Burden of osteoarthritis in India and its states, 1990-2019: findings from the Global Burden of disease study 2019.

OBJECTIVE: To describe the burden of osteoarthritis (OA) in India from 1990 to 2019. DESIGN: Data from Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 were used. The burden of OA -knee OA, hip OA, hand OA, and other OA- was estimated for India and its states from 1990 to 2019 through a systematic analysis of prevalence, incidence, years lived with disability (YLD), and disability-adjusted life years (DALY) using methods reported in GBD 2019 study. RESULT: Around 23.46 million individuals in India had OA in 1990; this increased to 62.35 million in 2019. The age-standardised prevalence of OA increased from 4,895 (95% uncertainty interval (UI):4,420-5,447) in 1990-5313 (95%UI:4,799-5,898) in 2019, per 100,000 persons. Similarly, DALYs due to OA increased from 0.79 million (95%UI:0.40-1.55) to 2.12 million (95%UI:1.07-4.23); while age-standardised DALYs increased from 164 (95%UI:83-325) to 180 (95%UI:91-361) per 100,000 persons from 1990 to 2019. OA was the 20th most common cause of YLDs in India in 2019, accounting for 1.48% (95%UI:0.88-2.78) of all YLDs; increasing from 23rd most common cause in 1990 (1.25%(95%UI:0.74-2.34)). Knee OA was the most common form of OA, followed by hand OA. The prevalence, incidence, and DALYs for OA and knee OA were consistently higher in females than males. CONCLUSION: The burden and impact of OA in India are substantial and is increasing. Adopting suitable control and preventive community measures to reduce modifiable risk factors (obesity, injuries, occupational stress) are needed to reduce the current and future burden of OA in India.

Effect of aerobic exercise on cancer-associated cognitive impairment: A proof-of-concept RCT.

BACKGROUND: Change in cognitive ability is a commonly reported adverse effect by breast cancer survivors. The underlying etiology of cognitive complaints is unclear and to date, there is limited evidence for effective intervention strategies. Exercise has been shown to improve cognitive function in older adults and animal models treated with chemotherapy. This proof-of-concept randomized controlled trial tested the effect of aerobic exercise versus usual lifestyle on cognitive function in postmenopausal breast cancer survivors. METHODS: Women, aged 40 to 65 years, postmenopausal, stages I to IIIA breast cancer, and who self-reported cognitive dysfunction following chemotherapy treatment, were recruited and randomized to a 24-week aerobic exercise intervention (EX; n = 10) or usual lifestyle control (CON; n = 9). Participants completed self-report measures of the impact of cognitive issues on quality of life (Functional Assessment of Cancer Therapy-Cognitive version 3), objective neuropsychological testing, and functional magnetic resonance imaging at baseline and 24 weeks. RESULTS: Compared to CON, EX had a reduced time to complete a processing speed test (trail making test-A) (-14.2 seconds, P < .01; effect size 0.35). Compared to CON, there was no improvement in self-reported cognitive function and effect sizes were small. Interestingly, lack of between-group differences in Stroop behavioral performance was accompanied by functional changes in several brain regions of interest in EX compared to CON at 24 weeks. CONCLUSION: These findings provide preliminary proof-of-concept results for the potential of aerobic exercise to improve cancer-related cognitive impairment and will serve to inform the development of future trials.

Does obesity modify the relationship between physical activity and breast cancer risk?

