Effect of Resveratrol on Serum Levels of Type II Collagen and Aggrecan in Patients with Knee Osteoarthritis: A Pilot Clinical Study

Treatment of knee osteoarthritis (OA) remains a challenging concern. Preclinical studies provided accumulating evidence on resveratrol efficacy in ameliorating degenerative articular damage. The present study was conducted to evaluate the effects of resveratrol as monotherapy on the serum level of type II collagen (Coll 2-1) and aggrecan in patients with knee osteoarthritis. The study was an open-labeled noncontrolled clinical trial. Resveratrol 500 mg/day in a single oral dose was given to the patients with knee osteoarthritis for 90 days. The serum levels of Coll-2-1, aggrecan, and biomarkers of inflammation were measured pre- and posttreatment. Hematological profiles and both hepatic and renal function markers were investigated at the baseline and at the end of the treatment for evaluating the tolerability and safety of resveratrol. Visual Analog Scale (VAS) for pain and Knee injury and Osteoarthritis Outcome Score (KOOS) for disease activity were clinically assessed monthly. Administration of 500 mg resveratrol for three months led to a nonsignificant decrease in the serum level of Coll 2-1 while a significant increase in aggrecan serum level. Resveratrol significantly improves pain score measured by VAS and KOOS after 30 days. Improvements in patients’ activity and functional status were also evident at day 30 and kept on for three months which was reflected by KOOS subscale scores and with a significant improvement in all KOOS areas. In conclusion, oral administration of resveratrol as a monotherapy provides a remarkable improvement in the clinical status of the patients but has no significant effect on serum levels of Coll 2-1.

Fluralaner 5.46% (W/W) Flavored Chewable Tablet (Bravecto® 1-Month) Is Effective for Treatment of Canine Generalized Demodicosis

Background: Orally administered fluralaner (13.64% w/w) is effective for treating canine generalized demodicosis. A study was initiated to assess the efficacy of a novel 5.46% w/w fluralaner chewable tablet formulation for monthly administration in the treatment of this disease.Methods: Client-owned dogs diagnosed with generalized demodicosis were acclimatized to laboratory conditions and randomized to receive either orally administered fluralaner (Bravecto® 1-Month) (10.0 to 14.4 mg/kg body weight) (n = 8) or topical imidacloprid-moxidectin (Advocate® for dogs, Elanco) applied per label on Days 0, 28 and 56 (n = 8), or more frequently for ongoing severe demodicosis. On Days -2, 28, 56 and 84, deep skin scrapings were taken from 5 sites on each dog for mite identification and counting, and semi-quantitative clinical assessments of generalized demodicosis were recorded. Primary efficacy was based upon arithmetic mean mite count reductions relative to pre-treatment.Results: By Day 28, mean pre-treatment mite counts, >600 in both groups, were significantly reduced by 99.7% and 89.5% (both P < 0.001) in the fluralaner and imidacloprid-moxidectin groups, respectively. Parasitological cure (100% reduction in mite counts on Days 56 and 84) was achieved in all fluralaner-treated dogs (100%) and in 2 imidacloprid-moxidectin treated dogs (25%). In the imidacloprid-moxidectin group, the reduction in mean mite counts was 89.5% (Day 28), 94.4% (Day 56) and 97.5% (Day 84). All study dogs were free of crusts on Days 56 and 84. Scales resolved by Day 84 in all fluralaner-treated dogs and in 3 imidacloprid-moxidectin treated dogs. All fluralaner-treated dogs and 5 imidacloprid-moxidectin treated dogs had > 90% hair re-growth on Day 84.Conclusion Three consecutive monthly oral administrations of fluralaner (5.46% w/w) flavored chewable tablets (minimum dose rate 10 mg/kg body weight) eliminated Demodex canis mites from dogs diagnosed with generalized demodicosis.

Vitamin D oral intermittent treatment (DO IT) study, a randomized clinical trial with individual loading regimen

