Zolbetuximab plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (SPOTLIGHT): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: Zolbetuximab, a monoclonal antibody targeting claudin-18 isoform 2 (CLDN18.2), has shown efficacy in patients with CLDN18.2-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma. We report the results of the SPOTLIGHT trial, which investigated the efficacy and safety of first-line zolbetuximab plus mFOLFOX6 (modified folinic acid [or levofolinate], fluorouracil, and oxaliplatin regimen) versus placebo plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma. METHODS: SPOTLIGHT is a global, randomised, placebo-controlled, double-blind, phase 3 trial that enrolled patients from 215 centres in 20 countries. Eligible patients were aged 18 years or older with CLDN18.2-positive (defined as ≥75% of tumour cells showing moderate-to-strong membranous CLDN18 staining), HER2-negative (based on local or central evaluation), previously untreated, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma, with radiologically evaluable disease (measurable or non-measurable) according to Response Evaluation Criteria in Solid Tumors version 1.1; an Eastern Cooperative Oncology Group performance status score of 0 or 1; and adequate organ function. Patients were randomly assigned (1:1) via interactive response technology and stratified according to region, number of organs with metastases, and previous gastrectomy. Patients received zolbetuximab (800 mg/m2 loading dose followed by 600 mg/m2 every 3 weeks) plus mFOLFOX6 (every 2 weeks) or placebo plus mFOLFOX6. The primary endpoint was progression-free survival assessed by independent review committee in all randomly assigned patients. Safety was assessed in all treated patients. The study is registered with ClinicalTrials.gov, NCT03504397, and is closed to new participants. FINDINGS: Between June 21, 2018, and April 1, 2022, 565 patients were randomly assigned to receive either zolbetuximab plus mFOLFOX6 (283 patients; the zolbetuximab group) or placebo plus mFOLFOX6 (282 patients; the placebo group). At least one dose of treatment was administered to 279 (99%) of 283 patients in the zolbetuximab group and 278 (99%) of 282 patients in the placebo group. In the zolbetuximab group, 176 (62%) patients were male and 107 (38%) were female. In the placebo group, 175 (62%) patients were male and 107 (38%) were female. The median follow-up duration for progression-free survival was 12·94 months in the zolbetuximab group versus 12·65 months in the placebo group. Zolbetuximab treatment showed a significant reduction in the risk of disease progression or death compared with placebo (hazard ratio [HR] 0·75, 95% CI 0·60-0·94; p=0·0066). The median progression-free survival was 10·61 months (95% CI 8·90-12·48) in the zolbetuximab group versus 8·67 months (8·21-10·28) in the placebo group. Zolbetuximab treatment also showed a significant reduction in the risk of death versus placebo (HR 0·75, 95% CI 0·60-0·94; p=0·0053). Treatment-emergent grade 3 or worse adverse events occurred in 242 (87%) of 279 patients in the zolbetuximab group versus 216 (78%) of 278 patients in the placebo group. The most common grade 3 or worse adverse events were nausea, vomiting, and decreased appetite. Treatment-related deaths occurred in five (2%) patients in the zolbetuximab group versus four (1%) patients in the placebo group. No new safety signals were identified. INTERPRETATION: Targeting CLDN18.2 with zolbetuximab significantly prolonged progression-free survival and overall survival when combined with mFOLFOX6 versus placebo plus mFOLFOX6 in patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Zolbetuximab plus mFOLFOX6 might represent a new first-line treatment in these patients. FUNDING: Astellas Pharma, Inc.

Phase 1 trial of zolbetuximab in Japanese patients with CLDN18.2+ gastric or gastroesophageal junction adenocarcinoma.

