Recent studies have reported associations of sirtuin 1 (SIRT1) single nucleotide polymorphisms (SNPs) to both obesity and BMI. This study was designed to investigate association between SIRT1 SNPs, SIRT1 gene expression and obesity. Case-control analyses were performed using 1,533 obese subjects (896 adults, BMI >40 kg/m2 and 637 children, BMI >97th percentile for age and sex) and 1,237 nonobese controls, all French Caucasians. Two SNPs (in high linkage disequilibrium (LD), r2 = 0.96) were significantly associated with adult obesity, rs33957861 (P value = 0.003, odds ratio (OR) = 0.75, confidence interval (CI) = 0.61–0.92) and rs11599176 (P value: 0.006, OR = 0.74, CI = 0.61–0.90). Expression of SIRT1 mRNA was measured in BMI-discordant siblings from 154 Swedish families. Transcript expression was significantly correlated to BMI in the lean siblings (r2 = 0.13, P value = 3.36 × 10−7) and lower SIRT1 expression was associated with obesity (P value = 1.56 × 10−35). There was also an association between four SNPs (rs11599176, rs12413112, rs33957861, and rs35689145) and BMI (P values: 4 × 10−4, 6 × 10−4, 4 × 10−4, and 2 × 10−3) with the rare allele associated with a lower BMI. However, no SNP was associated with SIRT1 transcript expression level. In summary, both SNPs and SIRT1 gene expression are associated with severe obesity.
Among patients receiving methadone maintenance treatment (MMT) for opioid dependence, receipt of unobserved dosing privileges (take homes) and adequate doses (i.e. ≥ 80mg) are each associated with improved addiction treatment outcomes, but the association with acute care hospitalization is unknown. We studied whether take-home dosing and adequate doses (i.e. ≥ 80 mg) were associated with decreased hospital admission among patients in a MMT program.
We reviewed daily electronic medical records of patients enrolled in one MMT program to determine receipt of take home doses, methadone dose ≥ 80mg and hospital admission date. Non-linear mixed effects logistic regression models were used to evaluate whether take home doses or dose ≥ 80mg on a given day were associated with hospital admission on the subsequent day. Covariates in adjusted models included age, gender, race/ethnicity, HIV status, medical illness, mental illness, and polysubstance use at program admission.
Subjects (n=138) had the following characteristics: mean age 43 years; 52% female; 17% HIV-infected; 32% medical illness; 40% mental illness; and 52% polysubstance use. During a mean follow-up of 20 months, 42 patients (30%) accounted for 80 hospitalizations. Receipt of take homes was associated with significantly lower odds of a hospital admission (AOR 0.26; 95%CI: 0.11-0.62), whereas methadone dose ≥ 80mg was not (AOR 1.01; 95% CI: 0.56-1.83).
Among MMT patients, receipt of take homes, but not dose of methadone, was associated with decreased hospital admission. Take home status may reflect not only patients’ improved addiction outcomes, but also reduced healthcare utilization.
Methadone maintenance treatment; dose; take home status; hospital admission
Variable number tandem repeats (VNTRs) constitute a relatively under-examined class of genomic variants in the context of complex disease because of their sequence complexity and the challenges in assaying them. Recent large-scale genome-wide copy number variant mapping and association efforts have highlighted the need for improved methodology for association studies using these complex polymorphisms. Here we describe the in-depth investigation of a complex region on chromosome 8p21.2 encompassing the dedicator of cytokinesis 5 (DOCK5) gene. The region includes two VNTRs of complex sequence composition which flank a common 3975 bp deletion, all three of which were genotyped by polymerase chain reaction and fragment analysis in a total of 2744 subjects. We have developed a novel VNTR association method named VNTRtest, suitable for association analysis of multi-allelic loci with binary and quantitative outcomes, and have used this approach to show significant association of the DOCK5 VNTRs with childhood and adult severe obesity (Pempirical= 8.9 × 10−8 and P= 3.1 × 10−3, respectively) which we estimate explains ∼0.8% of the phenotypic variance. We also identified an independent association between the 3975 base pair (bp) deletion and obesity, explaining a further 0.46% of the variance (Pcombined= 1.6 × 10−3). Evidence for association between DOCK5 transcript levels and the 3975 bp deletion (P= 0.027) and both VNTRs (Pempirical= 0.015) was also identified in adipose tissue from a Swedish family sample, providing support for a functional effect of the DOCK5 deletion and VNTRs. These findings highlight the potential role of DOCK5 in human obesity and illustrate a novel approach for analysis of the contribution of VNTRs to disease susceptibility through association studies.
