Objective Clinical Data Research Articles

THU0047 Baff and B2m, but not Free Light Chains, Correlate with Disease Activity in Primary SjÖGren's Syndrome (PSS)

BackgroundBoth kappa and lambda free light chain (FLC) levels appear to be elevated the serum of patients with pSS, in comparison to healthy controls [1,2]. Consequently, FLCs may represent potential...

The Clinical Efficacy of Dietary Fat Restriction in Treatment of Dogs with Intestinal Lymphangiectasia

BackgroundIntestinal lymphangiectasia (IL), a type of protein‐losing enteropathy (PLE), is a dilatation of lymphatic vessels within the gastrointestinal tract. Dietary fat restriction previously has been proposed as an effective treatment for dogs with PLE, but limited objective clinical data are available on the efficacy of this treatment.Hypothesis/ObjectivesTo investigate the clinical efficacy of dietary fat restriction in dogs with IL that were unresponsive to prednisolone treatment or showed relapse of clinical signs and hypoalbuminemia when the prednisolone dosage was decreased.AnimalsTwenty‐four dogs with IL.MethodsRetrospective study. Body weight, clinical activity score, and hematologic and biochemical variables were compared before and 1 and 2 months after treatment. Furthermore, the data were compared between the group fed only an ultra low‐fat (ULF) diet and the group fed ULF and a low‐fat (LF) diet.ResultsNineteen of 24 (79%) dogs responded satisfactorily to dietary fat restriction, and the prednisolone dosage could be decreased. Clinical activity score was significantly decreased after dietary treatment compared with before treatment. In addition, albumin (ALB), total protein (TP), and blood urea nitrogen (BUN) concentration were significantly increased after dietary fat restriction. At 2 months posttreatment, the ALB concentrations in the ULF group were significantly higher than that of the ULF + LF group.Conclusions and Clinical ImportanceDietary fat restriction appears to be an effective treatment in dogs with IL that are unresponsive to prednisolone treatment or that have recurrent clinical signs and hypoalbuminemia when the dosage of prednisolone is decreased.

Accuracy of Phenotyping Chronic Rhinosinusitis in the Electronic Health Record

Chronic rhinosinusitis (CRS) is prevalent, morbid, and poorly understood. Extraction of electronic health record (EHR) data of patients with CRS may facilitate research on CRS. However, the accuracy of using structured billing codes for EHR-driven phenotyping of CRS is unknown. We sought to accurately identify CRS cases and controls using EHR data and to determine the accuracy of structured billing codes for identifying patients with CRS. We developed and validated distinct algorithms to identify patients with CRS and controls using International Classification of Diseases, Ninth Revision (ICD-9) and Current Procedural Terminology codes. We used blinded clinician chart review as the reference standard to evaluate algorithm and billing code accuracy. Our initial control algorithm achieved a control positive predictive value (PPV) of 100% (i.e., negative predictive value of 100% for CRS). Our initial algorithm for CRS cases relied exclusively on billing codes and had a low case PPV (54%). Notably, ICD-9 code 471.x was associated with a case PPV of 85%, whereas the case PPV of ICD-9 code 473.x was only 34%. After multiple algorithm iterations, we increased the case PPV of our final algorithm to 91% by adding several requirements, e.g., that ICD-9 codes occur with 1 or more evaluations by a CRS specialist to enhance availability of objective clinical data for accurately phenotyping CRS. These algorithms are an important first step to identify patients with CRS, and may facilitate EHR-based research on CRS pathogenesis, morbidity, and management. Exclusive use of coded data for phenotyping CRS has limited accuracy, especially because CRS symptomatology overlaps with that of other illnesses. Incorporating natural language processing (e.g., to evaluate results of nasal endoscopy or sinus computed tomography) into future work may increase algorithm accuracy and identify patients whose disease status may not be ascertained by only using billing codes.