PURPOSE: With only 5-10% of breast cancer cases attributed to genetic inheritance, prevention efforts have focused on modifiable risk factors. Physical activity plays a role in reducing breast cancer risk; however, the interaction between physical activity and other modifiable risk factors, such as obesity, has received little attention. METHODS: A systematic review and meta-analysis was conducted of studies examining the relationship between physical activity and breast cancer and how it may be modified by body mass index (BMI). RESULTS: A total of 29 papers were included: 18 were cohort and 11 were case-control studies. Overall, a significant reduction in the relative risk of breast cancer was found in postmenopausal women with high versus low levels of physical activity for women with a BMI <25 kg/m2 (RR 0.85, 95% CI 0.79, 0.92) and ≥25 kg/m2 (RR 0.87, 95% CI 0.81, 0.93) but not ≥30 kg/m2 (RR: 0.93, 95% CI 0.76, 1.13). Physical activity was not associated with a significant reduction in risk of breast cancer in premenopausal women in any BMI group. CONCLUSION: The results of this meta-analysis suggest that physical activity is associated with a larger breast cancer risk reduction among women who are normal weight or overweight than among women who are obese. Since the included studies used diverse methods for assessment of physical activity and categories of BMI, results should be interpreted with caution and additional work is needed.

Utilization of bone mineral density testing among breast cancer survivors in British Columbia, Canada.

Breast cancer survivors are at high osteoporosis risk. Bone mineral density testing plays a key role in osteoporosis management. We analyzed a historical utilization of bone mineral density testing in breast cancer survivors. The utilization remained low in the 1995-2008 period. Lower socio-economic status and rural residency were associated with lower utilization. INTRODUCTION: To evaluate the utilization of bone mineral density (BMD) testing for female breast cancer survivors aged 65+ surviving ≥ 3 years in British Columbia, Canada. METHODS: A retrospecitve population-based data linkage study. Trends in proportion of survivors with ≥ 1 BMD test for each calendar year from 1995 to 2008 were evaluated with a serial cross-sectional analysis. Associations between factors (socio-demographic and clinical) and BMD testing rates over the period 2006-2008 for 7625 survivors were evaluated with a cross-sectional analysis and estimated as adjusted prevalence ratios (PRadj) using log-binomial models. RESULTS: Proportions of survivors with ≥ 1 BMD test increased from 1.0% in 1995 to 10.1% in 2008. The BMD testing rate in 2006-2008 was 26.5%. Socio-economic status (SES) and urban/rural residence were associated with BMD testing rates in a dose-dependent relationship (p for trend< 0.01). Survivors with lower SES (PRadj = 0.66-0.78) or rural residence (PRadj = 0.70) were 20-30% less likely to have BMD tests, compared with survivors with the highest SES or urban residence. BMD testing rates were also negatively associated with older age (75+) (PRadj = 0.47; 95% CI = 0.42, 0.52), nursing home residency (0.05; 0.01, 0.39), recent osteoporotic fractures (0.21; 0.14, 0.32), and no previous BMD tests (0.26; 0.23, 0.29). CONCLUSION: Utilization of BMD testing was low for breast cancer survivors in BC, Canada. Lower SES and rural residence were associated with lower BMD testing rates. IMPLICATION FOR CANCER SURVIVORS: Female breast cancer survivors, especially those with lower SES or rural residence, should be encouraged to receive BMD tests as recommended by Canadian guidelines.

Does change in health-related quality of life score predict survival? Analysis of EORTC 08975 lung cancer trial.

BACKGROUND: Little is known about whether changes in health-related quality of life (HRQoL) scores from baseline during treatment also predict survival, which we aim to investigate in this study. METHODS: We analysed data from 391 advanced non-small-cell lung cancer (NSCLC) patients enrolled in the EORTC 08975 study, which compared palliative chemotherapy regimens. HRQoL was assessed at baseline and after each chemotherapy cycle using the EORTC QLQ-C30 and QLQ-LC13. The prognostic significance of HRQoL scores at baseline and their changes over time was assessed with Cox regression, after adjusting for clinical and socio-demographic variables. RESULTS: After controlling for covariates, every 10-point increase in baseline pain and dysphagia was associated with 11% and 12% increased risk of death with hazard ratios (HRs) of 1.11 and 1.12, respectively. Every 10-point improvement of physical function at baseline (HR=0.93) was associated with 7% lower risk of death. Every 10-point increase in pain (HR=1.08) was associated with 8% increased risk of death at cycle 1. Every 10-point increase in social function (HR=0.91) at cycle 2 was associated with 9% lower risk of death. CONCLUSIONS: Our findings suggest that changes in HRQoL scores from baseline during treatment, as measured on subscales of the EORTC QLQ-C30 and QLQ-LC13, are significant prognostic factors for survival.