To evaluate systematically in real clinical settings whether functional genetic variations in drug metabolizing enzymes influence optimized doses, efficacy, and safety of antipsychotic medications.
DNA was collected from 750 patients with chronic schizophrenia treated with five antipsychotic drugs (olanzapine, quetiapine, risperidone, ziprasidone and perphenazine) as part of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study. Doses for each of the medicines were optimized to 1, 2, 3, or 4x units in identically-appearing capsules in a double blind design. We analyzed 25 known functional genetic variants in the major and minor metabolizing enzymes for each medication. These variants were tested for association with optimized dose and other relevant clinical outcomes.
None of the tested variants showed a nominally significant main effect in association with any of the tested phenotypes in European-Americans, African-Americans or all patients. Even after accounting for potential covariates no genetic variant was found to be associated with dosing, efficacy, overall tolerability, or tardive dyskinesia.
There are no strong associations between common functional genetic variants in drug metabolizing enzymes and dosing, safety or efficacy of leading antipsychotics, strongly suggesting merely modest effects on the use of these medicines in most patients in typical clinical settings.
Pharmacogenetics; CYP 450; Drug Metabolizing Enzymes; Antipsychotics; Personalized Medicine
Mobile technology has great potential to improve adherence and treatment outcomes in healthcare settings. However, text messaging and phone calls are unaffordable in many resource-limited areas. This study investigates the use of a no-cost alternative mobile phone technology using missed calls (‘buzzing’) to act as a patient reminder. The use of missed calls as a patient reminder was evaluated for feasibility and effectiveness as an appointment reminder in the follow-up of newly-diagnosed human immunodeficiency virus (HIV) positive patients in an HIV testing and counselling department in rural Swaziland.
This pilot study uses a before-and-after operational research study design, with all patients with mobile phones being offered the intervention. The primary outcome was the rate of attendance at the HIV testing and counselling department for collection of results in those with mobile phones before and after the introduction of the intervention.
Over two-thirds, 71.8% (459/639), of patients had a mobile phone. All patients with a mobile phone consented to being buzzed. There was no difference in attendance for follow-up at the clinic before and after the intervention was implemented (80.1% versus 83.3%, p = 0.401), or after adjusting for confounding factors (OR 1.13, p = 0.662).
This pilot study illustrates that mobile technology may be feasible in rural, resource-poor settings as there are high rates of mobile phone ownership and the intervention had a 100% uptake rate, with positive feedback from staff and patients. In this particular setting, the intervention did not improve attendance rates. However, further research is planned to investigate the impact on adherence to appointments and medications in other settings, such as HIV chronic care follow-up and as part of an enhanced package to improve adherence.
HIV infections; Mobile phone; Africa; Rural health; Text messaging; Buzzing; MHealth
Although behavioral deficits in bipolar disorder (BPD) are well described, the specific brain white matter (WM) disruptions have not been completely characterized, and neural mechanisms underlying dysfunction in BPD are not well established, particularly for youth with BPD and aggression. This preliminary study utilized diffusion tensor imaging (DTI) to investigate commissural tracts (corpus callosum [CC] and anterior commissure [AC]) in youth with BPD, because disruption of interhemispheric communication may contribute to the emotional deficits that are characteristic of the illness.