Body mass index, blood pressure, and glucose and lipid metabolism among permanent and fixed-term workers in the manufacturing industry: a cross-sectional study

BackgroundTemporary employment, a precarious form of employment, is recognized as social determinant of poor health. However, evidence supporting precarious employment as a risk factor for health is mainly obtained from subjective data. Studies using objective clinical measurement data in the assessment of health status are limited. This study compared body mass index (BMI), lipid and glucose metabolism, and health-related lifestyle factors between permanent workers and fixed-term workers employed in the manufacturing industry.MethodsData of 1,701 male manufacturing industry workers <50 years old in Japan were collected and analyzed. Anthropometric data were BMI, calculated using measured height and weight of study participants, and blood pressure. For lipid metabolism, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride levels were determined. For glucose metabolism, fasting plasma glucose and hemoglobin A1c (HbA1c) levels were measured. Multiple regression analysis adjusted for age and lifestyle factors was performed.ResultsBMI was significantly higher in permanent workers (22.9 kg/m2) compared with fixed-term workers (22.4 kg/m2). The leaner population (BMI < 18.5) was greater among fixed-term workers (8.3%) compared with permanent workers (4.0%), whereas the overweight population (BMI ≥ 25.0) was greater among permanent workers (21.4%) compared with fixed-term workers (18.1%). Although fixed-term workers tended not to be overweight, regression analysis adjusted for age and lifestyle factors suggested that fixed-term employment was significantly associated with higher blood pressure (systolic β = 2.120, diastolic β = 2.793), triglyceride (β = 11.147), fasting blood glucose (β = 2.218), and HbA1c (β = 0.107) compared with permanent workers (all p < 0.01).ConclusionsFixed-term workers showed more health risks, such as poorer blood pressure and lipid and glucose metabolism, even when adjusted for age and lifestyle variables, although BMI of fixed-term workers were lower than permanent workers. Precarious work might contribute to a deteriorating health status even among less overweight populations.

Association Between Body Mass Index, Sexually Transmitted Infections, and Contraceptive Compliance

Recent studies have examined the relationship between body mass index (BMI) and sexual behaviors, but little information exists on this relationship among racially diverse, low-income women using objectively measured clinical data. The purpose of this study was to examine the association between BMI and sexual behaviors, rates of sexually transmitted infections (STIs) and unintended pregnancy, and contraceptive adherence among adolescent and young adult women. As part of a larger study, 1,015 Hispanic (54.2%), Black (18.6%) and White (24.8%) women aged 16 to 24 years seeking family planning services at publicly funded reproductive health clinics provided data on their baseline sexual behaviors, and contraceptive use and pregnancy history over 12 months. Objective clinical data were available from medical records at baseline (i.e., height, weight, and Papanicolaou [Pap] smear results), and over a 12-month period (i.e., STI results). Multivariable analyses were used to compare sexual behaviors, STI rates, contraceptive compliance, and unintended pregnancy rates between obese, overweight, and normal weight participants after adjusting for age, race/ethnicity, and other confounders. Overall, 423 (36.6%), 304 (26.3%), and 288 (24.9%) participants were classified as normal weight, overweight, and obese, respectively. No statistically significant association was observed between BMI and sexual behaviors, STI rates (overweight odds ratio [OR] 0.67; 95% confidence interval [95% CI] [0.4, 1.08]; obese OR 0.68; 95% CI [0.42, 1.10]); contraceptive compliance (overweight OR 0.89; 95% CI [0.69, 1.16]; obese OR 0.89; 95% CI 0.68, 1.16]), or unintended pregnancy (overweight OR 1.08 95% CI [0.73, 1.60]; obese OR 1.09; 95% CI [0.72, 1.63]). STI history and contraceptive compliance did not vary by BMI. Therefore, all women should receive equal contraceptive counseling (including condoms) to reduce the risk of unplanned pregnancy and STIs.

Migraine and triggers: post hoc ergo propter hoc?

