ESWT and alendronate sodium demonstrate equal protective effects in osteoarthritis of the knee

NASA Astrophysics Data System (ADS)

Wang, Ching-Jen; Chou, Wen-Yi; Hsu, Shan-Ling; Huang, Chien-Yiu; Cheng, Jai-Hong

2016-01-01

This study compared the effects of extracorporeal shock wave therapy (ESWT) and alendronate sodium (alendronate) in osteoarthritis (OA) of rat knees. The control group was subjected to a sham surgery and did not receive either ESWT or alendronate treatment. The OA group underwent anterior cruciate ligament transection (ACLT) and medial meniscectomy (MM) surgery and did not receive either ESWT or alendronate. The ESWT group underwent ACLT and MM surgery and received ESWT after the surgery. The alendronate group received alendronate after ACLT and MM surgery. The evaluations included radiograph, bone mineral density (BMD), serum C-telopeptide collagen II (CTX-II), cartilage oligomeric protein (COMP), alkaline phosphatase and osteocalcin, histopathological examination and immunohistochemical analysis. Radiographs at 12 weeks showed pronounced OA changes in the OA group. The BMD values, CTX-II, COMP, alkaline phosphatase and osteocalcin showed no significant difference between ESWT and alendronate groups. In histopathology, the Mankin and Safranin O scores significantly increased in the OA, ESWT and alendronate groups, but without any significant difference between the ESWT and alendronate groups. In immunohistochemical analysis, the von Willebrand factor (vWF), vascular endothelial factor (VEGF), soluble vascular cell adhesion molecule (sVCAM), proliferating cell nuclear antigen (PCNA), bone morphogenetic protein 2 (BMP-2), and osteocalcin expressions in articular cartilage and subchondral bone showed a significant decrease in the OA group, but no difference was noted between the ESWT and alendronate groups. In conclusion, ESWT and alendronate sodium demonstrate equal protective effects from developing osteoarthritis of the knee in rats.

Glucocorticoid Steroid and Alendronate Treatment Alleviates Dystrophic Phenotype with Enhanced Functional Glycosylation of α-Dystroglycan in Mouse Model of Limb-Girdle Muscular Dystrophy with FKRPP448L Mutation.

PubMed

Wu, Bo; Shah, Sapana N; Lu, Peijuan; Richardson, Stephanie M; Bollinger, Lauren E; Blaeser, Anthony; Madden, Kyle L; Sun, Yubo; Luckie, Taylor M; Cox, Michael D; Sparks, Susan; Harper, Amy D; Lu, Qi Long

2016-06-01

Fukutin-related protein-muscular dystrophy is characterized by defects in glycosylation of α-dystroglycan with variable clinical phenotypes, most commonly as limb-girdle muscular dystrophy 2I. There is no effective therapy available. Glucocorticoid steroids have become the standard treatment for Duchenne and other muscular dystrophies with serious adverse effects, including excessive weight gain, immune suppression, and bone loss. Bisphosphonates have been used to treat Duchenne muscular dystrophy for prevention of osteoporosis. Herein, we evaluated prednisolone and alendronate for their therapeutic potential in the FKRPP448L-mutant mouse representing moderate limb-girdle muscular dystrophy 2I. Mice were treated with prednisolone, alendronate, and both in combination for up to 6 months. Prednisolone improved muscle pathology with significant reduction in muscle degeneration, but had no effect on serum creatine kinase levels and muscle strength. Alendronate treatment did not ameliorate muscle degeneration, but demonstrated a limited enhancement on muscle function test. Combined treatment of prednisolone and alendronate provided best improvement in muscle pathology with normalized fiber size distribution and significantly reduced serum creatine kinase levels, but had limited effect on muscle force generation. The use of alendronate significantly mitigated the bone loss. Prednisolone alone and in combination with alendronate enhance functionally glycosylated α-dystroglycan. These results, for the first time, demonstrate the efficacy and feasibility of this alliance treatment of the two drugs for fukutin-related protein-muscular dystrophy. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

[Clinical application of alendronate for osteoporosis/osteopenia secondary to hyperthyroidism].

PubMed

Yang, Li-Juan; Shen, Fei-Xia; Zheng, Jing-Chen; Zhang, Hai-Ling

2012-02-01

To evaluate the efficacy and safety of alendronate for the treatment of osteoporosis/osteopenia secondary to hyperthyroidism. From April 2008 to November 2009, 27 patients with hyperthyroidism with osteoporosis/ osteopenia measured by dual energy X-ray absorptiometry (DXA) were included in this study, and then they were randomly divided into two groups (group A and group B) by simple random sampling. Group A consisted of 14 patients treated with antithyroid drug and caltrate D, the antithyroid drug change with thyroid function, and caltrate D 600 mg per day. Group B consisted of 13 patients treated with antithyroid drug, caltrate D and alendronate, antithyroid drug and caltrate D the same as group A, and alendronate 70 mg weekly. Meanwhile, 21 healthy voluntary adults were chosen as control group. And compared with the control group which was treated with nothing. Followed-up for one year, the bone mineral density (including T-score, Z-score, BMD) in lumbar spine (LS), femoral neck (FN) and distal radius (DR) and general information, were compared before and after treatment. BMD at FN and DR were significantly higher at 12 months after treatment than at the baseline in group A (P = 0.000); T-score, Z-score, and BMD at the LS, FN and DR were all significantly higher at 12 months after treatment than at the baseline in group B (P < 0.05), but these data could not arrive to normal level. In group A, the percentage increased in BMD at the LS, FN, and DR were (4.34 +/- 10.5)%, (3.21 +/- 1.38)%, (1.95 +/- 0.44)%, respectively, at 12 months after treatment. In group B, the percentage increased in BMD at the LS, FN, and DR were (6.10 +/- 8.12)%, (4.10 +/- 5.64)%, (3.10 +/- 3.23)%, respectively, at 12 months after treatment. There was significant difference in the rate of increase between two groups (P < 0.05). AKP decreased, weight, BMI increased, and thyroid function decreased, after treatment than those before in both of the two groups. (P < 0.05). Alendronate can

Parathyroid hormone plus alendronate in osteoporosis: a meta-analysis of randomized controlled trials.

PubMed

Zhang, Qinggang; Qian, Jing; Zhu, Yuchang

2015-01-01

Parathyroid hormone (PTH) increases both bone formation (BMD) and bone resorption, whereas alendronate reduces bone resorption. It is possible that the combination therapy of PTH with alendronate will enhance their effects on BMD. Therefore, we conducted this meta-analysis to evaluate the efficacy of the combination therapy of PTH with alendronate in the treatment of patients with osteoporosis. A comprehensive literature search of PubMed, Embase, and Web of Science was conducted to identify relative studies. Eligible studies were randomized controlled trials (RCT), which assessed the efficacy of combination therapy in patients with osteoporosis. The outcomes included the mean percent increases in BMD of lumbar spine, femoral neck, total hip, and distal radius. Weighted mean difference (WMD) with 95% confidence intervals (CIs) were calculated using of random-effects or fixed-effects model, depending on the heterogeneity between the included studies. Six RCTs with a total number of 833 patients were included in this meta-analysis. The pooled estimates showed that, the combination therapy of PTH with alendronate resulted in a higher mean percent change of increased BMD in distal radius (WMD = 2.45, 95% CI: 1.58, 3.31; P = 0.000), but not in lumbar spine (WMD = -0.83, 95% CI: -3.48, 1.81; P = 0.538), femoral neck (WMD = -0.99, 95% CI: -2.04, 0.07; P = 0.068), and total hip (WMD = -0.06, 95% CI: -0.93, 0.81; P = 0.892). The subgroup analysis based on the dosage and schedule of PTH, study duration, gender of patients, and anabolic agents, were conducted. And results revealed that among the patients in the combination therapy group, greater increases in the spine BMD were observed when the PTH was administered with a dosage of 20 μg (WMD = 2.33, 95% CI: 1.24, 3.43; P = 0.000), or the treatment duration lasted more than 12 months (WMD = 2.23, 95% CI: 1.00, 3.47; P = 0.000), or the combination therapy was used in osteoporosis women (WMD = 1.58, 95% CI: 0.63, 2.53; P = 0

Cost-effectiveness of alendronate in the treatment of postmenopausal women in 9 European countries--an economic evaluation based on the fracture intervention trial.

PubMed

Ström, O; Borgström, F; Sen, S S; Boonen, S; Haentjens, P; Johnell, O; Kanis, J A

2007-08-01

Treatment with alendronate (Fosamax) has been shown to significantly reduce the risk of fragility fractures. Cost-effectiveness of treatment was assessed in nine European countries in a Markov model and was generally found to be cost effective in women with a previous spine fracture. Treatment with alendronate (Fosamax) reduces the risk of osteoporotic fractures at the spine, hip and wrist in women with and without prevalent vertebral fracture. Cost-effectiveness estimates in one country may not be applicable elsewhere due to differences in fracture risks, costs and drug prices. The aim of this study was to assess the cost-effectiveness of treating postmenopausal women with alendronate in nine European countries, comprising Belgium, Denmark, France, Germany, Italy, Norway, Spain, Sweden, and the UK. A Markov model was populated with data for the nine European populations. Effect of treatment was taken from the Fracture Intervention Trial, which recruited women with low BMD alone or with a prior vertebral fracture. The cost per QALY gained of treating postmenopausal women with prior vertebral fractures ranged in the base case from "cost saving" in the Scandinavian countries to 15,000 in Italy. Corresponding estimates for women without prior vertebral fractures ranged from "cost saving" to 40,000. In relation to thresholds generally used, the analysis suggests that alendronate is very cost effective in the treatment of women with previous vertebral fracture, and in women without previous vertebral fracture, cost-effectiveness depends on the country setting, discount rates, and chosen monetary thresholds.

Alendronate-associated osteonecrosis of the jaws: A review of the main topics

PubMed Central

Paiva-Fonseca, Felipe; Santos-Silva, Alan R.; Della-Coletta, Ricardo; Vargas, Pablo A.

2014-01-01

Bisphosphonates is a group of inorganic pyrophosphates analogues that suppress bone resorption by inducing osteoclast inactivation, being frequently used for management of diseases affecting bone metabolism, bone metastases and bone tumors. However, since 2003 many cases describing the presence of necrotic bone exposures in the jaws have been described in patients receiving these drugs, what represent a significant complication of bisphosphonates treatment. The overall incidence of bisphosphonate-related osteonecrosis of the jaws is low, ranging from 0.7% to 12%, mainly observed in those patients receiving intravenously treatment. Osteonecrosis of the jaws associated to oral bisphosphonate, particularly alendronate, has also been reported by a number of authors. Considering that alendronate is one of the most used drugs worldwide, specially for treatment of osteoporosis, a better understanding of osteonecrosis of the jaws related to its use and how to manage these patients is extremely important. Therefore, in the current manuscript the authors aim to review the most important topics related to this pathological presentation. Key words:Bisphosphonates, alendronate, bisphosphonate-related osteonecrosis of the jaws, osteonecrosis. PMID:23986020

Perioperative alendronate, risedronate, calcitonin and indomethacin treatment alters femoral stem fixation and periprosthetic bone mineral density in ovariectomized rats.

PubMed

Cankaya, Deniz; Tabak, Yalcin; Ozturk, Akif Muhtar; Gunay, Muhammed Cuneyd

2015-07-01

Many factors affect implant stability and periprosthetic bone mineral density (BMD) following total joint arthroplasty. We asked whether perioperative alendronate, risedronate, calcitonin and indomethacine administration altered (1) femoral stem shear strength and periprosthetic bone mineral density BMD in ovariectomized rats and (2) whether there were differences in the effect of these drugs. Thirty overiectomized rats were divided into five groups and implanted with intramedullary mini-cortical screws in the femur. Four groups were treated with alendronate, risedronate, salmon calcitonin and indomethacin for 4 weeks preoperatively and 8 weeks postoperatively. Although alendronate and risedronate increased the periprosthetic BMD more than calcitonin, they did not alter implant fixation compared to calcitonin. Indomethacin significantly decreased the BMD around the stem and implant stability compared to all other groups. This study showed that perioperative treatment with bisphosphonates and calcitonin improved the BMD around the stems and implant stability. Although bisphosphonates increased the BMD more than calcitonin, there was no difference in implant stability. Indomethacin markedly decreased the periprosthetic BMD and implant stability. The main clinical significance of our study was the finding about the need to strictly avoid long-term use of high-dose nonsteroidal antiinflammatory drugs for patients who have major joint arthritis and a previous history of arthroplasty.

