Complementary and alternative medicine (CAM) is a growing form of self-care and is related to other healthy behaviors. This study examines the relationship between CAM use and diabetes self-management. A survey of rural older African American, Native American, and White adults with diabetes was conducted. Data were collected on diabetes self-management domains and general and diabetes-specific CAM use. Some associations were observed, particularly for CAM use and following a healthy eating plan. CAM is part of the health maintenance strategy of rural older adults with diabetes. Further research should examine the health trajectory associated with CAM use in this population.

PURPOSE: It is well accepted that conditions that cause central vision loss (CVL) have a negative impact on functional ability and quality of life (QoL), but the impact of diseases that cause peripheral vision loss (PVL) is less well understood. Focusing on glaucoma and age-related macular degeneration (ARMD), the effects of CVL and PVL on QoL were compared. METHODS: A systematic literature review of publications reporting QoL in patients with CVL or PVL identified 87 publications using four generic (Short-Form Health Survey-36 and -12, EuroQoL EQ-5D and Sickness Impact Profile) and five vision-specific (National Eye Institute Visual Function Questionnaire-51,-39, and -25, Impact of Vision Impairment and Visual Function-14) QoL instruments; 33 and 15 publications reported QoL in ARMD and glaucoma, respectively. RESULTS: QoL was impaired to a similar extent by diseases associated with PVL and CVL, but different domains were affected. In contrast to ARMD, mental aspects appeared to be affected more than physical aspects in patients with glaucoma. CONCLUSIONS: The differential impact upon QoL might be a function of the pathology of the diseases, for example potential for blindness and better ability to perform physical tasks due to retention of central vision may explain these observations in glaucoma.

OBJECTIVE: To describe the state of diabetes care among Alberta First Nations individuals with diabetes living on reserves. DESIGN: Survey and screening for diabetes-related complications. SETTING: Forty-three Alberta First Nations communities. PARTICIPANTS: A total of 743 self-referred First Nations individuals with known diabetes. MAIN OUTCOME MEASURES: Clinical measurements (glycated hemoglobin A(1c) levels, body mass index, waist circumference, total cholesterol, blood pressure, and the presence of kidney complications or proteinuria, retinopathy, and foot abnormalities), self-reported health services utilization, clinical history, and knowledge of and satisfaction with diabetes services. RESULTS: Female participants tended to be more obese (P <.05) and to have abnormal waist circumferences more often than men (P <.05). Male participants, however, had a higher proportion of proteinuria (P <.05), hypertension (P <.05), limb complications (P <.05), and retinopathy (P <.05). Family physicians were the main diabetes care providers for most participants. Nearly half the participants felt they did not have care from a diabetes team. A total of 38% had never seen dietitians. Diabetes-related concerns were responsible for 24% of all hospitalizations and emergency department visits. Approximately 46% and 21% of participants had recommended hemoglobin A(1c) testing and foot examinations, respectively. Only 24% of participants with kidney complications were receiving treatment. A considerable proportion of participants had undiagnosed complications of diabetes: kidney damage or proteinuria (23%), high cholesterol (22%), foot complications (11%), hypertension (9%), and retinopathy (7%). CONCLUSION: Diabetes care is suboptimal in Alberta First Nations communities. Rural physicians caring for First Nations individuals on reserves should be involved, along with other members of diabetes health care teams, in strategies to improve diabetes care. Our results justify the need for community-based screening for diabetes control and complications in First Nation communities.

OBJECTIVES: To examine stress and health-related quality of life (HRQOL) among third-year doctor of pharmacy (PharmD) students. METHODS: Stress and HRQOL were determined using Perceived Stress and SF-12 HRQOL survey instruments. A questionnaire was administered to determine factors students believed produced and eliminated stress. RESULTS: Eighty percent of third-year students participated (n=109) in this pilot study. Mental HRQOL scores were significantly below US mean score for individuals aged 20-34 years (p<0.0001). As stress increased, mental HRQOL decreased and a significant negative correlation was found between the 2 measures (p<0.001). Family and relationships, examinations and scheduling, outside-of-class assignments, and finances were the most common stress triggers reported by students, while exercising, spending time with friends/family, sleeping, watching TV, and drinking alcohol were the most commonly reported stress-alleviating activities. CONCLUSION: Third-year PharmD students reported relatively high levels of stress and low mental HRQOL. Students employed mostly positive, but some negative, lifestyle choices to alleviate stress. Further investigation into the effectiveness of students' coping strategies is needed.

