An overview of local anesthetics in over-the-counter products.

Over-the-counter (OTC) local anesthetics have historically been used to alleviate pain in several common conditions including toothache and sore throat. With a rise in chronic conditions and an aging population, there has been an increase in associated chronic pain-related disorders. Individuals with chronic pain often seek OTC treatments for quick and accessible pain relief. There are several common OTC local anesthetics, including benzocaine, lidocaine, and dibucaine, which are readily available to patients in several formulations. In order to appropriately advise patients on the use of local anesthetics, it is important to understand their key characteristics, including the mechanism of action, clinical properties, pharmacokinetics, clinical applications, and adverse reactions, which may occur.

A pilot-randomized, double-blind crossover trial to evaluate the pharmacokinetics of orally administered 25-hydroxyvitamin D3 and vitamin D3 in healthy adults with differing BMI and in adults with intestinal malabsorption.

BACKGROUND: Obese and malabsorptive patients have difficulty increasing serum 25-hydroxyvitamin D [25(OH)D] after taking vitamin D supplementation. Since 25(OH)D is more hydrophilic than vitamin D, we hypothesized that oral 25(OH)D supplementation is more effective in increasing serum 25(OH)D concentrations in these patients. OBJECTIVES: We aimed to investigate the pharmacokinetics of oral 25-hydroxyvitamin D3 [25(OH)D3] and oral vitamin D3 in healthy participants with differing BMI and malabsorptive patients. METHODS: A randomized, double-blind crossover trial was performed in 6 malabsorptive patients and 10 healthy participants who were given 900 µg of either vitamin D3 or 25(OH)D3 orally followed by a pharmacokinetic study (PKS). After ≥28 d from the first dosing, each participant returned to receive the other form of vitamin D and undergo another PKS. For each PKS, serum vitamin D3 and 25(OH)D3 were measured at baseline and at 2, 4, 6, 8, and 12 h and days 1, 2, 3, 7, and 14. Pharmacokinetic parameters were calculated. RESULTS: Data were expressed as means ± SEMs. The PKS of 900 µg vitamin D3 revealed that malabsorptive patients had 64% lower AUC than healthy participants (1177 ± 425 vs. 3258 ± 496 ng · h/mL; P < 0.05). AUCs of 900 µg 25(OH)D3 were not significantly different between the 2 groups (P = 0.540). The 10 healthy participants were ranked by BMI and categorized into higher/lower BMI groups (5/group). The PKS of 900 µg vitamin D3 showed that the higher BMI group had 53% lower AUC than the lower BMI group (2089 ± 490 vs. 4427 ± 313 ng · h/mL; P < 0.05), whereas AUCs of 900 µg 25(OH)D3 were not significantly different between the 2 groups (P = 0.500). CONCLUSIONS: Oral 25(OH)D3 may be a good choice for managing vitamin D deficiency in malabsorption and obesity. This trial was registered at clinicaltrials.gov as (NCT03401541.

The Effect of Various Doses of Oral Vitamin D3 Supplementation on Gut Microbiota in Healthy Adults: A Randomized, Double-blinded, Dose-response Study.

BACKGROUND/AIM: To investigate the effects of vitamin D3 supplementation on gut microbiota. PATIENTS AND METHODS: Twenty adults with vitamin D insufficiency/deficiency [25(OH)D <30 ng/ml] were enrolled and given 600, 4,000 or 10,000 IUs/day of oral vitamin D3 Stool samples were collected at baseline and 8 weeks for identifying gut microbiota using 16S rRNA gene amplification and sequencing. RESULTS: Baseline serum 25(OH)D was associated with increased relative abundance of Akkermansia and decreased relative abundance of Porphyromonas (p<0.05). After the intervention, we observed a dose-dependent increase in relative abundance of Bacteroides with a significant difference between the 600 IUs and the 10,000 IUs groups (p=0.027), and Parabacteroides with a significant difference between the 600 IUs and the 4,000 IUs groups (p=0.039). CONCLUSION: Increased serum 25(OH)D was associated with increased beneficial bacteria and decreased pathogenic bacteria. A dose-dependent increase in bacteria associated with decreased inflammatory bowel disease activity was observed after vitamin D3 supplementation.