Adverse events, bone mineral density and discontinuation associated with generic alendronate among postmenopausal women previously tolerant of brand alendronate: a retrospective cohort study

PubMed Central

2010-01-01

Background A rise in gastrointestinal (GI) adverse events (AEs) and a decline in bone mineral density (BMD) was observed in patients previously tolerant to brand alendronate shortly after generic versions were introduced in July 2005 to the Canadian market. The objective of our study was to quantify changes in AE rates and BMD scores, as well as associated alendronate discontinuation among patients before and after switch from brand to generic alendronate. Methods A chart review of postmenopausal women 50 years of age and older between 2003 and 2007 was conducted in two specialized tertiary care referral centers. Patients on alendronate both before and after July 2005 were included. The change in the number of AEs, changes in BMD and associated alendronate discontinuation was compared before and after the switch from brand to generic alendronate. Results 301 women with an average age of 67.6 years (standard deviation (SD) = 9.5) had a total of 47 AEs between July 2003 and December 2007 that resulted in discontinuation of the medication. There was a significant increase in the rate of AEs per patient-months-at-risk from 0.0001 before to 0.0044 after October 2005 (p < 0.001). The most common AEs were GI in nature (stomach pain, GI upset, nausea, and reflux). In addition, 23 patients discontinued alendronate due to BMD reduction after January 2006. In these patients, BMD scores were significantly reduced from their prior BMD measures (change of -0.0534, p < 0.001 for spine BMD and change of -0.0338, p = 0.01 for femur BMD). Among patients who discontinued due to BMD reduction, BMD was stable in the period prior to January 2006 (change of -0.0066, p = 0.5 for spine BMD and change of 0.0011, p = 0.9 for femur BMD); however, testing for reduction after January 2006 in BMD measures (one-sided T-test) revealed there was a significant reduction in BMD scores for both anatomic sites (change of -0.0321, p = .005 for spine, change of -0.0205, p = 0.05 for femur). Conclusions

Alendronate and raloxifene affect the osteoprotegerin/RANKL system in human osteoblast primary cultures from patients with osteoporosis and osteoarthritis.

PubMed

Giner, Mercè; Rios, Ma José; Montoya, Ma José; Vázquez, Ma Angeles; Miranda, Cristina; Pérez-Cano, Ramón

2011-01-15

The osteoprotegerin/RANKL system modulates bone remodelling. Alendronate and raloxifene are anti-resorptive drugs effective in osteoporotic disease. They reduce fracture risk, the activity of bone remodelling and increase bone mineral density. It is not known if they can exert a direct effect in osteoblasts via the osteoprotegerin/RANKL system. Our objective was to assess the effects of alendronate and raloxifene among osteoprotegerin production (ELISA), as well as osteoprotegerin and RANKL expression (RT-PCR), in primary cultures of human osteoblasts (hOB). We compared 17 osteoporotic patients with 16 patients affected by osteoarthritis in basal conditions and after incubation with alendronate (10(-6) M), raloxifene (10(-7) M) or 17-β estradiol (10(-7) M) for 24 h. The statistical analysis was determined by ANOVA. Osteoprotegerin protein secretion in hOB cultures was higher in patients with osteoporosis than osteoarthritis. Osteoprotegerin secretion levels remained unchanged after each treatment. The osteoporotic group was more sensitive to treatment. Both raloxifene (34%) and estradiol (37%) increased osteoprotegerin mRNA expression, and alendronate (118%) and raloxifene (61%) increased the mRNA expression of RANKL. The RANKL/osteoprotegerin mRNA ratio was higher in osteoporotic than osteoarthritic patients. In the osteoporotic group, the RANKL/osteoprotegerin mRNA ratio was significantly increased after treatment with alendronate (112%) and after treatment with raloxifene (60%). These results indicate a direct action of alendronate and raloxifene on hOB cultures from osteoporotic patients, and the cited drugs are able to modulate the osteoprotegerin/RANKL system. Copyright © 2010 Elsevier B.V. All rights reserved.

Alendronate inhalation ameliorates elastase-induced pulmonary emphysema in mice by induction of apoptosis of alveolar macrophages.

PubMed

Ueno, Manabu; Maeno, Toshitaka; Nishimura, Satoshi; Ogata, Fusa; Masubuchi, Hiroaki; Hara, Kenichiro; Yamaguchi, Kouichi; Aoki, Fumiaki; Suga, Tatsuo; Nagai, Ryozo; Kurabayashi, Masahiko

2015-03-10

Alveolar macrophages play a crucial role in the pathogenesis of emphysema, for which there is currently no effective treatment. Bisphosphonates are widely used to treat osteoclast-mediated bone diseases. Here we show that delivery of the nitrogen-containing bisphosphonate alendronate via aerosol inhalation ameliorates elastase-induced emphysema in mice. Inhaled, but not orally ingested, alendronate inhibits airspace enlargement after elastase instillation, and induces apoptosis of macrophages in bronchoalveolar fluid via caspase-3- and mevalonate-dependent pathways. Cytometric analysis indicates that the F4/80(+)CD11b(high)CD11c(mild) population characterizing inflammatory macrophages, and the F4/80(+)CD11b(mild)CD11c(high) population defining resident alveolar macrophages take up substantial amounts of the bisphosphonate imaging agent OsteoSense680 after aerosol inhalation. We further show that alendronate inhibits macrophage migratory and phagocytotic activities and blunts the inflammatory response of alveolar macrophages by inhibiting nuclear factor-κB signalling. Given that the alendronate inhalation effectively induces apoptosis in both recruited and resident alveolar macrophages, we suggest this strategy may have therapeutic potential for the treatment of emphysema.

Greater first year effectiveness drives favorable cost-effectiveness of brand risedronate versus generic or brand alendronate: modeled Canadian analysis

PubMed Central

Papaioannou, A.; Thompson, M. F.; Pasquale, M. K.; Adachi, J. D.

2016-01-01

Summary The RisedronatE and ALendronate (REAL) study provided a unique opportunity to conduct cost-effectiveness analyses based on effectiveness data from real-world clinical practice. Using a published osteoporosis model, the researchers found risedronate to be cost-effective compared to generic or brand alendronate for the treatment of Canadian postmenopausal osteoporosis in patients aged 65 years or older. Introduction The REAL study provides robust data on the real-world performance of risedronate and alendronate. The study used these data to assess the cost-effectiveness of brand risedronate versus generic or brand alendronate for treatment of Canadian postmenopausal osteoporosis patients aged 65 years or older. Methods A previously published osteoporosis model was populated with Canadian cost and epidemiological data, and the estimated fracture risk was validated. Effectiveness data were derived from REAL and utility data from published sources. The incremental cost per quality-adjusted life-year (QALY) gained was estimated from a Canadian public payer perspective, and comprehensive sensitivity analyses were conducted. Results The base case analysis found fewer fractures and more QALYs in the risedronate cohort, providing an incremental cost per QALY gained of $3,877 for risedronate compared to generic alendronate. The results were most sensitive to treatment duration and effectiveness. Conclusions The REAL study provided a unique opportunity to conduct cost-effectiveness analyses based on effectiveness data taken from real-world clinical practice. The analysis supports the cost-effectiveness of risedronate compared to generic or brand alendronate and the use of risedronate for the treatment of osteoporotic Canadian women aged 65 years or older with a BMD T-score ≤−2.5. PMID:18008100

Cost-minimization study comparing annual infusion of zoledronic acid or weekly oral alendronate in women with low bone mineral density.

PubMed

Chávez-Valencia, Venice; Arce-Salinas, César Alejandro; Espinosa-Ortega, Fabricio

2014-01-01

Cost-minimization study to assess the annual direct costs of 2 antiresorptive strategies in postmenopausal women with low bone mineral densities (BMDs). Patients were randomly assigned to receive 70 mg of oral weekly alendronate or a 1-time 5mg of intravenous zoledronic acid. All medical and nonmedical direct costs were recorded for 1 yr. Student's t-test or the Chi-squared test was used. A total of 101 postmenopausal women were enrolled with a mean age of 58.3 ± 7.6 yr and a postmenopausal period of 13.5 ± 8.3 yr. A total of 50 patients completed 1 yr of alendronate and 51 patients received zoledronic acid. At baseline, no differences were seen between the 2 groups in anthropometric measures, comorbidities, and bone mineral density. The costs for medical attention for low bone mass were $81,532 (US Dollars) for the alendronate group and $69,251 for the zoledronic acid group; the cost per patient was $1631 in the alendronate group vs $1358 in the zoledronic acid group (p<0.0001). Therefore, zoledronic acid treatment provided an annual savings of 15% of the direct costs compared with oral alendronate treatment. Moreover, there was a significant increase in lumbar spine T-scores in the zoledronic acid group when compared with the alendronate group. Annual zoledronic acid infusion as an antiresorptive treatment in women with low BMD provides significant monetary savings when compared with weekly alendronate therapy for 1 yr. Zoledronic acid infusion is also linked to higher increase in BMD and compliance. Copyright © 2014 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.

Acute bilateral uveitis and right macular edema induced by a single infusion of zoledronic acid for the treatment of postmenopausal osteoporosis as a substitution for oral alendronate: a case report.

PubMed

Tian, Yiming; Wang, Rui; Liu, Lianyuan; Ma, Chunming; Lu, Qiang; Yin, Fuzai

2016-02-11

Zoledronic acid-induced uveitis (ZAIU) is rare but severe, and has been recently considered part of an acute phase reaction. Only 15 cases have been reported since 2005. Here we describe a case with macular edema, which is the first reported case observed after long-term alendronate tolerance. A 63-year-old Asian woman received her first intravenous zoledronic acid treatment for the management of postmenopausal osteoporosis as a more convenient substitute for oral alendronate. Twenty-four hours later, bilateral eye irritations, periorbital swelling, blurred vision, and diplopia presented. The complete blood count and transaminase levels were normal, but the erythrocytic sedimentation, C-reactive protein, and serum C4 levels were elevated. On detailed ophthalmological examination, a diagnosis of bilateral acute uveitis and macular edema in the right eye was made. The ocular symptoms were not improved until administration of topical and oral steroids. Complete resolution was achieved. There was no rechallenge of bisphosphonates, and no recurrence at 6 months follow-up. Based on an extensive review, abnormal fundus is rarely reported, especially in cases of macular edema. Rechallenge with zoledronic acid in five cases induced no additional uveitis, and changing the medication to pamidronate in another patient was also tolerated. Interestingly, our patient suffered from uveitis soon after intravenous zoledronate exposure after a two-year tolerance to oral alendronate. This is the first report of zoledronic acid induced uveitis with macular edema after long-term alendronate tolerance. Prior oral alendronate may not entirely prevent ZAIU. Steroids are usually necessary in the treatment of ZAIU. Bisphosphonate rechallenge is not fully contraindicated, and prior steroid administration may be a more reasonable treatment choice according to the available evidence.

Effect of insulin-like growth factor-1 (IGF-1) plus alendronate on bone density during puberty in IGF-1-deficient MIDI mice.

PubMed

Stabnov, L; Kasukawa, Y; Guo, R; Amaar, Y; Wergedal, J E; Baylink, D J; Mohan, S

2002-06-01

Insulin-like growth factor-1 (IGF-1) increases both bone formation and bone resorption processes. To test the hypothesis that treatment with an antiresorber along with IGF-1, during the pubertal growth phase, would be more effective than IGF-1 alone to increase peak bone mass, we used an IGF-1 MIDI mouse model, which exhibits a >60% reduction in circulating IGF-1 levels. We first determined an optimal IGF-1 delivery by evaluating IGF-1 administration (2 mg/kg body weight/day) by either a single daily injection, three daily injections, or by continuous delivery via a minipump during puberty. Of the three regimens, the three daily IGF-1 injections and IGF-1 through a minipump produced a significant increase in total body bone mineral density (BMD) (6.0% and 4.4%, respectively) and in femoral BMD (4.3% and 6.2%, respectively) compared with the control group. Single subcutaneous (s.c.) administration did not increase BMD. We chose IGF-1 administration three times daily for testing the combined effects of IGF-1 and alendronate (100 microg/kg per day). The treatment of IGF-1 + alendronate for a period of 2 weeks increased total body BMD at 1 week and 3 weeks after treatment (21.1% and 20.5%, respectively) and femoral BMD by 29% at 3 weeks after treatment. These increases were significantly greater than those produced by IGF-1 alone. IGF-1, but not alendronate, increased bone length. IGF-1 and/or alendronate increased both periosteal and endosteal circumference. Combined treatment caused a greater increase in the total body bone mineral content (BMC) and periosteal circumference compared with individual treatment with IGF-1 or alendronate. Our data demonstrate that: (1) inhibition of bone turnover during puberty increases net bone density; and (2) combined treatment with IGF-1 and alendronate is more effective than IGF-1 or alendronate alone in increasing peak bone mass in an IGF-1-deficient MIDI mouse model.

