Translational insights and overall survival in the U31402-A-U102 study of patritumab deruxtecan (HER3-DXd) in EGFR-mutated NSCLC.

BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. PATIENTS AND METHODS: Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. RESULTS: In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% [95% confidence interval (CI) 30.0% to 52.7%], median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. CONCLUSIONS: In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.

Phosphorus-bearing molecules PO and PN at the edge of the Galaxy.

Despite its importance in planet formation and biology1, phosphorus has been identified only in the inner 12 kpc of the Galaxy2-19. The study of this element has been hindered in part by unfavourable atomic transitions2,4,20. Phosphorus is thought to be created by neutron capture on 29Si and 30Si in massive stars20,21, and released into the interstellar medium by Type II supernova explosions2,22. However, models of galactic chemical evolution must arbitrarily increase the supernovae production23 to match observed abundances. Here we present the detection of gas-phase phosphorus in the Outer Galaxy through millimetre spectra of PO and PN. Rotational lines of these molecules were observed in the dense cloud WB89-621, located 22.6 kpc from the Galactic Centre24. The abundances of PO and PN in WB89-621 are comparable to values near the Solar System25. Supernovae are not present in the Outer Galaxy26, suggesting another source of phosphorus, such as 'Galactic Fountains', where supernova material is redistributed through the halo and circumgalactic medium27. However, fountain-enriched clouds are not found at such large distances. Any extragalactic source, such as the Magellanic Clouds, is unlikely to be metal rich28. Phosphorus instead may be produced by neutron-capture processes in lower mass asymptotic giant branch stars29 which are present in the Outer Galaxy. Asymptotic giant branch stars also produce carbon21, flattening the extrapolated metallicity gradient and accounting for the high abundances of C-containing molecules in WB89-621.

Climate Change Effects on Pathogen Emergence: Artificial Intelligence to Translate Big Data for Mitigation.

Plant pathology has developed a wide range of concepts and tools for improving plant disease management, including models for understanding and responding to new risks from climate change. Most of these tools can be improved using new advances in artificial intelligence (AI), such as machine learning to integrate massive data sets in predictive models. There is the potential to develop automated analyses of risk that alert decision-makers, from farm managers to national plant protection organizations, to the likely need for action and provide decision support for targeting responses. We review machine-learning applications in plant pathology and synthesize ideas for the next steps to make the most of these tools in digital agriculture. Global projects, such as the proposed global surveillance system for plant disease, will be strengthened by the integration of the wide range of new data, including data from tools like remote sensors, that are used to evaluate the risk ofplant disease. There is exciting potential for the use of AI to strengthen global capacity building as well, from image analysis for disease diagnostics and associated management recommendations on farmers' phones to future training methodologies for plant pathologists that are customized in real-time for management needs in response to the current risks. International cooperation in integrating data and models will help develop the most effective responses to new challenges from climate change.

Weekly paclitaxel, carboplatin, cetuximab, and cetuximab, docetaxel, cisplatin, and fluorouracil, followed by local therapy in previously untreated, locally advanced head and neck squamous cell carcinoma.

BACKGROUND: The survival advantage of induction chemotherapy (IC) followed by locoregional treatment is controversial in locally advanced head and neck squamous cell carcinoma (LAHNSCC). We previously showed feasibility and safety of cetuximab-based IC (paclitaxel/carboplatin/cetuximab-PCC, and docetaxel/cisplatin/5-fluorouracil/cetuximab-C-TPF) followed by local therapy in LAHNSCC. The primary end point of this phase II clinical trial with randomization to PCC and C-TPF followed by combined local therapy in patients with LAHNSCC stratified by human papillomavirus (HPV) status and T-stage was 2-year progression-free survival (PFS) compared with historical control. PATIENTS AND METHODS: Eligible patients were ≥18 years with squamous cell carcinoma of the oropharynx, oral cavity, nasopharynx, hypopharynx, or larynx with measurable stage IV (T0-4N2b-2c/3M0) and known HPV by p16 status. Stratification was by HPV and T-stage into one of the two risk groups: (i) low-risk: HPV-positive and T0-3 or HPV-negative and T0-2; (ii) intermediate/high-risk: HPV-positive and T4 or HPV-negative and T3-4. Patient reported outcomes were carried out. RESULTS: A total of 136 patients were randomized in the study, 68 to each arm. With a median follow up of 3.2 years, the 2-year PFS in the PCC arm was 89% in the overall, 96% in the low-risk and 67% in the intermediate/high-risk groups; in the C-TPF arm 2-year PFS was 88% in the overall, 88% in the low-risk and 89% in the intermediate/high-risk groups. CONCLUSION: The observed 2-year PFS of PCC in the low-risk group and of C-TPF in the intermediate/high-risk group showed a 20% improvement compared with the historical control derived from RTOG-0129, therefore reaching the primary end point of the trial.