Zolbetuximab is a chimeric monoclonal antibody that targets claudin-18.2, a candidate biomarker in patients with advanced gastric/gastroesophageal cancer. This nonrandomized phase 1 study (NCT03528629) enrolled previously treated Japanese patients with claudin-18.2-positive locally advanced/metastatic gastric/gastroesophageal cancer in two parts: Safety (Arms A and B, n = 3 each) and Expansion (n = 12). Patients received intravenous zolbetuximab 800 mg/m2 on cycle 1, day 1 followed by 600 mg/m2 every 3 weeks (Q3W; Safety Part Arm A and Expansion) or 1000 mg/m2 Q3W (Safety Part Arm B). For the Safety Part, the primary endpoint was safety (i.e., dose-limiting toxicities [DLTs]) and a secondary endpoint was objective response rate (ORR) by investigator. For the Expansion Part, the primary endpoint was ORR by investigator and secondary endpoints included ORR by central review and safety. Additional secondary endpoints for both the Safety and Expansion Parts were disease control rate (DCR), overall survival (OS), progression-free survival (PFS), duration of response, pharmacokinetics, and immunogenicity. In 18 patients, no DLTs (Safety Part) or drug-related treatment-emergent adverse events (TEAEs) grade ≥3 were observed. Most TEAEs were gastrointestinal. In 17 patients with measurable lesions, best overall response was stable disease (64.7%) or progressive disease (35.3%). The DCR was 64.7% (95% confidence interval 38.3-85.8). In Arm A and Expansion combined (n = 15), median OS was 4.4 months (2.6-11.4) and median PFS was 2.6 months (0.9-2.8). In Arm B (n = 3), median OS was 6.4 months (2.9-6.8) and median PFS was 1.7 months (1.2-2.1). Zolbetuximab exhibited no new safety signals with limited single-agent activity in Japanese patients.

A phase II study assessing the safety and efficacy of ASP1650 in male patients with relapsed refractory germ cell tumors.

Claudin6(CLDN6) is a tight junction protein of claudin-tetraspanin family and is of the earliest molecules expressed in embryonic epithelium. CLDN6 is frequently aberrantly expressed in testicular germ-cell tumors(GCT). ASP1650 is a chimeric-mouse/human-IgG1 antibody directed against CLDN6. Two-part, open-label, phase-II trial investigating ASP1650 in patients with relapsed/refractory GCT and no curable options. Part1 was a safety lead-in to establish the recommended-phase-II-dose(RP2D). Part2 was a phase-II study designed to evaluate the antitumor effects of ASP1650. CLDN6 expression was centrally assessed on archival tumor tissue using immunohistochemistry. The primary objectives were to establish the RP2D(safety lead-in) and the antitumor activity(phase-II) of ASP1650. Nineteen male patients were enrolled: 6 patients in 1000 mg/m2 safety lead-in group, and 13 in 1500 mg/m2 group. Median age 37.2 years(range,20-58). Histology was non-seminoma in 17/19 patients. Median number of previous chemotherapy regimens was 3. Thirteen patients had prior high-dose chemotherapy. No dose-limiting toxicity events were reported at any study drug dose. A RP2D of 1500 mg/m2 every 2 weeks was established. No partial or complete responses were observed. The study was stopped at the end of Simon Stage-I due to lack of efficacy. 15/16 subjects with available tissue had CLDN6 positive staining. The mean percent membrane staining was 71.6% and the mean membrane H score was 152.6(SD 76). ASP1650 did not appear to have clinically meaningful single-agent activity in relapsed/refractory GCT. CLDN6 expression seems ubiquitous in all elements of GCT and is worthy of investigation as a diagnostic biomarker and therapeutic target. (Clinical trial information: NCT03760081).

Causes and Means of Healing: An Islamic Ontological Perspective.

Healthcare practitioners are increasingly aware that patients may utilize faith-based healing practices in place of conventional medicine based on their spiritual and/or religious understandings of health and illness. Therefore, elucidating the ontological understandings of patients utilizing such religion-based treatments may clarify why patients and clinicians have differing understandings of 'who' heals and 'what' are means for healing. This paper describes an Islamic ontological schema that includes the following realms: Divine existence; spirits/celestial beings; non-physical forms/similitudes; and physical bodies. Ontological schema-based means of healing include conventional medicine, religion-based means (e.g., supplication, charity, prescribed incantations/amulets), and active adoption of Islamic virtues (e.g., reliance on God [tawakkul] and patience [sabr]). An ontological schema-based description of causes and means of healing can service a more holistic model of healthcare by integrating the overlapping worlds of religion and medicine and can support clinicians seeking to further understand and assess patient responses and attitudes toward illness and healing.

