Fabry Disease – Underestimated in the Differential Diagnosis of Multiple Sclerosis?

Objective

Fabry disease is a rare X-linked inherited lysosomal storage disorder affecting multiple organ systems. It includes central nervous system involvement via micro- and macroangiopathic cerebral changes. Due to its clinical symptoms and frequent MRI lesions, Fabry disease is commonly misdiagnosed as multiple sclerosis. We present an overview of cases from Fabry centres in Germany initially misdiagnosed with multiple sclerosis and report the clinical, MR-tomographical, and laboratory findings.

Methods

Eleven Fabry patients (one male, ten females) initially diagnosed with multiple sclerosis were identified from 187 patient records (5.9%) and analyzed for presenting symptoms, results of the initial diagnostic workup, and the clinical course of the disease.

Results

Four patients were identified as having a “possible” history of MS, and 7 patients as “definite” cases of multiple sclerosis (revised McDonald criteria). On average, Fabry disease was diagnosed 8.2 years (±9.8 years) after the MS diagnosis, and 12.8 years after onset of first symptoms (±10.3 years). All patients revealed white matter lesions on MRI. The lesion pattern and results of cerebrospinal fluid examination were inconsistent and non-specific. White matter lesion volumes ranged from 8.9 mL to 34.8 mL (mean 17.8 mL±11.4 mL). There was no association between extra-neurological manifestations or enzyme activity and lesion load.

Conclusion

There are several anamnestic and clinical hints indicating when Fabry disease should be considered a relevant differential diagnosis of multiple sclerosis, e.g. female patients with asymmetric, confluent white matter lesions on MRI, normal spinal MR imaging, ectatic vertebrobasilar arteries, proteinuria, or lack of intrathecally derived immunoglobulin synthesis.     

Faecal levels of calprotectin in systemic sclerosis are stable over time and are higher compared to primary Sj?gren’s syndrome and rheumatoid arthritis

Introduction

Faecal calprotectin (FC) has been proposed to be a biomarker of gastrointestinal (GI) disease in systemic sclerosis (SSc). The purpose of this study was to extend cross-sectional observations and prospectively assess the variability of FC over time in SSc patients. We also aimed to examine FC in relation to immunosuppressive therapy. Finally we wanted to analyse FC in other rheumatic diseases to evaluate the specificity of FC for SSc GI disease.

Methods

FC was measured in consecutive patients with SSc, primary Sjögren’s syndrome (pSS), rheumatoid arthritis (RA) and in healthy hospital workers. The intraindividual variability of FC in SSc was assessed with intra class correlation (ICC) and κ statistics. Associations between FC and objective markers of GI disease and immunosuppressive medication were investigated.

Results

FC was associated with micronutrient deficiency and GI pathology as assessed by cineradiography confirming our previous results. FC showed only a limited intra-individual variation in SSc, ICC = 0.69 (95% confidence interval, CI: 0.57-0.78) and κ = 0.64 (95% CI: 0.56-0.73). Generalised immunosuppression did not have any significant impact on FC. FC was significantly higher in SSc patients compared to patients with pSS or RA as well as compared to healthy subjects.

Conclusions

FC is a promising non-invasive biomarker for GI disease in SSc. In view of stable levels over time, FC could be a useful marker when novel, more specific drugs targeting the GI tract in SSc will be introduced.     

Muscle-invasive bladder cancer treated with TURB followed by concomitant boost with small reduction of radiotherapy field with or without of chemotherapy

Aim

To evaluate the clinical outcome and toxicity of the treatment of muscle-invasive bladder cancer (MIBC) that combined transurethral resection of bladder tumor (TURB) with “concomitant boost” radiotherapy delivered over a shortened overall treatment time of 5 weeks, with or without concurrent chemotherapy.

Background

Local control of MIBC by bladder-sparing approach is unsatisfactory. In order to improve the effectiveness of radiotherapy, we have designed a protocol that combines TURB with a non-conventionally fractionated radiotherapy “concomitant boost”.

Materials and methods

Between 2004 and 2010, 73 patients with MIBC cT2-4aN0M0, were treated with “concomitant boost” radiotherapy. The whole bladder with a 2–3 cm margin was irradiated with fractions of 1.8 Gy to a dose of 45 Gy, with a “concomitant boost” to the bladder with 1–1.5 cm margin, during the last two weeks of treatment, as a second fraction of 1.5 Gy, to a total dose of 60 Gy. Radiochemotherapy using mostly cisplatin was delivered in 42/73(58%) patients, 31/73(42%) patients received radiotherapy alone.