The influence of environmental factors on the clinical manifestation of migraine has been a matter of extensive debate over the past decades. Migraineurs commonly report foods, alcohol, meteorologic or atmospheric changes, exposure to light, sounds, or odors, as factors that trigger or aggravate their migraine attacks. In the same way, physicians frequently follow this belief in their recommendations in how migraineurs may reduce their attack frequency, especially with regard to the consumption of certain food components. Interestingly, despite being such a common belief, most of the clinical studies have shown conflicting results. The aim of the review is to critically analyze clinical and pathophysiological facts that support or refute a correlation between certain environmental stimuli and the occurrence of migraine attacks. Given the substantial discrepancy between patients' reports and objective clinical data, the methodological difficulties of investigating the link between environmental factors and migraine are highlighted.

The Integral Theory System Questionnaire: an anatomically directed questionnaire to determine pelvic floor dysfunctions in women

Anatomical damage to pelvic floor structures may cause multiple symptoms. The Integral Theory System Questionnaire (ITSQ) is a holistic questionnaire that uses symptoms to help locate damage in specific connective tissue structures as a guide to reconstructive surgery. It is based on the integral theory, which states that pelvic floor symptoms and prolapse are both caused by lax suspensory ligaments. The aim of the present study was to psychometrically validate the ITSQ. Established psychometric properties including validity, reliability, and responsiveness were considered for evaluation. Criterion validity was assessed in a cohort of 110 women with pelvic floor dysfunctions by analyzing the correlation of questionnaire responses with objective clinical data. Test-retest was performed with questionnaires from 47 patients. Cronbach's alpha and "split-half" reliability coefficients were calculated for inner consistency analysis. Psychometric properties of ITSQ were comparable to the ones of previously validated Pelvic Floor Questionnaires. Face validity and content validity were approved by an expert group of the International Collaboration of Pelvic Floor surgeons. Convergent validity assessed using Bayesian method was at least as accurate as the expert assessment of anatomical defects. Objective data measurement in patients demonstrated significant correlations with ITSQ domains fulfilling criterion validity. Internal consistency values ranked from 0.85 to 0.89 in different scenarios. The ITSQ proofed accurate and is able to serve as a holistic Pelvic Floor Questionnaire directing symptoms to site-specific pelvic floor reconstructive surgery.

Satisfaction for quality of life: a comparison of patient and occupational therapist perspectives

Objective: To verify whether the patient's satisfaction with quality of life (QoL) is similar to or different from the occupational therapist's perception of the patient's satisfaction. Materials and methods: Each patient enrolled was given the Satisfaction Profile (SAT-P) questionnaire to be filled out personally; the same questionnaire, the SAT-P, was given to the respective occupational therapist who was asked to fill it out by evaluating the patient's satisfaction as perceived by the therapist. A descriptive statistic was applied for socio-demographic data to describe the cohort. Differences between patient and therapist answers to the SAT-P were evaluated using a t-test. Results: 12 occupational therapists and 69 patients participated in the study. A significant difference between occupational therapist and patient was found for Factor II (physical functioning) (p = 0.048) and for Factor V (social functioning) (p = 0.011). The comparison of patient and therapist mean scores showed that therapists had a tendency to underestimate patient satisfaction levels for all factors except Factor IV. Discussion: The results showed similarities between the therapist and the patient's view of the patient's satisfaction with QoL, confirming occupational therapy as a client-centred discipline. However, as far as physical functioning is concerned, it is possible that the professional makes an “a priori” judgement, considering the objective clinical data regardless of the patient's subjective experience of his/her illness.

Point/Counterpoint

Point/Counterpoint

Long term follow-up of infliximab efficacy in pulmonary and extra-pulmonary sarcoidosis refractory to conventional therapy

