A qualitative investigation into the impact of hemophagocytic lymphohistiocytosis on children and their caregivers.

BACKGROUND: Primary hemophagocytic lymphohistiocytosis (pHLH) is a rare and life-threatening disorder, which usually occurs during infancy or early childhood and is characterized by abnormal activation of the immune system. However, the burden of pHLH on children and their families has not been previously evaluated. This qualitative study investigated the impact of pHLH and its treatment on the physical, emotional, and social well-being of patients and caregivers in the USA and UK using interviews to provide a comprehensive insight from the perspective of the caregivers and young survivors. RESULTS: Twenty-one caregivers were enrolled (median [range] age, 41.1 [26-58] years) and represented 20 patients, four from the UK and 16 from the USA. At enrollment, 17 of the 20 patients were alive with a median [range] age of 12.75 [5-31] years at a mean [range] of 7.8 [0.6-11.6] years after diagnosis. In addition, four adult survivors (median [range] age, 23.3 [21-30] years) were also enrolled (total participants n = 25). From noticing initial symptoms to receiving a diagnosis, caregivers reported a mean (range) of 25.9 (0-258) months. pHLH and its treatment had a substantial and long-lasting impact on patients and caregivers, affecting their physical, emotional and social well-being, family relationships, friendships, and ability to work and study. Many of the experiences reported were negative, even after curative treatment, and some participants experienced long-lasting physical and emotional issues. The most noticeable impact of pHLH for patients was on their physical well-being, whereas for caregivers it was emotional well-being. Across all participants there was a sense of isolation due to the illness and its treatment, particularly regarding the patient being immunocompromised and the fear of infection. Areas having a major impact and considered in need of improvement included: delays in diagnosis, lack of patient-specific information on pHLH and a lack of support and understanding about the condition. CONCLUSIONS: pHLH placed a substantial burden on patients and caregivers, which for some were long-lasting. This was compounded by the lack of awareness and understanding of pHLH by healthcare professionals, and a lack of accessible information for those affected by pHLH.

Equivalence of electronic and paper administration of patient-reported outcome measures: a systematic review and meta-analysis of studies conducted between 2007 and 2013.

OBJECTIVE: To conduct a systematic review and meta-analysis of the equivalence between electronic and paper administration of patient reported outcome measures (PROMs) in studies conducted subsequent to those included in Gwaltney et al's 2008 review. METHODS: A systematic literature review of PROM equivalence studies conducted between 2007 and 2013 identified 1,997 records from which 72 studies met pre-defined inclusion/exclusion criteria. PRO data from each study were extracted, in terms of both correlation coefficients (ICCs, Spearman and Pearson correlations, Kappa statistics) and mean differences (standardized by the standard deviation, SD, and the response scale range). Pooled estimates of correlation and mean difference were estimated. The modifying effects of mode of administration, year of publication, study design, time interval between administrations, mean age of participants and publication type were examined. RESULTS: Four hundred thirty-five individual correlations were extracted, these correlations being highly variable (I2 = 93.8) but showing generally good equivalence, with ICCs ranging from 0.65 to 0.99 and the pooled correlation coefficient being 0.88 (95% CI 0.87 to 0.88). Standardised mean differences for 307 studies were small and less variable (I2 = 33.5) with a pooled standardised mean difference of 0.037 (95% CI 0.031 to 0.042). Average administration mode/platform-specific correlations from 56 studies (61 estimates) had a pooled estimate of 0.88 (95% CI 0.86 to 0.90) and were still highly variable (I2 = 92.1). Similarly, average platform-specific ICCs from 39 studies (42 estimates) had a pooled estimate of 0.90 (95% CI 0.88 to 0.92) with an I2 of 91.5. After excluding 20 studies with outlying correlation coefficients (≥3SD from the mean), the I2 was 54.4, with the equivalence still high, the overall pooled correlation coefficient being 0.88 (95% CI 0.87 to 0.88). Agreement was found to be greater in more recent studies (p < 0.001), in randomized studies compared with non-randomised studies (p < 0.001), in studies with a shorter interval (<1 day) (p < 0.001), and in respondents of mean age 28 to 55 compared with those either younger or older (p < 0.001). In terms of mode/platform, paper vs Interactive Voice Response System (IVRS) comparisons had the lowest pooled agreement and paper vs tablet/touch screen the highest (p < 0.001). CONCLUSION: The present study supports the conclusion of Gwaltney's previous meta-analysis showing that PROMs administered on paper are quantitatively comparable with measures administered on an electronic device. It also confirms the ISPOR Taskforce´s conclusion that quantitative equivalence studies are not required for migrations with minor change only. This finding should be reassuring to investigators, regulators and sponsors using questionnaires on electronic devicesafter migration using best practices. Although there is data indicating that migrations with moderate changes produce equivalent instrument versions, hence do not require quantitative equivalence studies, additional work is necessary to establish this. Furthermore, there is the need to standardize migration practices and reporting practices (i.e. include copies of tested instrument versions and screenshots) so that clear recommendations regarding equivalence testing can be made in the future.raising questions about the necessity of conducting equivalence testing moving forward.