Results

Acute genitourinary toxicity of G3 was scored in 3/73(4%) patients. Late gastrointestinal toxicity higher than G2 and genitourinary higher than G3 were not reported. Complete remission was achieved in 48/73(66%), partial remission in 17/73(23%), and stabilization disease in 8/73(11%) patients. Three- and five-year overall, disease specific and invasive locoregional disease-free survival rates were 65% and 52%, 70% and 59%, 52% and 43%, respectively.

Conclusions

An organ-sparing approach using TURB followed by radio(chemo)therapy with “concomitant boost” in patients with MIBC allows to obtain long-term survival with acceptable toxicity.     

Accuracy of tracheal aspirate gram stain in predicting Staphylococcus aureus infection in ventilator-associated pneumonia

Background

The Gram stain can be used to direct initial empiric antimicrobial therapy when complete culture is not available. This rapid test could prevent the initiation of inappropriate therapy and adverse outcomes. However, several studies have attempted to determine the value of the Gram stain in the diagnosis and therapy of bacterial infection in different populations of patients with ventilator-associated pneumonia (VAP) with conflicting results. The objective of this study is to evaluate the accuracy of the Gram stain in predicting the existence of Staphylococcus aureus infections from cultures of patients suspected of having VAP.

Methods

This prospective single-center open cohort study enrolled 399 patients from December 2005 to December 2010. Patients suspected of having VAP by ATS IDSA criteria were included. Respiratory secretion samples were collected by tracheal aspirate (TA) for standard bacterioscopic analysis by Gram stain and culture.

Results

Respiratory secretion samples collected by tracheal aspirates of 392 patients were analyzed by Gram stain and culture. When Gram-positive cocci were arranged in clusters, the sensitivity was 68.4%, specificity 97.8%, positive predictive value 88.1% and negative predictive value 92.8% for predicting the presence of Staphylococcus aureus in culture (p < 0.001).

Conclusions

A tracheal aspirate Gram stain can be used to rule out the presence of Staphylococcus aureus in patients with a clinical diagnosis of VAP with a 92.8% Negative Predictive Value. Therefore, 7.2% of patients with Staphylococcus aureus would not be protected by an empiric treatment that limits antimicrobial coverage to Staphylococcus aureus only when Gram positive cocci in clusters are identified.     

High Utility of Contact Investigation for Latent and Active Tuberculosis Case Detection among the Contacts: A Retrospective Cohort Study in Tbilisi,Georgia, 2010–2011

Setting

The study was conducted at the National Center for Tuberculosis and Lung Diseases (NCTBLD) in Tbilisi, Georgia.

Objective

To assess the utility of contact investigation for tuberculosis (TB) case detection. We also assessed the prevalence and risk factors for active TB disease and latent TB infection (LTBI) among contacts of active pulmonary TB cases.

Design

A retrospective cohort study was conducted among the contacts of active pulmonary TB cases registered in 2010–2011 at the NCTBLD in Tbilisi, Georgia. Contacts of active TB patients were investigated according to an “invitation model”: they were referred to the NCTBLD by the index case; were queried about clinical symptoms suggestive of active TB disease; tuberculin skin testing and chest radiographs were performed. Demographic, laboratory, and clinical data of TB patients and their contacts were abstracted from existing records up to February 2013.

Results

869 contacts of 396 index cases were enrolled in the study; a median of 2 contacts were referred per index case. Among the 869 contacts, 47 (5.4%) were found to have or developed active TB disease: 30 (63.8%) were diagnosed with TB during the baseline period (co-prevalent cases) and 17 (36.2%) developed active TB disease during the follow-up period (mean follow up of 21 months) (incident TB cases). The incidence rate of active TB disease among contacts was 1126.0 per 100 000 person years (95% CI 655.7–1802.0 per 100,000 person-years). Among the 402 contacts who had a tuberculin skin test (TST) performed, 52.7% (95% CI 47.7–57.7%) had LTBI.

Conclusions

A high prevalence of LTBI and active TB disease was found among the contacts of TB cases in Tbilisi, Georgia. Our findings demonstrated that an “invitation” model of contact investigation was an effective method of case detection. Therefore, contact investigation should be scaled up in Georgia.     