IntroductionInfliximab, a humanized, chimeric, monoclonal antibody against tumor necrosis alpha (TNF-α), has been shown to reduce the pulmonary and extra-pulmonary manifestations of sarcoidosis, however, there is little information regarding sustained efficacy with long-term use of infliximab. We retrospectively investigate whether a reduction in disease response is maintained, over a prolonged course of therapy (up to 85 months) with infliximab, and report on adverse events associated with its use. MethodsSubjects with multi-organ sarcoidosis were prescribed infliximab, between January 2000 to June 2010 due to failure of conventional therapy and were identified from the Drexel University College of Medicine sarcoidosis clinic. Retrospective patient reported symptom and objective clinical data analyses of pulmonary and extra-pulmonary findings were evaluated pre-infliximab and post or concurrent infliximab therapy. Any adverse events or reasons for discontinuation during infliximab therapy were reported. ResultsTwenty-six patients with biopsy proven sarcoidosis received anti-TNF therapy and met the criteria for study inclusion. Clinical evidence of sustained resolution or improvement was demonstrated in 58.5% of all organs assessed (p =<0.001). No clinical change in disease activity was seen in 35.8% of all organs evaluated. Despite infliximab treatment, 5.7% had progressive disease activity. Adverse events were seen in 57.7% of patients treated with infliximab over a 46.2 month average duration of therapy. Three (12%) patients had an adverse event that required permanent discontinuation. ConclusionsInfliximab is efficacious in the treatment of extra-pulmonary sarcoidosis and the efficacy is maintained with prolonged treatment. In patients with pulmonary sarcoid, sustained improvement in pulmonary imaging was seen after initiation of infliximab, however, post-treatment pulmonary function testing was not conclusive. Long-term infliximab therapy was well tolerated for our study group.

EVAR for Ruptured Aneurysms: Are the Data Complete?

Endovascular abdominal aneurysm repair is now the preferred therapy for many patients with abdominal aortic aneurysms and has been associated with reduced immediate and short-term morbidity and mortality. Because perioperative complications so often compromise the open repair of ruptured aortic aneurysms, EVAR has been considered as an attractive option in these patients. A number of small, typically single-center studies have demonstrated excellent results. In the absence of compelling, objective clinical data, there are certainly many patients with ruptured aortic aneurysms who are well-suited for EVAR. The development of protocols and systems for the expeditious diagnosis and treatment of ruptured aneurysms should further improve therapy for this life-threatening condition.

Helicobacter pylori infection in patients with nonalcoholic fatty liver disease

ObjectiveClinical data regarding Helicobacter pylori (Hp) infection in nonalcoholic fatty liver disease (NAFLD) are limited. The aim was the evaluation of Hp infection in patients with NAFLD and its association with disease severity. Methods28 patients with biopsy-proven NAFLD (15 with simple nonalcoholic fatty liver [NAFL], 13 with nonalcoholic steatohepatitis [NASH]) and 25 matched healthy controls were recruited. Blood samples for anti-Hp Immunoglobulin G (IgG) and standard biochemical tests were obtained after overnight fasting, and 13C urea breath test was performed before liver biopsy in NAFLD group. ResultsHigher rates of anti-Hp IgG (P=.038) were observed in NAFLD compared to control group. Only two NAFLD patients neither were Hp IgG seropositive nor did they have a history of eradication treatment compared to 11 control subjects (P=.002). Both Hp infection (assessed by history of Hp eradication treatment and/or Hp IgG seropositivity) (P=.034) and log(HOMA-IR) (P=.007) could independently predict NAFLD in logistic regression analysis. There were similar rates of Hp IgG seropositivity or positivity in 13C urea breath test or their combination between NAFL and NASH patients. There were no significant differences in steatosis grade, fibrosis stage, lobular or portal inflammation, or ballooning, when NAFLD patients were divided according to Hp IgG seropositivity or 13C urea breath test positivity. ConclusionsHp infection may represent one more hit contributing to the pathogenesis of NAFL, though not to the progression from NAFL to NASH. These results warrant further validation. If confirmed, eradicating Hp infection may have certain therapeutic perspectives in NAFLD treatment.