Brain death in Islamic ethico-legal deliberation: challenges for applied Islamic bioethics.

Since the 1980s, Islamic scholars and medical experts have used the tools of Islamic law to formulate ethico-legal opinions on brain death. These assessments have varied in their determinations and remain controversial. Some juridical councils such as the Organization of Islamic Conferences' Islamic Fiqh Academy (OIC-IFA) equate brain death with cardiopulmonary death, while others such as the Islamic Organization of Medical Sciences (IOMS) analogize brain death to an intermediate state between life and death. Still other councils have repudiated the notion entirely. Similarly, the ethico-legal assessments are not uniform in their acceptance of brain-stem or whole-brain criteria for death, and consequently their conceptualizations of, brain death. Within the medical literature, and in the statements of Muslim medical professional societies, brain death has been viewed as sanctioned by Islamic law with experts citing the aforementioned rulings. Furthermore, health policies around organ transplantation and end-of-life care within the Muslim world have been crafted with consideration of these representative religious determinations made by transnational, legally-inclusive, and multidisciplinary councils. The determinations of these councils also have bearing upon Muslim clinicians and patients who encounter the challenges of brain death at the bedside. For those searching for 'Islamically-sanctioned' responses that can inform their practice, both the OIC-IFA and IOMS verdicts have palpable gaps in their assessments and remain clinically ambiguous. In this paper we analyze these verdicts from the perspective of applied Islamic bioethics and raise several questions that, if answered by future juridical councils, will better meet the needs of clinicians and bioethicists.

ILUSTRO: Phase II Multicohort Trial of Zolbetuximab in Patients with Advanced or Metastatic Claudin 18.2-Positive Gastric or Gastroesophageal Junction Adenocarcinoma.

PURPOSE: Zolbetuximab, an IgG1 monoclonal antibody, binds to claudin 18.2 (CLDN18.2) and mediates tumor cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. We sought to examine zolbetuximab combinations in CLDN18.2-positive HER2-negative gastric/gastroesophageal junction (G/GEJ) adenocarcinoma. PATIENTS AND METHODS: This phase II study assessed efficacy and safety of zolbetuximab, alone or with modified FOLFOX6 (mFOLFOX6) or pembrolizumab, in CLDN18.2-positive advanced/metastatic G/GEJ adenocarcinoma. Patients received zolbetuximab as monotherapy in third/later-line (Cohort 1A, n = 30), with mFOLFOX6 in first-line (Cohort 2, n = 21), or with pembrolizumab in third/later-line (Cohort 3A, n = 3) treatment. The primary endpoint for Cohort 1A was objective response rate (ORR). Key secondary endpoints were ORR (Cohorts 2 and 3A), overall survival (OS; Cohort 1A), and progression-free survival (PFS) and safety (all cohorts). RESULTS: ORR was 0% in Cohorts 1A and 3A, and 71.4% [95% confidence interval (CI), 47.82-88.72] in Cohort 2. Median PFS was 1.54 months (95% CI, 1.31-2.56) in Cohort 1A, 2.96 months (95% CI, 1.48-4.44) in Cohort 3A, and 17.8 months (95% CI, 8.05-25.69) in Cohort 2. Median OS in Cohort 1A was 5.62 months (95% CI, 2.27-11.53). Gastrointestinal adverse events occurred across cohorts [nausea, 63%-90% (grade ≥ 3, 4.8%-6.7%) and vomiting, 33%-67% (grade ≥ 3, 6.7%-9.5%)]. CONCLUSIONS: Zolbetuximab plus mFOLFOX6 demonstrated promising efficacy in previously untreated patients with CLDN18.2-positive G/GEJ adenocarcinoma. These data support the first-line development of zolbetuximab in patients whose tumors are CLDN18.2-positive. Across cohorts, zolbetuximab treatment was tolerable with no new safety signals.

