Determinants of glycaemic control in a practice setting: the role of weight loss and treatment adherence (The DELTA Study).

AIMS: Examine the association between weight loss and adherence with glycaemic goal attainment in patients with inadequately controlled T2DM. MATERIALS AND METHODS: Patients ≥ 18 years with T2DM from a US integrated health system starting a new class of diabetes medication between 11/1/10 and 4/30/11 (index date) with baseline HbA1c ≥ 7.0% were included in this cohort study. Target HbA1c and weight change were defined at 6-months as HbA1c < 7.0% and ≥ 3% loss in body weight. Patient-reported medication adherence was assessed per the Medication Adherence Reporting Scale. Structural equation modelling was used to describe simultaneous associations between adherence, weight loss and HbA1c goal attainment. RESULTS: Inclusion criteria were met by 477 patients; mean (SD) age 59.1 (11.6) years; 50.9% were female; 30.4% were treatment naïve; baseline HbA1c 8.6% (1.6); weight 102.0 kg (23.0). Most patients (67.9%) reported being adherent to the index diabetes medication. At 6 months mean weight change was -1.3 (5.1) kg (p = 0.39); 28.1% had weight loss of ≥ 3%. Mean HbA1c change was -1.2% (1.8) (p< 0.001); 42.8% attained HbA1c goal. Adherent patients (OR 1.70; p = 0.02) and diabetes therapies that lead to weight loss (metformin, GLP-1) were associated with weight loss ≥ 3% (OR 2.96; p< 0.001). Weight loss (OR 3.60; p < 0.001) and adherence (OR 1.59; p < 0.001) were associated with HbA1c goal attainment. CONCLUSIONS: Weight loss ≥ 3% and medication adherence were associated with HbA1c goal attainment in T2DM; weight loss was a stronger predictor of goal attainment than medication adherence in this study population. It is important to consider weight-effect properties, in addition to patient-centric adherence counselling, when prescribing diabetes therapy.

Implications of international law for the treatment of cancer: the Single Convention on Narcotic Drugs and the TRIPS Agreement.

The development, manufacture, trade and distribution of medicines all take place within a web of international legal obligations that states have accepted under a range of multilateral, plurilateral and bilateral agreements. International law can operate either to facilitate or hinder access, depending on how it is developed and implemented. This article examines two areas of international law that are relevant to cancer treatment: the international drug control system, which regulates opioid analgesics; and the World Trade Organization's Trade-Related Aspects of Intellectual Property Agreement. This article outlines recent developments in relation to both, including in the activities of the Vienna-based agencies that collectively oversee the implementation of the Single Convention on Narcotic Drugs, and in the negotiation of the recent United Nations General Assembly Political Declaration on Non-communicable Diseases. While underlining the importance of law, this article notes that battles over law should not distract from the importance of other essential efforts to enhance access to medicines within the context of the strengthening of health systems.

Survival of composite restorations after selective or total caries removal in primary teeth and predictors of failures: A 36-months randomized controlled trial.

OBJECTIVES: The aim of this study was to assess the survival of composite restorations after selective (SCR) or total caries removal (TCR) and determine predictors of failures after 36 months. METHODS: 120 teeth with deep occlusal or occlusal-proximal carious lesions were randomly divided into control (TCR; n = 54; 69% Class II) and test (SCR; n = 66; 63% Class II) groups. Clinical evaluation was applied using the USPHS criteria, and the presence of Charlie or Delta scores at the marginal integrity were considered as a failure. RESULTS: The overall survival rate of restorations was 68% after 36 months, 81% for TCR and 57% for SCR (p = 0.004). The multivariable Cox Regression model demonstrated that restorations performed after SCR had 3.44 times greater probability of failure compared to TCR (p = 0.006). The other two predictors for failure of restorations were teeth with Class II cavities (hazard ratio = 3.3) and children with gingival bleeding over 20% (hazard ratio = 2.5). CONCLUSIONS: Performing composite restorations after SCR in primary teeth had success rate significantly lower than restorations performed after TCR. Complex cavities and worst patient´s oral hygiene were found to be predictors of failure of restorations. CLINICAL SIGNIFICANCE: Although SCR has been demonstrating high rates of pulp preservation, clinicians should consider that composite restorations fail in a higher frequency compared to TCR in primary teeth and, in some circumstances, may be preferable in terms of restoration longevity.