Safety of Selegiline Transdermal System in Clinical Practice

The objective of this analysis is to present the safety profile of selegiline transdermal system (STS) in clinical practice after US Food and Drug Administration approval by analyzing reported postmarketing adverse events (AEs). Deidentified data were obtained on AEs, regardless of causality, as collected and compiled in the pharmaceutical company's adverse event collection systems/databases after the launch of STS in the United States. All reports of hypertensive crisis, suicide attempts, and STS overdoses were carefully examined to independently determine relation of the AE to STS. From April 2006 to October 2010, a total of 3,155 AEs in 1,516 patients were reported (5.2% of the total exposures; N = 29,141), regardless of causality. The most frequently reported categories of AEs were general disorders (no. of AEs = 1,037, 3.6%) and central nervous system (CNS) disorders (no. of AEs = 574, 2.0%). A total of 266 reports (0.9%) were classified as serious AEs; CNS disorders (no. of AEs = 71, 26.7%) and cardiac and vascular disorders (no. of AEs = 44, 16.5%) were most common. There were 13 self-reports of possible hypertensive events or hypertension, although objective clinical data were not submitted in any of these cases. Thirteen drug-drug interactions (0.04%) were reported, and 5 were classified as serious. The most commonly reported AEs were application site reactions and insomnia. Very few patients reported a hypertensive event, and there were no objectively confirmed reports of hypertensive crisis with food at any STS dose. Therapeutic doses of STS appear to have a safety profile in clinical practice that is consistent with that observed in clinical trials. However, given the relatively modest exposure numbers, continued safety monitoring is recommended.

Genomic pathology: a disruptive innovation.

237 ISSN 1741-0541 10.2217/PME.12.5 © 2012 Future Medicine Ltd Personalized Medicine (2012) 9(3), 237–239 “...genomic pathology [is] founded on the premise that sequencing the human genome is rapidly becoming so routine and inexpensive that it will inevitably find its way into fundamental aspects of healthcare – not only in disease diagnosis and management, but also disease prevention, risk mitigation and health maintenance.”

The long term effectiveness of intensive stuttering therapy: A mixed methods study

PurposeThe purpose of this study was to gain a deeper understanding of client perceptions of an intensive stuttering therapy program that utilizes a multi-faceted approach to therapy. The study also proposed to gain a deeper understanding about the process involved in long-term maintenance of meaningful changes made in therapy. MethodsThe study used a mixed methods design. The core method was a phenomenological approach using semi-structured interviews. Objective clinical data was gathered concurrently. This included archival records and current measures on a variety of assessments to evaluate stuttering severity and attitudes toward communication. ResultsThe major themes generated from participants’ transcripts included (1) the positive effects of the Duration and Nature of the Program; (2) Speech Techniques Learned; (3) Attitude Change and Counseling; and (4) activities related to Desensitization and Transfer. The participants also reported positive effects of their personal motivation and clinician attitudes. Clinical data indicated that the participants made measurable clinical gains on all measures of stuttering severity and attitude change following the intensive clinic and these changes were maintained long after the program was completed. ConclusionsIt appears that this intensive stuttering therapy program is effective for making positive changes in behavioral measures of speech disfluencies, and attitudes. Clients reported multiple factors directly related to the program and personal factors that contributed to treatment effectiveness. Hence, future studies should explore and report on a variety of factors related to communication attitudes and overall quality of life in addition to behavioral measures of speech.Educational objectives: After reading this article, the learner will be able to: (a) identify the basic tenets of evidence-based practice; (b) summarize what we currently know about the effectiveness of behavioral treatments of stuttering; (c) identify factors that client report as important to treatment effectiveness.

Basic Clinical and Laboratory Features of Filoviral Hemorrhagic Fever

The filoviruses Marburg and Ebola cause severe hemorrhagic fever (HF) in humans. Beginning with the 1967 Marburg outbreak, 30 epidemics, isolated cases, and accidental laboratory infections have been described in the medical literature. We reviewed those reports to determine the basic clinical and laboratory features of filoviral HF. The most detailed information was found in descriptions of patients treated in industrialized countries; except for the 2000 outbreak of Ebola Sudan HF in Uganda, reports of epidemics in central Africa provided little controlled or objective clinical data. Other than the case fatality rate, there were no clear differences in the features of the various filovirus infections. This compilation will be of value to medical workers responding to epidemics and to investigators attempting to develop animal models of filoviral HF. By identifying key unanswered questions and gaps in clinical data, it will help guide clinical research in future outbreaks.