Psychometric evaluation of the Sinonasal Outcome Test-16 and activity impairment assessment in acute bacterial sinusitis.

OBJECTIVE: To validate the Sinonasal Outcome Test-16 and Activity Impairment Assessment in patients with acute bacterial sinusitis. STUDY DESIGN: Data were used from a phase III clinical trial designed to evaluate the efficacy and safety of moxifloxacin 400 mg once daily for 5 consecutive days in the treatment of acute bacterial sinusitis. The psychometric properties and factor structure of the 2 measures were assessed. SETTING: Participants were given the measures to self-complete using either a telephone voice response system or a paper-and-pencil format. SUBJECTS AND METHODS: Three hundred seventy-four patients with acute bacterial sinusitis were used in the analysis. Patients received either a placebo or 400 mg moxifloxacin once daily. Patients were then reviewed at test of cure and follow-up. All analyses were conducted on a combined sample of placebo and active treatment patients. RESULTS: The Sinonasal Outcome Test-16 was associated with minimal missing data at baseline but a higher proportion by test of cure. There was no evidence of floor or ceiling effects and no significant skew. The Activity Impairment Assessment also had low missing data at baseline and no obvious floor or ceiling effects, but the data were not normally distributed. Both measures had good internal consistency. Convergent and divergent validity as well as sensitivity and the minimally important difference are also reported. CONCLUSION: The measures both have good psychometric properties and are suitable for use with patients with acute bacterial sinusitis. Both instruments are sensitive. The minimal important difference estimates for the Sinonasal Outcome Test-16 are quite high but are similar to estimates reported previously.

Patient Reported Outcome (PRO) assessment in epilepsy: a review of epilepsy-specific PROs according to the Food and Drug Administration (FDA) regulatory requirements.

Despite collection of patient reported outcome (PRO) data in clinical trials of antiepileptic drugs (AEDs), PRO results are not being routinely reported on European Medicines Agency (EMA) and Food and Drug Administration (FDA) product labels. This review aimed to evaluate epilepsy-specific PRO instruments against FDA regulatory standards for supporting label claims. Structured literature searches were conducted in Embase and Medline databases to identify epilepsy-specific PRO instruments. Only instruments that could potentially be impacted by pharmacological treatment, were completed by adults and had evidence of some validation work were selected for review. A total of 26 PROs were reviewed based on criteria developed from the FDA regulatory standards. The ability to meet these criteria was classified as either full, partial or no evidence, whereby partial reflected some evidence but not enough to comprehensively address the FDA regulatory standards. Most instruments provided partial evidence of content validity. Input from clinicians and literature was common although few involved patients in both item generation and cognitive debriefing. Construct validity was predominantly compromised by no evidence of a-priori hypotheses of expected relationships. Evidence for test-retest reliability and internal consistency was available for most PROs although few included complete results regarding all subscales and some failed to reach recommended thresholds. The ability to detect change and interpretation of change were not investigated in most instruments and no PROs had published evidence of a conceptual framework. The study concludes that none of the 26 have the full evidence required by the FDA to support a label claim, and all require further research to support their use as an endpoint. The Subjective Handicap of Epilepsy (SHE) and the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) have the fewest gaps that would need to be addressed through additional research prior to any FDA regulatory submission, although the NDDI-E was designed as a screening tool and is therefore unlikely to be suitable as an instrument for capturing change in a clinical trial and the SHE lacks the conceptual focus on signs and symptoms favoured by the FDA.

The translation and cultural adaptation of the Child Behavior Checklist for use in Israel (Hebrew), Korea, the US (Spanish), India (Malayalam and Kannada), and Spain.