How treatment priorities influence triptan preferences in clinical practice: perspectives of migraine sufferers, neurologists, and primary care physicians.

BACKGROUND: In treating migraine sufferers, physicians can choose from among seven triptans with different attributes. OBJECTIVE: To develop a system for selecting an oral triptan based on treatment priorities of migraine sufferers, neurologists, and primary care physicians (PCPs) in the United States, and evidence-based performance of triptans in clinical trials. METHODS: The TRIPSTAR project combines data on the treatment preferences of migraineurs and physicians with results from a meta-analysis of individual triptans, which evaluated their effectiveness on various clinical endpoints. Telephone interviews with migraine sufferers, neurol ogists, and PCPs were conducted to elicit individual views on the relative importance of a prespecified set of acute treatment outcomes. Four hundred and fifteen migraine sufferers, both triptan-experienced and triptan-naive, were interviewed. Also, 200 board-certified neurologists and 200 PCPs provided information on migraine patients from their clinical practice. A multiattribute decision model for selecting an oral triptan was constructed using attribute importance weights collected at telephone interview and the meta-analysis data, which were drawn from 53 clinical trials of 6 oral triptans. RESULTS: Efficacy attributes were rated significantly more important than tolerability or consistency in selecting an oral triptan, according to migraine sufferers and physicians. Freedom from cardiovascular adverse events was the most important tolerability attribute, according to migraine sufferers and physicians alike. Pain free at 1 h was the most important lower-level efficacy attribute for migraine sufferers, while sustained pain free was most important for physicians. When weighted treatment attributes were combined with meta-analysis data in a multi-attribute decision model, almotriptan 12.5 mg, eletriptan 80 mg, and rizatriptan 10 mg were significantly closer to the hypothetical ideal triptan than was suma triptan 100 mg. Triptans selected by the model were generally closer to the patient-specific ideal triptan than were the triptans prescribed by physicians. CONCLUSIONS: Almotriptan, eletriptan, and rizatriptan were the three triptans closest to the ideal, from the perspectives of migraine sufferers, PCPs, and neurologists alike. The TRIPSTAR model may be a potentially useful decision-support tool to help physicians select the triptan most likely to produce a successful outcome in migraine sufferers.

Ensuring smokers are adequately informed: reflections on consumer rights, manufacturer responsibilities, and policy implications.

The right to information is a fundamental consumer value. Following the advent of health warnings, the tobacco industry has repeatedly asserted that smokers are fully informed of the risks they take, while evidence demonstrates widespread superficial levels of awareness and understanding. There remains much that tobacco companies could do to fulfil their responsibilities to inform smokers. We explore issues involved in the meaning of "adequately informed" smoking and discuss some of the key policy and regulatory implications. We use the idea of a smoker licensing scheme-under which it would be illegal to sell to smokers who had not demonstrated an adequate level of awareness-as a device to explore some of these issues. We also explore some of the difficulties that addiction poses for the notion that smokers might ever voluntarily assume the risks of smoking.

Variation in migraine prevalence by race.

