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.

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.

Conclusion

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.

Background

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.

Aim

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.

Method

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.

Results

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.

Conclusion

A targeted approach using absolute risk calculators can be used in primary care to modify global CVD risk assessment.

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.

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.

Background:

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.

Methods:

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.

Results:

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.

Conclusion:

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.

Aims

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.

Results

Neither HLA-A*3101 nor any other genetic marker significantly predicted lamotrigine- or phenytoin-induced cADRs.

Conclusion

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.

Background

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.

Methodology/Principal Findings

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.

Conclusions/Significance

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.

Background

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.

Methods

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.

Results

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.

Conclusions

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.

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.

Mutations in IRAK4 have been associated with recurrent Gram-positive infections in children. Given the central role of IRAK4 in innate immunity signaling, we hypothesized that common genetic variants of IRAK4 may be associated with prevalence of Gram-positive infection in critically ill adults. Haplotype clade tag single nucleotide polymorphisms (SNPs) of the IRAK4 gene were selected and genotyped in a cohort of 1,029 critically ill patients with systemic inflammatory response syndrome (SIRS). We found that a haplotype clade tagged by the A allele of the htSNP G29429A (Ala428Thr) was associated with increased relative risk of Gram-positive infection at admission to ICU (RR = 1.2, p < 0.05). Furthermore, the 29429A allele was associated with decreased lymphoblastoid cell response to CpG (as measured by IL-6 production) (raw values ± 95% CI 40.3 ± 32.3 vs. 85.8 ± 29.4 pg/ml; log-transformed values ± 95% CI 1.13 ± 0.37 vs. 1.55 ± 0.18, p < 0.04). We also found that IRAK4-deficient fibroblasts transfected with an IRAK4 expression plasmid containing the 29429A allele produced less IL-6 in response to lipopolysaccharide (p = 0.07). Our data suggest that the IRAK4 haplotype clade marked by 29429A (428Thr) alters susceptibility to Gram-positive bacteria, by decreasing cellular response to TLR ligands.

Copyright © 2011 S. Karger AG, Basel

Background:

This paper considers a range of issues related to the financing of health care system and relevant government policies in Iran.

Methods:

This study used mixed methods. A systematic literature review was undertaken to identify relevant publications. This was supplemented by hand searching in books and journals, including government publications. The issues and uncertainties identified in the literature were explored in detail through semi-structured interviews with key informants. These were triangulated with empirical evidence in the form of the literature, government statistics and independent expert opinions to validate the views expressed in the interviews.

Results:

The systematic review of published literature showed that no previous publication has addressed issues relating to the financing of healthcare services in Iran. However, a range of opinion pieces outlined issues to be explored further in the interviews. Such issues summarised into four main categories.

Conclusion:

The health care market in Iran has faced a period in which financial issues have enhanced managerial complexity. Privatization of health care services would appear to be a step too far in assisting the system to confront its challenges at the current time. The most important step toward solving such challenges is to focus on a feasible, relevant and comprehensive policy, which optimises the use of health care resources in Iran.

Background

Two out of three neonatal deaths occur in just 10 countries and Pakistan stands third among them. Maternal mortality is also high with most deaths occurring during labor, birth, and first few hours after birth. Enhanced access and utilization of skilled delivery and emergency obstetric care is the demonstrated strategy in reducing maternal and neonatal mortality. This trial aims to compare reduction in neonate mortality and utilization of available safe birthing and Emergency Obstetric and Neonatal Care services among pregnant mothers receiving ‘structured birth planning’, and/or ‘transport facilitation’ compared to routine care.

Methods

A pragmatic cluster randomized trial, with qualitative and economic studies, will be conducted in Jhang, Chiniot and Khanewal districts of Punjab, Pakistan, from February 2011 to May 2013. At least 29,295 pregnancies will be registered in the three arms, seven clusters per arm; 1) structured birth planning and travel facilitation, 2) structured birth planning, and 3) control arm. Trial will be conducted through the Lady Health Worker program. Main outcomes are difference in neonatal mortality and service utilization; maternal mortality being the secondary outcome. Cluster level analysis will be done according to intention-to-treat.