DTI was used to investigate WM in 10 youth (7–17 years of age) with BPD and 10 typically developing age-matched controls. Tract-based spatial statistics voxel-wise analysis was used to compare fractional anisotropy (FA) of the two groups. We specifically focused on five subdivisions of the midsagittal CC as well as on the decussation of AC, which connects the temporal lobes. Exploratory correlations between FA values and life history of aggression scores were calculated for the BPD group.
Youth with BPD had significantly lower FA values in the callosal genu and AC. FA values in the AC were negatively correlated with a life history of aggression in the BPD group.
These results contribute to a growing literature implicating a role for the genu of the CC in BPD and are the first to report WM variations in the AC of children with BPD. Taken together with the correlational data for aggression and the role of the AC in emotional processing, our data provide preliminary evidence for a possible association between the structural integrity of the WM of the AC and aggression in pediatric BPD.
Combining large-scale immunohistochemical analysis and proteomics data, 7340 gene products are identified in human adipocytes. Based on this data, a genome-scale metabolic model is reconstructed and used to integrate clinical and transcriptome data from lean and obese subjects.
We simulated the metabolic differences between the individuals with different body mass indexes (BMIs) using transcriptome and fluxome data.An increase in the metabolic activity around androsterone, ganglioside GM2 and degradation products of heparan sulfate and keratan sulfate, and a decrease in mitochondrial metabolic activities are found in obese subjects compared with lean subjects.We simulated the change in lipid droplet (LD) size and found that lean subjects have large dynamic changes in LD formation compared with obese subjects.Besides enabling patient stratification, our study allows the identification of novel therapeutic targets for obesity.
We evaluated the presence/absence of proteins encoded by 14 077 genes in adipocytes obtained from different tissue samples using immunohistochemistry. By combining this with previously published adipocyte-specific proteome data, we identified proteins associated with 7340 genes in human adipocytes. This information was used to reconstruct a comprehensive and functional genome-scale metabolic model of adipocyte metabolism. The resulting metabolic model, iAdipocytes1809, enables mechanistic insights into adipocyte metabolism on a genome-wide level, and can serve as a scaffold for integration of omics data to understand the genotype–phenotype relationship in obese subjects. By integrating human transcriptome and fluxome data, we found an increase in the metabolic activity around androsterone, ganglioside GM2 and degradation products of heparan sulfate and keratan sulfate, and a decrease in mitochondrial metabolic activities in obese subjects compared with lean subjects. Our study hereby shows a path to identify new therapeutic targets for treating obesity through combination of high throughput patient data and metabolic modeling.
adipocyte; flux balance analysis; genome-scale metabolic model; obesity; proteome
Alternating hemiplegia of childhood (AHC) is a rare, severe neurodevelopmental syndrome characterized by recurrent hemiplegic episodes and distinct neurologic manifestations. AHC is usually a sporadic disorder with unknown etiology. Using exome sequencing of seven patients with AHC, and their unaffected parents, we identified de novo nonsynonymous mutations in ATP1A3 in all seven AHC patients. Subsequent sequence analysis of ATP1A3 in 98 additional patients revealed that 78% of AHC cases have a likely causal ATP1A3 mutation, including one inherited mutation in a familial case of AHC. Remarkably, six ATP1A3 mutations explain the majority of patients, including one observed in 36 patients. Unlike ATP1A3 mutations that cause rapid-onset-dystonia-parkinsonism, AHC-causing mutations revealed consistent reductions in ATPase activity without effects on protein expression. This work identifies de novo ATP1A3 mutations as the primary cause of AHC, and offers insight into disease pathophysiology by expanding the spectrum of phenotypes associated with mutations in this gene.