Eating difficulties and nutritional deficits are common among persons with acute stroke and during rehabilitation. Little is known about such problems after discharge from hospital. In addition the relationship between fatigue and nutritional status among stroke survivors living in the community remains to be explored. The aim of this pilot study was to describe mealtime preparation, eating, fatigue, mood and nutritional status among persons with stroke six months after discharge from hospital and to explore associations between these factors. Patients were interviewed six months poststroke. Standardised questions and methods were used. The mean age of the 89 respondents was 77.2 (SD 6.6) years, 44 were women and 45 men. Difficulties with swallowing, ingestion and energy to eat occurred among 27%, 20% and 7% respectively. Difficulties with cooking and buying food occurred among 57% and 56% respectively and 41% were at nutritional risk. Feeling full of energy less than some of the time was experienced by 61% while 15% had felt gloomy and sad at least some of the time during the previous four weeks. Considering activities of daily living (ADL), having a less favourable nutritional status was significantly predicted by difficulties with buying food, difficulties with ingestion and being a woman. Considering psychological state (mood and energy), having a less favourable nutritional status was significantly predicted by a lack of energy and high age. This study supports the occurrence of a nutritionally related fatigue by means of "lack of energy". The associations between poor nutritional status and fatigue can work in both directions. Thus persons with fatigue are more prone to have poor nutritional status and those with poor nutritional status are at greater risk of fatigue. Besides fatigue also difficulties with buying food and ingestion are associated with nutritional risk. As nutritional deficits occur a long time after stroke onset it is important to assess aspects of mealtime preparation and the eating process and when necessary provide food delivery service and eating assistance in order to prevent a vicious circle of undernourishment and fatigue to develop.

ABSTRACT: BACKGROUND: Latinos comprise the largest racial/ethnic group in the United States and have 2-3 times the prevalence of type 2 diabetes mellitus as Caucasians. METHODS: The Lawrence Latino Diabetes Prevention Project (LLDPP) is a community-based translational research study which aims to reduce the risk of diabetes among Latinos who have a [greater than or equal to] 30% probability of developing diabetes in the next 7.5 years per a predictive equation. The project was conducted in Lawrence, Massachusetts, a predominantly Caribbean-origin urban Latino community. Individuals were identified primarily from a community health center's patient panel, screened for study eligibility, randomized to either a usual care or a lifestyle intervention condition, and followed for one year. Like the efficacious Diabetes Prevention Program (DPP), the LLDPP intervention targeted weight loss through dietary change and increased physical activity. However, unlike the DPP, the LLDPP intervention was less intensive, tailored to literacy needs and cultural preferences, and delivered in Spanish. The group format of the intervention (13 group sessions over 1 year) was complemented by 3 individual home visits and was implemented by individuals from the community with training and supervision by a clinical research nutritionist and a behavioral psychologist. Study measures included demographics, Stern predictive equation components (age, gender, ethnicity, fasting glucose, systolic blood pressure, HDL-cholesterol, body mass index, and family history of diabetes), glycosylated hemoglobin, dietary intake, physical activity, depressive symptoms, social support, quality of life, and medication use. Body weight was measured at baseline, 6-months, and one-year; all other measures were assessed at baseline and one-year. All surveys were orally administered in Spanish. RESULTS: A community-academic partnership enabled the successful recruitment, intervention, and assessment of Latinos at risk of diabetes with a one-year study retention rate of 93%. Trial registration: NCT00810290.

ABSTRACT: BACKGROUND: While the evidence suggests that the way physicians provide information to patients is crucial in helping patients decide upon a course of action, the field of knowledge translation and exchange (KTE) is silent about how the physician and the patient influence each other during clinical interactions and decision-making. Consequently, based on a novel relationship-centered model, EXACKTE2 (EXploiting the clinicAl Consultation as a Knowledge Transfer and Exchange Environment), this study proposes to assess how patients and physicians influence each other in consultations. METHODS: We will employ a cross-sectional study design involving 300 pairs of patients and family physicians from two primary care practice-based research networks. The consultation between patient and physician will be audio-taped and transcribed. Following the consultation, patients and physicians will complete a set of questionnaires based on the EXACKTE2 model. All questionnaires will be similar for patients and physicians. These questionnaires will assess the key concepts of our proposed model based on the essential elements of shared decision-making (SDM): definition and explanation of problem; presentation of options; discussion of pros and cons; clarification of patient values and preferences; discussion of patient ability and self-efficacy; presentation of doctor knowledge and recommendation; and checking and clarifying understanding. Patients will be contacted by phone two weeks later and asked to complete questionnaires on decisional regret and quality of life. The analysis will be conducted to compare the key concepts in the EXACKTE2 model between patients and physicians. It will also allow the assessment of how patients and physicians influence each other in consultations. DISCUSSION: Our proposed model, EXACKTE2, is aimed at advancing the science of KTE based on a relationship process when decision-making has to take place. It fosters a new KTE paradigm by putting forward a relationship-centered perspective and has the potential to reveal unknown mechanisms that underline effective KTE in clinical contexts. This will result in better understanding of the mechanisms that may promote a new generation of knowledge transfer strategies.

OBJECTIVE: To estimate the prevalence of self-reported sexual problems (any, desire, arousal, and orgasm), the prevalence of problems accompanied by personal distress, and to describe related correlates. METHODS: The 31,581 female respondents aged 18 years and older were from 50,002 households sampled from a national research panel representative of U.S. women. Correlates of each distressing sexual problem were evaluated using multiple logistic regression techniques. RESULTS: The age-adjusted point prevalence of any sexual problem was 43.1% and 22.2% for sexually related personal distress (defined as a score of at least 15 on Female Sexual Distress Scale). Any distressing sexual problem (defined as reporting both a sexual problem and sexually related personal distress, Female Sexual Distress Scale score of at least 15) occurred in 12.0% of respondents and was more common in women aged 45-64 years (14.8%) than in younger (10.8%) or older (8.9%) women. Correlates of distressing sexual problems included poor self-assessed health, low education level, depression, anxiety, thyroid conditions, and urinary incontinence. CONCLUSION: The prevalence of distressing sexual problems peaked in middle-aged women and was considerably lower than the prevalence of sexual problems. This underlines the importance of assessing the prevalence of sexually related personal distress in accurately estimating the prevalence of sexual problems that may require clinical intervention. LEVEL OF EVIDENCE: III.