Alendronate promotes osteoblast differentiation and bone formation in ovariectomy-induced osteoporosis through interferon-β/signal transducer and activator of transcription 1 pathway

PubMed Central

Ma, Xiaoqing; Xu, Zhongyang; Ding, Shaofeng; Yi, Guangkun; Wang, Qian

2018-01-01

Alendronate is commonly used for the treatment of postmenopausal osteoporosis; however, the underlying pathological molecular mechanisms of its action remain unclear. In the present study, the alendronate-treated signaling pathway in bone metabolism in rats with ovariectomy induced by osteoporosis was investigated. Rats with osteoporosis were orally administered alendronate or phosphate-buffered saline (control). In addition, the interferon-β (IFN-β)/signal transducer and activator of transcription 1 (STAT1) signaling pathway was investigated in osteoblasts following treatment with alendronate in vitro and in vivo. During the differentiation period, IFN-β (100 ng/ml) was used to treat the osteoblast cells, and the activity, viability and bone metabolism-associated gene expression levels (STAT1, p-STAT1, Fra1, TRAF6 and SOCS1) were analyzed in osteoblast cells. Histopathological changes were used to evaluate osteoblasts, osteoclasts, inflammatory phase of bone healing and osteonecrotic areas. The results demonstrated that alendronate significantly inhibited the activity of osteoporotic osteoclasts by stimulating expression of IFN-β, as well as markedly improved the viability and activity of osteoblasts compared with the control group. In addition, alendronate increased the expression and phosphorylation levels of STAT1 in osteoclasts, enhanced osteoblast differentiation, upregulated the expression levels of alkaline phosphatase and osteocalcin, and increased the expression of osteoblast differentiation-associated genes (osteocalcin, osterix and Runx2). Inhibition of IFN-β expression canceled the benefits of alendronate-mediated osteoblast differentiation. Notably, alendronate enhanced bone formation in rats with osteoporosis induced by ovariectomy. In conclusion, these findings suggest that alendronate can regulate osteoblast differentiation and bone formation in rats with osteoporosis induced by ovariectomy through upregulation of IFN-β/STAT1 signaling

Biocompatibility evaluation of alendronate paste in rat's subcutaneous tissue.

PubMed

Mori, Graziela Garrido; de Moraes, Ivaldo Gomes; Nunes, Daniele Clapes; Castilho, Lithiene Ribeiro; Poi, Wilson Roberto; Capaldi, Maria Luciana P Manzoli

2009-04-01

Alendronate is a known inhibitor of root resorption and the development of alendronate paste would enhance its utilization as intracanal medication. Therefore, this study aimed to investigate the biocompatibility of experimental alendronate paste in subcutaneous tissue of rats, for utilization in teeth susceptible to root resorption. The study was conducted on 15 male rats, weighing approximately 180-200 grams. The rats' dorsal regions were submitted to one incision on the median region and, laterally to the incision, the subcutaneous tissue was raised and gently dissected for introduction of two tubes, in each rat. The tubes were sealed at one end with gutta-percha and taken as control. The tubes were filled with experimental alendronate paste. The animals were killed at 7, 15 and 45 days after surgery and the specimens were processed in laboratory. The histological sections were stained with hematoxylin-eosin and analyzed by light microscopy. Scores were assigned to the inflammatory process and statistically compared by the Tukey test (P < 0.05). Alendronate paste promoted severe inflammation process at 7 days, with statistically significant difference compared to the control (P < 0.05%). However, at 15 days, there was a regression of inflammation and the presence of connective tissue with collagen fibers, fibroblasts and blood vessels was observed. After 45 days, it was observed the presence of well-organized connective tissue, with collagen fibers and fibroblasts, and few inflammatory cells. No statistical difference was observed between the control and experimental paste at 15 and 45 days. The experimental alendronate paste was considered biocompatible with subcutaneous tissue of rat.

Long-term effects of local pretreatment with alendronate on healing of replanted rat teeth.

PubMed

Komatsu, K; Shimada, A; Shibata, T; Shimoda, S; Oida, S; Kawasaki, K; Nifuji, A

2008-04-01

Our previous study showed that topical alendronate, an inhibitor of bone resorption, reduces root resorption and ankylosis for 21 d after replantation of rat teeth. The aim of the present study was to evaluate the long-term inhibitory effects of topical alendronate in the replanted teeth. The rat maxillary first molars were extracted, placed in saline containing 1 mm alendronate (alendronate group) or saline (saline group) for 5 min and then replanted. The maxillae were dissected at 60 and 120 d. Microcomputed tomography horizontal sections at three root levels were analyzed for root and bone resorption, ankylosis and pulp mineralization. In the alendronate group at 60 and 120 d, the frequencies of resorption of roots and bone were lower than those in the saline group. The p values show statistical significances of lower frequencies in the alendronate group than in the saline group by chi-square test (see Table 1). Ankylosis and pulp mineralization occurred in the alendronate and saline groups. Bone marrow spaces were narrowed in conjunction with bone tissue expansion around the replanted teeth in the alendronate group. The inhibitory effects of topical alendronate were retained on root and bone resorption, but not on ankylosis and pulp mineralization, in the replanted teeth for 4 mo. Alendronate might also stimulate bone formation around the rat replanted teeth.

Comparing Tolerability and Efficacy of Generic versus Brand Alendronate: A Randomized Clinical Study in Postmenopausal Women with a Recent Fracture

PubMed Central

van den Bergh, Joop P. W.; Bouts, Marian E.; van der Veer, Eveline; van der Velde, Robert Y.; Janssen, Marcel J. W.; Geusens, Piet P.; Winkens, Bjorn; Oldenhof, Nico J. J.; van Geel, Tineke A. C. M.

2013-01-01

Introduction An increasing number of generic alendronate formulations have become available. Although expected to have the same tolerability and efficacy, head-to head comparison of generic and brand alendronate was never performed. Therefore, we compared the tolerability and efficacy of generic and brand alendronate. Methods In a randomized double-blinded single centre cross-over study in 37 postmenopausal women (mean age 65.4±6.4 years) with osteoporosis were treated with generic and branded alendronate during 24 (2x12) weeks. Tolerance was evaluated by the Gastro intestinal Symptom Rating Scale (GSRS) and self-reported side effects. Efficacy was assessed by serum bone turnover markers, carboxy terminal telopeptide (CTX) and procollagen type I N-terminal propeptide (PINP). No wash out period was allowed (ethical reasons). Because of possible carry over effect only data of the first 12 weeks were analyzed using linear mixed models. Results There were no significant differences in overall tolerance (GSRS) between treatment groups. However, for subscale abdominal pain, patients using generic had a significantly higher mean GSRS score at week 4 (estimated mean difference (B): 0.40; 95%CI: 0.05 to 0.74, p = 0.024). The level of bone turnover markers significantly decreased over 12 weeks of follow-up for generic and branded alendronate (p < 0.001). Mean level of CTX was significantly lower with branded at week 4 (B: 121.3; 95%CI: 52.0 to 190.5), but not at week 12 (B: 53.6; 95%CI:-3.7 to 110.9). No significant differences were found for PINP at week 4 or 12. Conclusions Bone turnover markers were significantly reduced with branded and generic alendronate. With branded, CTX was significantly lower at 4 weeks. Generic caused significantly higher abdominal pain scores in the first 4 weeks of treatment. Therefore, generic alendronate may not have the same tolerability and efficacy as branded alendronate in the first weeks after starting treatment in patients with a recent

Skeletal Health After Continuation, Withdrawal, or Delay of Alendronate in Men With Prostate Cancer Undergoing Androgen-Deprivation Therapy

PubMed Central

Greenspan, Susan L.; Nelson, Joel B.; Trump, Donald L.; Wagner, Julie M.; Miller, Megan E.; Perera, Subashan; Resnick, Neil M.

2008-01-01

Purpose Androgen-deprivation therapy (ADT) for prostate cancer is associated with bone loss and osteoporotic fractures. Our objective was to examine changes in bone density and turnover with sustained, discontinued, or delayed oral bisphosphonate therapy in men receiving ADT. Patients and Methods A total of 112 men with nonmetastatic prostate cancer receiving ADT were randomly assigned to alendronate 70 mg once weekly or placebo in a double-blind, partial-crossover trial with a second random assignment at year 2 for those who initially received active therapy. Outcomes included bone mineral density and bone turnover markers. Results Men initially randomly assigned to alendronate and randomly reassigned at year 2 to continue had additional bone density gains at the spine (mean, 2.3% ± 0.7) and hip (mean, 1.3% ± 0.5%; both P < .01); those randomly assigned to placebo in year 2 maintained density at the spine and hip but lost (mean, −1.9% ± 0.6%; P < .01) at the forearm. Patients randomly assigned to begin alendronate in year 2 experienced improvements in bone mass at the spine and hip, but experienced less of an increase compared with those who initiated alendronate at baseline. Men receiving alendronate for 2 years experienced a mean 6.7% (± 1.2%) increase at the spine and a 3.2% (± 1.5%) at the hip (both P < .05). Bone turnover remained suppressed. Conclusion Among men with nonmetastatic prostate cancer receiving ADT, once-weekly alendronate improves bone density and decreases turnover. A second year of alendronate provides additional skeletal benefit, whereas discontinuation results in bone loss and increased bone turnover. Delay in bisphosphonate therapy appears detrimental to bone health. PMID:18802155

Alendronate decreases orthotopic PC-3 prostate tumor growth and metastasis to prostate-draining lymph nodes in nude mice

PubMed Central

Tuomela, Johanna M; Valta, Maija P; Väänänen, Kalervo; Härkönen, Pirkko L

2008-01-01

Background Metastatic prostate cancer is associated with a high morbidity and mortality but the spreading mechanisms are still poorly understood. The aminobisphosphonate alendronate, used to reduce bone loss, has also been shown to inhibit the invasion and migration of prostate cancer cells in vitro. We used a modified orthotopic PC-3 nude mouse tumor model of human prostate cancer to study whether alendronate affects prostate tumor growth and metastasis. Methods PC-3 cells (5 × 105) were implanted in the prostates of nude mice and the mice were treated with alendronate (0.5 mg/kg/day in PBS, s.c.) or vehicle for 4 weeks. After sacrifice, the sizes of tumor-bearing prostates were measured and the tumors and prostate-draining regional iliac and sacral lymph nodes were excised for studies on markers of proliferation, apoptosis, angiogenesis and lymphangiogenesis, using histomorphometry and immunohistochemistry. Results Tumor occurrence in the prostate was 73% in the alendronate-treated group and 81% in the control group. Mean tumor size (218 mm3, range: 96–485 mm3, n = 11) in the alendronate-treated mice was 41% of that in the control mice (513 mm3, range: 209–1350 mm3, n = 13) (p < 0.05). In the iliac and sacral lymph nodes of alendronate-treated mice, the proportion of metastatic area was only about 10% of that in control mice (p < 0.001). Immunohistochemical staining of tumor sections showed that alendronate treatment caused a marked decrease in the number of CD34-positive endothelial cells in tumors (p < 0.001) and an increase in that of ISEL positive apoptotic cells in tumors as well as in lymph node metastases (p < 0.05) compared with those in the vehicle-treated mice. The density of m-LYVE-1-stained lymphatic capillaries was not changed. Conclusion Our results demonstrate that alendronate treatment opposes growth of orthotopic PC-3 tumors and decreases tumor metastasis to prostate-draining lymph nodes. This effect could be at least partly explained by

Alendronate augments interleukin-1{beta} release from macrophages infected with periodontal pathogenic bacteria through activation of caspase-1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng Xue; Tamai, Riyoko; Endo, Yasuo

2009-02-15

Nitrogen-containing bisphosphonates (NBPs) are anti-bone-resorptive drugs with inflammatory side effects that include osteomyelitis and osteonecrosis of the jaw. Oral bacteria have been considered to be a trigger for these NBP-associated jaw bone diseases. The present study examined the effects of alendronate (a typical NBP) and clodronate (a non-NBP) on the production of proinflammatory cytokines by macrophages infected with Porphyromonas gingivalis and Tannerella forsythia, which are important pathogens of periodontal diseases. Pretreatment with alendronate augmented IL-1{beta}, but not TNF{alpha}, production by macrophages infected with P. gingivalis or T. forsythia. This augmentation of IL-1{beta} production was inhibited by clodronate. Furthermore, caspase-1, amore » promoter of IL-1{beta} production, was activated by treatment with alendronate, and caspase-1 inhibitor reduced the production of IL-1{beta} induced by alendronate and P. gingivalis. These results suggest that NBPs augment periodontal pathogenic bacteria-induced IL-1{beta} release via caspase-1 activation, and this phenomenon may contribute to the development of NBP-associated inflammatory side effects including jaw osteomyelitis. Co-treatment with clodronate may prevent and/or reduce these inflammatory effects induced by NBPs.« less

Treatment of low bone density in young people with cystic fibrosis: a multicentre, prospective, open-label observational study of calcium and calcifediol followed by a randomised placebo-controlled trial of alendronate.