PURPOSE: Estimates of migraine prevalence from African and Asian populations are lower than those observed in European and North American populations. To determine if these international differences reflect differences in cultural, environmental, or genetic factors, we compared the prevalence of migraine among Caucasians, African Americans, and Asian Americans in the United States. If genetic factors predominate, racial differences should persist in the United States. METHODS: In Baltimore County, Maryland, 12,328 individuals 18 to 65 years of age were selected by random-digit dialing and interviewed by telephone about their headaches. Migraine diagnoses were assigned using International Headache Society criteria. RESULTS: In women, migraine prevalence was significantly higher in Caucasians (20.4%) than in African (16.2%) or Asian (9.2%) Americans. A similar pattern was observed among men (8.6%, 7.2%, and 4.2%). African Americans were less likely to report nausea or vomiting with their attacks, but more likely to report higher levels of headache pain. In contrast, African Americans tended to be less disabled by their attacks than Caucasians. There were no statistically significant differences in associated features between Asian American and Caucasian migraineurs. CONCLUSIONS: In the United States, migraine prevalence is highest in Caucasians, followed by African Americans and Asian Americans. While differences in socioeconomic status, diet, and symptom reporting may contribute to differences in estimated prevalence, we suggest that race-related differences in genetic vulnerability to migraine are more likely to predominate as an explanatory factor.

Longitudinal study of brainstem auditory evoked responses in 87 normal human subjects.

We evaluated the reproducibility of brainstem auditory evoked responses (BAERs) in 87 normal individuals in a longitudinal study by estimating the correlation coefficients and variability of the interpeak intervals and the V/I amplitude ratio between trials on the same day and between sessions spaced 2 years apart. The highest correlation coefficients occur for the I-V interpeak interval between trials on the same day. The coefficients for the I-III and III-V intervals are lower, due to the variability of wave III. The correlations between ears done on the same day are lower still and are similar to measures obtained from the same ear at a 2-year interval. BAERs are more variable than previously believed between ears and over time, but not in a manner that is clinically significant and can be used longitudinally as a measure of neurologic disease. Finally, we provide the sample size required to detect a significant change in interpeak intervals.

Migraine in the United States: epidemiology and patterns of health care use.

OBJECTIVE: To determine the prevalence and distribution of migraine in the United States as well as current patterns of health care use. METHODS: A random-digit-dial, computer-assisted telephone interview (CATI) survey was conducted in Philadelphia County, PA, in 1998. The CATI identifies individuals with migraine (categories 1.1 and 1.2) as defined by the diagnostic criteria of the International Headache Society with high sensitivity (85%) and specificity (96%). Interviews were completed in 4,376 subjects to identify 568 with migraine. Those with 6 or more attacks per year (n = 410) were invited to participate in a follow-up interview about health care utilization and family impact of migraine; 246 (60.0%) participated. RESULTS: The 1-year prevalence of migraine was 17.2% in females and 6.0% in males. Prevalence was highest between the ages of 30 and 49. Whereas 48% of migraine sufferers had seen a doctor for headache within the last year (current consulters), 31% had never done so in their lifetimes and 21% had not seen a doctor for headache for at least 1 year (lapsed consulters). Of current or lapsed consulters, 73% reported a physician-made diagnosis of migraine; treatments varied. Of all migraine sufferers, 49% were treated with over-the-counter medications only, 23% with prescription medication only, 23% with both, and 5% with no medications at all. CONCLUSION: Relative to prior cross-sectional surveys, epidemiologic profiles for migraine have remained stable in the United States over the last decade. Self-reported rates of current medical consultation have more than doubled. Moderate increases were seen in the percentage of migraine sufferers who use prescription medications and in the likelihood of receiving a physician diagnosis of migraine.

An international study to assess reliability of the Migraine Disability Assessment (MIDAS) score.