Autoantibodies and Sjogren’s Syndrome in Multiple Sclerosis,a Reappraisal

Background

Rheumatologic diseases may cause neurologic disorders that mimic multiple sclerosis (MS). A panel of serum autoantibodies is often obtained as part of the evaluation of patients suspected of having MS.

Objectives

To determine, in light of recently revised diagnostic criteria for MS, neuromyelitis optica, and Sjogren’s Syndrome, if testing for autoantibodies in patients with a confirmed diagnosis of MS would reveal a frequency or demonstrate a clinical utility divergent from previous reports or lead to identification of undiagnosed cases of Sjogren’s Syndrome.

Methods

Convenience sample cross-sectional study of MS patients recruited from the OHSU Multiple Sclerosis Center.

Results

Autoantibodies were detected in 38% (35/91) of patients with MS and were not significantly associated with disease characteristics or severity. While four patients had SSA antibodies, none met diagnostic criteria for Sjogren’s Syndrome.

Conclusions

Rheumatologic autoantibodies are frequently found in MS patients and are not associated with disease severity or systemic rheumatologic disease. Our demonstration of the low specificity of these autoantibodies suggests that the diagnostic utility and cost-effectiveness of testing is not supported when there is strong clinical suspicion of MS and low clinical suspicion of rheumatologic disease.     

Outcomes among HIV-1 Infected Individuals First Starting Antiretroviral Therapy with Concurrent Active TB or Other AIDS-Defining Disease

Background

Tuberculosis (TB) is common among HIV-infected individuals in many resource-limited countries and has been associated with poor survival. We evaluated morbidity and mortality among individuals first starting antiretroviral therapy (ART) with concurrent active TB or other AIDS-defining disease using data from the “Prospective Evaluation of Antiretrovirals in Resource-Limited Settings” (PEARLS) study.

Methods

Participants were categorized retrospectively into three groups according to presence of active confirmed or presumptive disease at ART initiation: those with pulmonary and/or extrapulmonary TB (“TB” group), those with other non-TB AIDS-defining disease (“other disease”), or those without concurrent TB or other AIDS-defining disease (“no disease”). Primary outcome was time to the first of virologic failure, HIV disease progression or death. Since the groups differed in characteristics, proportional hazard models were used to compare the hazard of the primary outcome among study groups, adjusting for age, sex, country, screening CD4 count, baseline viral load and ART regimen.

Results

31 of 102 participants (30%) in the “TB” group, 11 of 56 (20%) in the “other disease” group, and 287 of 1413 (20%) in the “no disease” group experienced a primary outcome event (p = 0.042). This difference reflected higher mortality in the TB group: 15 (15%), 0 (0%) and 41 (3%) participants died, respectively (p<0.001). The adjusted hazard ratio comparing the “TB” and “no disease” groups was 1.39 (95% confidence interval: 0.93–2.10; p = 0.11) for the primary outcome and 3.41 (1.72–6.75; p<0.001) for death.

Conclusions

Active TB at ART initiation was associated with increased risk of mortality in HIV-1 infected patients.     

The Clinical Significance of Vitamin D in Systemic Lupus Erythematosus: A Systematic Review

Background

Vitamin D deficiency is more prevalent among SLE patients than the general population. Over the past decade, many studies across the globe have been carried out to investigate the role of vitamin D in SLE from various clinical angles. Therefore, the aim of this systematic review is to summarise and evaluate the evidence from the published literature; focusing on the clinical significance of vitamin D in SLE.

Methods

The following databases were searched: MEDLINE, Scopus, Web of Knowledge and CINAHL, using the terms “lupus”, “systemic lupus erythematosus”, “SLE and “vitamin D”. We included only adult human studies published in the English language between 2000 and 2012.The reference lists of included studies were thoroughly reviewed in search for other relevant studies.

Results

A total of 22 studies met the selection criteria. The majority of the studies were observational (95.5%) and cross sectional (90.9%). Out of the 15 studies which looked into the association between vitamin D and SLE disease activity, 10 studies (including the 3 largest studies in this series) revealed a statistically significant inverse relationship. For disease damage, on the other hand, 5 out of 6 studies failed to demonstrate any association with vitamin D levels. Cardiovascular risk factors such as insulin resistance, hypertension and hypercholesterolaemia were related to vitamin D deficiency, according to 3 of the studies.

Conclusion

There is convincing evidence to support the association between vitamin D levels and SLE disease activity. There is paucity of data in other clinical aspects to make firm conclusions.     