CONTEXT: Little is known about selecting among second-step medications for major depressive disorder after intolerance or lack of remission with an initial selective serotonin reuptake inhibitor. OBJECTIVE: To determine whether sociodemographic, clinical, or first-step treatment features predict remission with or intolerance overall or differentially to any 1 of 3 second-step medications after an unsatisfactory outcome with citalopram hydrobromide. DESIGN: An equipoise stratified randomized study. Participants were recruited from July 17, 2001, through April 20, 2004. SETTING: Public or private sector primary care (n = 18) and psychiatric care (n = 23) settings across the United States. PARTICIPANTS: Representative outpatients aged 18 to 75 years with nonpsychotic major depressive disorder (N = 727). INTERVENTIONS: Sustained-release bupropion hydrochloride was started at 150 mg/d and incrementally increased to 400 mg/d. Sertraline hydrochloride was started at 50 mg/d and incrementally increased to 200 mg/d. Extended-release venlafaxine hydrochloride was started at 37.5 mg/d and incrementally increased to 375 mg/d. MAIN OUTCOME MEASURES: The 16-item Quick Inventory of Depressive Symptomatology, Self-Rated and the Frequency, Intensity, and Burden of Side Effects Rating. RESULTS: Remission was more likely among participants who were white, employed, cohabiting or married, or privately insured or who had prior intolerance to citalopram or at least a response to citalopram, and no prior suicide attempts. Remission was less likely among participants with concurrent generalized anxiety, obsessive-compulsive, panic, or posttraumatic stress disorders; social phobia; anxious or melancholic features; or more severe depression. Intolerance was less likely for Hispanic participants, but more likely for participants with previous suicide attempts or intolerance to citalopram. Participants with concurrent substance use were less likely to remit (odds ratio, 0.37) and more likely not to tolerate extended-release venlafaxine. Intolerance to citalopram was associated with intolerance to sertraline (P =.04). CONCLUSIONS: Clinical, demographic, and treatment history were of little value in recommending 1 medication vs another as a second-step treatment for major depressive disorder. Participants most likely to remit in the second step had less Axis I psychiatric disorder comorbidity, less social disadvantage, and at least a response to citalopram in the first step. Trial Registration clinicaltrials.gov Identifier: NCT00021528.

AIM: To compare prognosis for patients with a diagnosis of angina alone to patients post acute myocardial infarction (AMI) and / or revascularisation and/or angina. DESIGN: Community-based retrospective cohort study. SETTING: A random selection of 37 Irish general practices. PARTICIPANTS: 1,609 adults with ischaemic heart disease (IHD) identified in 2000/1. INTERVENTION: Medical records searches and postal questionnaires in 2000/1 and 2005/6. OUTCOME MEASURES: Primary: all-cause and IHD-related mortality. Secondary: acute myocardial infarction (AMI), cardiac artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA); physical and mental health status, process of care measurements and behavioural risk factor outcomes. RESULTS: Compared with patients with previous AMI and / or revascularisation and / or angina, patients with angina alone had similar risks of all-cause and IHD-related death: hazard ratios of 0.73 (95% CI 0.55 - 0.98) and 0.65 (95% CI 0.44 - 0.98) respectively were not significant at the p=0.01 level. No statistically significant differences were identified in risks of subsequent AMI, CABG or PTCA, or other outcomes. CONCLUSIONS: Prognosis for patients with angina alone was similar to those with previous AMI and/ or revascularization and /or angina. The clinical importance of angina should not be underestimated in primary care. Further descriptive research is needed amongst representative community cohorts of people with angina.

OBJECTIVE: To evaluate the validity of SF-36 Health Survey (SF-36) scale scores and summary measure scores to describe the health burden of arthritis and to be responsive to clinical indicators of arthritis severity used in four clinical trials. METHODS: Adults participating in four double-blinded, placebo-controlled clinical trials of therapy for osteoarthritis or rheumatoid arthritis were administered the SF-36 concurrent with clinical measures of disease severity (n = 1,016). Data were collected before treatment and 2 weeks after treatment. Mean SF-36 scores for all patients with arthritis at baseline were compared to a sociodemographically equivalent national norm to test the ability of the SF-36 to describe the burden of arthritis. To test the responsiveness of SF-36 scores to clinical measures of arthritis severity, mean SF-36 scale scores were compared across patients differing in arthritis severity before treatment. Two-week mean SF-36 change scores were compared across patients who improved in arthritis severity (responders) versus patients who did not improve (nonresponders). F-statistics and relative validity coefficients were computed to determine how well each SF-36 scale and summary measure discriminated among arthritis severity levels and distinguished treatment responders from nonresponders, relative to the best scale. RESULTS: Large and statistically significant differences in mean SF-36 scale scores and summary measures were found such that trial participants scored in worse health than a sociodemographically equivalent US general population norm. In addition, the largest SF-36 scale scores were found to significantly differ across clinically defined levels of arthritis severity. Finally, it was found that the SF-36 scales that best discriminate among arthritis severity groups cross-sectionally were also best at discriminating treatment responders from nonresponders. CONCLUSION: Results of this study support the validity of the SF-36 to document the health burden of arthritis and as a measure of generic health outcome for clinical trials of alternative treatments for osteoarthritis and rheumatoid arthritis patients.