PubMed

Bianchi, Maria Luisa; Colombo, Carla; Assael, Baroukh M; Dubini, Antonella; Lombardo, Mariangela; Quattrucci, Serena; Bella, Sergio; Collura, Mirella; Messore, Barbara; Raia, Valeria; Poli, Furio; Bini, Rita; Albanese, Carlina V; De Rose, Virginia; Costantini, Diana; Romano, Giovanna; Pustorino, Elena; Magazzù, Giuseppe; Bertasi, Serenella; Lucidi, Vincenzina; Traverso, Gabriella; Coruzzo, Anna; Grzejdziak, Amelia D

2013-07-01

Long-term complications of cystic fibrosis include osteoporosis and fragility fractures, but few data are available about effective treatment strategies, especially in young patients. We investigated treatment of low bone mineral density in children, adolescents, and young adults with cystic fibrosis. We did a multicentre trial in two phases. We enrolled patients aged 5-30 years with cystic fibrosis and low bone mineral density, from ten cystic fibrosis regional centres in Italy. The first phase was an open-label, 12-month observational study of the effect of adequate calcium intake plus calcifediol. The second phase was a 12-month, double-blind, randomised, placebo-controlled, parallel group study of the efficacy and safety of oral alendronate in patients whose bone mineral apparent density had not increased by 5% or more by the end of the observational phase. Patients were randomly assigned to either alendronate or placebo. Both patients and investigators were masked to treatment assignment. We used dual x-ray absorptiometry at baseline and every 6 months thereafter, corrected for body size, to assess lumbar spine bone mineral apparent density. We assessed bone turnover markers and other laboratory parameters every 3-6 months. The primary endpoint was mean increase of lumbar spine bone mineral apparent density, assessed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01812551. We screened 540 patients and enrolled 171 (mean age 13·8 years, SD 5·9, range 5-30). In the observational phase, treatment with calcium and calcifediol increased bone mineral apparent density by 5% or more in 43 patients (25%). 128 patients entered the randomised phase. Bone mineral apparent density increased by 16·3% in the alendronate group (n=65) versus 3·1% in the placebo group (n=63; p=0·0010). 19 of 57 young people (33·3%) receiving alendronate attained a normal-for-age bone mineral apparent density Z score. In the observational

Use of bone alkaline phosphatase to monitor alendronate therapy in individual postmenopausal osteoporotic women.

PubMed

Kress, B C; Mizrahi, I A; Armour, K W; Marcus, R; Emkey, R D; Santora, A C

1999-07-01

Biochemical bone markers are sensitive to the changes in bone turnover that result from treatment of postmenopausal osteoporotic women with antiresorptive therapies. Although information is available on the use of bone markers in monitoring therapy in groups of subjects, less is known regarding how these markers perform in individual patients. Serum bone alkaline phosphatase (bone ALP) concentrations, measured with the Tandem(R) Ostase(R) assay, were used to monitor the biochemical response of bone in postmenopausal women with osteoporosis receiving either 10 mg/day alendronate therapy (n = 74) or calcium supplementation (n = 148) for 24 months. Bone ALP decreased significantly from baseline at 3 months (P alendronate therapy. The magnitude of the bone ALP decrease in the treated osteoporotic population was consistent with normalization to premenopausal concentrations. Of the 74 alendronate-treated subjects, 63 (85.1%) demonstrated a decrease from baseline in bone ALP by 6 months that exceeded the least significant change of 25%. The bone ALP decrease from baseline exceeded 25% in 72 (97%) by the end of the study. The bone ALP assay is a sensitive and reliable tool that may be used to monitor the reduction in bone turnover after alendronate therapy in individual postmenopausal osteoporotic women.

Alendronate increases skeletal mass of growing rats during unloading by inhibiting resorption of calcified cartilage

NASA Technical Reports Server (NTRS)

Bikle, D. D.; Morey-Holton, E. R.; Doty, S. B.; Currier, P. A.; Tanner, S. J.; Halloran, B. P.

1994-01-01

Loss of bone mass during periods of skeletal unloading remains an important clinical problem. To determine the extent to which resorption contributes to the relative loss of bone during skeletal unloading of the growing rat and to explore potential means of preventing such bone loss, 0.1 mg P/kg alendronate was administered to rats before unloading of the hindquarters. Skeletal unloading markedly reduced the normal increase in tibial mass and calcium content during the 9 day period of observation, primarily by decreasing bone formation, although bone resorption was also modestly stimulated. Alendronate not only prevented the relative loss of skeletal mass during unloading but led to a dramatic increase in calcified tissue in the proximal tibia compared with the vehicle-treated unloaded or normally loaded controls. Bone formation, however, assessed both by tetracycline labeling and by [3H]proline and 45Ca incorporation, was suppressed by alendronate treatment and further decreased by skeletal unloading. Total osteoclast number increased in alendronate-treated animals, but values were similar to those in controls when corrected for the increased bone area. However, the osteoclasts had poorly developed brush borders and appeared not to engage the bone surface when examined at the ultrastructural level. We conclude that alendronate prevents the relative loss of mineralized tissue in growing rats subjected to skeletal unloading, but it does so primarily by inhibiting the resorption of the primary and secondary spongiosa, leading to altered bone modeling in the metaphysis.

Effect of 1% sodium alendronate in the non-surgical treatment of periodontal intraosseous defects: a 6-month clinical trial

PubMed Central

DUTRA, Bernardo Carvalho; OLIVEIRA, Alcione Maria Soares Dutra; OLIVEIRA, Peterson Antônio Dutra; MANZI, Flavio Ricardo; CORTELLI, Sheila Cavalca; COTA, Luís Otávio de Miranda; COSTA, Fernando Oliveira

2017-01-01

Abstract Background and objectives Few studies have evaluated the effect of the topical application of sodium alendronate (ALN) on the treatment of intrabuccal bone defects, especially those caused by periodontitis. This 6-month randomized placebo controlled clinical trial aimed at evaluating the effect of non-surgical periodontal treatment associated with the use of 1% ALN, through clinical evaluations and cone-beam computed tomography (CBCT). Material and Methods Twenty individuals with chronic periodontitis underwent periodontal examination at the baseline as well as 3 and 6 months after periodontal treatment, registering clinical attachment level (CAL), periodontal probing depth (PPD), and bleeding on probing (BOP) as the clinical outcomes. After manual scaling and root planing, 40 bilateral sites with interproximal vertical bone defects were randomly treated with either 1% ALN gel or a placebo. Bone defects were evaluated through CBCT at the baseline and 6 months post-treatment. The clinical and CBCT parameters were compared using the Wilcoxon and Friedman tests (p<0.05). Results Although ALN produced a greater CAL gain when compared to the placebo at 6 months post-treatment (p=0.021), both treatments produced similar effects on the PPD, BOP, and bone height. Significant differences in bone fill were observed only in patients of the ALN group (4.5 to 3.8 mm; p=0.003) at 6 months post-treatment. Conclusions Topical application of 1% ALN might be a beneficial adjuvant to non-surgical periodontal therapy. PMID:28678950

Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure.

PubMed Central

Sato, M; Grasser, W; Endo, N; Akins, R; Simmons, H; Thompson, D D; Golub, E; Rodan, G A

1991-01-01

Studies of the mode of action of the bisphosphonate alendronate showed that 1 d after the injection of 0.4 mg/kg [3H]alendronate to newborn rats, 72% of the osteoclastic surface, 2% of the bone forming, and 13% of all other surfaces were densely labeled. Silver grains were seen above the osteoclasts and no other cells. 6 d later the label was 600-1,000 microns away from the epiphyseal plate and buried inside the bone, indicating normal growth and matrix deposition on top of alendronate-containing bone. Osteoclasts from adult animals, infused with parathyroid hormone-related peptide (1-34) and treated with 0.4 mg/kg alendronate subcutaneously for 2 d, all lacked ruffled border but not clear zone. In vitro alendronate bound to bone particles with a Kd of approximately 1 mM and a capacity of 100 nmol/mg at pH 7. At pH 3.5 binding was reduced by 50%. Alendronate inhibited bone resorption by isolated chicken or rat osteoclasts when the amount on the bone surface was around 1.3 x 10(-3) fmol/microns 2, which would produce a concentration of 0.1-1 mM in the resorption space if 50% were released. At these concentrations membrane leakiness to calcium was observed. These findings suggest that alendronate binds to resorption surfaces, is locally released during acidification, the rise in concentration stops resorption and membrane ruffling, without destroying the osteoclasts. Images PMID:1661297

Efficacy of alendronate, a bisphosphonate, in the treatment of AVN of the hip. A prospective open-label study.

PubMed

Agarwala, S; Jain, D; Joshi, V R; Sule, A

2005-03-01

To study the efficacy of alendronate, in the treatment of avascular necrosis (AVN) of the hip. Sixty patients with AVN of the hip (100 hips with AVN) were studied. The follow-up period ranged from 3 months to 5 yr. The most common cause of AVN was steroids. Parameters studied were walking time, standing time, pain and disability on a visual analogue scale (VAS), range of motion of the hip, X-ray and MRI of the hip. All patients were treated with alendronate 10 mg/day (or 70 mg/week) along with 500-1000 mg of daily calcium and vitamin D supplements, and were advised to avoid weight-bearing. NSAIDs and analgesics were permitted as needed and were recorded. Forty-one patients (71 AVN hips) with AVN have been followed up for a minimum of 1 yr, 24 patients (42 AVN hips) for 2 yr and 21 patients (37 AVN hips) for more than 2 yr (average 37 month). Fourteen patients have been followed up for less than 1 yr (3-9 months). Significant reduction in pain and disability scores (P < 0.001) and significant increase in standing and walking time (P < 0.001) were observed. All hip movements improved at 1 yr (P value 0.000-0.009) with an insignificant decline after that (P > 0.001). Radiologically, the hips either stabilized in the same grade or progressed by one grade. MRI showed a decrease in marrow oedema in most cases at the 1-yr follow-up. Six patients (10 hips) required surgery and there were two (three hips) dropouts. The drug was well tolerated and there was a reduction in NSAID requirement. Alendronate reduces pain, improves function and retards AVN progression. Early surgical intervention can be avoided in most patients.

A urine midmolecule osteocalcin assay shows higher discriminatory power than a serum midmolecule osteocalcin assay during short-term alendronate treatment of osteoporotic patients.