Variable Genomic and Metabolomic Responses to Varying Doses of Vitamin D Supplementation.

BACKGROUND/AIM: To assess the impact of vitamin D supplementation on genomic and metabolomic profiles and relate them to the individual's responsiveness to varying doses of vitamin D3 Patients and Methods: Healthy adults were given either 600, 4000 or 10,000 IUs vitamin D3/day for 6 months. Circulating parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D], calcium, peripheral white blood cells broad gene expression and urine and serum metabolomic profiles were evaluated. RESULTS: There was a dose-dependent effect of vitamin D supplementation on serum 25(OH)D, PTH and broad gene expression. Serum calcium levels remained normal for all study subjects and no untoward toxicity was observed. The metabolomic profiles were related to the genomic expression analysis. There were significant inter-individual effects on gene expression and metabolomic profile in response to the same dose of vitamin D3 supplementation, despite similar changes in 25(OH)D and PTH concentrations. CONCLUSION: These results may help explain the variability observed in clinical trials regarding vitamin D's non-calcemic health benefits.

Disassociation of Vitamin D's Calcemic Activity and Non-calcemic Genomic Activity and Individual Responsiveness: A Randomized Controlled Double-Blind Clinical Trial.

The aims of this randomized controlled double-blind clinical trial were to assess the impact of vitamin D supplementation on calcium metabolism and non-calcemic broad gene expression by relating them to the individual's responsiveness to varying doses of vitamin D3. Thirty healthy adults were randomized to receive 600, 4,000 or 10,000 IU/d of vitamin D3 for 6 months. Circulating parathyroid hormone (PTH), 25(OH)D, calcium and peripheral white blood cells broad gene expression were evaluated. We observed a dose-dependent increase in 25(OH)D concentrations, decreased PTH and no change in serum calcium. A plateau in PTH levels was achieved at 16 weeks in the 4000 and 10,000 IU/d groups. There was a dose-dependent 25(OH)D alteration in broad gene expression with 162, 320 and 1289 genes up- or down-regulated in their white blood cells, respectively. Our results clearly indicated that there is an individual's responsiveness on broad gene expression to varying doses of vitamin D3. Vitamin D3 supplementation at 10,000 IU/d produced genomic alterations several fold higher than 4,000 IU/d even without further changes in PTH levels. Our findings may help explain why there are some inconsistency in the results of different vitamin D's clinical trials.

Expected Sonographic Appearance of the Spleen in Children and Young Adults With Sickle Cell Disease: An Update.

OBJECTIVES: To update the imaging literature regarding spleen appearances in young patients with sickle cell disease (SCD). METHODS: We conducted a retrospective study and included 112 patients age 0 to 21 years with SCD who had at least 1 abdominal sonogram at our institution between 1999 and 2011. Radiologic findings were compared between risk groups by χ(2) analysis. Findings were correlated with other imaging modalities when available. RESULTS: In our cohort, 35.7% of patients had autosplenectomy, and 8.0% had undergone surgical splenectomy. Only 5.0% of individuals age 0 to 5 years had autosplenectomy. In those who had not undergone surgical splenectomy or autosplenectomy, 76.2% had echogenic spleens, heterogeneous-appearing spleens, or both, and patients with the homozygous sickle cell anemia (HbSS) genotype were more likely to have an abnormal spleen echo texture. Patients treated with transfusions had echogenic spleens and had a higher frequency of splenic regeneration nodules. Most patients (80%) with splenomegaly did not require surgical splenectomy after 5.7 years of follow-up. CONCLUSIONS: Twenty years ago, children with HbSS SCD were expected to have autosplenectomy by age 5 years. There have been changes in the radiologic appearance of the spleen in patients with SDC, likely due to improved supportive care and the use of acute and chronic transfusion therapy. We found that autosplenectomy is rare by age 5 years, and during childhood and adolescence, the spleen typically appears echogenic, heterogeneous, or both, depending on disease severity.