Zolbetuximab plus CAPOX in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma: the randomized, phase 3 GLOW trial.

There is an urgent need for first-line treatment options for patients with human epidermal growth factor receptor 2 (HER2)-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (mG/GEJ) adenocarcinoma. Claudin-18 isoform 2 (CLDN18.2) is expressed in normal gastric cells and maintained in malignant G/GEJ adenocarcinoma cells. GLOW (closed enrollment), a global, double-blind, phase 3 study, examined zolbetuximab, a monoclonal antibody that targets CLDN18.2, plus capecitabine and oxaliplatin (CAPOX) as first-line treatment for CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. Patients (n = 507) were randomized 1:1 (block sizes of two) to zolbetuximab plus CAPOX or placebo plus CAPOX. GLOW met the primary endpoint of progression-free survival (median, 8.21 months versus 6.80 months with zolbetuximab versus placebo; hazard ratio (HR) = 0.687; 95% confidence interval (CI), 0.544-0.866; P = 0.0007) and key secondary endpoint of overall survival (median, 14.39 months versus 12.16 months; HR = 0.771; 95% CI, 0.615-0.965; P = 0.0118). Grade ≥3 treatment-emergent adverse events were similar with zolbetuximab (72.8%) and placebo (69.9%). Zolbetuximab plus CAPOX represents a potential new first-line therapy for patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or mG/GEJ adenocarcinoma. ClinicalTrials.gov identifier: NCT03653507 .

Effects of health literacy on health status and health service utilization amongst the elderly.

Amid increased concerns about the adverse consequences of low health literacy, it remains unclear how health literacy affects health status and health service utilization. With a sample of 489 elderly Medicare patients in a Midwestern city in the USA, we explored the intermediate factors that may link health literacy to health status and utilization of health services such as hospitalization and emergency care. We expected to find that individuals with higher health literacy would have better health status and less frequent use of emergency room and hospital services due to (1) greater disease knowledge, (2) healthier behaviors, (3) greater use of preventive care, and (4) a higher degree of compliance with medication. Using path analysis, we found, however, that health literacy had direct effects on health outcomes and that none of these variables of interest was a significant intermediate factor through which health literacy affected use of hospital services. Our findings suggest that improving health literacy may be an effective strategy to improve health status and to reduce the use of expensive hospital and emergency room services among elderly patients.

Multivariable predictors of postoperative respiratory failure after general and vascular surgery: results from the patient safety in surgery study.

BACKGROUND: Postoperative respiratory failure (RF) is associated with an increase in hospital morbidity, mortality, cost, and late mortality. We developed and tested a model to predict the risk of postoperative RF in patients undergoing major vascular and general surgical operations. This model is an extension of an earlier model that was derived and tested exclusively from a population of male patients from the Veterans Affairs National Surgical Quality Improvement Program. METHODS: Patients undergoing vascular and general surgical procedures at 14 academic and 128 Veterans Affairs Medical Centers from October 2001 through September 2004 were used to develop and test a predictive model of postoperative RF using logistic regression analyses. RF was defined as postoperative mechanical ventilation for longer than 48 hours or unanticipated reintubation. RESULTS: Of 180,359 patients, 5,389 (3.0%) experienced postoperative RF. Twenty-eight variables were found to be independently associated with RF. Current procedural terminology group, patients with a higher American Society of Anesthesiologists classification, emergency operations, more complex operation (work relative value units), preoperative sepsis, and elevated creatinine were more likely to experience RF. Older patients, male patients, smokers, and those with a history of congestive heart failure or COPD, or both, were also predisposed. The model's discrimination (c-statistic) was excellent, with no decrement from development (0.856) to validation (0.863) samples. CONCLUSIONS: This model updates a previously validated one and is more broadly applicable. Its use to predict postoperative RF risk enables the study of preventative measures or preoperative risk adjustment and intervention to improve outcomes.