Higher capecitabine AUC in elderly patients with advanced colorectal cancer (SWOGS0030).

BACKGROUND: The aging process is accompanied by physiological changes including reduced glomerular filtration and hepatic function, as well as changes in gastric secretions. To investigate what effect would aging have on the disposition of capecitabine and its metabolites, the pharmacokinetics between patients ≥70 years and <60 years were compared in SWOG0030. METHODS: Twenty-nine unresectable colorectal cancer patients were stratified to either ≥70 or <60 years of age, where the disposition of capecitabine and its metabolites were compared. RESULTS: Notable increase in capecitabine area under the curve (AUC) was accompanied by reduction in capecitabine clearance in ≥70 years patients (P<0.05). No difference in 5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine (DFUR), and 5-fluorouracil (5FU) AUCs between the two age groups, suggesting that carboxylesterase and cytidine deaminase (CDA) activity was similar between the two age groups. These results suggest that metabolic enzymes involved in converting capecitabine metabolites are not altered by age. An elevation in capecitabine Cmax and reduction in clearance was seen in females, where capecitabine AUC was 40.3% higher in women. Elevation of DFUR Cmax (45%) and AUC (46%) (P<0.05) was also noted, suggesting that CDA activity may be higher in females. CONCLUSION: Increases in capecitabine Cmax and AUC was observed in patients ≥70 years when compared with younger patients who were >60 years.

Effect of completion-time windows in the analysis of health-related quality of life outcomes in cancer patients.

BACKGROUND: We examined if cancer patients' health-related quality of life (HRQoL) scores on the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 are affected by the specific time point, before or during treatment, at which the questionnaire is completed, and whether this could bias the overall treatment comparison analyses. PATIENTS AND METHODS: A 'completion-time window' variable was created on three closed EORTC randomised control trials in lung (non-small cell lung cancer, NSCLC) and colorectal cancer (CRC) to indicate when the QLQ-30 was completed relative to chemotherapy cycle dates, defined as 'before', 'on' and 'after'. HRQoL mean scores were calculated using a linear mixed model. RESULTS: Statistically significant differences (P<0.05) were observed on 6 and 5 scales for 'on' and 'after' comparisons in the NSCLC and two-group CRC trial, respectively. As for the three-group CRC trial, several statistical differences were observed in the 'before' to 'on' and the 'on' to 'after' comparisons. For all three trials, including the 'completion-time window' variable in the model resulted in a better fit, but no substantial changes in the treatment effects were noted. CONCLUSIONS: We showed that considering the exact timing of completion within specified windows resulted in statistical and potentially clinically significant differences, but it did not alter the conclusions of treatment comparison in these studies.

Minimal clinically meaningful differences for the EORTC QLQ-C30 and EORTC QLQ-BN20 scales in brain cancer patients.

BACKGROUND: We aimed to determine the smallest changes in health-related quality of life (HRQoL) scores in the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire core 30 and the Brain Cancer Module (QLQ-BN20), which could be considered as clinically meaningful in brain cancer patients. MATERIALS AND METHODS: World Health Organisation performance status (PS) and mini-mental state examination (MMSE) were used as clinical anchors appropriate to related subscales to determine the minimal clinically important differences (MCIDs) in HRQoL change scores (range 0-100) in the QLQ-C30 and QLQ-BN20. A threshold of 0.2 standard deviation (SD) (small effect) was used to exclude anchor-based MCID estimates considered too small to inform interpretation. RESULTS: Based on PS, our findings support the following integer estimates of the MCID for improvement and deterioration, respectively: physical (6, 9), role (14, 12), and cognitive functioning (8, 8); global health status (7, 4*), fatigue (12, 9), and motor dysfunction (4*, 5). Anchoring with MMSE, cognitive functioning MCID estimates for improvement and deterioration were (11, 2*) and for communication deficit were (9, 7). Estimates with asterisks were <0.2 SD and were excluded from our MCID range of 5-14. CONCLUSION: These estimates can help clinicians evaluate changes in HRQoL over time, assess the value of a health care intervention and can be useful in determining sample sizes in designing future clinical trials.