Pilot Quasi-Randomized Controlled Study of Herbal Medicine Hochuekkito as an Adjunct to Conventional Treatment for Progressed Pulmonary Mycobacterium avium Complex Disease

Introduction

Hochuekkito, a traditional herbal medicine, is occasionally prescribed in Japan to treat patients with a poor general condition. We aimed to examine whether this medicine was beneficial and tolerable for patients with progressed pulmonary Mycobacterium avium complex (MAC) disease.

Methods

This pilot open-label quasi-randomized controlled trial enrolled 18 patients with progressed pulmonary MAC disease who had initiated antimycobacterial treatment over one year ago but were persistently culture-positive or intolerant. All patients continued their baseline treatment regimens with (n = 9) or without (n = 9) oral Hochuekkito for 24 weeks.

Results

Baseline characteristics were generally similar between the groups. Most patients were elderly (median age 70 years), female, had a low body mass index (<20 kg/m²), and a long-term disease duration (median approximately 8 years). After the 24-week treatment period, no patient achieved sputum conversion. Although the number of colonies in sputum tended to increase in the control group, it generally remained stable in the Hochuekkito group. Radiological disease control was frequently observed in the Hochuekkito group than the control group (8/9 vs. 3/9; p = 0.05). Patients in the Hochuekkito group tended to experience increase in body weight and serum albumin level compared with those in the control group (median body weight change: +0.4 kg vs. −0.8 kg; median albumin change: +0.2 g/dl vs. ±0.0 g/dl). No severe adverse events occurred.

Conclusions

Hochuekkito could be an effective, feasible adjunct to conventional therapy for patients with progressed pulmonary MAC disease. Future study is needed to explore this possibility.

Trial Registration

UMIN Clinical Trials Registry UMIN000009920     

Causes of Death among Commercially Insured Multiple Sclerosis Patients in the United States

Background

Information on causes of death (CODs) for patients with multiple sclerosis (MS) in the United States is sparse and limited by standard categorizations of underlying and immediate CODs on death certificates. Prior research indicated that excess mortality among MS patients was largely due to greater mortality from infectious, cardiovascular, or pulmonary causes.

Objective

To analyze disease categories in order to gain insight to pathways, which lead directly to death in MS patients.

Methods

Commercially insured MS patients enrolled in the OptumInsight Research database between 1996 and 2009 were matched to non-MS comparators on age/residence at index year and sex. The cause most-directly leading to death from the death certificate, referred to as the “principal” COD, was determined using an algorithm to minimize the selection of either MS or cardiac/pulmonary arrest as the COD. Principal CODs were categorized into MS, cancer, cardiovascular, infectious, suicide, accidental, pulmonary, other, or unknown. Infectious, cardiovascular, and pulmonary CODs were further subcategorized.

Results

30,402 MS patients were matched to 89,818 controls, with mortality rates of 899 and 446 deaths/100,000 person-years, respectively. Excluding MS, differences in mortality rate between MS patients and non-MS comparators were largely attributable to infections, cardiovascular causes, and pulmonary problems. Of the 95 excessive deaths (per 100,000 person-years) related to infectious causes, 41 (43.2%) were due to pulmonary infections and 45 (47.4%) were attributed to sepsis. Of the 46 excessive deaths (per 100,000 person-years) related to pulmonary causes, 27 (58.7%) were due to aspiration. No single diagnostic entity predominated for the 60 excessive deaths (per 100,000 person-years) attributable to cardiac CODs.

Conclusions

The principal COD algorithm improved on other methods of determining COD in MS patients from death certificates. A greater awareness of the common CODs in MS patients will allow physicians to anticipate potential problems and, thereby, improve the care that they provide.     

Patent and Exclusivity Status of Essential Medicines for Non-Communicable Disease

Objective

The threat of non-communicable diseases (“NCDs”) is increasingly becoming a global health crisis and are pervasive in high, middle, and low-income populations resulting in an estimated 36 million deaths per year. There is a need to assess intellectual property rights (“IPRs”) that may impede generic production and availability and affordability to essential NCD medicines.

Methods

Using the data sources listed below, the study design systematically eliminated NCD drugs that had no patent/exclusivity provisions on API, dosage, or administration route. The first step identified essential medicines that treat certain high disease burden NCDs. A second step examined the patent and exclusivity status of active ingredient, dosage and listed route of administration using exclusion criteria outlined in this study.