Discussion

A nationwide network of about 100,000 lady health workers is already involved in antenatal and postnatal care of pregnant women. They also act as “gatekeepers” for the child birthing services. This gate keeping role mainly includes counseling and referral for skill birth attendance and travel arrangements for emergency obstetric care (if required). The review of current arrangements and practices show that the care delivery process needs enhancement to include adequate information provision as well as informed “decision” making and planned “action” by the pregnant women. The proposed three-year research is to develop, through national technical working group process, and then test a set of arrangements for achieving the enhanced utilization of safe birthing services.

Trial registration

Current Controlled Trials ISRCTN86264432

Summary: A program package to enable genome-wide association of copy number variants (CNVs) with quantitative phenotypes in families of arbitrary size and complexity. Intensity signals that act as proxies for the number of copies are modeled in a variance component framework and association with traits is assessed through formal likelihood testing.

Availability and implementation: The Java package is made available at www.imperial.ac.uk/medicine/people/m.falchi/.

Contact: m.falchi@imperial.ac.uk

Objective

To use a unique obesity-discordant sib-pair study design to combine differential expression analysis, expression quantitative trait loci (eQTLs) mapping, and a co-expression regulatory network approach in subcutaneous human adipose tissue to identify genes relevant to the obese state.

Study design

Genome-wide transcript expression in subcutaneous human adipose tissue was measured using Affymetrix U133+2.0 microarrays and genomewide genotyping data was obtained using an Applied Biosystems SNPlex linkage panel.

Subjects

154 Swedish families ascertained through an obese proband (Body Mass Index >30kg/m2) with a discordant sibling (BMI>10kg/m2 less than proband).

Results

Approximately one-third of the transcripts were differentially expressed between lean and obese siblings. The cellular adhesion molecules (CAMs) KEGG grouping contained the largest number of differentially expressed genes under cis-acting genetic control. By using a novel approach to contrast CAMs co-expression networks between lean and obese siblings, a subset of differentially regulated genes was identified, with the previously GWAS obesity-associated NEGR1 as a central hub. Independent analysis using mouse data demonstrated that this finding for NEGR1 is conserved across species.

Conclusion

Our data suggests that, in addition to its reported role in the brain, NEGR1 is also expressed in subcutaneous adipose tissue and acts as a central “hub” in an obesity-related transcript network.

Objective

To implement and evaluate a formal pre-antiretroviral therapy (ART) care service at a district hospital in Swaziland.

Design

Operational research.

Setting

District hospital in Southern Africa.

Participants

1171 patients with a previous diagnosis of HIV. A baseline patient group consisted of the first 200 patients using the service. Two follow-up groups were defined: group 1 was all patients recruited from April to June 2009 and group 2 was 200 patients recruited in February 2010.

Intervention

Introduction of pre-ART care—a package of interventions, including counselling; regular review; clinical staging; timely initiation of ART; social and psychological support; and prevention and management of opportunistic infections, such as tuberculosis.

Primary and secondary outcome measures

Proportion of patients assessed for ART eligibility, proportion of eligible patients who were started on ART and proportion receiving defined evidence-based interventions (including prophylactic co-trimoxazole and tuberculosis screening).

Results

Following the implementation of the pre-ART service, the proportion of patients receiving defined interventions increased; the proportion of patient being assessed for ART eligibility significantly increased (baseline: 59%, group 1: 64%, group 2: 76%; p=0.001); the proportion of ART-eligible patients starting treatment increased (baseline: 53%, group 1: 81%, group: 2, 81%; p<0.001) and the median time between patients being declared eligible for ART and initiation of treatment significantly decreased (baseline: 61 days, group 1: 39 days, group 2: 14 days; p<0.001).

Conclusions

This intervention was part of a shift in the model of care from a fragmented acute care model to a more comprehensive service. The introduction of structured pre-ART was associated with significant improvements in the assessment, management and timeliness of initiation of treatment for patients with HIV.

Article summary

Article focus

Impact of pre-ART care on the quality of care in a district hospital in Southern Africa.

Key messages

After introduction of a pre-ART care service, a higher proportion of patients were assessed for ART, a higher proportion of those eligible started on ART and a higher proportion received key interventions.

Strengths and limitations of this study

This was a pragmatic evaluation in a routine service setting.

The intervention was implemented as part of routine health service delivery by existing clinical staff.

Routine data collection systems do not link testing and HIV care data, preventing an evaluation from testing to initiation.

The evaluation focuses on those with a known status, rather than new testers, those with tuberculosis or those who are pregnant.