PubMed

Srivastava, A K; Mohan, S; Singer, F R; Baylink, D J

2002-07-01

We isolated and characterized a peptide fragment corresponding to amino acid sequence 14-28 of human osteocalcin in urine from Paget's disease, and developed a polyclonal antibody reactive to this peptide in urine. We used this antibody to measure urinary fragments of osteocalcin and compared to efficacy of the urinary osteocalcin assay with a serum osteocalcin (sOC) assay (ELISA-Osteo, Cis-Bio International) to monitor the short-term changes in bone turnover in response to alendronate treatment. The synthetic peptide-based urinary osteocalcin (uOC) radioimmunoassay (RIA) showed an analytical sensitivity of 6.25 ng/mL, standard curve range of 3.12-400 ng/mL, and mean intra- (n = 20) and interassay (n = 30) coefficient of variation (CV) of <15%. Urine osteocalcin concentrations in postmenopausal osteoporotic patients were approximately 90% higher than in normal premenopausal controls. Series of 24 h urine and matched serum samples were collected at baseline, 30 days, and 90 days after treatment of postmenopausal osteoporotic patients with daily dose of 10 mg alendronate. We measured urinary osteocalcin (uOc) levels and urinary N-telopeptide (uNTx, Ostex) in urine samples and serum N-telopeptide (sNTx), C-telopeptide (sCTx, Osteometer), serum osteocalcin (sOC) as well as bone-specific alkaline phosphatase (sALP) (Alkphose-B, Metra Biosystems) in serum samples. The percent change data obtained between baseline and 30 days (n = 18) posttreatment suggested a rapid decline in uOC concentration (-27%, p < 0.01) in response to alendronate treatment, as compared with a marginal and nonsignificant decrease in sOC (-7.2%, p = 0.417) or sALP (-3.4%, p = 0.689), two specific markers of bone formation. As expected, due to the coupling of bone formation and bone resorption, the concentration of all markers showed a 30%-45% decline compared with baseline values after 90 days (n = 16) of treatment. Correlation of markers after a 30 day treatment with alendronate revealed a higher

Alendronate Sodium as Enteric Coated Solid Lipid Nanoparticles; Preparation, Optimization, and In Vivo Evaluation to Enhance Its Oral Bioavailability

PubMed Central

Hosny, Khaled Mohamed

2016-01-01

Treatment of osteoporosis with alendronate sodium has several challenges. The first challenge is the low bioavailability. The second main challenge is side effects, which include oesophageal ulceration. The aim of this research was to reformulate alendronate sodium as enteric coated solid lipid nanoparticles in order to enhance its bioavailability, and preventing the free alendronate sodium from coming into direct contact with the gastrointestinal mucosa, and thereby reducing the possibility of side effects. Enteric coated solid lipid nanoparticles were prepared according to the Box-Behnken design employing Design expert® software, and characterized for size, morphology, and entrapment efficiency. The optimized formula was coated with an Eudragit S100 and evaluated for drug release in acidic and basic media, stability studies and pharmacokinetic evaluations on rabbits. The results indicated that, using Derringer's desirability functional tool for optimization, the highest entrapment efficiency value of 74.3% and the smallest size value of 98 nm were predicted under optimum conditions with a desirability value of 0.917. The optimized nanoparticles released alendronate sodium only at an alkaline pH. The pharmacokinetic evaluation revealed that alendronate sodium bioavailability was enhanced by more than 7.4-fold in rabbits. In conclusion, enteric coated solid lipid nanoparticles is a promising formula for the delivery of alendronate sodium, eliminating its oesophageal side effects and enhancing its bioavailability. PMID:27148747

Alendronate Sodium as Enteric Coated Solid Lipid Nanoparticles; Preparation, Optimization, and In Vivo Evaluation to Enhance Its Oral Bioavailability.

PubMed

Hosny, Khaled Mohamed

2016-01-01

Treatment of osteoporosis with alendronate sodium has several challenges. The first challenge is the low bioavailability. The second main challenge is side effects, which include oesophageal ulceration. The aim of this research was to reformulate alendronate sodium as enteric coated solid lipid nanoparticles in order to enhance its bioavailability, and preventing the free alendronate sodium from coming into direct contact with the gastrointestinal mucosa, and thereby reducing the possibility of side effects. Enteric coated solid lipid nanoparticles were prepared according to the Box-Behnken design employing Design expert® software, and characterized for size, morphology, and entrapment efficiency. The optimized formula was coated with an Eudragit S100 and evaluated for drug release in acidic and basic media, stability studies and pharmacokinetic evaluations on rabbits. The results indicated that, using Derringer's desirability functional tool for optimization, the highest entrapment efficiency value of 74.3% and the smallest size value of 98 nm were predicted under optimum conditions with a desirability value of 0.917. The optimized nanoparticles released alendronate sodium only at an alkaline pH. The pharmacokinetic evaluation revealed that alendronate sodium bioavailability was enhanced by more than 7.4-fold in rabbits. In conclusion, enteric coated solid lipid nanoparticles is a promising formula for the delivery of alendronate sodium, eliminating its oesophageal side effects and enhancing its bioavailability.

Alendronate-coated long-circulating liposomes containing 99mtechnetium-ceftizoxime used to identify osteomyelitis

PubMed Central

Ferreira, Diego dos Santos; Boratto, Fernanda Alves; Cardoso, Valbert Nascimento; Serakides, Rogéria; Fernandes, Simone Odília; Ferreira, Lucas Antônio Miranda; Oliveira, Mônica Cristina

2015-01-01

Osteomyelitis is a progressive destruction of bones caused by microorganisms. Inadequate or absent treatment increases the risk of bone growth inhibition, fractures, and sepsis. Among the diagnostic techniques, functional images are the most sensitive in detecting osteomyelitis in its early stages. However, these techniques do not have adequate specificity. By contrast, radiolabeled antibiotics could improve selectivity, since they are specifically recognized by the bacteria. The incorporation of these radiopharmaceuticals in drug-delivery systems with high affinity for bones could improve the overall uptake. In this work, long-circulating and alendronate-coated liposomes containing 99mtechnetium-radiolabeled ceftizoxime were prepared and their ability to identify infectious foci (osteomyelitis) in animal models was evaluated. The effect of the presence of PEGylated lipids and surface-attached alendronate was evaluated. The bone-targeted long-circulating liposomal 99mtechnetium–ceftizoxime showed higher uptake in regions of septic inflammation than did the non-long-circulating and/or alendronate-non-coated liposomes, showing that both the presence of PEGylated lipids and alendronate coating are important to optimize the bone targeting. Scintigraphic images of septic or aseptic inflammation-bearing Wistar rats, as well as healthy rats, were acquired at different time intervals after the intravenous administration of these liposomes. The target-to-non-target ratio proved to be significantly higher in the osteomyelitis-bearing animals for all investigated time intervals. Biodistribution studies were also performed after the intravenous administration of the formulation in osteomyelitis-bearing animals. A significant amount of liposomes were taken up by the organs of the mononuclear phagocyte system (liver and spleen). Intense renal excretion was also observed during the entire experiment period. Moreover, the liposome uptake by the infectious focus was significantly

Prevention of aromatase inhibitor-induced bone loss with alendronate in postmenopausal women: The BATMAN Trial.

PubMed

Lomax, Anna J; Yee Yap, Saw; White, Karen; Beith, Jane; Abdi, Ehtesham; Broad, Adam; Sewak, Sanjeev; Lee, Chooi; Sambrook, Philip; Pocock, Nicholas; Henry, Margaret J; Yeow, Elaine G; Bell, Richard

2013-12-01

Postmenopausal women on aromatase inhibitors (AI) are at risk of aromatase inhibitor-associated bone loss (AIBL) and fractures. In 2005 Osteoporosis Australia proposed an algorithm for bisphosphonate intervention. Three hundred and three postmenopausal women with early breast cancer (EBC) were enrolled (osteoporotic, n=25; osteopaenic, n=146; normal bone mineral density (BMD), n=126). Weekly alendronate (70 mg) treatment efficacy as triggered by the algorithm in preventing bone loss was evaluated. All patients received anastrozole (1 mg daily), calcium and vitamin D. All osteoporotic patients received alendronate at baseline. Eleven out of the 146 (7.5%) osteopaenic patients commenced alendronate within 18 months of participation and eleven commenced after. One hundred and twenty four out of the 146 (84.9%) osteopaenic patients and all 126 with normal baseline BMD did not trigger the algorithm. At three years, lumbar spine mean BMD increased (15.6%, p<0.01) in the osteoporotic group. BMD in the osteopaenic group with early intervention significantly increased at three years (6.3%, p=0.02). No significant change was seen in the late intervention group. No change was observed in those with osteopaenia without alendronate. There was a significant drop in lumbar spine (-5.4%) and hip (-4.5%) mean BMD, in the normal BMD group, none of whom received alendronate. Fracture data will be presented. In postmenopausal women with endocrine-responsive EBC, BMD improved over time when a bisphosphonate is administered with anastrozole in osteoporotic patients using an osteoporosis schedule. Subjects with normal baseline BMD experienced the greatest BMD loss, although none became osteoporotic.

Effect of an estrogen-deficient state and alendronate therapy on bone loss resulting from experimental periapical lesions in rats.

PubMed

Xiong, Haofei; Peng, Bin; Wei, Lili; Zhang, Xiaolei; Wang, Li

2007-11-01

The aim of the research was to evaluate the impact of an estrogen-deficient state and alendronate (ALD) therapy on bone loss resulting from experimental periapical lesions in rats. Periapical lesions were induced on ovariectomized (OVX) and sham-ovariectomized (Sham) rats. After sample preparation, histologic and radiographic examination for periapical bone loss area and an enzyme histochemical test for tartrate-resistant acid phosphatase (TRAP) were performed. The results showed that OVX significantly increased bone loss resulting from periradicular lesions. After daily subcutaneous injection of ALD, the bone loss area and the number of TRAP-positive cells (osteoclasts) were reduced. These findings suggested that alendronate may protect against increased bone loss from experimental periapical lesions in estrogen-deficient rats. Given recent recognition of adverse effects of bisphosphonates, including an increased risk for osteonecrosis, the findings from this study should not be interpreted as a new indication for ALD treatment. However, they may offer insight into understanding and predicting outcomes in female postmenopausal patients already on ALD therapy for medical indications.

Controlled release of alendronate from nitrogen-doped mesoporous carbon

DOE PAGES

Saha, Dipendu; Spurri, Amanda; Chen, Jihua; ...

2016-04-13

With this study, we have synthesized a nitrogen doped mesoporous carbon with the BET surface area of 1066 m 2/g, total pore volume 0.6 cm 3/g and nitrogen content of 0.5%. Total alendronate adsorption in this carbon was ~5%. The release experiments were designed in four different media with sequential pH values of 1.2, 4.5, 6.8 and 7.4 for 3, 1, 3 and 5 h, respectively and at 37 °C to imitate the physiological conditions of stomach, duodenum, small intestine and colon, respectively. Release of the drug demonstrated a controlled fashion; only 20% of the drug was released in themore » media with pH = 1.2, whereas 64% of the drug was released in pH = 7.4. This is in contrary to pure alendronate that was completely dissolved within 30 min in the first release media (pH = 1.2) only. The relatively larger uptake of alendronate in this carbon and its sustained fashion of release can be attributed to the hydrogen bonding between the drug and the nitrogen functionalities on carbon surface. Based on this result, it can be inferred that this formulation may lower the side effects of oral delivery of alendronate.« less

Effect of alendronate on early bone loss of renal transplant recipients.

PubMed

Abediazar, S; Nakhjavani, M R

2011-03-01

Renal transplant recipients (RTRs) are at risk of developing osteoporosis and osteopenia due to underlying renal osteodystrophy, hypophosphatemia, and immunosuppression. This process occurs more frequently in the first year after renal transplantation (RTX), resulting in eventual bone loss and fractures. The purpose of this study was to evaluate the effect of low-dose alendronate to prevent early bone loss after RTX. We prospectively studied 43 successful RTR including 22 men and 21-women with a mean overall age of 39.16±11.73 years, mean body mass index of 23.6±3.73, and mean dialysis duration of 25.73±17.67 months. We matched them based on age and sex: the alendronate-treated group received vitamin D (Vit D) during the study plus 30 mg alendronate weekly from 1 month after RTX. The control group only received Vit D. We measured serum calcium, phosphate, alkaline phosphatase, blood urea, creatinine, and intact parathyroid hormone (iPTH) at the pretransplant baseline and monthly thereafter as well as BMD of the lumbar spine, femur, and radius pretransplant baseline versus 3 and 6 months after RTX. At 6 month after RTX, the lumbar BMD in the alendronate group increased significantly from 0.819±0.11 to 0.863±0.14 (P<.01), while it decreased in the control group from 0.897±0.17 to 0.817±0.16 (P<.001). There was also a significant increase in radius BMD (P<.001) and a nonsignificant increase in femoral BMD in the alendronate versus a significant decrease of femoral and radius BMD (P<.001) in the control group at 6 months. Upon multivariate analysis, there was a significant correlation between alendronate and spine BMD (r=.45, P<.001) but no linear regression between age, sex, BMI, dialysis duration of or iPTH with femoral, spine, or radius BMD changes at month 6. Low-dose alendronate was significantly useful to mitigate fast bone loss and increase BMD immediately after RTX. Copyright © 2011. Published by Elsevier Inc.

Cytotoxicity evaluation of sodium alendronate on cultured human periodontal ligament fibroblasts.

PubMed

Correia, Vera de Fátima Padrão; Caldeira, Celso L; Marques, Márcia Martins

2006-12-01

External root resorption processes are usually associated with dental trauma, mainly avulsion and intrusion. In such cases endodontic therapy aims to prevent this process by using medications that can inhibit osteoclastic activity, such as bisphosphonates. However, these drugs must be biocompatible to the periapical tissues. The aim of this study was to analyze the cytotoxicity of a bisphosphonate (sodium alendronate) on human periodontal ligament fibroblasts (PDL cells). Cells were plated in a density of 1 x 10(3) cells per dish. The experimental groups were GI (control) no sodium alendronate, and GII, GIII, and GIV with sodium alendronate at the concentrations of 10(-5), 10(-6), and 10(-7) M, respectively. The experimental times were 1, 6, 12, and 24 h (short-term) for viability and 2, 4, 6, and 8 days (long-term) for cell survival. Data in triplicate were statistically analyzed. Cultures treated with the highest alendronate concentration (GII) showed cell viability percentages significantly lower (P < 0.01) than those of the other groups (GI, GIII, and GIV), at 12 and 24 h. Cell growth on GII and GIII groups was similar. GII presented smaller growth than the other groups (P < 0.05). We concluded that sodium alendronate, on direct contact with human periodontal ligament fibroblasts, is cytotoxic in concentrations higher than of 10(-6) M.