Materials

We examined the patent and exclusivity status of medicines listed in the World Health Organization’s (“WHO”) Model List of Essential Drugs (Medicines) (“MLEM”) and other WHO sources for drugs treating certain NCDs. i.e., cardiovascular and respiratory disease, cancers, and diabetes. We utilized the USA Food and Drug Administration Orange Book and the USA Patent and Trademark Office databases as references given the predominant number of medicines registered in the USA.

Results

Of the 359 MLEM medicines identified, 22% (79/359) address targeted NCDs. Of these 79, only eight required in-depth patent or exclusivity assessment. Upon further review, no NCD MLEM medicines had study patent or exclusivity protection for reviewed criteria.

Conclusions

We find that ensuring availability and affordability of potential generic formulations of NCD MLEM medicines appears to be more complex than the presence of IPRs with API, dosage, or administration patent or exclusivity protection. Hence, more sophisticated analysis of NCD barriers to generic availability and affordability should be conducted in order to ensure equitable access to global populations for these essential medicines.     

Low-dose oral imatinib in the treatment of systemic sclerosis interstitial lung disease unresponsive to cyclophosphamide: a phase II pilot study

Introduction

Pulmonary involvement represents a major cause of death of systemic sclerosis (SSc) patients. Recent data suggest that tyrosine kinase inhibitors, such as imatinib, may be a therapeutic option for SSc patients. However, preliminary published clinical trials were inconclusive about imatinib efficacy and showed side effects. The purpose of this study was to verify efficacy and tolerability of low-dose imatinib on interstitial lung disease in a cohort of SSc patients unresponsive to cyclophosphamide therapy.

Methods

Thirty consecutive SSc patients with active pulmonary involvement, unresponsive to cyclophosphamide, were treated with imatinib 200 mg/day for 6 months followed by a 6-month follow-up. A “good response” was defined as an increase of forced vital capacity (FVC) by more of 15% and/or increase of diffusing capacity of carbon monoxide (DL_CO) >15% and PaO₂ > 90% of initial value and high-resolution computed tomography (HRCT)-scan pattern unchanged or improved.

Results

Twenty-six patients completed the study. Three patients died and one patient was lost to follow-up. Four patients (15.32%) had a good response, 7 worsened and 15 had a stabilized lung disease. Overall, 19 (73.07%) patients had an improved or stabilized lung disease. After a 6-month follow-up, 12 (54.5%) of the 22 patients showed an improved or stabilized lung disease.

Conclusions

Lung function was stabilized in a large proportion of patients unresponsive to cyclophosphamide therapy and a beneficial outcome emerged from the analysis of HRCT lung scans. There was no significant improvement of skin involvement, and the low dose was well tolerated. These data provide useful suggestions to design future randomized clinical trials for SSc therapeutics.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00573326","term_id":"NCT00573326"}}NCT00573326. Registered 13 December 2007.     

Coliform Bacteria as Indicators of Diarrheal Risk in Household Drinking Water: Systematic Review and Meta-Analysis

Background

Current guidelines recommend the use of Escherichia coli (EC) or thermotolerant (“fecal”) coliforms (FC) as indicators of fecal contamination in drinking water. Despite their broad use as measures of water quality, there remains limited evidence for an association between EC or FC and diarrheal illness: a previous review found no evidence for a link between diarrhea and these indicators in household drinking water.

Objectives

We conducted a systematic review and meta-analysis to update the results of the previous review with newly available evidence, to explore differences between EC and FC indicators, and to assess the quality of available evidence.

Methods

We searched major databases using broad terms for household water quality and diarrhea. We extracted study characteristics and relative risks (RR) from relevant studies. We pooled RRs using random effects models with inverse variance weighting, and used standard methods to evaluate heterogeneity and publication bias.

Results

We identified 20 relevant studies; 14 studies provided extractable results for meta-analysis. When combining all studies, we found no association between EC or FC and diarrhea (RR 1.26 [95% CI: 0.98, 1.63]). When analyzing EC and FC separately, we found evidence for an association between diarrhea and EC (RR: 1.54 [95% CI: 1.37, 1.74]) but not FC (RR: 1.07 [95% CI: 0.79, 1.45]). Across all studies, we identified several elements of study design and reporting (e.g., timing of outcome and exposure measurement, accounting for correlated outcomes) that could be improved upon in future studies that evaluate the association between drinking water contamination and health.