OBJECTIVE: To evaluate the psychometric assumptions underlying the construction and scoring of SF-36 scales and summary measures among clinical trial participants with arthritis. METHODS: Cross-sectional SF-36 data from the baseline assessment of adult patients (n = 1,016) participating in four placebo-controlled clinical trials of treatment for arthritis were analyzed with blinding as to treatment. Tests of the completeness of data, scaling assumptions, internal-consistency reliability, and factor structure of SF-36 scales were performed for the combined sample. Eligible participants had at least a 6-month history of moderate to severe osteoarthritis or rheumatoid arthritis of the knee or hip. Participants meeting inclusion criteria had undergone a washout period of 3-14 days before baseline assessment to bring about a flare state in osteoarthritis or rheumatoid arthritis symptoms. Baseline sample sizes for the three osteoarthritis trials were n = 121, n = 341, and n = 187. The baseline sample size for the rheumatoid arthritis trial was n = 367. The average age of participants was 60 years, and the majority were females (72%). Measured were functional health and well-being scales and physical and mental health summary measures from the SF-36 Health Survey acute form. RESULTS: Missing responses ranged from 0.0% to 1.5% across SF-36 items, and scale scores could be computed for 96.8% to 100% of participants across trials. In all four trials, item internal consistency tests were passed (91.4%-97.1%) and item discriminant validity tests were passed (96.9%-100.0%). Across the four trials, internal-consistency reliability coefficients ranged from a low of 0.75 to a high of 0.91 for the eight scales (median = 0.84), exceeding the minimum standards for group comparisons. Ceiling effects were minimal for most scales, and floor effects were noteworthy for the role physical and role emotional scales. Physical and mental health factors identified in previous studies were replicated. CONCLUSION: The SF-36 Health Survey proved to be a psychometrically sound tool for the assessment of the health status of adult participants in clinical trials of arthritis.

As shown here, general health measures cover much of the content included in arthritis-specific measures, but, are they equally sensitive to changes in disease condition? We reviewed the literature on the most widely used general health measure, the SF-36 Health Survey, to see if the empirical evidence supported its validity for use in arthritis patients. As of this writing, there was no documentation of the sensitivity of the SF-36 to short-term changes in arthritic condition over the course of clinical trials and few studies that compared the sensitivity of the SF-36 to arthritis-specific measures. The empirical research reported in this special supplement contributes to the literature on the use of the SF-36 in arthritis patients and demonstrates methods of studying the validity of general health measures to monitor change in specific conditions.

We studied 31 previously validated and newly developed generic and epilepsy-specific scales to evaluate their usefulness for assessing the impact of epilepsy and anti-epileptic drug (AED) therapy on health-related quality of life (HRQOL). Included were the MOS SF-36 Health Survey, additional measures of mental health, cognition, epilepsy-specific perception of control, behavioural problems, distress, worries and experiences, the Liverpool Epilepsy Impact and Seizure Severity scales, and a patient-completed symptom checklist. Questionnaires were completed twice by 136 patients on AED therapy in a multicentre study in the UK. Validity was assessed in relation to disease severity, defined as time since last seizure, and to patient-reported symptoms. Statistical analyses to estimate the contribution of HRQOL information of each scale relative to that of others were conducted. The 171-item questionnaire could be completed by out-patients with epilepsy with good data quality. With few exceptions, generic and epilepsy-specific measures satisfied psychometric tests of hypothesized item groupings and scale score reliability (internal consistency and test-retest reliability) and differentiated well between groups of patients differing in time since last seizure and in symptom impact, regardless of time since last seizure. However, scales differed widely in their validity in discriminating between groups of patients known to differ clinically. The SF-36 Role Physical scale best discriminated among groups differing in disease severity. The epilepsy-specific Mastery, Impact, Experience, Worry, Distress, and Agitation scales were among the 10 best measures in discriminating among groups differing in disease severity. Generic measures, especially measures of social and role functioning and mental health, were best at differentiating groups of patients differing in symptom impact. Recommendations are offered for concepts and specific scales most likely to be useful in future studies of the HRQOL burden of epilepsy and the HRQOL benefits of AED therapy.