In a novel knowledge translation initiative, the Government of Ontario’s Asthma Plan of Action funded the development of an Asthma Care Map to enable adherence with the Canadian Asthma Consensus Guidelines developed under the auspices of the Canadian Thoracic Society (CTS). Following its successful evaluation within the Primary Care Asthma Pilot Project, respiratory clinicians from the Asthma Research Unit, Queen’s University (Kingston, Ontario) are leading an initiative to incorporate standardized Asthma Care Map data elements into electronic health records in primary care in Ontario. Acknowledging that the issue of data standards affects all respiratory conditions, and all provinces and territories, the Government of Ontario approached the CTS Respiratory Guidelines Committee. At its meeting in September 2010, the CTS Respiratory Guidelines Committee agreed that developing and standardizing respiratory data elements for electronic health records are strategically important. In follow-up to that commitment, representatives from the CTS, the Lung Association, the Government of Ontario, the National Lung Health Framework and Canada Health Infoway came together to form a planning committee. The planning committee proposed a phased approach to inform stakeholders about the issue, and engage them in the development, implementation and evaluation of a standardized dataset. An environmental scan was completed in July 2011, which identified data definitions and standards currently available for clinical variables that are likely to be included in electronic medical records in primary care for diagnosis, management and patient education related to asthma and COPD. The scan, sponsored by the Government of Ontario, includes compliance with clinical nomenclatures such as SNOMED-CT® and LOINC®. To help launch and create momentum for this initiative, a national forum was convened on October 2 and 3, 2011, in Toronto, Ontario. The forum was designed to bring together key stakeholders across the spectrum of respiratory care, including clinicians, researchers, health informaticists and administrators to explore and recommend a potential scope, approach and governance structure for this important project. The Pan-Canadian REspiratory STandards INitiative for Electronic Health Records (PRESTINE) goal is to recommend respiratory data elements and standards for use in electronic medical records across Canada that meet the needs of providers, administrators, researchers and policy makers to facilitate evidence-based clinical care, monitoring, surveillance, benchmarking and policy development. The focus initially is expected to include asthma, chronic obstructive pulmonary disease and pulmonary function standards elements that are applicable to many respiratory conditions. The present article summarizes the process and findings of the forum deliberations.
Asthma; Clinical practice guidelines; Clinical variables; COPD; Data definitions; Electronic health records; Electronic medical records; Knowledge translation; Respiratory data sets; Surveillance
Public hospitals in China play an important role in tuberculosis (TB) control. Three models of hospital and TB control exist in China. The dispensary model is the most common one in which a TB dispensary provides both clinical and public health care. The specialist model is similar to the former except that a specialist TB hospital is located in the same area. The specialist hospital should treat only complicated TB cases but it also treats simple cases in practice. The integrated model is a new development to integrate TB service in public hospitals. Patients were diagnosed, treated and followed up in this public hospital in this model while the TB dispensary provides public health service as case reporting and mass education. This study aims to compare patient care seeking pathways under the three models, and to provide policy recommendation for the TB control system reform in China.
Six sites, two in each model, were selected across four provinces, with 293 newly treated uncomplicated TB patients being randomly selected.
The majority (68%) of TB patients were diagnosed in hospitals. Patients in the integrated model presented the simplest care seeking pathways, with the least number of providers visited (2.2), shortest treatment delays (2 days) and the least medical expenditure (2729RMB/401USD). On the contrary, patients in the specialist model had the highest number of provider visits (4), longest treatment delays (23 days) and the highest medical expenditure (11626RMB/1710USD). Logistic regression suggested that patients who were hospitalised tended to have longer treatment delays and higher medical expenditure.
Specialist hospital treating uncomplicated cases not using the standard regimens posed a threat to TB control. The integrated model has shortened patient treatment pathways, and reduced patient costs; therefore, it could be considered as the direction for future reform of China’s TB control system.
Tuberculosis; Care pathway; Hospital TB collaboration; China
It has recently been suggested that the low-frequency c.136–14_136–13insC variant in high-mobility group A1 (HMGA1) may strongly contribute to insulin resistance and type 2 diabetes risk. In our study, we attempted to confirm that HMGA1 is a novel type 2 diabetes locus in French Caucasians. The gene was sequenced in 368 type 2 diabetic case subjects with a family history of type 2 diabetes and 372 normoglycemic control subjects without a family history of type 2 diabetes. None of the 41 genetic variations identified were associated with type 2 diabetes. The lack of association between the c.136–14_136–13insC variant and type 2 diabetes was confirmed in an independent French group of 4,538 case subjects and 4,015 control subjects and in a large meta-analysis of 16,605 case subjects and 46,179 control subjects. Finally, this variant had no effects on metabolic traits and was not involved in variations of HMGA1 and insulin receptor (INSR) expressions. The c.136–14_136–13insC variant was not associated with type 2 diabetes in individuals of European descent. Our study emphasizes the need to analyze a large number of subjects to reliably assess the association of low-frequency variants with the disease.