The roles of low literacy and social support in predicting the preventability of hospital admission.

BACKGROUND: Prior studies found higher hospitalization rates among patients with low literacy, but did not determine the preventability of these admissions or consider other determinants of hospitalization, such as social support. This study evaluated whether low literacy was a predictor for preventability of hospitalization when considered in the context of social support, sociodemographics, health status, and risk behaviors. METHODS: A convenience sample of 400 patients, admitted to general medicine wards in a university-affiliated Veterans Affairs hospital between August 1, 2001 and April 1, 2003, completed a face-to-face interview to assess literacy, sociodemographics, social support, health status, and risk behaviors. Two Board-certified Internists independently assessed preventability of hospitalization and determined the primary preventable cause through blinded medical chart reviews. RESULTS: Neither low literacy ( or =12 people talked to weekly (P<.023). Among nonbinge drinkers with lower social support for medical care, larger social networks were predictive of preventability of hospitalization. Among nonbinge drinkers with higher support for medical care, lower outpatient utilization was predictive of the preventability of hospitalization. CONCLUSIONS: While low literacy was not predictive of admission preventability, the formal assessment of alcohol binge drinking, social support for medical care, social network size, and prior outpatient utilization may enhance our ability to predict the preventability of hospitalizations and develop targeted interventions.

Implementation and evaluation of a low-literacy diabetes education computer multimedia application.

OBJECTIVE: To evaluate a clinic-based multimedia intervention for diabetes education targeting individuals with low health literacy levels in a diverse population. RESEARCH DESIGN AND METHODS: Five public clinics in Chicago, Illinois, participated in the study with computer kiosks installed in waiting room areas. Two hundred forty-four subjects with diabetes were randomized to receive either supplemental computer multimedia use (intervention) or standard of care only (control). The intervention includes audio/video sequences to communicate information, provide psychological support, and promote diabetes self-management skills without extensive text or complex navigation. HbA(1c) (A1C), BMI, blood pressure, diabetes knowledge, self-efficacy, self-reported medical care, and perceived susceptibility of complications were evaluated at baseline and 1 year. Computer usage patterns and implementation barriers were also examined. RESULTS: Complete 1-year data were available for 183 subjects (75%). Overall, there were no significant differences in change in A1C, weight, blood pressure, knowledge, self-efficacy, or self-reported medical care between intervention and control groups. However, there was an increase in perceived susceptibility to diabetes complications in the intervention group. This effect was greatest among subjects with lower health literacy. Within the intervention group, time spent on the computer was greater for subjects with higher health literacy. CONCLUSIONS: Access to multimedia lessons resulted in an increase in perceived susceptibility to diabetes complications, particularly in subjects with lower health literacy. Despite measures to improve informational access for individuals with lower health literacy, there was relatively less use of the computer among these participants.

Relationship between health insurance and medical care for patients hospitalized with human immunodeficiency virus-related Pneumocystis carinii pneumonia, 1995-1997: Medicaid, bronchoscopy, and survival.

In the late 1980s, Medicaid-insured human immunodeficiency virus (HIV)-infected patients with Pneumocystis carinii pneumonia (PCP) were 40% less likely to undergo diagnostic bronchoscopy and 75% more likely to die than were privately insured patients, whereas rates of use of other, less resource-intensive aspects of PCP care were similar. We reviewed 1395 medical records at 59 hospitals in 6 cities for the period 1995-1997 to examine the impact of insurance status on PCP-related care. Medicaid patients were only one-half as likely to undergo diagnostic bronchoscopy as were privately insured patients, yet we found no evidence that mortality was greater among patients who received empirical treatment. The bronchoscopy rates were primarily related to patients' personal insurance status. A weaker hospital-level effect was seen that was related to hospitals' Medicaid/private insurance case mix ratios. The situation has evolved from one in which Medicaid coverage was associated with underuse of bronchoscopy and poorer survival among empirically treated persons with HIV-related PCP to one in which empirical therapy is effective in treating this disease and expensive diagnostic procedures may be overused for privately insured patients.