Parents' and healthcare professionals' experiences of care after stillbirth in low- and middle-income countries: a systematic review and meta-summary.

BACKGROUND: Stillbirth has a profound impact on women, families, and healthcare workers. The burden is highest in low- and middle-income countries (LMICs). There is need for respectful and supportive care for women, partners, and families after bereavement. OBJECTIVE: To perform a qualitative meta-summary of parents' and healthcare professionals' experiences of care after stillbirth in LMICs. SEARCH STRATEGY: Search terms were formulated by identifying all synonyms, thesaurus terms, and variations for stillbirth. Databases searched were AMED, EMBASE, MEDLINE, PsychINFO, BNI, CINAHL. SELECTION CRITERIA: Qualitative, quantitative, and mixed method studies that addressed parents' or healthcare professionals' experience of care after stillbirth in LMICs. DATA COLLECTION AND ANALYSIS: Studies were screened, and data extracted in duplicate. Data were analysed using the Sandelowski meta-summary technique that calculates frequency and intensity effect sizes (FES/IES). MAIN RESULTS: In all, 118 full texts were screened, and 34 studies from 17 countries were included. FES range was 15-68%. Most studies had IES 1.5-4.5. Women experience a broad range of manifestations of grief following stillbirth, which may not be recognised by healthcare workers or in their communities. Lack of recognition exacerbates negative experiences of stigmatisation, blame, devaluation, and loss of social status. Adequately developed health systems, with trained and supported staff, are best equipped to provide the support and information that women want after stillbirth. CONCLUSIONS: Basic interventions could have an immediate impact on the experiences of women and their families after stillbirth. Examples include public education to reduce stigma, promoting the respectful maternity care agenda, and investigating stillbirth appropriately. TWEETABLE ABSTRACT: Reducing stigma, promoting respectful care and investigating stillbirth have a positive impact after stillbirth for women and families in LMICs.

Making stillbirths visible: a systematic review of globally reported causes of stillbirth.

