while awaiting consultation, many patients experience an impaired quality of life because of their gastrointestinal symptoms.

Medical Oncology Workload in Europe: One Continent, Several Worlds.

AIMS: The workload pressure on medical oncologists will increase in the near future. There are no comprehensive data available about the current workload of medical oncologists in Europe. Here we report the European results of a global survey of the workload of medical oncologists. MATERIALS AND METHODS: An online survey was distributed through a snowball method via national oncology societies to chemotherapy-prescribing physicians in 21 European countries. We compared the workload of medical oncologists in Eastern European countries (EECs) and Western European countries (WECs). The primary measure of workload was the annual number of new cancer patient consults seen per oncologist. RESULTS: In total, 495 oncologists from 16 European countries completed our survey: 100 from seven EECs and 395 from nine WECs. The median number of annual consults per medical oncologist was 225 in EECs compared with 175 in WECs (P < 0.001). The proportion of medical oncologists seeing more than 300 consults/year was 35% (35/100) in EECs compared with 18% (68/395) in WECs. The median number of patients seen in a full day clinic was 25 in EECs and 15 in WECs (P < 0.001). Eastern European medical oncologists reported spending a median of 25 min per new consultation compared with 45 min in WECs (P < 0.001). The top two reported barriers in both EECs and WECs to patient care were high clinical volumes and insufficient time for reading. CONCLUSION: The clinical workload of medical oncologists in EECs was substantially higher than in WECs. European health policymakers and educators need to address existing disparities in the workload of medical oncologist, undertake plans for future workforce supply and consider alternative models of care.

The impact of incident fractures on health-related quality of life: 5 years of data from the Canadian Multicentre Osteoporosis Study.

UNLABELLED: Using prospective data from the Canadian Multicentre Osteoporosis Study (CaMos), we compared health utilities index (HUI) scores after 5 years of follow-up among participants (50 years and older) with and without incident clinical fractures. Incident fractures had a negative impact on HUI scores over time. INTRODUCTION: This study examined change in health-related quality of life (HRQL) in those with and without incident clinical fractures as measured by the HUI. METHODS: The study cohort was 4,820 women and 1,783 men (50 years and older) from the CaMos. The HUI was administered at baseline and year 5. Participants were sub-divided into incident fracture groups (hip, rib, spine, forearm, pelvis, other) and were compared with those without these fractures. The effects of both time and fracture type on HUI scores were examined in multivariable regression analyses. RESULTS: Men and women with hip fractures, compared to those without, had lower HUI measures that ranged from -0.05 to -0.25. Both women and men with spine fractures had significant deficits on the pain attributes (-0.07 to -0.12). In women, self-care (-0.06), mobility and ambulation (-0.05) were also negatively impacted. Women with rib fractures had deficits similar to women with spine fractures, and these effects persisted over time. In men, rib fractures did not significantly affect HUI scores. Pelvic and forearm fractures did not substantially influence HUI scores. CONCLUSION: The HUI was a sensitive measure of HRQL change over time. These results will inform economic analyses evaluating osteoporosis therapies.

Associations between chronic disease, age and physical and mental health status.

This paper examines the associations between chronic disease, age, and physical and mental health-related quality of life (HRQOL), using data collected in 10 studies representing five chronic conditions. HRQOL was measured using the SF-36 or the shorter subset, SF-12. Physical Component Summary (PCS) and Mental Component Summary (MCS) scores were graphed by condition in age increments of 10 years, and compared to age- and sex-adjusted normative data. Linear regression models for the PCS and MCS were controlled for available confounders. The sample size of 2418 participants included 129 with renal failure, 366 with osteoarthritis (OA), 487 with heart failure, 1160 with chronic wound (leg ulcer) and 276 with multiple sclerosis (MS). For the PCS, there were large differences between the normative data and the mean scores of those with chronic diseases, but small differences for the MCS. Female gender and comorbid conditions were associated with poorer HRQOL; increased age was associated with poorer PCS and better MCS. This study provided additional evidence that, while physical function could be severely and negatively affected by both chronic disease and advanced age, mental health remained relatively high and stable.

Decreased dose density of standard chemotherapy does not compromise survival for ovarian cancer patients.

For women diagnosed with ovarian cancer, the standard practice of surgery followed by adjuvant platinum-taxane combination chemotherapy, with cycles administered every 3 weeks, is based on randomized control trials. However, a substantial number of patients require delays or reductions on this schedule. The Cancer Centre of Southeastern Ontario (CCSEO) has historically administered chemotherapy every 4 weeks. We analyzed survival outcomes of our cohort. All ovarian cancer patients treated with chemotherapy at the CCSEO from 1995 to end-2002 were included in this study. Overall survival and progression-free survival were calculated from initiation of chemotherapy using the Kaplan-Meier technique and log-rank tests. Cox regression analysis was used to adjust for age and disease stage. A total of 171 patients were treated with chemotherapy (cisplatin-paclitaxel or carboplatin-paclitaxel), of which 144 received chemotherapy every 4 weeks and 27 every 3 weeks. Median progression-free survival was 19.2 months for the group treated every 4 weeks vs 13.2 months for the 3-weekly group. Median overall survival was 36.5 months compared to 27.1 months, respectively. Trends favored treatment every 4 weeks. In early-stage disease, 5-year overall survival was 74% and 5-year progression-free survival was 68%. Administration of platinum-paclitaxel chemotherapy every 4 weeks did not reduce survival of ovarian cancer patients. Importantly, median survival is favorable compared to results from landmark trials where patients were treated every 3 weeks. These results suggest that decreasing the frequency of chemotherapy cycles does not decrease survival. Prospective trials would be required to compare quality of life and cost-effectiveness.

Effects of smoke exposure and other lifestyle factors on pain response to electrical stimulation in women.

BACKGROUND: A relationship between smoking and development of pain syndromes has been suggested in the literature. The present study examined associations between smoke exposure and other related variables, and pain response to suprathreshold electrical stimulation. METHODS: Subjects were prospectively recruited from a population referred to an electrodiagnostic clinic. Information about age, smoke exposure, caffeine and alcohol consumption was obtained, as well as documented objective signs of stress through physical assessment. One investigator applied two standardized 0.1 ms electrical stimulations (50 mA followed by 100 mA) to asymptomatic extremities at the beginning of each electrodiagnostic session, using consistent technique. Subjects used a visual analogue scale to indicate the level of pain felt after each stimulation. RESULTS: Two hundred fifteen women were included. Current smokers and those currently exposed to second-hand smoke had significantly higher pain ratings (P=0.003 for 50 mA, P=0.005 for 100 mA) than those not currently exposed to smoke. Time since exposure was negatively associated with pain ratings. Those with objective signs of stress reported higher levels of pain, which was significant for the 100 mA stimulation (P=0.046). Linear regression modelling indicated that current smoke exposure and alcohol use were associated with higher pain ratings at both 50 mA and 100 mA, while stress was associated with higher pain ratings and older age was associated with lower pain ratings at 100 mA only. INTERPRETATION: Exposure to cigarette smoke is significantly related to higher reported levels of pain experienced in response to electrical stimulation in this study population. Exposure to smoke can add 10 points to the 100-point visual analogue scale compared with subjects without exposure, with alcohol use adding another eight points. Reported pain decreases as length of time since previous exposure to smoke increases.