Aim: 125I-iododeoxyuridine is a potential Auger radiation therapy agent. Its incorporation in DNA of proliferating cells is enhanced by fluorodeoxyuridine. Here, we evaluated therapeutic activities of 125I-iododeoxyuridine in an optimized fluorodeoxyuridine pre-treatment inducing S-phase synchronization. Methods: after S-phase synchronization by fluorodeoxyuridine, cells were treated with 125I-iododeoxyuridine. Apoptosis analysis and S-phase synchronization were studied by flow cytometry. Cell survival was determined by colony-forming assay. Based on measured growth parameters, the number of decays per cell that induced killing was extrapolated. Results: treatment experiments showed that 72 to 91 % of synchronized cells were killed after 0.8 and 8 kBq/ml 125I-iododeoxyuridine incubation, respectively. In controls, only 8 to 38 % of cells were killed by corresponding 125I-iododeoxyuridine activities alone and even increasing the activity to 80 kBq/ml gave only 42 % killing. Duplicated treatment cycles or repeated fluorodeoxyuridine pre-treatment allowed enhancing cell killing to >95 % at 8 kBq/ml 125I-iododeoxyuridine. About 50 and 160 decays per S-phase cells in controls and S-phase synchronization, respectively, were responsible for the observed cell killing at 0.8 kBq/ml radio-iododeoxyuridine. Conclusion: these data show the successful application of fluorodeoxyuridine that provided increased 125I-iododeoxyuridine Auger radiation cell killing efficacy through S-phase synchronization and high DNA incorporation of radio-iododeoxyuridine.

Paclitaxel (Tx)-loaded anti-HER2 immunonanoparticles (NPs-Tx-HER) were prepared by the covalent coupling of humanized monoclonal anti-HER2 antibodies (trastuzumab, Herceptin((R))) to Tx-loaded poly (DL-lactic acid) nanoparticles (NPs-Tx) for the active targeting of tumor cells that overexpress HER2 receptors. The physico-chemical properties of NPs-Tx-HER were compared to unloaded immunonanoparticles (NPs-HER) to assess the influence of the drug on anti-HER2 coupling to the NP surface. The immunoreactivity of sulfo-MBS activated anti-HER2 mAbs and the in vitro efficacy of NPs-Tx-HER were tested on SKOV-3 ovarian cancer cells that overexpress HER2 antigens. Tx-loaded nanoparticles (NPs-Tx) obtained by a salting-out method had a size of 171+/-22nm (P.I.=0.1) and an encapsulation efficiency of about of 78+/-10%, which corresponded to a drug loading of 7.8+/-0.8%(w/w). NPs-Tx were then thiolated and conjugated to activated anti-HER2 mAbs to obtain immunonanoparticles of 237+/-43nm (P.I.=0.2). The influence of the activation step on the immunoreactivity of the mAbs was tested on SKOV-3 cells using (125)I-radiolabeled mAbs, and the activity of the anti-HER2 mAbs was minimally affected after sulfo-MBS functionalization. Approximately 270 molecules of anti-HER2 mAbs were bound per nanoparticle. NPs-Tx-HER exhibited a zeta potential of 0.2+/-0.1mV. The physico-chemical properties of the Tx-loaded immunonanoparticles were very similar to unloaded immunonanoparticles, suggesting that the encapsulation of the drug did not influence the coupling of the mAbs to the NPs. No drug loss was observed during the preparation process. DSC analysis showed that encapsulated Tx is in an amorphous or disordered crystalline phase. These results suggest that Tx is entrapped in the polymeric matrix and not adsorbed to the surface of the NPs. In vitro studies on SKOV-3 ovarian cancer cells demonstrated the greater cytotoxic effect of NPs-Tx-HER compared to other Tx formulations. The results showed that at 1 ng Tx/ml, the viability of cells incubated with drug encapsulated in NP-Tx-HER was lower (77.32+/-5.48%) than the viability of cells incubated in NPs-Tx (97.4+/-12%), immunonanoparticles coated with Mabthera((R)), as irrelevant mAb,(NPs-Tx-RIT)(93.8+/-12%) or free drug (92.3+/-9.3%).

Summary Background: Crohn's disease (CD) is a chronic inflammatory illness characterized by episodic abdominal pain, diarrhea, fever, bleeding, and obstruction. While the Crohn's Disease Activity Index (CDAI) remains the most commonly accepted measure for assessing disease status in clinical trials, patient-reported outcome (PRO) instruments are being utilized more frequently to provide information about health-related quality of life (HRQOL). To facilitate interpretation of results, it is common to identify a meaningful unit of PRO score change, such as a minimal clinically important difference (MCID). Aim: Define and apply MCID estimates for the SF-36 and EQ-5D VAS for use in CD treatment evaluation. Methods: Data from two Phase III randomized controlled trials of certolizumab pegol were utilized. MCID estimates were computed from one trial using anchor-based and distribution-based methods. These estimates were applied to data from the other trial. Results: SF-36 PCS and MCS MCID estimates ranged from 1.6 to 7.0 and 2.3 to 8.7, respectively, depending on approach. EQ-5D VAS MCID estimates ranged from 4.2 to 14.8. Conclusions: For the first time, the MCID values provided interpretation guidelines for PRO results in CD. This research demonstrates that patients treated with certolizumab pegol benefit from meaningful and sustained health-related quality of life improvements.