BACKGROUND: Stillbirth is a global health problem. The World Health Organization (WHO) application of the International Classification of Diseases for perinatal mortality (ICD-PM) aims to improve data on stillbirth to enable prevention. OBJECTIVES: To identify globally reported causes of stillbirth, classification systems, and alignment with the ICD-PM. SEARCH STRATEGY: We searched CINAHL, EMBASE, Medline, Global Health, and Pubmed from 2009 to 2016. SELECTION CRITERIA: Reports of stillbirth causes in unselective cohorts. DATA COLLECTION AND ANALYSIS: Pooled estimates of causes were derived for country representative reports. Systems and causes were assessed for alignment with the ICD-PM. Data are presented by income setting (low, middle, and high income countries; LIC, MIC, HIC). MAIN RESULTS: Eighty-five reports from 50 countries (489 089 stillbirths) were included. The most frequent categories were Unexplained, Antepartum haemorrhage, and Other (all settings); Infection and Hypoxic peripartum (LIC), and Placental (MIC, HIC). Overall report quality was low. Only one classification system fully aligned with ICD-PM. All stillbirth causes mapped to ICD-PM. In a subset from HIC, mapping obscured major causes. CONCLUSIONS: There is a paucity of quality information on causes of stillbirth globally. Improving investigation of stillbirths and standardisation of audit and classification is urgently needed and should be achievable in all well-resourced settings. Implementation of the WHO Perinatal Mortality Audit and Review guide is needed, particularly across high burden settings. FUNDING: HR, SH, SHL, and AW were supported by an NHMRC-CRE grant (APP1116640). VF was funded by an NHMRC-CDF (APP1123611). TWEETABLE ABSTRACT: Urgent need to improve data on causes of stillbirths across all settings to meet global targets. PLAIN LANGUAGE SUMMARY: Background and methods Nearly three million babies are stillborn every year. These deaths have deep and long-lasting effects on parents, healthcare providers, and the society. One of the major challenges to preventing stillbirths is the lack of information about why they happen. In this study, we collected reports on the causes of stillbirth from high-, middle-, and low-income countries to: (1) Understand the causes of stillbirth, and (2) Understand how to improve reporting of stillbirths. Findings We found 85 reports from 50 different countries. The information available from the reports was inconsistent and often of poor quality, so it was hard to get a clear picture about what are the causes of stillbirth across the world. Many different definitions of stillbirth were used. There was also wide variation in what investigations of the mother and baby were undertaken to identify the cause of stillbirth. Stillbirths in all income settings (low-, middle-, and high-income countries) were most frequently reported as Unexplained, Other, and Haemorrhage (bleeding). Unexplained and Other are not helpful in understanding why a baby was stillborn. In low-income countries, stillbirths were often attributed to Infection and Complications during labour and birth. In middle- and high-income countries, stillbirths were often reported as Placental complications. Limitations We may have missed some reports as searches were carried out in English only. The available reports were of poor quality. Implications Many countries, particularly those where the majority of stillbirths occur, do not report any information about these deaths. Where there are reports, the quality is often poor. It is important to improve the investigation and reporting of stillbirth using a standardised system so that policy makers and healthcare workers can develop effective stillbirth prevention programs. All stillbirths should be investigated and reported in line with the World Health Organization standards.

Who tells a mother her baby has died? Communication and staff presence during stillbirth delivery and early infant death.

OBJECTIVE: Perinatal loss (stillbirth or early infant death) is often a sudden, unexpected event for families. We evaluated who communicates the loss to the parents and who is there for support at the delivery or death. STUDY DESIGN: We conducted a mail survey of 900 bereaved and 500 live-birth mothers to assess emotional, physical and reproductive health outcomes. RESULTS: We had a 44% response rate at 9 months after birth or loss from 377 bereaved mothers and 232 with surviving infants. Bereaved women were less likely to have hospital staff or family members present at delivery. African-American (versus Caucasian) mothers were half as likely to have first heard about their stillbirth from a physician or midwife. CONCLUSION: This is the first large study documenting who communicates perinatal death to families and who is present for support. Hospitals should be aware that many bereaved families may lack support at critical times.

Maternal complications associated with stillbirth delivery: A cross-sectional analysis.

This study sought to identify delivery complications associated with stillbirth labour and delivery. We conducted a retrospective chart review evaluating stillbirth demographics, pregnancy and maternal risk factors, and complications of labour and delivery. We performed bivariable analysis and multivariable logistic regression to evaluate factors associated with medical complications and variations by race. Our cohort included 543 mothers with stillbirth, of which two-thirds were African-American. We noted high rates of shoulder dystocia, clinical chorioamnionitis, postpartum haemorrhage and retained placenta in women with stillbirths. Thirty-three women (6%) experienced at least one serious maternal complication. Complication rates did not vary by maternal race. Providers who perform obstetrical care should be alert to the high rate of maternal medical complications associated with labour and delivery of a stillbirth foetus.

Regulation of self-renewal and differentiation in the Drosophila nervous system.

Stem cells can divide symmetrically to generate two similar daughter cells and expand the stem cell pool or asymmetrically to self-renew and generate differentiating daughter cells. The proper balance between symmetric and asymmetric division is critical for the generation and subsequent repair of tissues. Furthermore, unregulated stem cell division has been shown to result in tumorous overgrowth. The Drosophila nervous system has proved to be a fruitful model system for studying the biology of neural stem cell division and uncovering the molecular mechanisms that, when disrupted, can lead to tumor formation. We are using the Drosophila embryonic and larval nervous systems as models to study the regulation of symmetric and asymmetric stem cell division.