Quality of life in long-term survivors of adult-onset cancers.

The long-term survival of cancer patients has risen dramatically during the last few decades, yet little is known about the quality of life experienced by these survivors. This paper reviews research on the quality of life in long-term cancer survivors to identify quality-of-life concerns in this population, to provide a critical evaluation of the literature, and to suggest areas for future research. Searches of computerized literature databases were conducted to identify all studies of quality of life in cancer survivors that were published in English language journals during the period from January 1, 1980, through February 12, 1998, and that were based on responses from individuals who have survived 5 or more years after the diagnosis of adult-onset cancers. Thirty-four papers were identified. Most studies utilized self-report questionnaires to measure quality of life. Although methodologies and cancer patient populations varied greatly, most studies showed that many survivors continue to experience negative effects of cancer and/or treatment on their daily lives well beyond the completion of therapy. Sexual functioning and/or satisfaction and psychological functioning were found to be concerns for many survivors. Several reports documented positive coping strategies and enhanced quality of life in long-term cancer survivors, supporting the need to measure positive aspects of quality of life as well as problems in this population. Study designs that more accurately measure quality of life among survivors of cancer by adjusting for the effects of aging and long-term therapy and the impact of second cancers should be utilized. Additional data are needed to understand the needs of long-term survivors, especially of those in groups underrepresented in published quality-of-life studies, and to determine what kinds of support survivors want.

Quality-of-life assessment in cancer treatment protocols: research issues in protocol development.

BACKGROUND: Interest in incorporating quality of life as an end point in clinical studies of cancer treatment has intensified in recent years. PURPOSE: We provide practical suggestions that will assist investigators considering including quality-of-life assessment in phase III therapeutic trials. METHODS: We discuss issues important in study planning, including quality-of-life definition, priority studies for quality-of-life assessment, eligibility requirements, and design. CONCLUSIONS: Many of the problems that quality-of-life studies have encountered, from protocol approval to data analysis, could be addressed and alleviated during protocol development. This discussion is intended to assist and stimulate investigators conducting research in this area.

Trial-related quality of life: using quality-of-life assessment to distinguish among cancer therapies.

Issues in selecting quality-of-life (QOL) measures that are best suited to assessing differences among treatments in cancer clinical trials, as well as challenges to interpreting QOL outcome data, are discussed. When used in the context of randomized trials of cancer therapies, QOL assessments must provide an answer to the question, "Did the treatments differentially affect patient well-being?" In order to detect differences in treatment efficacy against a background of great similarity, the broad concept of QOL needs to be refined to reflect "trial-related QOL." In many cases, this will entail emphasis on actual patient experience of symptoms and functional changes, as opposed to emphasis solely on evaluation and satisfaction. A model is proposed to identify cognitive, emotional, and sociocultural factors that influence a patient's QOL evaluation and that need to be considered in understanding the meaning of QOL data.

Perceptions of informed consent by participants in a prostate cancer prevention study.