GARDASIL((R))(Merck, Whitehouse Station, NJ) is a non-infectious recombinant, quadrivalent vaccine prepared from the highly purified virus-like particles (VLPs) of the major capsid proteins of human papillomavirus (HPV) types 6, 11, 16, and 18. GARDASIL((R)) is the first vaccine approved for use in women aged 9-26 years for the prevention of cervical cancer and genital warts, as well as vulvar and vaginal precancerous lesions. This report describes some of the key preclinical efforts, achievements in pharmaceutical development, in vivo animal evaluation, and clinical trial data.Clinical Pharmacology & Therapeutics (2007) 81, 259-264. doi:10.1038/sj.clpt.6100055.

We present the long-term results of 18 chemotherapy relapsed indolent (N=12) or transformed (N=6) NHL patients of a phase II anti-CD20 (131)I-tositumomab (Bexxar((R))) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with (131)I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion,(131)I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46-70 months.British Journal of Cancer advance online publication, 9 May 2006; doi:10.1038/sj.bjc.6603166 www.bjcancer.com.

AIMS: Isolated hepatic perfusion (IHP) allows loco-regional administration of high drug doses for cancer treatment. Minimally invasive endovascular occlusion techniques can be used for IHP, but control of leakage remains a major drawback. We hypothesized that the increased intraabdominal pressure generated by a CO(2)-pneumoperitoneum (PP) can reduce the leakage rate of hypoxic endovascular IHP by mechanical compression of the capillary beds connecting the liver to the systemic circulation. METHODS: IHP was performed on adult pigs through laparotomy using a fenestrated double balloon-catheter placed into the retrohepatic vena cava to collect the hepatic outflow which was reinfused into the hepatic artery through an extracorporeal circulation system. Each pig underwent IHP during four consecutive phases: abdomen open (Phase I), abdomen closed under a 15 and 20mmHg pneumoperitoneum (Phase II and III, respectively) and abdomen re-opened (Phase IV). The leakage rate from the liver to the systemic circulation was continuously monitored using a nuclear medicine technique. The systemic arterial pressure, the IHP inflow and outflow pressures and the flow rate were recorded. RESULTS: Leakage from the hepatic extracorporeal circulation to the systemic circulation occurred in all animals during Phase I. Under PP (Phases II and III), two leakage profiles were observed:(1) a major increase of the leakage rate in two animals with a high differential pressure (>50mmHg) between the IHP inflow and the systemic pressures;(2) no change or a decrease of the leakage rate in the other three animals who had a low or negative differential pressure (<30mmHg). Leakage was undetectable in all animals after exsufflation of the PP (Phase IV). CONCLUSIONS: IHP under PP is feasible. Leakage is not reduced during PP. A high gradient between the IHP inflow and the systemic pressure increases systemic leakage during PP. Upon release of the PP, the leakage is most likely redirected towards the volume depleted low resistance portal territory.

OBJECTIVES: Pain is identified as the third largest health problem in the world, impacting sleep, physical functioning, and psychologic functioning. Pain has been viewed as a multidimensional experience influenced by biology, psychology, cultural conditioning, expectancies, and social contingencies. The aims of this study were to examine the psychometric properties and the differential item functioning (DIF) of the short-form McGill Pain Questionnaire (SF-MPQ) to test the cultural differences in verbally based pain expression. METHODS: Data were drawn from the medical records of 134 Hispanic and 134 non-Hispanic White patients with pain. Cases were matched on total SF-MPQ score, sex, and age. Estimates of reliability and validity were assessed. Using a traditional moderated regression approach, each of the 15 items on the SF-MPQ was analyzed for DIF using matched moderated regression methodology. RESULTS: Internal consistency was high: Hispanics 0.90 and non-Hispanics 0.89. Factor analysis revealed 2 components for each ethnic group. DIF analyses revealed statistically significant group differences for the 5 items (ie, throbbing, gnawing, aching, tiring-exhausting, and sickening) potentially due to cultural-linguistic factors. The remaining 10 items revealed no significant differences. Group differences were not accounted for by sex, age, marital status, education, pain location, or pain duration. DISCUSSION: Test bias was relatively small (0.74) given the entire scale of the SF-MPQ (0 to 45), indicating that this measure seems to be used equivalently across these 2 groups. This study shows 1 method in evaluating the cross-cultural validity of pain assessment instruments, and contributes to the understanding of cross-cultural variability in item reporting on the SF-MPQ.

ABSTRACT Objectives: The objective of this study was twofold: 1) to confirm the hypothetical eight scales and two-component summaries of the questionnaire Short Form 36 Health Survey (SF-36), and 2) to evaluate the performance of two alternative measures to the original physical component summary (PCS) and mental component summary (MCS). Methods: We performed principal component analysis (PCA) based on 35 items, after optimal scaling via multiple correspondence analysis (MCA), and subsequently on eight scales, after standard summative scoring. Item-based summary measures were planned. Data from the European Community Respiratory Health Survey II follow-up of 8854 subjects from 25 centers were analyzed to cross-validate the original and the novel PCS and MCS. Results: Overall, the scale- and item-based comparison indicated that the SF-36 scales and summaries meet the supposed dimensionality. However, vitality, social functioning, and general health items did not fit data optimally. The novel measures, derived a posteriori by unit-rule from an oblique (correlated) MCA/PCA solution, are simple item sums or weighted scale sums where the weights are the raw scale ranges. These item-based scores yielded consistent scale-summary results for outliers profiles, with an expected known-group differences validity. Conclusions: We were able to confirm the hypothesized dimensionality of eight scales and two summaries of the SF-36. The alternative scoring reaches at least the same required standards of the original scoring. In addition, it can reduce the item-scale inconsistencies without loss of predictive validity.