Navigating care after a baby dies: a systematic review of parent experiences with health providers.

INTRODUCTION: Health care providers are on the front lines of care when a baby dies, but there is no consensus about which behaviors are most helpful or harmful for families. MATERIALS AND METHODS: This systematic review of more than 1100 English-language articles from 1966 to 2006 addressed fetal and early infant loss and extracted information about interactions with health providers. RESULTS: Sixty-one studies, covering over 6000 parents, met criteria. Nurses were generally viewed as more emotionally supportive than physicians. Parents valued emotional support, attention to mother and baby and grief education. Avoidance, insensitivity and poor staff communication were the most distressing behaviors encountered. DISCUSSION: Interactions with health providers has profound effects on parents with perinatal losses. Grieving parents perceive many behaviors to be thoughtless or insensitive. Physicians and nurses may benefit from increased training in bereavement support.

Quality of life of patients with Fabry disease.

This paper is the first of its kind to study the impact of Fabry disease (FD) in affected males, and shows that FD is associated with a significant decline in several domains. Using the medical outcomes study (MOS) SF-36 and a FD-specific questionnaire, we compared the observations found among these patients with that obtained for the general US population and other chronic disease states, including Gaucher disease (GD) (another lysosomal storage disorder), end-stage renal disease, stoke and AIDS. Patients with FD have a score profile most similar to patients with AIDS. In comparison with patients with GD, Fabry patients score substantially lower across all domains. Using simple linear regression, potential predictors of health-related quality of life (HRQOL) for Fabry patients were also determined. As in the general population, stroke, cardiac problems and renal disease lead to substantial decrement in HRQOL. In addition, two disease specific symptoms (acroparesthesia and anhidrosis) and pain are also predictors of decreased quality of life. Currently, no specific therapy for FD exists. As enzyme therapy for FD becomes increasingly available, it will be interesting to evaluate the therapy's impact on the quality of life of patients.

Validation of the rhinitis outcomes questionnaire (ROQ).

BACKGROUND: Currently, there is no easy-to-use and comprehensive questionnaire that measures the effectiveness of treatment of rhinitis-related symptoms in a private practice setting. OBJECTIVE: To validate a brief, effective, self-administered rhinitis symptoms questionnaire that can easily be used in a private practice setting for tracking treatment outcomes. METHODS: One hundred seventy-five patients were randomly chosen from three private practices nationwide and were surveyed regarding systemic problems, nasal, eye, and chest symptoms, as well as medical treatment obtained. This survey was administered twice in one sitting with the first administration a recall of symptoms before immunotherapy, and the second administration an evaluation of current symptoms. Appropriate statistical methods were used to evaluate the validity, reliability, and responsiveness of the questionnaire presented. The validation of this instrument included content, statistical, construct, and predictive validity. RESULTS: Both the content and statistical validity were very good in that the questionnaire was easily understood and covered required domains. Construct validity revealed that the items were sensibly related to the domains that contained them and had less association with items from different domains. The reliability of the scales was very good (Cronbach's alpha = 0.80) to outstanding (Cronbach's alpha = 0.92). CONCLUSIONS: Functionality was established for the rhinitis outcomes questionnaire (ROQ) for use in a private practice setting. This allows private practice allergists to collect reliable data with the ROQ.

Measuring and predicting surgeons' practice styles for breast cancer treatment in older women.