BACKGROUND: The Migraine Disability Assessment (MIDAS) instrument is a five-item questionnaire developed to measure headache-related disability and improve doctor-patient communication about the functional consequences of migraine. OBJECTIVES: To examine the test-retest reliability and internal consistency of the five items and of the overall MIDAS score in population-based samples of migraine sufferers in two countries and to compare consistency across countries. METHODS: Using a clinically validated telephone interview, population-based samples of migraine-headache sufferers were identified in the United States (Baltimore, MD) and the United Kingdom (Merton and Sutton, Surrey). Eligible individuals completed the MIDAS questionnaire on two occasions an average of 3 weeks apart. The MIDAS score is derived from five questions about missed time from work and household work (one question each about missed days and days with at least 50% reduced productivity) and missed days of nonwork activities. RESULTS: A total of 97 migraine-headache sufferers from the United States and 100 from the United Kingdom completed the MIDAS questionnaire twice. Mean and median item values and overall MIDAS scores were similar between the United States and the United Kingdom. Test-retest Spearman correlations of individual items ranged from 0.46 to 0.78. No significant differences in item-specific correlations were observed between the United States and United Kingdom. The test-retest Pearson correlation of the MIDAS score (i.e., sum of lost days and reduced-effectiveness days in each domain) was 0.80 in the United States and 0.83 in the United Kingdom. The Cronbach alpha, a measure of internal consistency, was 0.76 in the United States and 0.73 in the United Kingdom. CONCLUSIONS: This is the first international population-based study to assess the reliability of a disability-related illness severity score for migraine. The reliability and internal consistency of the Migraine Disability Assessment score are similar to that of a previous questionnaire (Headache Impact Questionnaire). However, the Migraine Disability Assessment score requires fewer questions, is easier to score, and provides intuitively meaningful information on lost days of activity in three domains.

Validity of an illness severity measure for headache in a population sample of migraine sufferers.

The headache impact questionnaire (HImQ) is used to measure pain and activity limitations from headache over a 3-month recall period. In a prior study, the test-retest reliability of the eight-item HImQ score was found to be relatively high (0.86). In the current study, we examined the validity of the eight-item HImQ by comparing the overall score and individual items to equivalent measures from a 90-day diary. Pain and activity limitations due to headache were assessed in a population-based sample of 132 migraine headache sufferers enrolled in a 90-day daily diary study who completed the HImQ at the end of the study. The HImQ score was derived from four frequency-based questions (i.e. number of headaches, missed days of work, missed days of chores, or missed days of non-work activity) and four summary measures of average experience across headaches (i.e. average pain intensity, and average reduced effectiveness when having a headache at work, during household chores, and in non-work activity). Diary based measures were used as the gold standard in evaluating the HImQ score. Mean and median values of frequency-based HImQ items (e.g. number of headaches) were similar to equivalent diary measures, indicating no systematic bias. In contrast, HImQ measures of average experience across attacks (e.g. average pain intensity) overestimated equivalent diary measures and, in general, better approximated diary measures for migraine headaches, rather than all headaches. The highest correlations between HImQ and diary items were observed for headache frequency and average pain intensity, the two general headache measures, followed by measures of reduced effectiveness. Among frequency-based measures, the strength of the correlation was directly related to the magnitude of the mean. The higher the mean value, the higher the correlation. The correlation between the HImQ score and diary based score was 0.49. The HImQ score is moderately valid. Frequency-based items (e.g. number of missed work days) were found to be unbiased and the highest correlation coefficients were observed for frequency-based items with relatively high mean counts (number of headaches, number of missed non-work days). These findings have implications for measuring severity of chronic episodic conditions like headache, asthma, back pain, arthritis, epilepsy, and panic disorder, which can cause limitations to activities. The validity of illness severity measures may be improved by using frequency-based questions to assess both missed activity days and days with significantly reduced effectiveness or productivity (e.g. by 50% or more). By combining the count for both missed days and days where productivity is substantially reduced, the mean of the frequency-based measure will be increased, a factor which may improve the overall validity of the item. A severity measure can be derived from such items by simple addition and provides a scale with intuitively meaningful units.

Physician consultation for headache pain and history of panic: results from a population-based study.