Conclusions

Our findings, based on a review of the published literature, suggest that these two coliform groups have different associations with diarrhea in household drinking water. Our results support the use of EC as a fecal indicator in household drinking water.     

Measuring Unsafe Abortion-Related Mortality: A Systematic Review of the Existing Methods

Background

The WHO estimates that 13% of maternal mortality is due to unsafe abortion, but challenges with measurement and data quality persist. To our knowledge, no systematic assessment of the validity of studies reporting estimates of abortion-related mortality exists.

Study Design

To be included in this study, articles had to meet the following criteria: (1) published between September 1^st, 2000-December 1^st, 2011; (2) utilized data from a country where abortion is “considered unsafe”; (3) specified and enumerated causes of maternal death including “abortion”; (4) enumerated ≥100 maternal deaths; (5) a quantitative research study; (6) published in a peer-reviewed journal.

Results

7,438 articles were initially identified. Thirty-six studies were ultimately included. Overall, studies rated “Very Good” found the highest estimates of abortion related mortality (median 16%, range 1–27.4%). Studies rated “Very Poor” found the lowest overall proportion of abortion related deaths (median: 2%, range 1.3–9.4%).

Conclusions

Improvements in the quality of data collection would facilitate better understanding global abortion-related mortality. Until improved data exist, better reporting of study procedures and standardization of the definition of abortion and abortion-related mortality should be encouraged.     

Is Clinical Practice Concordant with the Changes in Guidelines for Antiretroviral Therapy Initiation during Primary and Chronic HIV-1 Infection? The ANRS PRIMO and COPANA Cohorts

Objective

Guidelines for initiating HIV treatment are regularly revised. We explored how physicians in France have applied these evolving guidelines for ART initiation over the last decade in two different situations: chronic (CHI) and primary HIV-1 infection (PHI), since specific recommendations for PHI are also provided in France.

Methods

Data came from the ANRS PRIMO (1267 patients enrolled during PHI in 1996–2010) and COPANA (800 subjects enrolled at HIV diagnosis in 2004–2008) cohorts. We defined as guidelines-inconsistent during PHI and CHI, patients meeting criteria for ART initiation and not treated in the following month and during the next 6 months, respectively.

Results

ART initiation during PHI dramatically decreased from 91% of patients in 1996–99 to 22% in 2007 and increased to 60% in 2010, following changes in recommendations. In 2007, however, after the CD4 count threshold was raised to 350 cells/mm³ in 2006, only 55% of the patients with CD4≤350 were treated and 66% in 2008. During CHI, ART was more frequently initiated in patients who met the criteria at entry (96%) than during follow-up: 83% when recommendation to treat was 200 and 73% when it was 350 cells/mm³. Independent risk factors for not being treated during CHI despite meeting the criteria were lower viral load, lower educational level, and poorer living conditions.

Conclusion

HIV ART initiation guidelines are largely followed by practitioners in France. What can still be improved, however, is time to treat when CD4 cell counts reach the threshold to treat. Risk factors for lack of timely treatment highlight the need to understand better how patients’ living conditions and physicians’ perceptions influence the decision to initiate treatment.     

Expanding Disease Definitions in Guidelines and Expert Panel Ties to Industry: A Cross-sectional Study of Common Conditions in the United States

Background

Financial ties between health professionals and industry may unduly influence professional judgments and some researchers have suggested that widening disease definitions may be one driver of over-diagnosis, bringing potentially unnecessary labeling and harm. We aimed to identify guidelines in which disease definitions were changed, to assess whether any proposed changes would increase the numbers of individuals considered to have the disease, whether potential harms of expanding disease definitions were investigated, and the extent of members'' industry ties.

Methods and Findings

We undertook a cross-sectional study of the most recent publication between 2000 and 2013 from national and international guideline panels making decisions about definitions or diagnostic criteria for common conditions in the United States. We assessed whether proposed changes widened or narrowed disease definitions, rationales offered, mention of potential harms of those changes, and the nature and extent of disclosed ties between members and pharmaceutical or device companies.Of 16 publications on 14 common conditions, ten proposed changes widening and one narrowing definitions. For five, impact was unclear. Widening fell into three categories: creating “pre-disease”; lowering diagnostic thresholds; and proposing earlier or different diagnostic methods. Rationales included standardising diagnostic criteria and new evidence about risks for people previously considered to not have the disease. No publication included rigorous assessment of potential harms of proposed changes.Among 14 panels with disclosures, the average proportion of members with industry ties was 75%. Twelve were chaired by people with ties. For members with ties, the median number of companies to which they had ties was seven. Companies with ties to the highest proportions of members were active in the relevant therapeutic area. Limitations arise from reliance on only disclosed ties, and exclusion of conditions too broad to enable analysis of single panel publications.