Background and Aims
Current cardiovascular disease (CVD) prevention is based on diagnosis and treatment of specific disease. Little is known for high risk people with CVD at the community level. In rural China, health records of all residents were established after the recent health reforms. This study aims to describe the characters of the rural population with high CVD risk regarding their clinical indicators, disease patterns, drug treatment and adherence.
Methods and Results
17042 (87%) of all the 19500 rural residents in the two townships had valid health records in 2009. We employed a validated tool, the Asian Equation, to screen 8182 (48%) resident health records of those aged between 40–75 years in 2010. Those who were identified with a CVD risk of 20% or higher were selected for a face-to-face questionnaire survey regarding their diagnosed disease and drug treatment. 453 individuals were identified as high risk of CVD, with an average age of 53 years, 62% males, 50% smoking rate and average systolic blood pressure of 161 mmHg. 386 (85%) participated in the survey, while 294 (76%) were diagnosed with and 88 (23%) were suspects of CVD, hypertension, diabetes or hyperlipidaemia. 75 (19%) took drug regularly and 125 (32%) either stopped treatment or missed drugs. The most often used drugs were calcium channel blockers (20%). Only 2% used aspirins and 0.8% used statins. The median costs of drugs were 17 RMB (USD2.66) per month.
The majority of the high risk population in our setting of rural China had already been diagnosed with a CVD related disease, but very few took any drugs, and less still took highly effective drugs to prevent CVD. A holistic strategy focused on population with high risk CVD and based on the current China public health reform is suggested in the context of primary care.
Cardiovascular disease (CVD) is the leading cause of global mortality. Risk factor management in clinical practice often relies on relative risk modification rather than the more appropriate absolute risk assessment.
To determine whether patients receiving more-frequently designated GP visits had increased benefit in terms of their absolute CVD risk assessment, as compared with patients in receipt of their usual GP care.
Design and setting
Prospective, open, pragmatic block randomised study in a 1:1 group allocation ratio in three Western Australian general practices.
A convenience sample (n = 1200) of patients aged 40–80 years were randomised to 3-monthly GP visits (five in total for the intensive) or usual GP care (two in total for the opportunistic), with 12 months’ follow-up. The main outcome was absolute CVD risk scores based on the New Zealand Cardiovascular Risk Calculator. Others outcome measures were weight, height, waist circumference, blood pressure, and fasting blood lipids and glucose.
There were 600 patients per group at baseline. At 12 months’ analysis there were 543 in the intensive group and 569 in the opportunistic group. Mean (standard deviation [SD]) absolute CVD risk reduced significantly between baseline and 12 months in the intensive group (6.28% [5.11] to 6.10% [4.94]) but not in the opportunistic group (6.27% [5.10] to 6.24% [5.38]). There was a significant reduction between baseline and 12 months in mean (SD) total cholesterol (5.28 mmol/l [0.94] to 5.08 mmol/l [0.96]); low-density lipoprotein cholesterol (3.08 mmol/l [0.87] to 2.95 mmol/l [0.89]); triglyceride (1.45 mmol/l [0.86] to 1.36 mmol/l [0.84]); and in mean (SD) waist circumference in men (98.74 cm [10.70] to 97.13 cm [10.20]) and females (90.64 cm [14.62] to 88.96 cm [14.00]) in the intensive group.
A targeted approach using absolute risk calculators can be used in primary care to modify global CVD risk assessment.
cardiovascular diseases; general practice; general practitioners; primary care; primary prevention; risk factors
This article presents an update on addiction-related medical literature for the calendar years 2010 and 2011, focusing on studies that have implications for generalist practice. We present articles pertaining to medical comorbidities and complications, prescription drug misuse among patients with chronic pain, screening and brief interventions (SBIs), and pharmacotherapy for addiction.