Systematic review and meta-analysis of the efficacy and safety of alendronate and zoledronate for the treatment of postmenopausal osteoporosis.

PubMed

Serrano, Ana Julissa; Begoña, Leire; Anitua, Eduardo; Cobos, Raquel; Orive, Gorka

2013-12-01

The aim of this meta-analysis was to evaluate the efficacy and safety of two bisphosphonates (alendronate and zoledronate) in the treatment of postmenopausal osteoporosis. The incidence of fractures was considered as primary endpoint. Only randomized trials with a follow-up period of 1 year or more were included in this systematic review and meta-analysis. We excluded studies that included patients with secondary osteoporosis especially in relation to therapy with corticosteroids or other drugs or diseases known to affect bone mineral density. Studies published as subgroup analysis, extension studies, economic evaluations, and comparisons with active control were excluded. The methodological quality of controlled clinical trials that met these inclusion criteria was evaluated. No studies were excluded from analysis due to lack of quality. The risk ratio of hip, vertebral and wrist fractures for alendronate were 0.61 [95% confidence interval (CI) 0.40-0.93], 0.54 (95% CI 0.44-0.66) and 0.65 (95% CI 0.33-1.25), respectively. Zoledronate risk ratio was 0.62 (95% CI 0.46-0.82) and 0.38 (95% CI 0.22-0.67) for hip and vertebral fractures, respectively.

Cost-effectiveness analysis of once-yearly injection of zoledronic acid for the treatment of osteoporosis in Japan.

PubMed

Moriwaki, K; Mouri, M; Hagino, H

2017-06-01

Model-based economic evaluation was performed to assess the cost-effectiveness of zoledronic acid. Although zoledronic acid was dominated by alendronate, the incremental quality-adjusted life year (QALY) was quite small in extent. Considering the advantage of once-yearly injection of zoledronic acid in persistence, zoledronic acid might be a cost-effective treatment option compared to once-weekly oral alendronate. The purpose of this study was to estimate the cost-effectiveness of once-yearly injection of zoledronic acid for the treatment of osteoporosis in Japan. A patient-level state-transition model was developed to predict the outcome of patients with osteoporosis who have experienced a previous vertebral fracture. The efficacy of zoledronic acid was derived from a published network meta-analysis. Lifetime cost and QALYs were estimated for patients who had received zoledronic acid, alendronate, or basic treatment alone. The incremental cost-effectiveness ratio (ICER) of zoledronic acid was estimated. For patients 70 years of age, zoledronic acid was dominated by alendronate with incremental QALY of -0.004 to -0.000 and incremental cost of 430 USD to 493 USD. Deterministic sensitivity analysis indicated that the relative risk of hip fracture and drug cost strongly affected the cost-effectiveness of zoledronic acid compared to alendronate. Scenario analysis considering treatment persistence showed that the ICER of zoledronic acid compared to alendronate was estimated to be 47,435 USD, 27,018 USD, and 10,749 USD per QALY gained for patients with a T-score of -2.0, -2.5, or -3.0, respectively. Although zoledronic acid is dominated by alendronate, the incremental QALY is quite small in extent. Considering the advantage of annual zoledronic acid treatment in compliance and persistence, zoledronic acid may be a cost-effective treatment option compared to alendronate.

Effect of a sequential treatment combining abaloparatide and alendronate for the management of postmenopausal osteoporosis.

PubMed

Reginster, J Y; Al Daghri, Nasser; Kaufman, Jean-Marc; Bruyère, Olivier

2018-02-01

The recently published results of the sequential treatment of postmenopausal osteoporotic women with subcutaneous abaloparatide (80 µg/day) (ABL) for 18 months followed by 6 months of oral alendronate (70 mg/week) (ALN) support the administration of an anti-resorptive agent after completion of a treatment course with an osteoanabolic agent. The ABL/ALN sequence resulted in greater bone mineral density gains at all skeletal sites and in a reduction of vertebral, non-vertebral, major and clinical fractures compared to what is observed after 18 months of placebo followed by 6 months of ALN. Whereas questions remained unanswered about the ideal anti-resorptive agent to be used after ABL, the optimal duration of the administration of the anti-resorptive drug or the potential interest of re-initiating a course of ABL after a limited administration of ALN, these results support the use of the ABL/ALN sequence in the management of postmenopausal osteoporosis.

A fast and simple spectrofluorometric method for the determination of alendronate sodium in pharmaceuticals

PubMed Central

Ezzati Nazhad Dolatabadi, Jafar; Hamishehkar, Hamed; de la Guardia, Miguel; Valizadeh, Hadi

2014-01-01

Introduction: Alendronate sodium enhances bone formation and increases osteoblast proliferation and maturation and leads to the inhibition of osteoblast apoptosis. Therefore, a rapid and simple spectrofluorometric method has been developed and validated for the quantitative determination of it. Methods: The procedure is based on the reaction of primary amino group of alendronate with o-phthalaldehyde (OPA) in sodium hydroxide solution. Results: The calibration graph was linear over the concentration range of 0.0-2.4 μM and limit of detection and limit of quantification of the method was 8.89 and 29 nanomolar, respectively. The enthalpy and entropy of the reaction between alendronate sodium and OPA showed that the reaction is endothermic and entropy favored (ΔH = 154.08 kJ/mol; ΔS = 567.36 J/mol K) which indicates that OPA interaction with alendronate is increased at elevated temperature. Conclusion: This simple method can be used as a practical technique for the analysis of alendronate in various samples. PMID:24790897

Diagnostic PET Imaging of Mammary Microcalcifications Using 64Cu-DOTA-Alendronate in a Rat Model of Breast Cancer

PubMed Central

Ahrens, Bradley J.; Li, Lin; Ciminera, Alexandra K.; Chea, Junie; Poku, Erasmus; Bading, James R.; Weist, Michael R.; Miller, Marcia M.; Colcher, David M.

2017-01-01

The development of improved breast cancer screening methods is hindered by a lack of cancer-specific imaging agents and effective small-animal models to test them. The purpose of this study was to evaluate 64Cu-DOTA-alendronate as a mammary microcalcification-targeting PET imaging agent, using an ideal rat model. Our long-term goal is to develop 64Cu-DOTA-alendronate for the detection and noninvasive differentiation of malignant versus benign breast tumors with PET. Methods: DOTA-alendronate was synthesized, radiolabeled with 64Cu, and administered to normal or tumor-bearing aged, female, retired breeder Sprague–Dawley rats for PET imaging. Mammary tissues were subsequently labeled and imaged with light, confocal, and electron microscopy to verify microcalcification targeting specificity of DOTA-alendronate and elucidate the histologic and ultrastructural characteristics of the microcalcifications in different mammary tumor types. Tumor uptake, biodistribution, and dosimetry studies were performed to evaluate the efficacy and safety of 64Cu-DOTA-alendronate. Results: 64Cu-DOTA-alendronate was radiolabeled with a 98% yield. PET imaging using aged, female, retired breeder rats showed specific binding of 64Cu-DOTA-alendronate in mammary glands and mammary tumors. The highest uptake of 64Cu-DOTA-alendronate was in malignant tumors and the lowest uptake in benign tumors and normal mammary tissue. Confocal analysis with carboxyfluorescein-alendronate confirmed the microcalcification binding specificity of alendronate derivatives. Biodistribution studies revealed tissue alendronate concentrations peaking within the first hour, then decreasing over the next 48 h. Our dosimetric analysis demonstrated a 64Cu effective dose within the acceptable range for clinical PET imaging agents and the potential for translation into human patients. Conclusion: 64Cu-DOTA-alendronate is a promising PET imaging agent for the sensitive and specific detection of mammary tumors as well as

The association between automatic generic substitution and treatment persistence with oral bisphosphonates.

PubMed

Ström, O; Landfeldt, E

2012-08-01

Automatic generic substitution of alendronate products, used to reduce drug costs, and medication persistence was studied retrospectively between 2006 and 2009. During this period the number of, and the rate of substitution between, alendronate products increased while persistence decreased. Patient preferences should be considered when designing and evaluating generic policies. Automatic generic substitution (AGS) was implemented in Sweden in 2002. The objective of this study was to investigate the association between AGS and persistence with alendronate treatment of primary osteoporosis in Sweden. An open historical cohort of women and men (n = 36,433) was identified in the Swedish Prescribed Drug Register through filled prescriptions for alendronate or risedronate between 2005 and 2009. Co-morbidity data was extracted from the National Patient Register. The association between AGS and medication persistence was investigated using non-parametric and parametric survival analysis. Between 2006 and 2009, the number of alendronate products increased from 15 to 25, the proportion of prescriptions constituting a substitution increased from 10.8% to 45.2%, and the proportion of patients persisting with alendronate treatment for 12 months fell from 66.9% to 51.7%. Patients starting alendronate treatment in 2006 had lower risk of stopping treatment compared with those starting in 2007 (HR 1.34, 95% CI 1.29-1.39), 2008 (HR 1.49, 95% CI 1.43-1.55), and 2009 (HR 1.50, 95% CI 1.40-1.60). No difference was observed in persistence with proprietary risedronate during the same period. Individuals who had their alendronate product substituted at the first prescription refill had significantly higher probability of discontinuation (HR 1.25, 95% CI 1.20-1.30). AGS causes increased product substitution which appears to be associated with reduced treatment persistence. Poor health outcomes and associated costs due to forgone drug exposure should be taken into account in the

Effects of alendronate on restoration of biomechanical properties of periodontium in replanted rat molars.

PubMed

Shibata, T; Komatsu, K; Shimada, A; Shimoda, S; Oida, S; Kawasaki, K; Chiba, M

2004-12-01

We examined the effect of the pretreatment of roots with alendronate on the restoration of the support function of the healing periodontal ligament in replanted rat molars. The left maxillary first molars were extracted, placed in 0.9% NaCl containing 1 mm alendronate (alendronate group) or 0.9% NaCl (control group) for 5 min, and were replanted into their sockets. Groups of animals were killed at 7, 14, and 21 days after replantation. Normal control rats were also killed on the same days. The force required to extract the replanted or normal tooth from its socket was measured, and a load-deformation curve was developed and analyzed. Micro-computed tomography and histologic analyses were also made. The mechanical properties of the healing periodontal ligament in the alendronate group were gradually restored from 7 to 21 days. However, fractures of the roots and bones during mechanical testing occurred in most of the replanted teeth in the control group at 21 days. The rates of restoration of the mechanical strength, extensibility, stiffness, and toughness for the alendronate group at 21 days were 67, 98, 74, and 68% of the normal controls, respectively. Micro-computed tomography and histologic observations revealed that bone-like structures within the pulp and ankylosis between the roots and socket bones occurred commonly in the control group, but were uncommon in the alendronate group. Our findings suggest that the pretreatment with alendronate inhibits the formation of abnormal mineralized tissues and results in better restoration of the support function of the healing periodontal ligament in replanted teeth. (c)Blackwell Munksgaard 2004

Effect of alendronate on bone mineral density in adult patients with Laron syndrome (primary growth hormone insensitivity).

PubMed

Eshed, Varda; Benbassat, Carlos A; Laron, Zvi

2006-04-01

Severe short stature resulting from a deficiency in insulin-like growth factor-I (IGF-I) is a prominent feature of Laron syndrome (LS). Whether patients with LS are osteopenic or not, and whether they need treatment with bisphosphonates, remains uncertain. The aim of this study was to investigate the action of alendronate on the IGF-I-deficient bones of adult patients with LS and osteoporosis, as determined by dual X-ray absorptiometry . Seven patients (5 women and 2 men) of mean age 40.8+/-7.6 years and mean bone mass density (BMD) 0.843+/-0.06 g/cm2 (T score -2.9+/-0.5) at the lumbar spine and 0.734+/-0.11 g/cm2 (T score -2.2+/-0.9) at the femoral neck were treated with alendronate 70 mg once/weekly over a 12-month period. Treatment led to an increase of 5.3% in BMD (p=0.038) at the femoral neck. There was a similar trend at the lumbar spine, but the difference was not statistically significant (2.3%, p=0.34). Mean total alkaline phosphatase decreased by 14% from normal range at baseline (p=0.007). Urinary deoxypyridinoline levels, which were elevated at baseline (10+/-2.3 nM/mMcre), showed a nonsignificant change during treatment. Our study suggests that treatment with alendronate may have positive effects in patients with LS and low BMD on dual X-ray absorptiometry.