In a population-based telephone interview survey of 10,169 respondents aged 12-29 years in Washington County, Maryland, data were collected on history of panic attacks, on the most recent headache and associated symptoms in the 2 weeks before the interview, and on physician consultation for headache-related problems. Of those who had a headache in the previous 12 months, 14.2% of females and 5.8% of males consulted a physician for headache. The proportion who recently consulted a physician increased with age among females but not among males. An unexpectedly high proportion of those who recently sought physician care for their headache problem had a history of panic. In particular, among those who sought care, 15% of females and 12.8% of males ages 24-29 had a history of panic disorder. Overall, females with panic disorder who had recently seen a physician for headache exhibited the most frequent, severe, and complex headaches. In particular, headaches were of considerably longer duration, more severe, and greater than 50% of these females had five or more headaches in a 4-week period. A very high proportion experienced disability (up to 46.7%) from their headache. Males with a history of panic who did or did not seek physician care differed only in that a considerably higher proportion of the former group (up to 45%) had frequent headaches. Overall, 11.8% of the total population had a migraine headache in the 2 weeks before the interview. In contrast, 21.8% of those who sought physician care and 36% of those with panic disorder who sought physician care had a migraine headache.

Studies on thyroid and hypophysary thyrotrophic hormone (TSH) in Down syndrome.

Serum TSH was studied in 22 patients with Down syndrome, from 4 to 15 years old. In 6 of these patients radioidine uptake by thyroid gland after 2 and 24 hours of administration and clearance rates before and after TSH stimulus (10 mul-IM) were measured. Results show that serum TSH was normal in 17 patients and above normal limits in 5 patients. Thyroid uptake after 2 hours as well clearance rates, both below normal, had a response to TSH stimulus with normal or below values. These data along with previous reports, suggest, that in children with Down syndrome, there is a thyroid dysfunction in which a slow response no TSH stimulus seems to be the basic defect.

Change in psychoanalysis: epistemological aspects.

The paper addresses the objectives of therapeutic work, emphasising processes of change which move an 'inadequate' state towards another, more 'adequate' one. Different types of change are considered, and the factors necessary for detecting them. Following the mathematical model, we distinguish between continuous and discontinuous change. In social processes also there are continuous changes, where a transition occurs cumulatively and slowly. In another type of change a drastic modification is produced, implying discontinuity and a sudden jump. On this point it is necessary to distinguish between removable discontinuities having little significance, and essential ones which have significant effects. 'Levels of change' imply categorical or structural differences. We consider different forms of obstacle which get in the way of the adequate management of change: non-perception of change on the part of the therapist, epistemological inertia and therapeutic zeal. We address the location of change in the psychoanalytic process in relation to the patient-analyst couple.

Inside-of-the-Body test drawings performed by patients with neuromuscular diseases: a preliminary report.

Inside-of-the-Body test drawings were obtained from 50 individuals with various neuromuscular diseases. A mean of 18.0 +/- 5.1 body parts were identified in the drawings. Diseased body structures were emphasized by most patients; for example, thymus was only drawn by individuals with myasthenia gravis, while muscle was only identified by individuals with polymyositis. In contrast, drawings by individuals with neuropathic atrophy omitted the atrophic extremities.

Individual caspase-10 isoforms play distinct and opposing roles in the initiation of death receptor-mediated tumour cell apoptosis.

The cysteine protease caspase-8 is an essential executioner of the death receptor (DR) apoptotic pathway. The physiological function of its homologue caspase-10 remains poorly understood, and the ability of caspase-10 to substitute for caspase-8 in the DR apoptotic pathway is still controversial. Here, we analysed the particular contribution of caspase-10 isoforms to DR-mediated apoptosis in neuroblastoma (NB) cells characterised by their resistance to DR signalling. Silencing of caspase-8 in tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-sensitive NB cells resulted in complete resistance to TRAIL, which could be reverted by overexpression of caspase-10A or -10D. Overexpression experiments in various caspase-8-expressing tumour cells also demonstrated that caspase-10A and -10D isoforms strongly increased TRAIL and FasL sensitivity, whereas caspase-10B or -10G had no effect or were weakly anti-apoptotic. Further investigations revealed that the unique C-terminal end of caspase-10B was responsible for its degradation by the ubiquitin-proteasome pathway and for its lack of pro-apoptotic activity compared with caspase-10A and -10D. These data highlight in several tumour cell types, a differential pro- or anti-apoptotic role for the distinct caspase-10 isoforms in DR signalling, which may be relevant for fine tuning of apoptosis initiation.

