Serum 25-Hydroxyvitamin D Insufficiency in Search of a Bone Disease.

Context: Vitamin D "insufficiency" and "deficiency" are defined as serum 25-hydroxyvitamin D [25(OH)D] levels <75 and <30 nmol/L, respectively. We aimed to determine whether these values signal hypocalcemia and hypophosphatemia, secondary hyperparathyroidism, high bone remodeling, low areal bone mineral density (aBMD), microstructural deterioration, or reduced matrix mineralization density (MMD) and so suggest whether bone fragility is present. Methods: Concentrations of 25(OH)D, calcium, phosphate, creatinine, and parathyroid hormone (PTH) were measured in 11,855 participants. Serum C-terminal telopeptide of type 1 collagen, procollagen type 1 N-terminal propeptide (P1NP), aBMD, and distal radius microstructure and MMD were measured in a second subset of 150 participants. Results: A breakpoint for calcium, PTH, and alkaline phosphatase was identified at a threshold 25(OH)D level <30 nmol/L. There was no plateau beyond 75 nmol/L. In the subgroup with measurements of bone morphology, no associations were detectable between serum 25(OH)D concentration, aBMD, trabecular density, cortical porosity, or MMD. Among 1439 participants with serum 25(OH)D <30 nmol/L, 6.1% had low serum calcium, 3.4% had low serum phosphate, 6.1% had high alkaline phosphatase, and 34.2% had elevated PTH. Most participants did not have any abnormalities. Conclusion: At a 25(OH)D threshold of ≤30 nmol/L, abnormalities in biochemical features support the notion of a "deficiency" state predisposing to bone disease. However, no deleterious effects were found in participants within an insufficiency threshold of a 25(OH)D level of 30 to 75 nmol/L, which challenges the rationale justifying vitamin D supplementation in these individuals.

Patient characteristics and healthcare utilization of a chronic pain population within an integrated healthcare system.

OBJECTIVES: We sought to characterize the chronic pain (CP) population and healthcare utilization across types of CP within a community-based healthcare system. STUDY DESIGN: Cross-sectional study of electronic health records data from 2012. METHODS: Patients 18 years or older with at least 2 encounter diagnoses for CP conditions in 2012 were included in the study. Patients were categorized into non-mutually exclusive CP types: arthritis/joint pain, back/cervical pain, neuropathies/neuralgias, headaches/migraines, and unclassified pain. RESULTS: Of 1,784,114 patients, 120,481 (6.8%) met the criteria for the CP study cohort. Within the cohort, the most common types of CP were arthritis/joint pain (57%), back/cervical pain (49%), and neuropathy/neuralgias (40%). Patients with neuropathies/neuralgias were older than patients with other pain types and had more comorbidities (for neuropathies/neuralgias: mean age, 59 years; Charlson Comorbidity Index score >3, in 28% of patients). Patients with unclassified pain were most likely to be female (82%). Rates of office and emergency department (ED) visits were highest in patients with unclassified pain (5136 events and 209 events per 1000 patients, respectively). Rates of hospitalizations and 30-day hospital readmissions were highest in patients with neuropathies/neuralgias (70 events and 287 events per 1000 patients, respectively). An increased number of CP types was linearly associated with higher rates of office, ED, and hospital visits. CONCLUSIONS: Based on prevalence, comorbidities, and healthcare utilization, several types of CP, including neuropathies/neuralgias, arthritis/joint pain, and unclassified pain, appear to be most impactful. Health systems can use these findings to target efforts to improve the management of patients with CP, particularly those with multiple pain-related conditions.

Bromelain limits airway inflammation in an ovalbumin-induced murine model of established asthma.