Primary care; Alcoholism; Addictive behavior; Drug abuse; Substance-related disorders; Screening and brief intervention
The impact of the human immunodeficiency virus (HIV) on tuberculosis (TB), and the implications for TB and HIV control, is a public health challenge in Ghana – almost a quarter (23%) of all TB cases were HIV positive in 2010. The integration of TB/HIV services has therefore emerged as an essential component of the national response to TB and HIV. The aim is to reduce fragmentation, improve access, enhance efficiency and improve quality of care. Ghana’s TB/HIV policy comprises three linked sets of activities: effective implementation of the Stop TB Strategy for TB control, improved HIV prevention and care, and the implementation of additional TB/HIV activities. Different models of service delivery with increasing integration of TB/HIV activities are expected to provide greater access to more comprehensive care. The objective of this paper is to assess the impact of TB/HIV integration on TB treatment outcomes and to explore the usefulness of TB treatment outcomes as TB/HIV indicators.
A before-and-after study to observe the introduction of TB/HIV activities into TB programmes in three hospitals with different levels of integration was conducted. Anonymised patient data was collated from TB registers from each facility, and analysed to determine if TB treatment outcomes changed significantly after integration.
TB treatment success was 50% (95% CI 49 – 52) prior to, and 69% (95% CI 65 – 73) after, integration (Χ2 43.96, p < 0.00). Treatment success increased from 43% to 53% at the one-stop shop (OSS), from 69% to 78% at the partially integrated site (PIS) and substantially from 46% to 78% at the referral site (RS) (Χ2 64.54; p<0.01). Defaults and cases transferred out reduced from 14.3% and 15.3% prior to integration, to 1.4% and 9.0% after integration, respectively, accounting for a significant increase in treatment success. Death rates remained high at 18% in all cases studied and 25% in HIV-associated cases after integration.
TB/HIV integration may improve TB treatment success, but its exact impact is difficult to ascertain due to non-specificity and design limitations. TB mortality may be more useful as an indicator for monitoring TB/HIV activities in Ghana.
Tuberculosis; HIV; Integration; Indicator; Treatment outcome; Referral; Partial integration; One-stop shop
According to recent theoretical accounts of place of articulation perception, global, invariant properties of the stop CV syllable onset spectrum serve as primary, innate cues to place of articulation, whereas contextually variable formant transitions constitute secondary, learned cues. By this view, one might expect that young infants would find the discrimination of place of articulation contrasts signaled by formant transition differences more difficult than those cued by gross spectral differences. Using an operant head-turning paradigm, we found that 6-month-old infants were able to discriminate two-formant stimuli contrasting in place of articulation as well as they did five-formant + burst stimuli. Apparently, neither the global properties of the onset spectrum nor simply the additional acoustic information contained in the five-formant + burst stimuli afford the infant any advantage in the discrimination task. Rather, formant transition information provides a sufficient basis for discriminating place of articulation differences.
A great deal of research has focused on the perception of voice onset time (VOT) differences in stop consonants. Yet, the nature of the mechanisms responsible for the perception of these differences is still the subject of much debate. Recently Pisoni [J. Acoust. Soc. Am. 61, 1352–1361 (1977)] has presented evidence which suggested that the perception of VOT differences by adult listeners may reflect a basic limitation on processing temporal order information by the auditory system. For adults, stimuli with onset differences approximately greater than 20 ms are perceived as successive events (either leading or lagging), while stimuli with onset differences less than about 20 ms are perceived as simultaneous events. Thus, differences in voicing may have an underlying perceptual basis in terms of three well-defined temporal attributes corresponding to leading, lagging, or simultaneous events at onset. The present experiment was carried out to determine whether young infants can discriminate differences in temporal order information in nonspeech signals and whether their discrimination performance parallels the earlier data obtained with adults. Discrimination was measured with the high-amplitude sucking (HAS) procedure. The results indicated that infants can discriminate differences in the relative onset of two events; the pattern of discrimination also suggested the presence of three perceptual categories along this temporal continuum although the precise alignment of these categories differed somewhat from the values found in the earlier study with adults.