BACKGROUND: The Child Behavior Checklist (CBCL) is a caregiver rating scale for assessing the behavioral profile of children. It was developed in the US, and has been extensively translated and used in a large number of studies internationally. OBJECTIVE: The objective of this study was to translate the CBCL into six languages using a rigorous translation methodology, placing particular emphasis on cultural adaptation and ensuring that the measure has content validity with carers of children with epilepsy. METHODS: A rigorous translation and cultural adaptation methodology was used. This is a process which includes two forward translations, reconciliation, two back-translations, and cognitive debriefing interviews with five carers of children with epilepsy in each country. In addition, a series of open-ended questions were asked of the carers in order to provide evidence of content validity. RESULTS: A number of cultural adaptations were made during the translation process. This included adaptations to the examples of sports and hobbies. An addition of "milk delivery" was made to the job examples in the Malayalam translation. In addition, two sexual problem items were removed from the Hebrew translation for Israel. CONCLUSION: An additional six translations of the CBCL are now available for use in multinational studies. These translations have evidence of content validity for use with parents of children with epilepsy and have been appropriately culturally adapted so that they are acceptable for use in the target countries. The study highlights the importance of a rigorous translation process and the process of cultural adaptation.

How do children and their caregivers perceive the benefits of inhaled asthma therapy?

OBJECTIVE: Although well reported in adults, there is relatively little data on how children with asthma and their parents describe their attitudes to the disease, expectations of therapy, and perception of treatment benefit. We investigated this to determine if they differed from reports by adults with asthma. METHODS: We recruited families with an asthmatic child (4-11 years) who had recently been prescribed a change in treatment [starting inhaled corticosteroid monotherapy (ICS) or changing from ICS to inhaled corticosteroid/long-acting ß(2)-agonist combination therapy (ICS/LABA)]. Semi-structured interviews were conducted with the parents and the children if aged 7-11 years. RESULTS: We interviewed 28 parents and 13 children. All children on ICS/LABA had been changed from ICS monotherapy because of poor asthma control. Pediatric asthma had a significant impact on the whole family and both parents and children hoped the new medication would improve symptoms, increase their participation in physical activities, and decrease unscheduled visits to the GP (General Practitioner)/hospital. Positive effects of treatment change were reported by both parents and children, particularly in those changing from ICS to ICS/LABA. The most commonly reported benefits were reduced cough and wheeze, increased participation in sport or play activities, and reduced rescue medication use. These effects resulted in fewer visits to the GP/hospital and better attendance at school. CONCLUSIONS: While asthma symptoms prevent adults and children from participating in different types of activities (e.g., school, employment), children and their parents report the same benefits as previously reported in adults with asthma.

Assessing and demonstrating data saturation in qualitative inquiry supporting patient-reported outcomes research.

In the patient-reported outcomes (PROs) field, strict regulatory requirements must be met for qualitative research that contributes to labeling claims for medicinal products. These requirements not only emphasize the importance of reaching saturation but also of providing documentary evidence that saturation has been reached. This paper reviews qualitative literature for useful definitions of the concept and for practical approaches for assessing saturation. The paper considers approaches in light of the rigorous regulatory requirements for PRO research that are used to support labeling claims for medicinal products and the wider requirements for flexibility and creativity in qualitative research in general. This assessment is facilitated by the use of examples from our past qualitative PRO studies. Based on conclusions from this assessment, we offer preliminary recommendations for future qualitative PRO studies for assessing and documenting saturation.

Lennox-Gastaut syndrome (LGS): development of conceptual models of health-related quality of life (HRQL) for caregivers and children.

LGS is a severe form of childhood epilepsy which is characterized by multiple seizures and cognitive impairment. Semi-structured interviews were conducted with 40 parents of children with LGS in the US, UK, and Italy. Parents were asked to report on their perceptions of the HRQL of their child and also to describe the impact on their own HRQL. Thematic analysis was conducted to develop themes relating to the impact on HRQL. The themes were organized into conceptual models of the impact of LGS on the HRQL of the parent and the child. The models demonstrate the complex relationships between the components of LGS and their impact on HRQL.

Reimbursement agency requirements for health related quality-of-life data: a case study.