CONTEXT: Allergic asthma continues to increase despite new pharmacological advances for both acute treatment and chronic-disease management. Asthma is a multifactorial disease process with genetic, allergic, infectious, environmental, and dietary origins. Researchers are investigating the benefits of lifestyle changes and alternative asthma treatments, including the ability of bromelain to inhibit inflammation. Bromelain is a commonly used, proteolytically active pineapple extract. OBJECTIVE: The present study intended to determine the ability of bromelain to reduce the inflammation of preexisting asthma via an ovalbumin (OVA)-induced murine model of allergic airway disease (AAD). DESIGN: The research team designed a study examining the effects of bromelain in a control group of mice that received phosphate buffered saline (PBS) only and in an intervention group that received bromelain in PBS. Setting The study took place in the Department of Immunology at the University of Connecticut's School of Medicine, Farmington. Intervention The research team sensitized female C57BL/6J mice with intraperitoneal OVA/alum and then challenged them with OVA aerosolization for 10 consecutive days. On day 4, the team began administering daily doses of PBS to the control group (n = 10) and bromelain (6mg/kg) in PBS to the bromelain (intervention) group (n = 10). OUTCOME MEASURES: The primary measures included bronchoalveolar lavage (BAL) cellular differential, cellular phenotype via flow cytometry, and lung histology. Additional outcomes included testing for serum cytokines and immunoglobulin. RESULTS: Bromelain treatment of AAD mice (bromelain group) resulted in significant anti-inflammatory activity as indicated by reduced BAL total leukocytes (P < .05), eosinophils (P < .05), and cellular infiltrates via lung pathology (P < .005), as compared to the control group. In addition, bromelain significantly reduced BAL CD4+ and CD8+ T cells without affecting cell numbers in the spleen or hilar lymph node. The study found decreased interleukins IL-4, IL-12, IL-17, as well as IFN-α in the serum of bromelain-treated animals. CONCLUSIONS: The results suggest that bromelain has a therapeutic effect in established AAD, which may translate into an effective adjunctive therapy in patients with similar conditions, such as allergic asthma, who have chosen to initiate treatment after the onset of symptoms.

The effect of 595 nm pulsed dye laser on superficial and nodular basal cell carcinomas.

BACKGROUND AND OBJECTIVE: Basal cell carcinomas (BCCs) have supporting vasculature that could serve as a target for 595 nm pulsed dye laser (PDL). The objective of this study was to determine the effect of repeated PDL treatments on BCCs of superficial and nodular subtypes and of varying diameters. STUDY DESIGN/MATERIALS AND METHODS: Twenty biopsy-proven BCCs received four 595 nm PDL treatments at 2-week intervals. The tumor and 4 mm of peripheral skin were treated using a set of previously optimized laser parameters: one pass, 15 J/cm2 energy, 3 ms pulse length, no cooling, and 7 mm spot size with 10% overlap. The treated area was excised and evaluated histologically for residual tumor. Histologic response rates of the PDL treated BCCs were compared with that of non-PDL treated, matched control tumors. RESULTS: Nearly all BCCs <1.5 cm in diameter (n = 12) showed complete response to four PDL treatments (91.7%; n = 11/12) versus 16.7% of controls (n = 2/12, P-value = 0.0003). BCCs > or =1.5 cm in diameter (n = 8) showed a complete response rate of 25% (n = 2/8) versus 0% of controls (n = 0/8, P-value = 0.2). Mean clinical tumor diameter of the complete responders was 1.1 cm (n = 13) versus 2.2 cm (n = 7) for incomplete responders (P-value = 0.005). Tumor histologic types among the complete responders included superficial, nodular, micronodular, and keratinizing. Incompletely responding BCCs showed a significant reduction in tumor burden after PDL treatment, with residual histologic tumor burden ranging from <1% to 29% of the original clinical tumor diameter, compared to 13-68% residual tumor burden for the corresponding controls (P-value = 0.05). CONCLUSIONS: PDL is an effective means of reducing tumor burden in patients with large BCCs and may be an alternative therapy in BCCs <1.5 cm in diameter.

Quality of life terminology included in package inserts for US approved medications.

OBJECTIVES: To identify and review prescription drugs approved in the US containing quality of life (QoL) terminology within the package inserts (PIs). METHODS: The electronic Physician Desk Reference (PDR) was searched for the terminology 'Quality of Life' or 'QoL' as of December 2000. Summary basis of approvals (SBAs) served as the primary data sources were retrieved. The two categories evaluated within the SBAs were QoL components (year submitted, trials, efficacy, statistics, type of submission) and QoL instruments utilized within clinical studies. RESULTS: Eighteen medications comprising 20 indications with QoL claims were documented in the PIs. The first approved QoL claim was submitted in 1989 and the most recent was in 1998. Eight (40%) of the drug indications had QoL measures included in two trials. One quarter of the PI listings used QoL measures as primary efficacy endpoints. Many sponsors provided detailed information on the types or categories of QoL data collected. CONCLUSION: Many drug development programs incorporate QoL measures into clinical studies however only a few are accepted into the PI. Despite this study finding, the increased interest in assessing the value and full impact of new therapies has led to greater inclusion of all types of patient assessments in clinical trials.