Comparison of several regimens of oral vitamin D including an individually calculated loading regimen with the aim of achieving serum values > 75 nmol/l. Interventional, randomized, 3-arm study in vitamin D-deficient outpatients. Participants were allocated to supplementation of 24,000 IU vitamin D monthly over three months, using either a monthly drinking solution (Vi-De 3) or capsule (D3 VitaCaps), or an individualized loading regimen with the capsules taken weekly. For the loading regimen, the cumulative dose was calculated according to baseline 25-hydroxy-vitamin D (25(OH)D) serum value and body weight. Main inclusion criteria were age ≥ 18 years and 25(OH)D serum concentration < 50 nmol/l. The primary outcome was 25(OH)D serum concentration one week after treatment termination. Secondary endpoints were patient’s preferences and adverse events. Full datasets were obtained from 52 patients. Mean 25(OH)D values were statistically significant higher after a loading regimen compared to a monthly administration of 24,000 IU vitamin D (76.4 ± 15.8 vs 61.4 ± 10.8 nmol/l; p < 0.01). All patients treated with the loading regimen reached sufficient 25(OH)D values > 50 nmol/l. Serum 25(OH)D values > 75 nmol/l were observed more frequently in patients taking the loading regimen (47% vs 11% drinking solution vs 12% capsules). Vitamin D-related adverse effects did not occur in any treatment groups. Capsules were preferred by 88.5% of the patients. Compared to treatments with monthly intake of 24,000 IU vitamin D, the intake of an individually calculated weekly loading regimen was able to raise serum concentrations > 50 nmol/l in all cases within a safe range.

Effectiveness of intermittent preventive treatment in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) in Ghana

IntroductionGhana adopted the revised WHO recommendation on intermittent preventive treatment in pregnancy using sulfadoxine-pyrimethamine (IPTp-SP) in 2012. This study has assessed the effectiveness and safety of this policy in Ghana.MethodsA total of 1926 pregnant women enrolled at antenatal care (ANC) clinics were assessed for birth outcomes at delivery, and placental histology results for malaria infection were obtained from 1642 participants. Association of reduced placental or peripheral malaria, anaemia and low birth weight (LBW) in women who received ≥4 IPTp-SP doses compared with 3 or ≤2 doses was determined by logistic regression analysis.ResultsAmong the 1926 participants, 5.3% (103), 19.2% (369), 33.2% (640) and 42.3% (817) of women had received ≤1, 2, 3 or ≥4 doses, respectively. There was no difference in risk of active placental malaria (PM) infection in women who received 3 doses compared with ≥4 doses (adjusted OR (aOR) 1.00, 95% CI 0.47 to 2.14). The risk of overall PM infection was 1.63 (95% CI 1.07 to 2.48) in 2 dose group and 1.06 (95% CI 0.72 to 1.57) in 3 dose group compared with ≥4 dose group. The risk of LBW was 1.55 (95% CI 0.97 to 2.47) and 1.06 (95% CI 0.68 to 1.65) for 2 and 3 dose groups, respectively, compared with the ≥4 dose group. Jaundice in babies was present in 0.16%, and 0% for women who received ≥4 doses of SP.ConclusionThere was no difference in the risk of PM, LBW or maternal anaemia among women receiving 3 doses compared with ≥4 doses. Receiving ≥3 IPTp-SP doses during pregnancy was associated with a lower risk of overall PM infection compared with 2 doses. As there are no safety concerns, monthly administration of IPTp-SP offers a more practical opportunity for pregnant women to receive ≥3 doses during pregnancy.

Use of Buprenorphine for the Treatment of Opioid Use Disorder

Buprenorphine is a mu-opioid partial agonist that was first developed as a parenteral analgesic and subsequently as a treatment for opioid dependence. In the United States, the first two products approved by the US Food and Drug Administration (in 2002) for the latter indication were buprenorphine (Subutex) and buprenorphine/naloxone (Suboxone) tablet formulations for sublingual administration. Since that time, additional products for both sublingual and buccal administration have also been approved, as well as a subcutaneous injection for once-monthly administration for the treatment of moderate or severe opioid use disorder (OUD) and a subdermal implant for the maintenance treatment of opioid dependence that delivers buprenorphine over a 6-month period. Under the Drug Addiction Treatment Act of 2000 (DATA 2000), qualified practitioners may apply for waivers to treat opioid dependence/OUD with approved buprenorphine products in any setting in which they are qualified to practice. Like other opioids, buprenorphine has the potential for being misused and abused.