A review was undertaken to identify relevant and appropriate heath-utility estimates for patients with atrial fibrillation who had stroke and to appraise them against the published requirements for several countries' Health Technology Assessment agencies: Australia (Pharmaceutical Benefits Advisory Committee), Canada (Common Drug Review), England and Wales (NICE), Germany (Institut für Qualität und Wirtschaftlichkeit im Gesundheitswesen), Scotland (Scottish Medicines Consortium) and Sweden (Tandvårds-och läkemedelsförmånsverket). National agencies have created guidelines to support economic evaluations for their own countries but these guidelines differ. It may be more appropriate for agencies to be concerned primarily with the methodological quality of studies that report utilities rather than identifying local values. As such, we recommend some steps that could be considered when assessing the quality of utility studies in a systematic review or meta-analysis. These steps include considering the methods of utility estimation, model needs, generalizability, sample size and the use of large databases. This may, thus, facilitate consistent and rational Health Technology Assessment decision making.

Patient perspectives on taking vitamin K antagonists: a qualitative study in the UK, USA and Spain.

AIM: Limitations of vitamin K antagonists (VKAs) include frequent monitoring, dietary restrictions and drug interactions. This study conducted an indepth exploration of perspectives of VKA therapy in respondents with atrial fibrillation or venous thromboembolism. METHODS: A total of 60 respondents, recruited from the UK, USA and Spain, were interviewed on their experiences and views of VKA therapy. Thematic analysis was conducted on the data. RESULTS: Although there were some differences between the countries and some small differences between atrial fibrillation and venous thromboembolism respondents, many respondents found various aspects of VKA to be burdensome, including the international normalized ratio monitoring and dietary considerations. CONCLUSION: Atrial fibrillation and venous thromboembolism respondents accept the limitations of VKAs and the adjustments to their lifestyles, but recognize a lack of alternative treatment.

Impact of Lennox-Gastaut Syndrome (LGS) on health-related quality of life (HRQL) of patients and caregivers: literature review.

The aim of this study was to conduct a review of the literature to evaluate the impact of LGS on the HRQL of children with LGS and their caregivers. The literature search revealed that there is limited published research on the impact of LGS on the HRQL of the child or caregiver. LGS has a major physical impact on a child, with a high frequency of seizures, and a high rate of seizure-related injuries. It interferes with all aspects of the child's intellectual and social development. The patient, and also his/her entire family are affected. Caring for a child with LGS is described as a 'burden', with increased anxiety about injury from seizures as well as the strain associated with providing continuous care. Overall, there is a lack of research on LGS, specifically the extent of the impact of LGS on the HRQL of the child and caregiver is under-explored.

Reliability, validity and ability to detect change of the clinician-rated Personal and Social Performance scale in patients with acute symptoms of schizophrenia.

OBJECTIVE: To describe the measurement properties of the Personal and Social Performance scale (PSP), a clinician-reported measure of severity of personal and social dysfunction, in subjects with acute symptoms of schizophrenia. METHODS: Pooled data from three paliperidone extended-release clinical studies (n = 1665) and data from a separate noninterventional, cross-sectional, validation study (n = 299) were analyzed. RESULTS: The PSP showed good interrater (intraclass correlation coefficient [ICC] = 0.87) and test-retest (ICCs > 0.90) reliability. Pearson correlation coefficient for association between baseline PSP and Positive and Negative Syndrome Scale (PANSS) total scores was -0.32 for subjects assessed by the same rater and -0.29 for subjects assessed by different raters, suggesting low overlap in measurement constructs between the PANSS and PSP. Spearman Rank correlation coefficient for association between baseline PSP and Clinical Global Impression-Severity (CGI-S) scores was -0.51 with the same rater and -0.15 with different raters. Hypothesized relationships between the PSP and the PANSS or CGI-S based on levels of disease severity were prospectively defined. These hypotheses were confirmed by analyses showing statistically significant differences between baseline mean PSP scores in subjects grouped by severity rating on the CGI-S (mild or less vs. at least moderate) (p < 0.001) and the PANSS ('low symptom severity' vs. 'high symptom severity') (p = 0.005). The PSP was sensitive to change based on statistically significant correlations between change in the PSP and change in the CGI-S (p < 0.001) and the PANSS (p < 0.001). Limitations of analyses include pooling data across studies, interrater reliability assessment in the validation study only, post hoc assessment of test-retest reliability in the paliperidone ER studies, different raters for the PSP and PANSS not specified in the paliperidone ER studies, PSP validity assessment based on the PANSS and the CGI-S as comparators rather than another social function instrument. CONCLUSION: These initial reliability and validity assessments suggest the PSP has promise as a measure of social functioning in patients with acute symptoms of schizophrenia.