Mental health research among Latino farmworkers is hampered by the absence of measurement evaluation that ensures farmworkers understand and can consistently and appropriately respond to questions about mental health. Cross-sectional data were obtained from 409 farmworkers via interviewer-administered survey questionnaires. Mental health was operationalized with the short-form Center for Epidemiologic Studies, Depression (CES-D) scale. The structured interviewer-administered survey questionnaires included measures to capture personal and work-related factors that could affect farmworkers' ability to understand and respond to mental health questions probed by the CES-D. Good variability in item response was observed across the 10 short-form CES-D items. There was no evidence of differential response across sub-groups of farmworkers for six of the 10 items. Responses to four of the 10 items differed by educational attainment, country of origin, and language preference. Overall, the internal consistency of the 10 items exceeded standard conventions, and observed differences in depressive symptoms were as expected. Researchers in farmworker mental health must remain attentive to the strength and validity of available measures for migrants, different ethnic groups and different socioeconomic backgrounds. Nevertheless, the overall pattern suggests that the CES-D is a viable tool for advancing farmworker mental health research.

The purpose of this study was to examine validity and reliability of a community-environmental assessment instrument analysing community-environmental conditions among the mental disorders in a community. Thirty-three factors were extracted from the data based on a nationwide investigation by the factor analysis. The principal component analysis was applied to these extracted factors, and the first principal component score (1PCS) was interpreted as a synthetic index regarding daily living of the mental disorders in the community. Then, validity and reliability of 1PCS were confirmed. The item analyses from a viewpoint of statistics processing were adopted. As a result, coefficient alpha of the reliability was calculated from the scores and variances, and its value was 0.96. Next, kappa statistic was calculated in order to confirm whether two indices derived from the 52-item and 33-item questionnaires had the correspondence of the actual conditions with 1PCS in regard to the population scale of the municipality. As a result, the kappa was 0.94. In this study, we proposed the 33-item questionnaire composed of 33 factors. This was called as the Morita's community-environmental index (MCEI). It was suggested that the MCEI was useful to assess community-environmental conditions regarding daily living of the mental disorders in the community.

OBJECTIVE: To determine the measurement properties of an Italian Version of the Lower Extremity Functional Scale (LEFS) in patients with lower extremity musculoskeletal dysfunction. STUDY DESIGN AND SETTING: This is a prospective methodological study of repeated measures with a sample of 250 consecutive patients. Reliability, validity, and responsiveness were evaluated. RESULTS: The Italian version of the LEFS showed a high degree of internal consistency with a Cronbach alpha of 0.94 (95% confidence interval [CI]: 0.91, 0.96). The test-retest reliability was high for both intra-interviewer and inter-interviewer measures with an ICC((2,1 and 2,k)) of 0.91 (95% CI: 0.86, 0.93) and 0.89 (95% CI: 0.83, 0.91), respectively. The LEFS showed a better correlation with the 36-Item Short-Form Health Survey (SF-36) physical component summary score rather than with the SF-36 mental component summary score both at the initial assessment (r=0.61 and 0.26, respectively) and at the discharge (r=0.72 and 0.22, respectively). Receiver operating characteristic curve analysis revealed a large responsiveness for the LEFS (area under the curve [AUC]=0.97) and a moderate responsiveness for the SF-36 (AUC=0.68). CONCLUSION: The Italian version of the LEFS is a valid, reliable, and responsive tool that can be used to measure function in Italian patients with lower extremity musculoskeletal dysfunction.

BACKGROUND: Persistent symptoms, mainly joint and muscular pain and depression, have been reported several months after Chikungunya virus (CHIKV) infection. Their frequency and their impact on quality of life have not been compared with those of an unexposed population. In the present study, we aimed to describe the frequency of prolonged clinical manifestations of CHIKV infection and to measure the impact on quality of life and health care consumption in comparison with that of an unexposed population, more than one year after infection. METHODOLOGY/PRINCIPAL FINDINGS: In a retrospective cohort study, 199 subjects who had serologically confirmed CHIKV infection (CHIK+) were compared with 199 sero-negative subjects (CHIK-) matched for age, gender and area of residence in La Réunion Island. Following an average time of 17 months from the acute phase of infection, participants were interviewed by telephone about current symptoms, medical consumption during the last 12 months and quality of life assessed by the 12-items Short-Form Health Survey (SF-12) scale. At the time of study, 112 (56%) CHIK+ persons reported they were fully recovered. CHIK+ complained more frequently than CHIK- of arthralgia (relative risk = 1.9; 95% confidence interval: 1.6-2.2), myalgia (1.9; 1.5-2.3), fatigue (2.3; 1.8-3), depression (2.5; 1.5-4.1) and hair loss (3.8; 1.9-7.6). There was no significant difference between CHIK+ and CHIK- subjects regarding medical consumption in the past year. The mean (SD) score of the SF-12 Physical Component Summary was 46.4 (10.8) in CHIK+ versus 49.1 (9.3) in CHIK-(p = 0.04). There was no significant difference between the two groups for the Mental Component Summary. CONCLUSIONS/SIGNIFICANCE: More than one year following the acute phase of infection, CHIK+ subjects reported more disabilities than those who were CHIK-. These persistent disabilities, however, have no significant influence on medical consumption, and the impact on quality of life is moderate.