Pharmacokinetic characteristics of formulated alendronate transdermal delivery systems in rats and humans.

PubMed

Choi, Ahyoung; Gang, Hyesil; Whang, Jiae; Gwak, Hyesun

2010-05-01

The objective of this study was to examine the absorption of alendronate from formulated transdermal delivery systems in rats and humans. When alendronate was applied to rats by transdermal delivery systems (7.2 mg) and oral administration (30 mg/kg), a statistically significant difference was found in the amount remaining to be excreted at time t (Ae(t)) and the amount remaining to be excreted at time 0 (Ae(infinity)) (p < 0.01). The highest Ae(infinity) (1267.7+/-65.2 ng) was found in the formulation containing 6% caprylic acid in propylene glycol (PG), which was 5.4- and 2.0-times higher than the PG only formulation and oral administration, respectively. Compared to oral administration, significantly delayed half-life values were obtained from all the formulated transdermal delivery systems. There was a linear relationship (r(2) = 0.9854) between the drug loading dose and Ae(infinity). The Ae(infinity) values from the transdermal delivery system containing 6% caprylic acid (53.8 mg as alendronate) and an oral product (Fosamax), 70 mg as alendronate) in humans were 127.0 +/- 34.2 microg and 237.2 +/- 56.3 microg, respectively. The dose-adjusted relative Ae(infinity) ratio of the transdermal delivery system to oral product was calculated to be 69.7%. The long half-life of alendronate in the transdermal delivery system (50.6 +/- 6.4 h), compared to that of the oral product (3.5 +/- 1.1 h) could allow less-frequent dosing. In conclusion, this study showed that a transdermal delivery system containing 6% caprylic acid in PG could be a favorable alternative for alendronate administration.

Short term sodium alendronate administration improves the peri-implant bone quality in osteoporotic animals

PubMed Central

de OLIVEIRA, Danila; HASSUMI, Jaqueline Suemi; GOMES-FERREIRA, Pedro Henrique da Silva; POLO, Tárik Ocon Braga; FERREIRA, Gabriel Ramalho; FAVERANI, Leonardo Perez; OKAMOTO, Roberta

2017-01-01

Abstract Sodium alendronate is a bisphosphonate drug that exerts antiresorptive action and is used to treat osteoporosis. Objective The aim of this study was to evaluate the bone repair process at the bone/implant interface of osteoporotic rats treated with sodium alendronate through the analysis of microtomography, real time polymerase chain reactions and immunohistochemistry (RUNX2 protein, bone sialoprotein (BSP), alkaline phosphatase, osteopontin and osteocalcin). Material and Methods A total of 42 rats were used and divided in to the following experimental groups: CTL: control group (rats submitted to fictitious surgery and fed with a balanced diet), OST: osteoporosis group (rats submitted to a bilateral ovariectomy and fed with a low calcium diet) and ALE: alendronate group (rats submitted to a bilateral ovariectomy, fed with a low calcium diet and treated with sodium alendronate). A surface treated implant was installed in both tibial metaphyses of each rat. Euthanasia of the animals was conducted at 14 (immunhostochemistry) and 42 days (immunohistochemistry, micro CT and PCR). Data were subjected to statistical analysis with a 5% significance level. Results Bone volume (BV) and total pore volume were higher for ALE group (P<0.05). Molecular data for RUNX2 and BSP proteins were significantly expressed in the ALE group (P<0.05), in comparison with the other groups. ALP expression was higher in the CTL group (P<0.05). The immunostaining for RUNX2 and osteopontin was positive in the osteoblastic lineage cells of neoformed bone for the CTL and ALE groups in both periods (14 and 42 days). Alkaline phosphatase presented a lower staining area in the OST group compared to the CTL in both periods and the ALE at 42 days. Conclusion There was a decrease of osteocalcin precipitation at 42 days for the ALE and OST groups. Therefore, treatment with short-term sodium alendronate improved bone repair around the implants installed in the tibia of osteoporotic rats. PMID

Effects of odanacatib on BMD and safety in the treatment of osteoporosis in postmenopausal women previously treated with alendronate: a randomized placebo-controlled trial.

PubMed

Bonnick, Sydney; De Villiers, Tobias; Odio, Alberto; Palacios, Santiago; Chapurlat, Roland; DaSilva, Carolyn; Scott, Boyd B; Le Bailly De Tilleghem, Celine; Leung, Albert T; Gurner, Deborah

2013-12-01

Odanacatib (ODN) is a selective cathepsin K inhibitor being developed to treat osteoporosis. The effects of ODN were evaluated on bone mineral density (BMD), biochemical markers of bone turnover, and safety in patients previously treated with alendronate. This was a randomized, double-blind, placebo-controlled, 24-month study. The study was conducted at private or institutional practices. Postmenopausal women (n = 243) ≥ 60 years of age with low BMD at the total hip, femoral neck, or trochanter (T-score ≤-2.5 but >-3.5 without prior fracture or ≤-1.5 but >-3.5 with prior fracture) on alendronate for ≥ 3 years. The intervention included ODN 50 mg or placebo weekly. The primary end point was percentage change from baseline of femoral neck BMD at month 24. BMD was assessed by dual-energy x-ray absorptiometry at baseline and 6, 12, and 24 months. Biochemical markers of bone turnover (serum C-telopeptides of type 1 collagen, urinary N-telopeptides of type 1 collagen, serum bone specific alkaline phosphatase, and serum N-terminal propeptide of type 1 collagen) were measured at baseline and 3, 6, 12, 18, and 24 months. In the ODN group, BMD changes from baseline at the femoral neck, trochanter, total hip, and lumbar spine at 24 months (1.7%, 1.8%, 0.8%, and 2.3%, respectively) were significantly different from the placebo group. ODN significantly decreased urinary N-telopeptides of type 1 collagen to creatinine ratio and significantly increased serum N-terminal propeptide of type 1 collagen compared with placebo. Serum C-telopeptides of type 1 collagen was unexpectedly increased with ODN treatment. The safety profile appeared similar between groups. ODN provided incremental BMD gains in osteoporotic women after alendronate treatment.

Hydroxyapatite nanocrystals functionalized with alendronate as bioactive components for bone implant coatings to decrease osteoclastic activity

NASA Astrophysics Data System (ADS)

Bosco, Ruggero; Iafisco, Michele; Tampieri, Anna; Jansen, John A.; Leeuwenburgh, Sander C. G.; van den Beucken, Jeroen J. J. P.

2015-02-01

The integration of bone implants within native bone tissue depends on periprosthetic bone quality, which is severely decreased in osteoporotic patients. In this work, we have synthesized bone-like hydroxyapatite nanocrystals (nHA) using an acid-base neutralization reaction and analysed their physicochemical properties. Subsequently, we have functionalized the nHA with alendronate (nHAALE), a well-known bisphosphonate drug used for the treatment of osteoporosis. An in vitro osteoclastogenesis test was carried out to evaluate the effect of nHAALE on the formation of osteoclast-like cells from monocytic precursor cells (i.e. RAW264.7 cell line) showing that nHAALE significantly promoted apoptosis of osteoclast-like cells. Subsequently, nHA and nHAALE were deposited on titanium disks using electrospray deposition (ESD), for which characterisation of the deposited coatings confirmed the presence of alendronate in nHAALE coatings with nanoscale thickness of about 700 nm. These results indicate that alendronate linked to hydroxyapatite nanocrystals has therapeutic potential and nHAALE can be considered as an appealing coating constituent material for orthopaedic and oral implants for application in osteoporotic patients.

Diagnostic PET Imaging of Mammary Microcalcifications Using 64Cu-DOTA-Alendronate in a Rat Model of Breast Cancer.

PubMed

Ahrens, Bradley J; Li, Lin; Ciminera, Alexandra K; Chea, Junie; Poku, Erasmus; Bading, James R; Weist, Michael R; Miller, Marcia M; Colcher, David M; Shively, John E

2017-09-01

The development of improved breast cancer screening methods is hindered by a lack of cancer-specific imaging agents and effective small-animal models to test them. The purpose of this study was to evaluate 64 Cu-DOTA-alendronate as a mammary microcalcification-targeting PET imaging agent, using an ideal rat model. Our long-term goal is to develop 64 Cu-DOTA-alendronate for the detection and noninvasive differentiation of malignant versus benign breast tumors with PET. Methods: DOTA-alendronate was synthesized, radiolabeled with 64 Cu, and administered to normal or tumor-bearing aged, female, retired breeder Sprague-Dawley rats for PET imaging. Mammary tissues were subsequently labeled and imaged with light, confocal, and electron microscopy to verify microcalcification targeting specificity of DOTA-alendronate and elucidate the histologic and ultrastructural characteristics of the microcalcifications in different mammary tumor types. Tumor uptake, biodistribution, and dosimetry studies were performed to evaluate the efficacy and safety of 64 Cu-DOTA-alendronate. Results: 64 Cu-DOTA-alendronate was radiolabeled with a 98% yield. PET imaging using aged, female, retired breeder rats showed specific binding of 64 Cu-DOTA-alendronate in mammary glands and mammary tumors. The highest uptake of 64 Cu-DOTA-alendronate was in malignant tumors and the lowest uptake in benign tumors and normal mammary tissue. Confocal analysis with carboxyfluorescein-alendronate confirmed the microcalcification binding specificity of alendronate derivatives. Biodistribution studies revealed tissue alendronate concentrations peaking within the first hour, then decreasing over the next 48 h. Our dosimetric analysis demonstrated a 64 Cu effective dose within the acceptable range for clinical PET imaging agents and the potential for translation into human patients. Conclusion: 64 Cu-DOTA-alendronate is a promising PET imaging agent for the sensitive and specific detection of mammary tumors as

Microarchitectural Deterioration of Cortical and Trabecular Bone: Differing Effects of Denosumab and Alendronate

PubMed Central

Seeman, Ego; Delmas, Pierre D; Hanley, David A; Sellmeyer, Deborah; Cheung, Angela M; Shane, Elizabeth; Kearns, Ann; Thomas, Thierry; Boyd, Steven K; Boutroy, Stephanie; Bogado, Cesar; Majumdar, Sharmila; Fan, Michelle; Libanati, Cesar; Zanchetta, Jose

2015-01-01

The intensity of bone remodeling is a critical determinant of the decay of cortical and trabecular microstructure after menopause. Denosumab suppresses remodeling more than alendronate, leading to greater gains in areal bone mineral density (aBMD). These greater gains may reflect differing effects of each drug on bone microarchitecture and strength. In a phase 2 double-blind pilot study, 247 postmenopausal women were randomized to denosumab (60mg subcutaneous 6 monthly), alendronate (70mg oral weekly), or placebo for 12 months. All received daily calcium and vitamin D. Morphologic changes were assessed using high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and distal tibia and QCT at the distal radius. Denosumab decreased serum C-telopeptide more rapidly and markedly than alendronate. In the placebo arm, total, cortical, and trabecular BMD and cortical thickness decreased (−2.1% to −0.8%) at the distal radius after 12 months. Alendronate prevented the decline (−0.6% to 2.4%, p = .051 to < .001 versus placebo), whereas denosumab prevented the decline or improved these variables (0.3% to 3.4%, p < .001 versus placebo). Changes in total and cortical BMD were greater with denosumab than with alendronate (p ≤ .024). Similar changes in these parameters were observed at the tibia. The polar moment of inertia also increased more in the denosumab than alendronate or placebo groups (p < .001). Adverse events did not differ by group. These data suggest that structural decay owing to bone remodeling and progression of bone fragility may be prevented more effectively with denosumab. PMID:20222106

Iontophoresis significantly increases the trans-dentinal delivery of osteoprotegerin, alendronate, and calcitonin.

PubMed

Kitchens, James A; Schwartz, Scott A; Schindler, William G; Hargreaves, Kenneth M

2007-10-01

The purpose of this study was to evaluate the delivery of alendronate, calcitonin, and osteoprotegerin (OPG) through human dentin by both diffusion and iontophoresis for the potential treatment of invasive cervical resorption. Radiolabeled alendronate, calcitonin, and OPG were added to the top of a split chamber device that contained 1-mm thick dentin disks devoid of a smear layer. Transdentinal movement of medicaments by either random diffusion or application of an iontophoretic current was measured by analysis of gamma emission of effluent fractions. In addition, calcitonin delivery was evaluated at differing magnitudes of current (0-4 mA) by using the aforementioned chamber. Diffusion of all 3 medicaments was minimal. In contrast, the application of a 3-mA iontophoretic gradient significantly increased delivery for all 3 compounds at 10-, 20-, and 30-minute intervals. In addition, a linear increase in permeability was seen for calcitonin as milliamperes were increased from 0 to 4 (r = 0.947), with more than a 100-fold increase in delivery observed with iontophoresis. Delivery of the tested medicaments by using iontophoresis might prove to be a useful technique for treatment of invasive cervical resorption.