A rapid staging system for predicting mortality from HIV-associated community-acquired pneumonia.

STUDY OBJECTIVE: Community-acquired pneumonia (CAP) accounts for an increasing proportion of the pulmonary infections in individuals with HIV infection. During the mid-1990s, hospital mortality rates for HIV-associated CAP ranged from 0 to 28%. While hospital differences in case mix may account for mortality rate variation, few methods to evaluate illness severity for HIV-associated CAP have been reported previously. The study objective was to develop a staging system for categorizing mortality risk of patients with HIV-associated CAP using information available prior to hospital admission. DESIGN/SETTING/PATIENTS: Retrospective medical records review of 1,415 patients hospitalized with HIV-associated CAP from 1995 to 1997 at 86 hospitals in seven metropolitan areas. MEASUREMENTS: In-patient mortality rate. RESULTS: Hierarchically optimal classification tree analysis was used to develop a preadmission staging system for predicting inpatient mortality. The overall inpatient mortality rate was 9.1%. The significant predictors of mortality included the presence of neurologic symptoms, respiratory rate > or = 25 breaths/min, and creatinine > 1.2 mg/dL. The model identified a five-category staging system, with the mortality rate increasing by stage: 2.3% for stage 1, 5.8% for stage 2, 12.9% for stage 3, 22.0% for stage 4, and 40.5% for stage 5. The classification accuracy of the model was 85.2%. CONCLUSIONS: Our staging system categorizes inpatient mortality risk for patients with HIV-associated CAP using three routinely available variables. The staging system may be useful for guiding clinical decisions about the intensity of patient care and for case-mix adjustment in future studies addressing variation in hospital mortality rates.

Preoperative evaluation for postoperative pulmonary complications.

Preoperative risk assessment for postoperative pulmonary complications is essential when counseling patients about the risks of surgery because of their significant associated morbidity and mortality. There are many patient-related, operation-related, and anesthesia-related risk factors for the development of PPCs. Though many of these risk factors are not modifiable, they can be useful in evaluating preoperative risk, especially when combined into formal risk indices. Preoperative risk assessment enables clinicians to target preoperative testing and perioperative risk reduction strategies to high-risk patients. Reducing PPC risk at the patient level will require a greater understanding of the impact of modifying risk factors through interventional trials. Reducing hospital PPC rates will require future research into the processes of care associated with PPCs through controlled observational and interventional trials.

Health literacy, social support, and health: a research agenda.

Amid increased concerns about the adverse consequences of low health literacy, it remains unclear how health literacy affects health status and health service utilization. Moreover, studies have shown significant variation in individual adaptation to health literacy problems. This article proposes research hypotheses to address two questions: (1) What are the causal pathways or intermediate steps that link low health literacy to poor health status and high utilization of expensive services such as hospitalization and emergency care? (2) What impact does social support have on the relationships between health literacy and health service utilization? Empirical studies of health literacy are reviewed to indicate the limitations of current literature and to highlight the importance of the proposed research agenda. In particular, we note the individualistic premise of current literature in which individuals are treated as isolated and passive actors. Thus, low health literacy is considered simply as an individual trait independent of support and resources in an individual's social environment. To remedy this, research needs to take into account social support that people can draw on when problems arise due to their health literacy limitations. Examination of the proposed agenda will make two main contributions. First, we will gain a better understanding of the causal effects of health literacy and identify missing links in the delivery of care for patients with low health literacy. Second, if social support buffers the adverse effects of low health literacy, more effective interventions can be designed to address differences in individuals' social support system in addition to individual differences in reading and comprehension. More targeted and more cost-efficient efforts could also be taken to identify and reach those who not only have low health literacy but also lack the resources and support to bridge the unmet literacy demands of their health conditions.

The financial burden of cancer: estimates from a study of insured women with breast cancer.