Implications of radiologic-pathologic correlation for gallbladder disease in children and young adults with sickle cell disease.

The purpose of this study is to describe gallbladder imaging findings in patients with sickle cell disease, and to determine how they correspond with occurrence of complications, need for cholecystectomy, and surgical pathology. This study is IRB approved and HIPAA compliant. Informed consent requirements were waived. We reviewed records of 77 children with sickle cell disease ages 0-18 years at the time of their first gallbladder imaging study. Demographics, hospital courses, and radiologic and pathologic reports were collected. Two pediatric radiologists independently and retrospectively reviewed the imaging studies. Statistical analysis was performed using kappa statistic, chi-squared test, and ANOVA F-test. Continuous variables were described with mean, median, variance, and range. Patients who underwent cholecystectomy (N = 25) were more likely than the patients who did not undergo cholecystectomy (N = 52) to have gallstones or sludge (100 versus 36.5 %, p = <0.0001) or other gallbladder or biliary abnormality (70.8 versus 1.9 %, p = <0.0001). Patients who did not undergo cholecystectomy more frequently had normal-appearing gallbladders and biliary tracts (63.5 versus 0 %, p = <0.0001). Ninety-two percent of patients with cholecystectomy had chronic cholecystitis on pathology, and 96 % had a complication, including chronic cholecystitis and sequelae of biliary obstruction. Young patients with sickle cell disease, cholelithiasis, and any other biliary imaging abnormality will almost certainly require cholecystectomy, and many will experience complications. The most common surgical pathologic diagnosis in this group is chronic cholecystitis, which has a variable radiologic appearance. Our findings support recommendations to perform elective cholecystectomy for children and young adults with sickle cell disease and cholelithiasis or gallbladder sludge.

A prospective randomized clinical trial of prescription of full-time versus as-desired splint wear for de Quervain tendinopathy.

PURPOSE: There is no consensus on the best protocol for splint wear in the non-operative management of de Quervain tendinopathy. This study aimed to determine if there is a difference between prescription of strict splint wear compared to selective splint wear in patients with de Quervain tendinopathy. We tested the primary null hypothesis that there is no difference in upper-extremity disability eight weeks after initiating splinting between patients prescribed full-time or as-desired splint wear. Secondary study questions addressed differences in grip strength, pain intensity, and treatment satisfaction. Additionally, we evaluated the influence of psychological factors on disability. METHODS: Eighty-three patients diagnosed with de Quervain tendinopathy were randomly allocated into two different splint-wearing instructions: full-time wear (N = 43) or as-desired wear (N = 40). At enrollment, patients had grip strength measured and completed measures of upper-extremity disability, pain intensity, and psychological distress. An average of 7.5 weeks later, patients returned for a second visit. Analysis was by intention-to-treat and with use of mean imputation for missing data. RESULTS: Fifty-eight patients (70 %; 26 in the full-time cohort and 32 in the as-desired cohort) completed the study. There were no statistically significant differences in disability (p = 0.77), grip strength (p = 0.82), pain intensity (p = 0.36), and treatment satisfaction (p = 0.91) between patients instructed to wear the splint full-time and those instructed to use it as desired. Disability at final evaluation correlated significantly with baseline levels of pain anxiety (p = 0.008), catastrophic thinking (p = 0.001), and symptoms of depression (p < 0.001). The best multivariable linear regression model included symptoms of depression alone and accounted for 32 % of the variability in disability (p < 0.001). CONCLUSION: There is no difference in patient-reported outcomes and grip strength with prescription of full-time or as-desired splinting, and patients can wear the splint as they prefer. These results suggest that splinting for de Quervain tendinopathy is palliative at best and strict rest is not disease modifying.