BACKGROUND: Few measures exist to assess physicians' practice style, and there are few data on physicians' practice styles and patterns of care. OBJECTIVES: To use clinical vignettes to measure surgeons' "propensity" for local treatments for early-stage breast cancer and to describe factors associated with propensity. RESEARCH DESIGN AND SUBJECTS: A cross-sectional mailed survey with telephone follow-up of a random sample of 1,000 surgeons treating Medicare beneficiaries in fee-for-service settings. MEASURES: Outcome measures include treatment propensity, self-reported practice, and actual treatment received by the surgeons' patients. RESULTS: Propensities were significantly associated with actual treatment, controlling for covariates. Area Medicare fees were the strongest predictor of propensity, followed by region, attitudes, volume, and gender. For instance, after other factors were considered, surgeons practicing in areas with the highest breast-conserving surgery (BCS) fees were 8.61 (95% CI 2.26-32.73) times more likely to have a BCS propensity than surgeons in areas with the lowest fees. Surgeons with the strongest beliefs in patient participation in treatment decisions were nearly 6 times (95% CI 1.67-20.84) more likely to have a BCS propensity than surgeons with the lowest such beliefs, controlling for covariates. Male surgeons were also independently more likely to have a mastectomy propensity than female surgeons. CONCLUSIONS: Surgeons' propensities explain some of the observed variations in breast cancer treatment patterns among older women. Standardized scenarios provide a practical method to measure practice style and could be used to evaluate physician contributions to shared decision making, practice patterns, costs and outcomes, and adherence to guidelines.

Imputing physical health status scores missing owing to mortality: results of a simulation comparing multiple techniques.

BACKGROUND: Having missing data complicates the statistical analysis of health-related quality-of-life (HRQOL) data and, depending on the extent and nature of missing data, can introduce significant bias in treatment comparisons. OBJECTIVE: We evaluated the bias associated with 4 different imputation methods for estimating physical health status (PHS) scores missing as a result of mortality. METHODS: A simulation study was conducted in which we systematically varied mortality rates from 0% to 30% and change in PHS scores from -20 to 20 on a 100-point scale for a 2-group clinical trial with follow-up over 18 months. The 4 imputation methods were last value carried forward (LVCF), arbitrary substitution (ARBSUB), empirical Bayes (BAYES), and within-subject modeling (WSMOD). Pseudo-root mean square residuals (RMSRs) and differences between true and estimated slopes were used to evaluate how well the imputation methods reproduced the true characteristics of the simulated population data. RESULTS: ARBSUB and BAYES methods have the smallest RMSRs compared with LVCF and WSMOD across all mortality rates. As the rate of missing data resulting from mortality increased, all imputation techniques deviated more from population data. The BAYES technique was best at reproducing group slopes in cases with differential mortality rates or when mortality rates exceeded 15%. WSMOD and LVCF significantly underestimated changes in PHS. CONCLUSIONS: The different imputation methods produced comparable results when there were few missing data. The BAYES approach most closely estimated true population differences and change in PHS regardless of missing data rates. These findings are limited to physical health and functioning measures.

A claims data approach to defining an episode of care.

OBJECTIVE: To utilize health services research techniques in developing an episode of care using an administrative data set. This method is demonstrated for an episodic clinical condition, migraine. DATA SOURCES: Medicaid administrative data set of 3,372 patients with a diagnosis of migraine (ICD-9-CM 346.0, 346.1) in the state of Pennsylvania between May 1990 and March 1992. STUDY DESIGN: The duration of a migraine episode was measured by assessing the magnitude of resource utilization and the proportion of patients with charges in the period after the index migraine as compared to the period before the index migraine. A confidence interval (CI) was developed around each measure using bootstrap techniques. DATA COLLECTION METHODS: All charge data were extracted daily for a 113-day observation period surrounding each index migraine in order to observe the duration of impact of a migraine diagnosis on resource utilization. PRINCIPAL FINDINGS: The lower limits of both the 95% and 99% CIs for the difference in charges are greater than 0 for three weeks. The lower limits of both CIs for the difference in the proportion of patients with charges are above 0 for six weeks. CONCLUSIONS: Our analysis demonstrates that a health services research framework can be used to define an episode of care for a chronic disease category such as migraine. This method can be used to evaluate episodes of care for clinical studies of limited or episodic conditions and to complement clinical expertise in developing time horizons for clinical trials.

Constructs of burden of illness in older patients with breast cancer: a comparison of measurement methods.