The financial impact of cancer can be large, even among persons with comprehensive health insurance policies. Prior studies have found that women with cancer are especially likely to suffer financial hardship. Although controversial, cancer insurance policies are designed to reduce the financial burden of cancer. In this study, we provide estimates of the costs incurred by a cohort of breast cancer patients who were covered by private, Medicare, or Medicaid health insurance. In all, 156 women were interviewed about cancer-related out-of-pocket costs and their knowledge and use of cancer insurance policies. Out-of-pocket expenditures and lost income costs averaged $1,455 per month and varied widely. The majority of out-of-pocket costs were for co-payments for hospitalizations and physician visits. The financial burden of breast cancer accounted for a mean of 98%, 41%, and 26% of monthly income among female breast cancer patients with annual household income levels of < or = $30,000, $30,001-$60,000, and > $60,000, respectively. Cancer insurance policies provided reimbursement for out-of-pocket expenditures for 3% of the women in our study. Our data indicate that even among women with comprehensive health insurance policies, the financial burden of breast cancer can be substantial. Affordable programs that provide reimbursement for medical and nonmedical costs incurred following a diagnosis of breast cancer should be developed, especially for lower income women.

Wilayah (authority and governance) and its implications for Islamic bioethics: a Sunni Maturidi perspective.

Juridical councils that render rulings on bioethical issues for Muslims living in non-Muslim lands may have limited familiarity with the foundational concept of wilayah (authority and governance) and its implications for their authority and functioning. This paper delineates a Sunni Maturidi perspective on the concept of wilayah, describes how levels of wilayah correlate to levels of responsibility and enforceability, and describes the implications of wilayah when applied to Islamic bioethical decision making. Muslim health practitioners and patients living in the absence of political wilayah may be tempted to apply pragmatic and context-focused approaches to address bioethical dilemmas without a full appreciation of significant implications in the afterlife. Academic wilayah requires believers to seek authentication of uncertain actions through scholarly opinions. Fulfilling this academic obligation naturally leads to additional mutually beneficial discussions between Islamic scholars, healthcare professionals, and patients. Furthermore, an understanding derived from a Maturidi perspective provides a framework for Islamic scholars and Muslim health care professionals to generate original contributions to mainstream bioethics and public policy discussions.

Racial differences in medication adherence: A cross-sectional study of Medicare enrollees.

BACKGROUND: Racial differences in adherence to prescribed medication regimens have been reported among the elderly. It remains unclear, however, whether these differences persist after controlling for confounding variables. OBJECTIVE: The objective of this study was to determine whether racial differences in medication adherence between African American and white seniors persist after adjusting for demographic characteristics, health literacy, depression, and social support. We hypothesized that differences in adherence between the 2 races would be eliminated after adjusting for confounding variables. METHODS: A survey on medication adherence was conducted using face-to-face interviews with Medicare recipients >or=65 years of age living in Chicago. Participants had to have good hearing and vision and be able to speak English to enable them to respond to questions in the survey and sign the informed-consent form. Medication adherence measures included questions about: (1) running out of medications before refilling the prescriptions; (2) following physician instructions on how to take medications; and (3) forgetting to take medications. Individual crude odds ratios (CORs) were calculated for the association between race and medication adherence. Adjusted odds ratios (AORs) were calculated using the following covariates in multivariate logistic regression analyses: race; age; sex; living with a spouse, partner, or significant other; income; Medicaid benefits; prescription drug coverage; having a primary care physician; history of hypertension or diabetes; health status; health literacy; depression; and social support. RESULTS: Six hundred thirty-three eligible cases were identified. Of the 489 patients who responded to the survey, 450 (266 African American [59%; mean age, 78.2 years] and 184 white [41%; mean age, 76.8 years]; predominantly women) were included in the sample. The overall response rate for the survey was 77.3%. African Americans were more likely than whites to report running out of medications before refilling them (COR = 3.01; 95% CI, 1.72-5.28) and not always following physician instructions on how to take medications (COR = 2.64; 95% CI, 1.50-4.64). However, no significant difference between the races was observed in forgetting to take medications (COR = 0.90; 95% CI, 0.61-1.31). In adjusted analyses, race was no longer associated with low adherence due to refilling (AOR = 1.60; 95% CI, 0.74-3.42). However, race remained associated with not following physician instructions on how to take medications after adjusting for confounding variables (AOR = 2.49; 95% CI, 1.07-5.80). CONCLUSION: Elderly African Americans reported that they followed physician instructions on how to take medications less frequently than did elderly whites, even after adjusting for differences in demographic characteristics, health literacy, depression, and social support.