This study examined perceptions of the informed consent process in healthy men participating in a cancer prevention clinical trial. Specifically, we examined influence of the consent form on participation and understanding, adequacy of the consent process in preparing participants for trial experiences, and perceived needs for additional follow-up strategies. Participants (n = 69) enrolled in the Prostate Cancer Prevention Trial at our institution completed mailed questionnaires approximately 2 years after joining the study. Results indicated that many participants had no remembrance of the consent process, and only a minority reported that the consent process had helped in decision-making about study participation. Eleven men (16%) reported experiencing unexpected study side effects, most related to sexual functioning. Most men (78%) did not feel that they currently needed more information about the study, although virtually all of the respondents wanted to learn the study results. Almost one-third wished to interact with other Prostate Cancer Prevention Trial participants. Results indicate that a signed consent form and initial counseling for a prevention study does not ensure that participants feel they are adequately informed about the study or the side effects. Providing and reinforcing information on a regular and continuous basis is especially important in studies where compliance is required over a period of years.

Underreporting of family history of colon cancer: correlates and implications.

Scientific advances in cancer genetics, risk counseling, and management of high-risk individuals require information about familial cancer history. Because some people may not report, or may be unaware of, cancer in their families, it is important to examine the extent of underreporting of family history. We mailed a survey to first-degree relatives of patients with histologically confirmed diagnoses of colorectal cancer (CRC) before age 60 (n = 426, 77% response rate). Analyses examined the extent of underreporting of family history and its predictors (demographics, cancer characteristics, knowledge, and communication) and correlates (cancer worry, perceived risk). Logistic regression analysis was performed using generalized estimating equations to account for family clusters. Despite confirmed diagnosis of CRC in a parent or sibling, 25.4% of respondents reported having no first-degree relative with colon cancer. In multivariate models, the most significant predictor of awareness of a relative's CRC was the stage-at-diagnosis; also, males and those with low knowledge about colon cancer were significantly less aware. Awareness of a relative's CRC was associated with higher cancer worry and risk perception, and being a college graduate contributed independently to increased risk perception. Sole dependence on mailed self-administered questionnaires may lead to substantial underreporting of familial colon cancers, especially those that are in situ or localized.

Correlates of intentions to obtain genetic counseling and colorectal cancer gene testing among at-risk relatives from three ethnic groups.

OBJECTIVES: An understanding of factors associated with interest in genetic counseling and intentions to obtain colorectal cancer susceptibility testing is an important foundation for developing education, counseling, and genetic services and policies. MATERIALS AND METHODS: A survey was mailed to first-degree relatives of patients diagnosed with colorectal cancer. The respondents (n = 426, 77% response rate) are siblings and adult children of Caucasian, Japanese, and Hawaiian ethnicity. Data collection was guided by a conceptual framework and included questions on demographics, family cancer history, predisposing factors (cancer worry, perceived risk, well-being), and enabling factors (decision preferences, social support, and health care factors). Logistic regression analysis on two binary dependent variables (interest in counseling and intentions to get genetic testing) was performed using Generalized Estimating Equations to account for family clusters. RESULTS: Forty-five % of respondents were interested in genetic counseling, and 26% "definitely" intended to get genetic testing for colon cancer when available. For counseling interest, the most important predictors were education, Hawaiian ethnicity, cancer worry, and family support. Cancer worry, perceived risk, and age (older) were directly, and Japanese ethnicity was inversely, associated with testing intentions. CONCLUSIONS: High rates of interest in cancer genetic testing are similar to those found in other studies. Ethnic differences reveal a paradox between objective population risk (higher for Japanese) and greater concerns (among Hawaiians). The substantial lack of awareness of family history warrants further research. Culturally sensitive education and counseling are needed for managing the likely high demand for personalized information about hereditary cancer risk.

Physicians' and medical students' perspectives on patients' quality of life.