OBJECTIVE: The burden of illness can influence treatment decisions, but there are limited data comparing the performance of different illness burden measures. We assessed the correlations between five previously validated measures of illness burden and global health and physical function and evaluated how each measure correlates with breast cancer treatment patterns in older women. DATA SOURCE: A cohort of 718 women > 67 years with early-stage breast cancer formed the study group. STUDY DESIGN/DATA COLLECTION METHODS: The study made a cross-sectional comparison of illness burden measures (Charlson index, Index of Co-existent Diseases, cardiopulmonary burden of illness, patient-specific life expectancy, and disease counts) and physical function and self-rated global health status. Data were collected from records and patient interviews. PRINCIPAL FINDINGS: All of the measures were significantly correlated with each other and with physical function and self-rated health (p < .001). After controlling for age and stage, life expectancy had the largest effect on surgical treatment, followed by self-rated physical function and health; life expectancy was also independent of physical function. For instance, women with higher life expectancy and better self-rated physical function and health were more likely to receive breast conservation and radiation than sicker women. Women with higher physical functioning were more likely to receive adjuvant chemotherapy than women with lower functioning. CONCLUSIONS: Several measures of illness burden were associated with breast cancer therapy, but each measure accounted for only a small amount of variance in treatment patterns. Future work is needed to develop and validate measures of burden of illness that are feasible, comprehensive, and relevant for diverse clinical and health services objectives.

Patterns of breast carcinoma treatment in older women: patient preference and clinical and physical influences.

BACKGROUND: Older women have high rates of breast carcinoma, and there are substantial variations in the patterns of care for this population group. METHODS: The authors studied 718 breast carcinoma patients age 67 years and older who were diagnosed with localized disease between 1995 and 1997 from 29 hospitals in 5 regions. Data were collected from patients, charts, and surgeons. Logistic regression analysis was used to evaluate determinants of treatment. RESULTS: Women who were concerned about body image were 1.8 times more likely (95% confidence interval [95% CI], 1.1-2.8) to receive breast conservation surgery and radiotherapy than women without this preference, controlling for other factors. In contrast, women who preferred receiving no therapy beyond surgery were 3.9 times more likely (95% CI, 2.9-6.1) to undergo mastectomy than other women, after considering other factors. Radiotherapy was omitted after breast conservation 3.4 times more often (95% CI, 2.0-5.6) among women age 80 years and older than among women ages 67-79 years, controlling for covariates. Black women tended to have radiotherapy omitted after breast conservation surgery 2.0 times more often (95% CI, 0.9-4.4) than white women (P = 0.09). Women age 80 years and older also were 70% less likely (odds ratio = 0.3; 95% CI, 0.1-0.8) to receive chemotherapy than women ages 67-79 years, controlling for health, functional status, and other covariates. CONCLUSIONS: After considering other factors, patient preferences and age were found to be associated with breast carcinoma treatment patterns in older women. Further research and training are needed to provide care for the growing population of older women that is both clinically appropriate and consonant with a woman's preferences.

Probing the building blocks of eumelanins using scanning electron microscopy.

Scanning electron microscopy (SEM) is used to examine the structure of natural and synthetic melanins. Eumelanin from Sepia officinalis and synthetic eumelanin are found to be structurally dissimilar. The natural sample has a significant structural order with subunits that have a lateral dimension of approximately 15 nm. The synthetic samples, on the other hand, appear to be amorphous solids. These results lend support for the existence of fundamental structural units proposed from the analyses of wide-angle X-ray diffraction measurements and previous mass-spectrometry results. These findings also provide insight into the disparate photophysical behavior of Sepia and synthetic eumelanin.

Item responsiveness of a rhinitis and asthma symptom score during a pollen season.

Twenty-one asthma patients with allergic rhinitis completed a series of self-administered questionnaires (21-item symptom score for rhinosinusitis and asthma, bother scale, McMaster Asthma Quality of Life Questionnaire [MAQOL] and Euroqol) at 2-week intervals from August to November 1994. Relative responsiveness of the instruments was assessed in reference to the maximum and minimum average scores for MAQOL, with area under the curve (AUC) and correlation coefficients between the different instruments. Symptom score, MAQOL, and bother scale provided similar results for both extreme values and AUC, whereas Euroqol utilities were less responsive. These results suggest that the symptom scores and bother scales are responsive and valid, and might prove valuable in everyday practice, clinical trials, and quality assurance programs.