Do observer and self-reports of ictal eye closure predict psychogenic nonepileptic seizures?

PURPOSE: Diagnostic delay in distinguishing psychogenic nonepileptic seizures (PNES) from epileptic seizures may result in unnecessary therapeutic interventions and higher health care costs. Previous studies demonstrated that video-recorded eye closure is associated with PNES. The present study prospectively assessed whether observer or self-report of eye closure could predict PNES, prior to video-EEG monitoring. METHODS: Adults referred to an epilepsy monitoring unit (EMU) were prospectively enrolled into the study. At baseline, self-report of eye closure was assessed by questionnaire, and observer report was obtained by interview. Physicians viewed video clips independent of EEG tracings and determined the duration of eye closure during PNES and epileptic seizures. We evaluated whether video-recorded eye closure identified an episode as PNES using random effects models that accounted for episode clustering by subject. The utility of observer and self-report of eye closure in predicting a diagnosis of PNES was tested using logistic regression. RESULTS: Of 132 enrolled subjects, 112 met study criteria during EMU stay for either PNES (n = 43, 38.4%) or epilepsy (n = 84, 75.0%). Fifteen of the 43 PNES subjects (34.9%) had coexisting epilepsy. Self and observer reports of eye closure were neither sensitive nor specific for the diagnosis of PNES. Self-report of eye closure more accurately predicted actual video-recorded eye closure than observer report. Video-recorded eye closure was 92% specific, but only 64% sensitive for PNES identification. DISCUSSION: Neither observer nor self-report of eye closure, prior to VEEG monitoring, predicts PNES. Video-recorded eye closure may not be as sensitive an indicator of PNES as previously reported.

Development and validation of a short-form, rapid estimate of adult literacy in medicine.

BACKGROUND: Although prior studies used the 66-item Rapid Estimate of Adult Literacy in Medicine (REALM instrument) for literacy assessment, researchers may require a shorter, validated instrument when designing interventions for clinical contexts. OBJECTIVE: To develop and validate a very brief literacy assessment tool, the REALM-Short Form (REALM-SF). PATIENTS: The model development, validation, and field testing validation samples included 1336, 164, and 50 patients, respectively. SETTING: General medicine and subspecialty clinics and medicine inpatient wards. DESIGN: For development and validation samples, indicator variables for REALM instrument items were evaluated as potential predictors of REALM instrument score by stepwise multiple regression analysis with subsequent bootstrap and confirmatory factor analysis of selected items. Pearson correlations compared REALM-SF and REALM instrument scores and kappa analyses compared grade level assignments. For the field testing validation sample, Pearson correlations compared Wide Range Achievement Test and REALM-SF scores. RESULTS: The REALM-SF included 7 items with stable model coefficients and 1 underlying linear factor. REALM-SF and REALM instrument scores were highly correlated in development (r = 0.95, P < 0.001) and validation (r = 0.94, P < 0.001) samples. There was excellent agreement between REALM-SF and REALM instrument grade-level assignments when dichotomized at the 6th grade (development: 97% agreement, K = 0.88, P < 0.001; validation: 88% agreement, K = 0.75, P < 0.001) and 8th grade levels (development: 94% agreement, K = 0.78, P < 0.001; validation: 84% agreement, K = 0.67, P < 0.001). REALM-SF and Wide Range Achievement Test scores were highly correlated (r = 0.83, P < 0.001) in field testing validation. CONCLUSIONS: The REALM-SF provides researchers a brief, validated instrument for assessing patient literacy in diverse research settings.