The evaluation relies on intermediate outcomes, that is, initiation on ART, rather than long-term outcomes, such as mortality.

There is a lack of information on those requiring long-term follow-up but not ART.

Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction. However, a comprehensive genetic assessment of the inter-individual variability of circulating haptoglobin levels has not been conducted so far.

We used a genome-wide association study initially conducted in 631 French children followed by a replication in three additional European sample sets and we identified a common single nucleotide polymorphism (SNP), rs2000999 located in the Haptoglobin gene (HP) as a strong genetic predictor of circulating Haptoglobin levels (Poverall = 8.1×10−59), explaining 45.4% of its genetic variability (11.8% of Hp global variance). The functional relevance of rs2000999 was further demonstrated by its specific association with HP mRNA levels (β = 0.23±0.08, P = 0.007). Finally, SNP rs2000999 was associated with decreased total and low-density lipoprotein cholesterol in 8,789 European children (Ptotal cholesterol = 0.002 and PLDL = 0.0008).

Given the central position of haptoglobin in many inflammation-related metabolic pathways, the relevance of rs2000999 genotyping when evaluating haptoglobin concentration should be further investigated in order to improve its diagnostic/therapeutic and/or prevention impact.

Abstract

Coinfection with hepatitis C (HCV) significantly increases the risk of acute and chronic renal disease in HIV-infected individuals. However, the burden of acute kidney injury (AKI) directly attributable to HIV among HCV-infected individuals and associated risk factors are not well understood. Within a prospective cohort, AKI episodes were identified by a rise in creatinine of 0.5 mg/dL. Incidence of first AKI events was calculated for HIV/HCV coinfected versus HCV monoinfected subjects, and multivariable analyses using Cox proportional hazards were performed to identify predictors of AKI. Throughout the study period, 35% HIV/HCV coinfected and 17% HCV monoinfected subjects developed AKI, with incidence of 8.74/100 person-years and 3.53/100 person-years, respectively (hazard ratio (HR) 2.48; [95% confidence interval (CI) 1.50, 3.74]). In multivariable analysis, HIV coinfection (HR 2.19 [1.33, 3.62]), decompensated cirrhosis (HR 6.64 [3.81, 11.6]), and cocaine use (HR 2.06 [1.15, 3.71]) were independently associated with AKI. HCV genotype, HCV viral load, hazardous drinking, and heroin use were not associated with AKI. Study limitations included potential misclassification bias of HCV-infected individuals as serial HIV antibody testing was not routinely performed after study entry, and inability to adjust for tenofovir use in multivariable analysis. In conclusion, among subjects with HCV infection, decompensated cirrhosis, HIV coinfection, and cocaine use are associated with increased risk of AKI. These findings highlight the importance of preventing and treating cirrhosis, controlling HIV coinfection, and reducing cocaine use in HIV/HCV coinfected persons.

Background

In the majority of China, the Centre for Disease Control (CDC) at the county level provides both clinical and public health care for TB cases, with hospitals and other health facilities referring suspected TB cases to the CDC. In recent years, an integrated model has emerged, where the CDC remains the basic management unit for TB control, while a general hospital is designated to provide clinical care for TB patients. This study aims to explore the factors that influence the integration of TB services in general hospitals and generate knowledge to aid the scale-up of integration of TB services in China.

Methods

This study adopted a qualitative approach using interviews from sites in East and West China. Analysis was conducted using a thematic framework approach.

Results

The more prosperous site in East China was more coordinated and thus had a better method of resource allocation and more patient-orientated service, compared with the poorer site in the West. The development of public health organizations appeared to influence how effectively integration occurred. An understanding from staff that hospitals had better capacity to treat TB patients than CDCs was a strong rationale for integration. However, the economic and political interests might act as a barrier to effective integration. Both sites shared the same challenges of attracting and retaining a skilled workforce for the TB services. The role of the health bureau was more directive in the Western site, while a more participatory and collaborative approach was adopted in the Eastern site.

Conclusion

The process of integration identifies similarities and differences between sites in more affluent East China and poorer West China. Integration of TB services in the hospitals needs to address the challenges of stakeholder motivations and resource allocation. Effective inter-organizational collaboration could help to improve the efficiency and quality of TB service. Key words: TB control, service delivery, integration, hospitals, China.