PURPOSE: To compare medical students' and oncologists' perspectives about patient-related quality of life (QOL). METHOD: In 1996, the authors compared the questionnaire responses of 65 oncologists and 105 medical students in the state of Hawai'i. RESULTS: Participants returned 146 usable questionnaires (response rates: 69% of oncologists and 97% of students). Both groups saw pain and suffering as central to QOL, while medical students also valued autonomy. Both groups indicated that QOL was at least as important as survival in treatment decision making. Students were significantly more likely to emphasize the importance of QOL over survival. Students strongly preferred physician interviews to assess QOL. Most physicians reported assessing QOL in every patient, but only one in ten had used a QOL assessment questionnaire. CONCLUSION: Both students and oncologists expressed considerable interest in QOL and virtually all regarded it as an important part of care. There were more similarities than differences in responses. Future educational programs in both medical school and continuing education should build on these positive attitudes.

Male-female differences in the impact of cancer therapy.

Sex has been shown to be a significant predictor of cancer survival, with females living longer than males. This survival differential could occur because women benefit more than men from cancer treatments. This article reports the results of a study of the adequacy of the current clinical trials literature to examine sex differences in response to cancer therapy. All phase III (randomized) trials of cancers in non-sex-specific sites published between 1988 and 1990 were identified in three cancer-specific and four general medical journals. Of 55 studies that investigated outcomes by sex, 33% reported differences. Future studies should include adequate numbers of male and female participants, where appropriate, to allow generalization of study findings; routine reporting of the sex composition of the study sample in clinical trials reports; and routine analysis of the effects of sex on prognosis and responses to specific treatments.

Building quality of life assessment into cancer treatment studies.

Quality of life is increasingly recognized as an important outcome of cancer treatment. However, quality of life research poses considerable problems in design and implementation. This article provides guidelines for the preparation of phase III therapeutic protocols that include quality of life assessment. The guidelines emphasize the distinct requirements of quality of life research and provide specific recommendations for the questions that need to be addressed in protocol development.

Accrual to cancer clinical trials: directions from the research literature.

Although randomized clinical trials are the predominant method used to evaluate cancer therapies, only a small proportion of potential participants actually enter onto trials. This paper analyzes the research literature on accrual to cancer therapy trials. The research shows that nonparticipation is influenced by physician and patient variables, as well as by characteristics of the specific protocols. Trials design, especially pre-existing treatment preferences, pose significant problems for physicians and patients. Intervention strategies have focused on alternate trial designs, improving the informed consent process, and increasing knowledge about trials. Additional research should focus on the perspectives of patients who accept and decline trial participation and on interventions designed to affect accrual. Future studies need to be sensitive to patient quality of life considerations as well as practical and ethical issues.

Why me? Attributions and adjustment by cancer patients and their mates at two stages in the disease process.

This research investigated how cancer patients at early and advanced stage disease (N = 73) and their mates (N = 39) attributed causality for the disease, their levels of adjustment and the relationship between attributions and adjustment. Data were collected through semi-structured home interviews. Results indicated that the largest numbers of individuals cited chance as the cause of the cancer, although many reported that they had not asked themselves the question, 'Why me?'. Adjustment measures indicated, in general, more similarities than differences between groups. Attributions were not significant predictors of adjustment. It is suggested that not making strong causal attributions may be adaptive for cancer patients and their families.

The experience of cancer during early and advanced stages: the views of patients and their mates.

Problems, coping mechanisms and problem resolution were assessed in 112 individuals: patients with early stage cervical cancer or pre-cancer (N = 42) and their mates (N = 19), and patients with advanced stage breast or gynecological cancer (N = 31) and their mates (N = 20). The most common source of concern for all groups was the disease itself; the men were also more likely than the patients to be disturbed by the possibility of the women dying. Taking firm action was the most frequently-mentioned coping strategy; information-seeking was also common among the early stage groups, and religious faith often cited by the advanced stage respondents. Analysis of a particular problem--fear of cancer--showed different coping strategies to be predominant; mates, in contrast to patients, were likely to take direct action and advanced stage groups more likely to discuss their fear of cancer with others. Problem resolution did not vary from group to group. Overall, the similarities among reactions of early and advanced stage patients and mates were more striking than differences, indicating the profound impact of cancer over the course of the disease on patient and family alike.