Multinational trials-recommendations on the translations required, approaches to using the same language in different countries, and the approaches to support pooling the data: the ISPOR Patient-Reported Outcomes Translation and Linguistic Validation Good Research Practices Task Force report.

OBJECTIVES: With the internationalization of clinical trial programs, there is an increased need to translate and culturally adapt patient-reported outcome (PRO) measures. Although guidelines for good practices in translation and linguistic validation are available, the ISPOR Patient-Reported Outcomes Translation and Linguistic Validation Task Force identified a number of areas where they felt that further discussion around methods and best practices would be beneficial. The areas identified by the team were as follows: 1) the selection of the languages required for multinational trials; 2) the approaches suggested when the same language is required across two or more countries; and 3) the assessment of measurement equivalence to support the aggregation of data from different countries. METHODS: The task force addressed these three areas, reviewed the available literature, and had multiple discussions to develop this report. RESULTS: Decision aid tools have also been developed and presented for the selection of languages and the approaches suggested for the use of the same language in different countries. CONCLUSION: It is hoped that this report and the decision tools proposed will assist those involved with multinational trials to 1) decide on the translations required for each country; 2) choose the approach to use when the same language is spoken in more than one country; and 3) choose methods to gather evidence to support the pooling of data collected using different language versions of the same tool.

Impact of schizophrenia and schizophrenia treatment-related adverse events on quality of life: direct utility elicitation.

OBJECTIVE: To examine the impact of schizophrenia, its treatment and treatment-related adverse events related to antipsychotics, on quality of life from the perspective of schizophrenia patients and laypersons. METHODS: Health state descriptions for stable schizophrenia, extra pyramidal symptoms (EPS), hyperprolactinemia, diabetes, weight gain and relapse were developed based on a review of the literature and expert opinion. The quality of life impact of each health state was elicited using a time trade-off instrument administered by interview to 49 stable schizophrenia patients and 75 laypersons. Regression techniques were employed to examine the importance of subject characteristics on health-related utility scores. RESULTS: Patients and laypersons completed the interview in similar times. Stable schizophrenia had the highest mean utility (0.87 and 0.92 for laypersons and patients respectively), while relapse (0.48 and 0.60) had the lowest mean utility. Of the treatment-related adverse events, EPS had the lowest mean utility (0.57 and 0.72, respectively). Age, gender and PANSS score did not influence the utility results independently of health state. On average, patient utilities are 0.077 points higher than utilities derived from laypersons, although the ranking was similar between the two groups. CONCLUSION: Events associated with schizophrenia and treatment of schizophrenia can bring about a significant detriment in patient quality of life, with relapse having the largest negative impact. Results indicate that patients with stable schizophrenia are less willing to trade years of life to avoid schizophrenia-related symptoms compared to laypersons. Both sets of respondents showed equal ability to complete the questionnaire.

Psychometric evaluation of the Satisfaction with Oral Anti-Diabetic Agent Scale (SOADAS).

In this study we developed and evaluated the psychometric properties of the Satisfaction with Oral Anti-Diabetic Agent Scale (SOADAS), the first treatment satisfaction instrument specific to oral anti-diabetic agents (OADs). Three focus groups and three rounds of cognitive debriefing interviews with type 2 diabetes patients using OADs informed the development of the six-item SOADAS. The measurement properties of the SOADAS were evaluated in a US cross-sectional study. Patients completed the SOADAS, Treatment Satisfaction for Medication Questionnaire (TSQM), the Short Form-12 (SF-12) Health Survey and a demographic questionnaire. The first half of the recruited patient population was asked to return at 7 days follow-up to complete the SOADAS again. An exploratory factor analysis on the SOADAS yielded a one-factor solution, indicating that the SOADAS was uni-dimensional. The SOADAS had high internal consistency reliability (Cronbach's alpha=0.86) and acceptable test-retest reliability (ICC=0.79). It was correlated most highly with the TSQM (r=0.71, p<0.001) and least with the mental summary component score of the SF-12 (r=0.24, p=0.014). Mean SOADAS scores were approximately two points higher for participants with lower HbA(1c) values (<7%) versus those with higher values, and for participants without versus with selected symptoms (p<0.05). The findings from this study suggest that the SOADAS is a valid and reliable measure of patient satisfaction with oral anti-diabetic medications. This questionnaire may be useful for assessing outcomes in future clinical studies of oral anti-diabetic medications.