T-cell responses in two unrelated hemophilia A inhibitor subjects include an epitope at the factor VIII R593C missense site.

BACKGROUND: Development of neutralizing anti-factor (F)VIII antibodies ('inhibitors') is a serious clinical problem in hemophilia A. Increased inhibitor risk has been associated with certain FVIII missense substitutions, including R593C in the A2 domain. OBJECTIVES: The aim of the present study was to identify T-cell epitopes in FVIII and characterize T-cell responses in two unrelated hemophilia A subjects sharing F8-R593C and HLA-DRB1*1101 genotypes. We hypothesized that the hemophilic substitution site coincides with an important T-cell epitope. PATIENTS/METHODS: The binding affinities of peptides for recombinant HLA-DR proteins were measured and compared with epitope prediction results. CD4+ T cells were stimulated using peptides and stained with fluorescent, peptide-loaded tetramers. RESULTS: The inhibitor subjects, but not HLA-matched controls, had high-avidity HLA-DRB1*1101-restricted T-cell responses against FVIII(589-608), which contains the hemophilic missense site. Antigen-specific T cells secreted Th1 and Th2 cytokines and proliferated in response to FVIII and FVIII(592-603). FVIII(589-608) bound with physiologically relevant (micromolar) IC(50) values to recombinant DR0101, DR1101 and DR1501 proteins. CONCLUSIONS: Hemophilia A patients with R593C missense substitutions and these HLA haplotypes had an increased incidence of inhibitors in our cohorts, supporting a paradigm in which presentation of FVIII epitopes containing the wild-type R593 influences inhibitor risk in this hemophilia A sub-population.

Familial risk of migraine: variation by proband age at onset and headache severity.

BACKGROUND: It is well established that migraine aggregates within families. Less is known about the influence of proband characteristics (e.g., age at onset, headache severity) on familial aggregation. OBJECTIVE: To examine the association between the proband's migraine severity and age at migraine onset and familial aggregation of migraine. METHODS: The authors investigated the migraine prevalence in first-degree relatives of 532 persons with migraine and control subjects in a population study. Familial aggregation was expressed as the risk of migraine in family members of probands divided by risk in control family members. RESULTS: The relative risk (RR) of migraine in first-degree relatives of migraine probands was elevated compared with family members of controls (RR = 1.88; 95% CI: 1.30 to 2.72). The RR was also significantly higher for relatives of probands reporting onset of migraine before age 16 (2.50; 95% CI: 1.65 to 3.79) compared with those with onset at age 16 or older (1.44; 95% CI: 0.93 to 2.23). Among probands with very severe average pain scores (i.e., 9 to 10 on a 0 to 10 scale), the RR of migraine in family members was 2.38 (95% CI: 1.56 to 3.62) compared with 1.52 (0.99 to 2.34) for less severe pain (p < 0.05). CONCLUSION: Early onset of migraine in the proband as well as the severity of migraines are associated with higher levels of family aggregation.

The shredding of BAT's defence: McCabe v British American Tobacco Australia.

On 11 April 2002, a Victorian supreme court jury ordered British American Tobacco Australia to pay Rolah McCabe $A700 000 in damages. Rolah McCabe is a 51 year old woman dying of lung cancer. She is the first smoker ever in Australia to obtain a damages verdict against the tobacco industry

Responsibilities of health care supervisors and employees: seven recommended tenets.

This article proposes seven tenets of responsibility for health care managers and the employees under their supervision. The damaging consequences of workplace misbehavior are chronicled, and the importance of establishing forthright supervisor/employee relationships is documented. Seven recommended tenets of responsibility are proposed as guideposts for managers and employees alike.