Oral intermittent Vitamin D substitution: Influence of pharmaceutical form and dosage frequency on medication adherence: A randomized clinical trial

Background To assess adherence to and preference for vitamin D substitution with different pharmaceutical forms and frequencies of administration. Methods A focus group of stakeholders aimed at preparing the design of an interventional, randomized, cross-over study with 2 x 2 groups obtaining monthly or weekly vitamin D products in liquid or solid form for 3 months each. Dosage corresponds to cumulated amount of recommended 800 IU daily (5.600 IU weekly / 24.000 IU monthly). Main inclusion criteria were a vitamin D serum value <50 nmol/l and age ≥18 years. Primary endpoint was adherence, secondary endpoints were preferences and vitamin D serum levels. Results The focus group reached consensus for preference of a monthly administration of solid forms to adults. Full datasets were obtained from 97 participants. Adherence was significantly higher with monthly (79.5 – 100.0%) than weekly (66.4 – 98.1%) administration. Vitamin D levels increased significantly (p<0.001) in all participants. An optimal value of >75 nmol/l was achieved by 32% after 3 months and by 50% after 6 months. Preferred formulation was solid form (tablets, capsules) for 71% of participants, and preferred dosage frequency was monthly for 39% of participants. Conclusions Monthly oral vitamin D in solid form lead to the highest adherence, and is preferred by the participants. However, only one third of study participants achieved values in the optimal range of >75 nmol/l cholecalciferol using weekly or monthly administration providing an average daily cholecalciferol dose of 800 IU.

Oral intermittent Vitamin D substitution: Influence of pharmaceutical form and dosage frequency on medication adherence: A randomized clinical trial

Background: To assess adherence to and preference for vitamin D substitution with different pharmaceutical forms and frequencies of administration.Methods: A focus group of stakeholders aimed at preparing the design of an interventional, randomized, cross-over study with 2 x 2 groups obtaining monthly or weekly vitamin D products in liquid or solid form for 3 months each. Dosage corresponds to cumulated amount of recommended 800 IU daily (5.600 IU weekly / 24.000 IU monthly). Main inclusion criteria were a vitamin D serum value <50 nmol/l and age ≥18 years. Primary endpoint was adherence, secondary endpoints were preferences and vitamin D serum levels. Results: The focus group reached consensus for preference of a monthly administration of solid forms to adults. Full datasets were obtained from 97 participants. Adherence was significantly higher with monthly (79.5 – 100.0%) than weekly (66.4 – 98.1 %) administration. Vitamin D levels increased significantly (p<0.001) in all participants. An optimal value of >75 nmol/l was achieved by 32% after 3 months and by 50% after 6 months. Preferred formulation was solid form (tablets, capsules) for 71% of participants, and preferred dosage frequency was monthly for 39% of participants.Conclusions: Monthly oral vitamin D in solid form lead to the highest adherence, and is preferred by the participants. However, only one third of study participants achieved values in the optimal range of >75 nmol/l cholecalciferol using weekly or monthly administration providing an average daily cholecalciferol dose of 800 IU.

Monthly Intramuscular Neridronate for the Treatment of Postmenopausal Osteoporosis: Results of a 6-Year Prospective Italian Study

Purpose. Oral bisphosphonates (BPs) are the most commonly used medications for osteoporosis (OP), but their poor gastrointestinal (GI) absorption and tolerance hamper compliance. Intramuscular (IM) neridronate (NE), an amino-BP, is an easy-to-administer, effective, and safe alternative to oral BPs. We assessed the 6-year effects of monthly IM NE on bone mineral density (BMD) and bone turnover biomarkers (BMs) in postmenopausal OP. Methods. This single-center, prospective study enrolled postmenopausal osteoporotic outpatients with gastric intolerance to BPs (based on Tuscany Region’s law GRT n. 836 20/10/2008). They received 25 mg IM NE once a month (with vitamin D and calcium if necessary) for 6 years. BMD was evaluated at lumbar spine (L1-L4), femoral neck (FN), and total femur (TF) at baseline (BL) and every 12 months afterwards. At BL, month 3, and every 12 months after BL, total and ionized calcium, vitamin D, parathyroid hormone 1-84, bone alkaline phosphatase (BALP), osteocalcin, and N- and C-terminal telopeptides were assayed. Results. Overall, 60 women (mean age: 62.3±7.5 years) received monthly IM NE for 6 years, with vitamin D and calcium supplementation in 81.3% of cases. Compared to BL, BMD increased significantly already after 1 year at all sites (4.5±0.9% for L1-L4, 4.5±0.8% for TF, and 2.1±0.6% for FN, P≤0.05), and the changes were maintained over time, whereas FN further improved up to year 3 and remained stable afterwards (P≤0.05). All BMs, except for total calcium and BALP, progressively decreased over time (P≤0.05). No fractures and significant adverse events were reported. Conclusion. The monthly administration of IM NE represents a manageable and effective option, in terms of BMD and bone BM improvement, for the long-term treatment of postmenopausal OP women with gastric intolerance to BPs. This trial is registered with ClinicalTrials.gov Identifier: NCT03699150.