Conclusions

For the common conditions studied, a majority of panels proposed changes to disease definitions that increased the number of individuals considered to have the disease, none reported rigorous assessment of potential harms of that widening, and most had a majority of members disclosing financial ties to pharmaceutical companies. Please see later in the article for the Editors'' Summary     

The Frequency and Determinants of Liver Stiffness Measurement Failure: A Retrospective Study of “Real-Life” 38,464 Examinations

Objective

To investigate the frequency and determinants of liver stiffness measurement (LSM) failure by means of FibroScan in “real-life” Chinese patients.

Methods

A total of 38,464 “real-life” Chinese patients in 302 military hospital of China through the whole year of 2013, including asymptomatic carrier, chronic hepatitis B, chronic hepatitis C, liver cirrhosis (LC), alcoholic liver disease, autoimmune liver disease, hepatocellular carcinoma (HCC) and other, were enrolled, their clinical and biological parameters were retrospectively investigated. Liver fibrosis was evaluated by FibroScan detection. S probe (for children with height less than 1.20 m) and M probe (for adults) were used. LSM failure defined as zero valid shots (unsuccessful LSM), or the ratio of the interquartile range to the median of 10 measurements (IQR/M) greater than 0.30 plus median LSM greater or equal to 7.1 kPa (unreliable LSM).

Results

LSM failure occurred in 3.34% of all examinations (1286 patients out of 38,464), among them, there were 958 cases (2.49%) with unsuccessful LSM, and 328 patients (0.85%) with unreliable LSM. Statistical analyses showed that LSM failure was independently associated with body mass index (BMI) greater than 30 kg/m², female sex, age greater than 50 years, intercostal spaces (IS) less than 9 mm, decompensated liver cirrhosis and HCC patients. There were no significant differences among other diseases. By changing another skilled operator, success was achieved on 301 cases out of 1286, which reduced the failure rate to 2.56%, the decrease was significant (P<0.0001).

Conclusions

The principal reasons of LSM failure are ascites, obesity and narrow of IS. The failure rates of HCC, decompensated LC, elder or female patients are higher. These results emphasize the need for adequate operator training, technological improvements and optimal criteria for specific patient subpopulations.     

Assessment of the Reporting Quality of Randomized Controlled Trials on the Treatment of Diabetes Mellitus with Traditional Chinese Medicine: A Systematic Review

Background

After the publication of the CONSORT 2010 statement, few studies have been conducted to assess the reporting quality of randomized clinical trials (RCTs) on treatment of diabetes mellitus with Traditional Chinese Medicine (TCM) published in Chinese journals.

Objective

To investigate the current situation of the reporting quality of RCTs in leading medical journals in China with the CONSORT 2010 statement as criteria.

Methods

The China National Knowledge Infrastructure (CNKI) electronic database was searched for RCTs on the treatment of diabetes mellitus with TCM published in the Journal of Traditional Chinese Medicine, Chinese Journal of Integrated Traditional & Western Medicine, and the China Journal of Chinese Materia Medica from January to December 2011. We excluded trials reported as “animal studies”, “in vitro studies”, “case studies”, or “systematic reviews”. The CONSORT checklist was applied by two independent raters to evaluate the reporting quality of all eligible trials after discussing and comprehending the items thoroughly. Each item in the checklist was graded as either “yes” or “no” depending on whether it had been reported by the authors.

Results

We identified 27 RCTs. According to the 37 items in the CONSORT checklist, the average reporting percentage was 45.0%, in which the average reporting percentage for the “title and abstract”, the “introduction”, the “methods”, the “results”, the “discussion” and the “other information” was 33.3%, 88.9%, 36.4%, 54.4%, 71.6% and 14.8%, respectively. In the Journal of Traditional Chinese Medicine, Chinese Journal of Integrated Traditional & Western Medicine, and the China Journal of Chinese Materia Medica the average reporting percentage was 42.2%, 56.8%, and 46.0%, respectively.

Conclusions

The reporting quality of RCTs in these three journals was insufficient to allow readers to assess the validity of the trials. We recommend that editors require authors to use the CONSORT statement when reporting their trial results as a condition of publication.