Patient-reported treatment satisfaction measures for long-term anticoagulant therapy.

A comprehensive literature search identified seven instruments, of which three had psychometric data available. These were the 'Sawicki instrument', the Duke Anticoagulation Satisfaction Scale (DASS) and Deep Vein Thrombosis Quality of Life (DVTQoL). Sawicki assessed five domains with acceptable internal reliability. The six DVTQoL domains had good internal consistency, construct validity and reliability, although test-retest reliability and responsiveness have not been published. The DASS instrument covers three dimensions: limitations, burdens (i.e., negative impacts) and positive impacts. The burdens dimension correlated with short form-36 generic scales. The DASS had good internal consistency and item variability, and acceptable test-retest reliability and scale structure. DASS has the potential to help identify reasons for dissatisfaction and poor compliance across multiple models of care. Oral anticoagulation with vitamin K antagonists affects patients' quality of life, and is further complicated by variations in compliance and ability to self-manage anticoagulation. This paper reviews instruments designed specifically to assess treatment satisfaction in patients receiving oral anticoagulation.

The venous leg ulcer quality of life (VLU-QoL) questionnaire: development and psychometric validation.

To develop and validate a disease-specific quality of life (QoL) measure, based on the conceptual model of the SKINDEX-29 for patients with a chronic venous leg ulcer (VLU), in-depth interviews, and focus groups of patients (n=36) with VLU were used to generate VLU-specific items. These items were added to selected SKINDEX-29 items that were adapted for use in VLU. Further samples of VLU patients were used for item reduction (n=124) and to assess the psychometric properties of the new tool (n=120). The final VLU-QoL contained 34 items: 17 items adapted from the SKINDEX-29 and 17 VLU-specific items. Factor analysis of the items confirmed the existence of three hypothesized domains: Activities (12 items), Psychological (12 items), and Symptom Distress (10 items). Reliability in terms of internal consistency and test-retest reliability was found to be good. The measure was also found to be valid and responsive to clinical change. The VLU-QoL has good psychometric properties. The instrument's sensitivity to differences in clinical outcome and responsiveness to change in clinical parameters makes it a useful tool to assess the outcomes of treatment from the patients' perspective.

A critical review of the literature on fear of hypoglycemia in diabetes: Implications for diabetes management and patient education.

OBJECTIVE: In many individuals with diabetes, the unpleasant symptoms and negative consequences associated with hypoglycemia may result in significant anxiety or even a fear of hypoglycemia (FoH). This fear may have significant clinical implications for diabetes management. The aim of this review is to integrate existing research on FoH (its measurement, predictors, correlates, impact and treatment) and discuss its implications for diabetes management and patient education. METHODS: A literature search was conducted using Medline and Embase. The search was limited to journal articles published in English from 1985 to 2007 inclusive. Three hundred and one abstracts were reviewed and 273 were rejected on the basis of non-relevance. In addition to the 28 papers included, six additional papers were identified by further searches and were added to this review. RESULTS: FoH appears to be a widespread phenomenon. It is measured primarily through the use of a specific scale, the Hypoglycemic Fear Survey (HFS). There are a number of factors that relate to whether an individual is likely to develop FoH including whether there is a history of hypoglycemia in an individual, length of time since first insulin treatment, and a higher level of variability in blood glucose level. FoH has been linked to both state and trait anxiety although the relationship is complex. CONCLUSIONS: There is evidence that FoH may have a significant negative impact on diabetes management, metabolic control and subsequent health outcomes. There is evidence that blood glucose (BG) awareness training and CBT can reduce levels of fear and improve disease management. More research is needed on how FoH arises and the individual variables which predict its development. In addition, well designed research is required to better understand the behavioral and medical impact of FoH, and interventions to reduce it. PRACTICE IMPLICATIONS: There is some evidence to suggest that interventions including BG awareness training and cognitive behavioral therapy can reduce levels of fear and improve disease management. While many aspects of FoH require further well-designed research, it is evident that this phenomenon can have a major impact on diabetes management and needs to be specifically addressed in patient education programs.

A comparative review of health-related quality-of-life measures for use in HIV/AIDS clinical trials.