OBJECTIVES: The authors examined whether selected demographic and psychological factors would predict physical health dimensions in a sample of 53 cognitively high-functioning and ethnically diverse women (age 65-105). METHOD: Predictors encompassed posttraumatic stress disorder (PTSD) symptomatology and perceived stress (of a nontraumatic nature and beyond health status) in relation to all dimensions of physical health of the Medical Outcome Study 36-item Short Form Health Survey (MOS SF-36);(Ware, J.E.,& Sherbourne, C.D., 1992). The MOS 36-item short-form health survey (SF-36): I. Conceptual framework and item selection. Medical Care, 30(6), 473-483). Age and income, well-known correlates of health in the target population, were included as potential predictors. The authors first tested the relationship between potential predictors and health dimensions via a canonical correlation analysis, and then employed full multiple regression analyses to simultaneously test the predictors in each health dimension model. RESULTS: Perceived stress was a significant predictor of lower levels of general health (GH), but not of role limitations or physical functioning (PF). Conversely, PTSD symptomatology predicted more limitations in role fulfillment (and, to a lesser extent, impaired PF), but not lower levels of GH. As expected, age and income were predictive of some physical health dimensions. The hypothesized predictors failed to account for a significant portion of variance in pain scores. CONCLUSION: PTSD symptomatology and perceived stress might influence older women's physical health dimensions differentially; additional research on larger samples is needed to corroborate these findings.

Identification and prevention of community reintegration problems of veterans is an important public health mandate. However, no veteran-specific measure exists. Study purposes were to (1) develop the Community Reintegration for Service Members (CRIS) measure and (2) test the validity and reliability of the measure. Formative research identified challenges in community reintegration postdeployment. The World Health Organization's International Classification of Functioning, Disability and Health participation domain guided item-bank development. Items were refined through cognitive interviews and clinician consultation. Pilot studies with 126 veterans examined unidimensionality, internal consistency, reliability, and construct validity. Three unidimensional CRIS scales were developed. Working subjects had better CRIS scores then unemployed subjects. Subjects with posttraumatic stress disorder, substance abuse, or mental health problems had worse scores than subjects without these conditions. The correlations between the CRIS and the 36-Item Short Form Health Survey scales of role physical, role emotional, and social functioning were 0.44-0.80. CRIS has strong reliability, conceptual integrity, and construct validity.

Few studies have assessed the psychometric properties of the Personality Assessment Inventory short-form (PAI-SF) clinical scales, and none have conducted these evaluations using participants from psychiatric inpatient units. The present study evaluated item-level tests of scaling assumptions of the PAI-SF using a large (N=503) clinical sample of participants who completed the PAI during their admission to a psychiatric inpatient unit. Internal consistency reliability was high across scales, and tests of item-scale convergence and discrimination generally confirmed hypothesized item groupings. Scale-level correlations supported unique variance being measured by each scale. Finally, agreement between the PAI short- and full-form scales was found to be high. The results are discussed with regards to scale interpretation.

OBJECTIVES: Treatments of patients with chronic mental disorders are increasingly focusing on salutogenetic aims to support human health and well-being. Up to now, standardized instruments to evaluate these treatment goals are still missing. We present results of analyses of the psychometric properties of the Hamburg Self-Care Questionnaire (HamSCQ). Besides reliability we are focusing on different aspects of validity: factor structure, concurrent validity, and sensitivity to change. METHODS: A total sample of 7 478 inpatients with mental disorders from four different psychotherapeutic clinics participated in the study. Patients completed self-rating questionnaires at admission and discharge: Besides the HamSCQ we used the Symptom Checklist SCL-14, the Short Form SF-8, the CES-D depression scale, the Inventory of Interpersonal Problems IIP-25 and the AVEM. RESULTS: The two-dimensional structure of the HamSCQ with the two subscales PACING and POSITIVE EXPERIENCE could be replicated by means of both principal component and confirmatory factor analysis. The two scales correlate with r=0.56. Both scales show a high internal consistency (alpha >/=0.90), they correlate with the selected measures of concurrent validity (except the AVEM scales) with medium (Pacing) or high (Positive Experience) effect sizes, and their mean scores differ significantly from admission to discharge with large effect sizes. CONCLUSIONS: The HamSCQ proves to be a reliable questionnaire, which is also sensitive to change. The two-dimensional factor structure could be replicated, and some aspects of concurrent validity could be demonstrated, but concerning criterion validity further research is still necessary. Thus we recommend the use of the HamSCQ for inpatients with mental disorders treated in psychotherapeutic/rehabilitative clinics.