Financial issues are major barriers for rural-to-urban migrants accessing tuberculosis (TB) care in China. This paper discusses the effectiveness of providing financial incentives to migrant TB patients (with a focus on poor migrants in one district of Shanghai using treatment completion and default rates), the effect of financial incentives in terms of reducing the TB patient cost, and the incremental cost-effectiveness ratio of the intervention.
Ninety and ninety-three migrant TB patients were registered in the intervention and control districts respectively. TB treatment completion rates significantly improved by 11% (from 78% to 89%) in the intervention district, compared with only a 3% increase (from 73% to 76%) in the control district (P = 0.03). Default rates significantly decreased by 11% (from 22% to 11%) in the intervention district, compared with 1% (from 24% to 23%) in the control district (P = 0.03). In the intervention district, the financial subsidy (RMB 1,080/US$170) accounted for 13% of the average patient direct cost (RMB 8,416/US$1,332). Each percent increase in treatment completion costs required an additional RMB 6,550 (US$1,301) and each percent reduction in defaults costs required an additional RMB 5,240 (US$825) in the intervention district.
Overall, financial incentives proved to be effective in improving treatment completion and reducing default rates among migrant TB patients in Shanghai. The results suggest that financial incentives can be effectively utilized as a strategy to enhance case management among migrant TB patients in large cities in China, and this strategy may be applicable to similar international settings.
Public health; Tuberculosis; Domestic migrants; Poverty; Financial incentive; Treatment completion; Effectiveness
The Iranian healthcare system is primarily an insurance based system. This structure has an important influence on the efficiency and equity of the provision of healthcare in Iran. This paper reviews the history of the Iranian healthcare system and the impact of the Iranian health insurance system on healthcare performance based on the results of interviews with key opinion leaders and empirical evidence.
This review uses mixed methods: a systematic literature review of electronic databases supplemented by hand searching of books and journals including Government publications and other grey literature. The issues identified were explored through a series of semi-structured interviews with key informants from within the Iranian healthcare system. The interviews were recorded transcribed, coded, classified, and analysed thematically. Empirical evidence was also sought to support or contradict the views expressed in the interviews.
Sixteen interviews with key informants were conducted and presented anonymously. The interviewees raised many issues which were summarised into five main issues: increasing health expenditures, lack of systematic health technology assessment, very limited financial resources, challenging management and regulation, and uncovered population.
A wide range of issues have affected the efficiency, quality and equity of the services provided by the Iranian healthcare system. The initial and most important step toward improving the efficiency, equity and quality of the health insurance system is to focus on evidence-based policy making to generate feasible, reasonable and comprehensive reforms.
Health; Insurance; Strategy; Iran
An association between carbamazepine-induced hypersensitivity and HLA-A*3101 has been reported in populations of both European and Asian descent. We aimed to investigate HLA-A*3101 and other common variants across the genome as markers for cutaneous adverse drug reactions (cADRs) attributed to lamotrigine and phenytoin.
Materials & methods
We recruited patients with lamotrigine-induced cADRs (n = 46) and patients with phenytoin-cADRs (n = 44) and the 1958 British birth cohort was used as a control (n = 1296). HLA-A*3101 was imputed from genome-wide association study data. We applied genome-wide association to study lamotrigine- and phenytoin-induced cADR, and total cADR cases combined.
Neither HLA-A*3101 nor any other genetic marker significantly predicted lamotrigine- or phenytoin-induced cADRs.