With the advent of highly active antiretroviral therapy (HAART), HIV-infected patients are living longer and are concerned not only with a treatment's ability to extend their life but also with the quality of the life they are able to lead. Regulatory authorities are also paying closer attention to the use of health-related quality-of-life (HR-QOL) measures in clinical trials and to the subsequent claims that are made based on the results. This paper reviews existing HR-QOL measures reported in the HIV/AIDS literature since 1990 and identifies those most worthy of consideration for use in future clinical trials.A comprehensive review following predefined selection criteria was conducted. Generic and HIV-targeted measures were assessed for content and practicality for the clinical trial setting. The generic measures were additionally reviewed for the ability to produce preference-based index scores and for the existence of normative general population data. Three generic and six HIV-targeted measures met these selection criteria and were then assessed more fully in terms of their development (HIV-targeted measures), psychometric properties and appropriateness for use in clinical trials.It was determined that each of the selected generic measures (i.e. Medical Outcomes Study [MOS] 36-Item Short Form Survey Instrument [SF-36], EQ-5D, Health Utilities Index [HUI]) could serve as a useful adjunct to an HIV-targeted measure in a trial. The Functional Assessment of HIV Infection (FAHI) and MOS-HIV health survey were deemed the two most appropriate HIV-targeted measures. Each of the measures can be self-administered in < or = 10 minutes and there was ample evidence of their excellent psychometric properties. However, they would not be optimal in all HIV-infected subgroups (e.g. treatment naive vs advanced; adolescents vs older adults) targeted for clinical trial interventions. Although there is no one best HR-QOL measure for use in HIV/AIDS clinical trials, based on our review criteria we identified three generic and two HIV-targeted candidate measures. However, these measures have their limitations and it is clear that greater consensus needs to develop regarding more effective and efficient approaches to HR-QOL measurement in HIV/AIDS clinical trials. Along with the increasingly complex HR-QOL measurement task resulting from changes in the HIV-infected population and shifts in the HR-QOL burden associated with HIV infection and its treatment over the past 25 years, it is increasingly important that HR-QOL outcomes become viable endpoints in HIV/AIDS clinical trials.

Validation of a patient-administered questionnaire to measure the severity and bothersomeness of lower urinary tract symptoms in uncomplicated urinary tract infection (UTI): the UTI Symptom Assessment questionnaire.

OBJECTIVE: To develop and validate a self-administered questionnaire to assess the 'severity' and 'bothersomeness' of the most frequently reported signs and symptoms of uncomplicated urinary tract infection (uUTI). SUBJECTS AND METHODS: The UTI Symptoms Assessment questionnaire (UTISA) is a 14-item instrument asking about the severity and bothersomeness of seven key uUTI symptoms. It was developed after comprehensive literature and data review and administration in draft form to a sample of 30 women with uUTI. The final questionnaire was completed by 276 women with uUTI who participated in a noncomparative clinical trial of ciprofloxacin. The women completed the questionnaire in electronic format at baseline (before the first dose of ciprofloxacin once-daily), at 3-h and 8-h intervals until all UTI symptoms were resolved, and at the test-of-cure visit. Baseline scores on the King's Health Questionnaire (KHQ) were used to assess convergent and divergent validity; responses to the Global Rating of Change (GRC) were used to assess both responsiveness and the 'minimally important difference'. Discriminant validity and responsiveness were assessed by comparing UTISA scores with a clinical evaluation of UTI symptoms performed by the investigator at baseline and at the test-of-cure visit. RESULTS: The UTISA was found to comprise three four-item domains named 'urination regularity', 'problems with urination', and 'pain associated with UTI'. Two questions asking about haematuria loaded on a fourth factor. The three domains were homogeneous (with high inter-item correlations) and internally consistent. Convergent validity was shown by high correlations between similar UTISA and KHQ domains (all r(s) > 0.40), and divergent validity by small correlations between unlike domains (all r(s) < 0.15). In general, the UTISA domains showed excellent discriminant validity, with scores on selected domains discriminating between women with different clinical evaluations. The responsiveness of the UTISA was also excellent, with high correlations between changes in domain scores and the clinical evaluation and GRC items. Symptom improvement was highest in the first 3 h, leading to greater responsiveness and minimally important difference during this period. However, the UTISA could detect even small subsequent changes. CONCLUSION: The three-domain UTISA has excellent psychometric properties and it is likely to prove an excellent tool for assessing uUTI outcome from a patient's perspective, both in research and clinical settings.