Lobar Atrophy in Frontotemporal Dementia: Diagnostic and Prognostic Implications

We review the practical importance of lobar atrophy in frontotemporal dementia (FTD), for diagnosis and prognosis. We discuss specific patterns of frontotemporal atrophy that denote clinical and pathological subtypes of FTD (e.g. semantic dementia). We also discuss the unsatisfactory clinical experience of interpreting MRI scans in individual FTD cases, especially the behavioural presentations (without aphasic or motor impairments). This issue is explored by examining the FTD phenocopy concept. Lobar atrophy emerges as a key observation in defining behavioural FTD patients whose symptoms are likely to progress. In a situation where objective clinical data are few, we highlight the importance of applying caution before diagnosing FTD is the absence of visible brain atrophy.

Sweating ability and genotype in individuals with X-linked hypohidrotic ectodermal dysplasia

BackgroundX-linked hypohidrotic ectodermal dysplasia (XLHED), the most common type of ectodermal dysplasia, is caused by EDA gene mutations. Reduced sweating contributes substantially to XLHED associated morbidity and mortality. To characterise...

Keratoconus-integrated characterization considering anterior corneal aberrations, internal astigmatism, and corneal biomechanics

To evaluate the clinical features of keratoconus taking into consideration anterior corneal aberrations, internal astigmatism, and corneal biomechanical properties and to define a new grading system based on visual limitation. Vissum Corporation, Alicante, Spain. Retrospective case series. This multicenter study comprised consecutive keratoconic eyes with no previous ocular surgery or active ocular disease. Visual, refractive, corneal topography, and pachymetry outcomes were analyzed. Internal astigmatism was calculated by vectorial analysis. Corneal aberrations and corneal biomechanics characterized by the Ocular Response Analyzer were evaluated in some eyes. Correlations between clinical data and a linear multiple regression analysis for characterizing the relationship between visual limitation and objective clinical data were performed. This study comprised 776 eyes of 507 patients (age range 11 to 79 years) The mean keratometry (K) correlated significantly with logMAR corrected distance visual acuity (CDVA) (r = 0.591, P<.01), internal astigmatism (r = 0.497, P<.01), corneal asphericity (r = -0.647, P<.01), and several corneal higher-order aberrometric coefficients (r≥0.603, P<.01). Significant correlations were found between some corneal aberrometric parameters and CDVA (r≥0.444, P<.01). Multiple regression analysis showed that CDVA was significantly correlated with the mean K, intraocular pressure, corneal resistance factor, and spherical equivalent (r(2) = 0.69, P<.01). There were significant differences in mean K, internal astigmatism, and corneal higher-order aberrations between 4 groups differentiated by visual limitation (P<.01). The visual limitation in keratoconus could be explained by different alterations that occur in these corneas and allowed development of a new grading system for this condition.

Pneumococcal meningitis post‐cochlear implantation: Preventative measures

Objective Both clinical data and laboratory studies demonstrated the risk of pneumococcal meningitis post-cochlear implantation. This review examines strategies to prevent post-implant meningitis. Data Sources Medline/PubMed database; English articles after 1980. Search terms: cochlear implants, pneumococcus meningitis, streptococcus pneumonia, immunization, prevention. Review Methods Narrative review. All articles relating to post-implant meningitis without any restriction in study designs were assessed and information extracted. Results The presence of inner ear trauma as a result of surgical technique or cochlear implant electrode array design was associated with a higher risk of post-implant meningitis. Laboratory data demonstrated the effectiveness of pneumococcal vaccination in preventing meningitis induced via the hematogenous route of infection. Fibrous sealing around the electrode array at the cochleostomy site, and the use of antibiotic-coated electrode array reduced the risk of meningitis induced via an otogenic route. Conclusion The recent scientific data support the U.S. Food and Drug Administration recommendation of pneumococcal vaccination for the prevention of meningitis in implant recipients. Nontraumatic cochlear implant design, surgical technique, and an adequate fibrous seal around the cochleostomy site further reduce the risk of meningitis.