HLA-A*3101 does not appear to be a predictor for lamotrigine- and phenytoin-induced cADRs in Europeans. Our genome-wide association study results do not support the existence of a clinically relevant common variant for the development of lamotrigine- or phenytoin-induced cADRs. As a predictive marker, HLA-A*3101 appears to be specific for carbamazepine-induced cADRs.
epilepsy; GWAS; HLA-A*3101; hypersensitivity; lamotrigine; phenytoin
Altered fibrin clot architecture is increasingly associated with cardiovascular diseases; yet, little is known about how fibrin networks are affected by small molecules that alter fibrinogen structure. Based on previous evidence that S-nitrosoglutathione (GSNO) alters fibrinogen secondary structure and fibrin polymerization kinetics, we hypothesized that GSNO would alter fibrin microstructure.
Accordingly, we treated human platelet-poor plasma with GSNO (0.01–3.75 mM) and imaged thrombin induced fibrin networks using multiphoton microscopy. Using custom designed computer software, we analyzed fibrin microstructure for changes in structural features including fiber density, diameter, branch point density, crossing fibers and void area. We report for the first time that GSNO dose-dependently decreased fibrin density until complete network inhibition was achieved. At low dose GSNO, fiber diameter increased 25%, maintaining clot void volume at approximately 70%. However, at high dose GSNO, abnormal irregularly shaped fibrin clusters with high fluorescence intensity cores were detected and clot void volume increased dramatically. Notwithstanding fibrin clusters, the clot remained stable, as fiber branching was insensitive to GSNO and there was no evidence of fiber motion within the network. Moreover, at the highest GSNO dose tested, we observed for the first time, that GSNO induced formation of fibrin agglomerates.
Taken together, low dose GSNO modulated fibrin microstructure generating coarse fibrin networks with thicker fibers; however, higher doses of GSNO induced abnormal fibrin structures and fibrin agglomerates. Since GSNO maintained clot void volume, while altering fiber diameter it suggests that GSNO may modulate the remodeling or inhibition of fibrin networks over an optimal concentration range.
A 2003 survey suggested the number of noncommercial trials in the UK was declining. Formation of the NIHR in 2006 and increased research spending by the Department of Health may have increased the number of noncommercial trials but no data are available.
Available data on UK noncommercial trials (were obtained from the two relevant registries: ISRCTN register for the UK, and US ClinicalTrials.gov. Data on each trial were sorted by start year, and compared with the: 2003 survey, and UKCRN portfolio database from 2007.
The number of UK noncommercial trials registered rose from 25 in 1990 to 188 in 1999, peaked at 533 in 2003, and fell back to 334 in 2009. Total trials registered was similar to but slightly above those in the 2003 survey up to 1998, then rose sharply to 2002 before falling to 2007. From 2007 to 2009 the number registered to start each year was similar to but slightly above the UKCRN database. Less than 10% of UK noncommercial trials registered with ClinGov for most years before 2005, but this rose to 35% by 2009.
For the periods of overlap, trial registration data provide fairly similar totals to other sources on the number of noncommercial trials starting each year. The rise and fall in the number of trials registered between 1999 and 2007 was due to those registered in the ISRCTN database as funded by NHS Trusts. After 2007, the number of trials registered as funded by NHS Trusts has fallen in the ISRCTN register but these trials may have migrated to the US ClinGov register. The total number of noncommercial trial starts, excluding those funded by NHS Trusts, has been upward since around 2002. By 2009 the two main funders were NIHR and charities. Feasibility of using registration data to monitor the number of noncommercial trials has been demonstrated but is complicated by the use of two registers and difficulties in accessing the data. We recommend an annual report on the number of noncommercial trials registering each year.
Trial registration; Noncommercial randomised clinical trials
Hemodynamic monitoring plays a fundamental role in the management of acutely ill patients. With increased concerns about the use of invasive techniques, notably the pulmonary artery catheter, to measure cardiac output, recent years have seen an influx of new, less-invasive means of measuring hemodynamic variables, leaving the clinician somewhat bewildered as to which technique, if any, is best and which he/she should use. In this consensus paper, we try to provide some clarification, offering an objective review of the available monitoring systems, including their specific advantages and limitations, and highlighting some key principles underlying hemodynamic monitoring in critically ill patients.