Zoledronic acid and alendronate sodium and the implications in orthodontic movement.

PubMed

Franzoni, J S; Soares, F M P; Zaniboni, E; Vedovello Filho, M; Santamaria, M P; Dos Santos, G M T; Esquisatto, M A M; Felonato, M; Mendonca, F A S; Franzini, C M; Santamaria, M

2017-08-01

To evaluate orthodontic tooth movement (OTM) in rats treated with two types of bisphosphonates (BPs), alendronate sodium (A) and zoledronic acid (Z). In all, 15 male Wistar rats were randomly divided into three groups. Group OTM+A: orthodontic tooth movement and subcutaneous administration of alendronate sodium (2.5 mg/kg); Group OTM+Z: orthodontic tooth movement and subcutaneous administration of zoledronic acid (0.02 mg/kg), and Group OTM: orthodontic tooth movement and subcutaneous injection of saline. The BPs were administered once a day during 25 days before OTM started and during 10 days of OTM. The left upper first molar was moved with a stainless-steel closed coil spring which delivered an initial force of 0.4N. OTM was measured with a digital caliper comparing the moved and the contralateral side. The histomorphometric analysis counted the number of osteoclasts, inflammatory cells, blood vessels and fibroblasts (n/10 4  m 2 ) in periodontal ligament (PDL) of the distobuccal root. A reduction of 58.3% of OTM was found in Group OTM+A and 99.6% in Group OTM+Z, when compared with Group OTM. There was a significant decrease of osteoclasts and inflammatory cells in BP-treated groups. Blood vessels and fibroblastic cells decreased mainly in Group OTM+Z. Alendronate sodium and zoledronic acid have similar effects on the periodontal tissue during orthodontic treatment in rats. Especially, zoledronic acid can affect orthodontic tooth movement. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Whole body vibration exercise improves body balance and walking velocity in postmenopausal osteoporotic women treated with alendronate: Galileo and Alendronate Intervention Trail (GAIT).

PubMed

Iwamoto, J; Sato, Y; Takeda, T; Matsumoto, H

2012-09-01

A randomized controlled trial was conducted to determine the effect of 6 months of whole body vibration (WBV) exercise on physical function in postmenopausal osteoporotic women treated with alendronate. Fifty-two ambulatory postmenopausal women with osteoporosis (mean age: 74.2 years, range: 51-91 years) were randomly divided into two groups: an exercise group and a control group. A four-minute WBV exercise was performed two days per week only in the exercise group. No exercise was performed in the control group. All the women were treated with alendronate. After 6 months of the WBV exercise, the indices for flexibility, body balance, and walking velocity were significantly improved in the exercise group compared with the control group. The exercise was safe and well tolerated. The reductions in serum alkaline phosphatase and urinary cross-linked N-terminal telopeptides of type I collagen during the 6-month period were comparable between the two groups. The present study showed the benefit and safety of WBV exercise for improving physical function in postmenopausal osteoporotic women treated with alendronate.

Effect of heparin and alendronate coating on titanium surfaces on inhibition of osteoclast and enhancement of osteoblast function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moon, Ho-Jin; Yun, Young-Pil; Han, Choong-Wan

2011-09-23

Highlights: {yields} We examine bone metabolism of engineered alendronate attached to Ti surfaces. {yields} Alendronate-immobilized Ti enhances activation of osteoblast differentiation. {yields} Alendronate-immobilized Ti inhibits osteoclast differentiation. {yields} Alendronate-immobilized Ti may be a bioactive implant with dual functions. -- Abstract: The failure of orthopedic and dental implants has been attributed mainly to loosening of the implant from host bone, which may be due to weak bonding of the implant material to bone tissue. Titanium (Ti) is used in the field of orthopedic and dental implants because of its excellent biocompatibility and outstanding mechanical properties. Therefore, in the field of materialsmore » science and tissue engineering, there has been extensive research to immobilize bioactive molecules on the surface of implant materials in order to provide the implants with improved adhesion to the host bone tissue. In this study, chemically active functional groups were introduced on the surface of Ti by a grafting reaction with heparin and then the Ti was functionalized by immobilizing alendronate onto the heparin-grafted surface. In the MC3T3-E1 cell osteogenic differentiation study, the alendronate-immobilized Ti substrates significantly enhanced alkaline phosphatase activity (ALP) and calcium content. Additionally, nuclear factor kappa B ligand (RANKL)-induced osteoclast differentiation of RAW264.7 cells was inhibited with the alendronate-immobilized Ti as confirmed by TRAP analysis. Real time PCR analysis showed that mRNA expressions of osteocalcin and osteopontin, which are markers for osteogenesis, were upregulated in MC3T3-E1 cells cultured on alendronate-immobilized Ti. The mRNA expressions of TRAP and Cathepsin K, markers for osteoclastogenesis, in RAW264.7 cells cultured on alendronate-immobilized Ti were down-regulated. Our study suggests that alendronate-immobilized Ti may be a bioactive implant with dual functions to

Highly sensitive determination of alendronate in human plasma and dialysate using metal-free HPLC-MS/MS.

PubMed

Yamada, Miho; Lee, Xiao-Pen; Fujishiro, Masaya; Iseri, Ken; Watanabe, Makoto; Sakamaki, Hiroshi; Uchida, Naoki; Matsuyama, Takaaki; Kumazawa, Takeshi; Takahashi, Haruo; Ishii, Akira; Sato, Keizo

2018-01-01

A highly sensitive method was developed for the analysis of alendronate in human plasma and dialysate using MonoSpin™ SAX ® extraction and metal-free high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS) following methylation with trimethylsilyldiazomethane. The chromatographic separation of the derivatives for alendronate and alendronate-d 6 was achieved on an L-column2 ODS metal-free column (50 mm  ×  2 mm i.d., particle size 3 µm) with a linear gradient elution system composed of 10 mM ammonium acetate (pH 6.8) and acetonitrile at a flow rate of 0.3 ml/min. Quantification was performed by multiple reaction monitoring (MRM) with positive-ion electrospray ionization (ESI). Distinct peaks were observed for alendronate and for the internal standard on each channel within 1 min. The regression equations showed good linearity within the ranges of 2.0-100 ng/0.5 ml for the plasma and 1.0-100 ng/0.5 ml for the dialysate, with the limits of detection at 1.0 ng/0.5 ml for the plasma and 0.5 ng/0.5 ml for the dialysate. Extraction efficiencies for alendronate for the plasma and dialysate were 41.1-51.2% and 63.6-73.4%, respectively. The coefficient of variation (CV) was ≤8.5%. The method was successfully applied to the analyses of real plasma and dialysate samples derived after intravenous administration of alendronate. Copyright © 2017 Elsevier B.V. All rights reserved.

Are the results of multiple drilling and alendronate for osteonecrosis of the femoral head better than those of multiple drilling? A pilot study.

PubMed

Kang, Pengde; Pei, Fuxing; Shen, Bin; Zhou, Zongke; Yang, Jing

2012-01-01

The treatment of osteonecrosis of the femoral head (ONFH) remains controversial. A recently proposed treatment is multiple drilling core decompression combined with systemic alendronate as a femoral head-preserving procedure for ONFH. However, it is not known whether alendronate enhances the risk of collapse. We wondered whether the combined procedure could delay or prevent progression of ONFH compared to multiple drilling alone. Patients with early-stage ONFH were randomly assigned to be treated with either multiple drilling combined with alendronate (47 patients, 67 hips) or multiple drilling alone (46 patients, 60 hips). We defined failure as the need for THA or a Harris score less than 70. The minimum follow-up was 48 months for the 77 patients completing the protocol. After a minimum 4-year follow-up, 91% (40/44) of patients with Stage II disease and 62% (8/13) of patients with Stage III disease had not required THA in alendronate group, compared to 79% (31/39) of patients with Stage II disease and 46% (6/13) of patients with Stage III disease had not required THA in control group (P=0.12, P=0.047, respectively). Small or medium and central lesions had a better successful rate in both groups. Risk factors did not seem to affect the clinical successful rate of this procedure. Multiple small-diameter drilling core decompression combined with systemic alendronate administration can reduce pain and delay progression of early-stage ONFH. Even in Ficat IIA and III hips, some benefit was obtained from this approach at least delay in the need for THA. Copyright © 2011. Published by Elsevier SAS.

Differences in otosclerotic and normal human stapedial osteoblast properties are normalized by alendronate in vitro.

PubMed

Gronowicz, Gloria; Richardson, Yvonne L; Flynn, John; Kveton, John; Eisen, Marc; Leonard, Gerald; Aronow, Michael; Rodner, Craig; Parham, Kourosh

2014-10-01

Identify and compare phenotypic properties of osteoblasts from patients with otosclerosis (OSO), normal bones (HOB), and normal stapes (NSO) to determine a possible cause for OSO hypermineralization and assess any effects of the bisphosphonate, alendronate. OSO (n = 11), NSO (n = 4), and HOB (n = 13) cultures were assayed for proliferation, adhesion, mineralization, and gene expression with and without 10(-10)M-10(-8)M alendronate. Academic hospital. Cultures were matched for age, sex, and passage number. Cell attachment and proliferation + alendronate were determined by Coulter counting cells and assaying tritiated thymidine uptake, respectively. At 7, 14, and 21 days of culture + alendronate, calcium content and gene expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were determined. OSO had significantly more cells adhere but less proliferation than NSO or HOB. Calcification was significantly increased in OSO compared to HOB and NSO. NSO and HOB had similar cell adhesion and proliferation rates. A dose-dependent effect of alendronate on OSO adhesion, proliferation, and mineralization was found, resulting in levels equal to NSO and HOB. All cultures expressed osteoblast-specific genes such as RUNX2, alkaline phosphatase, type I collagen, and osteocalcin. However, osteopontin was dramatically reduced, 9.4-fold at 14 days, in OSO compared to NSO. Receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG), important in bone resorption, was elevated in OSO with decreased levels of OPG levels. Alendronate had little effect on gene expression in HOB but in OSO increased osteopontin levels and decreased RANKL/OPG. OSO cultures displayed properties of hypermineralization due to decreased osteopontin (OPN) and also had increased RANKL/OPG, which were normalized by alendronate. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2014.

Alendronate as an Effective Countermeasure to Disuse Induced Bone loss

NASA Technical Reports Server (NTRS)

LeBlanc, Adrian D.; Driscol, Theda B.; Shackelford, Linda C.; Evans, Harlan J.; Rianon, Nahid J.; Smith, Scott M.; Lai, Dejian

2002-01-01

Microgravity, similar to diuse immobilization on earth, causes rapid bone loss. This loss is believed to be an adaptive response to the reduced musculoskelatal forces in space and occurs gradually enough that changes occurring during short duration space flight are not a concern. Bone loss, however, will be a major impediment for long duration missions if effective countermeasures are not developed and implemented. Bed rest is used to simulate the reduced mechanical forces in humans and was used to test the hypothesis that oral alendronate would reduce the effects of long duration (17 weeks) inactivity on bone. Eight male subjects were given daily oral doses of alendronate during 17 weeks of horizontal bed rest and compared with 13 male control subjects not given the drug. Efficacy was evaluated based on measurements of bone markers, calcium balance and bone density performed before, during and after the bed rest. The results show that oral alendronate attenuates most of the characteristic changes associated with long duration bed rest and presumably space flight.

Alendronate for fracture prevention in postmenopause.

PubMed

Holder, Kathryn K; Kerley, Sara Shelton

2008-09-01

Osteoporosis is an abnormal reduction in bone mass and bone deterioration leading to increased fracture risk. Alendronate (Fosamax) belongs to the bisphosphonate class of drugs, which act to inhibit bone resorption by interfering with the activity of osteoclasts. To assess the effectiveness of alendronate in the primary and secondary prevention of osteoporotic fractures in postmenopausal women. The authors searched Central, Medline, and EMBASE for relevant randomized controlled trials published from 1966 to 2007. The authors undertook study selection and data abstraction in duplicate. The authors performed meta-analysis of fracture outcomes using relative risks, and a relative change greater than 15 percent was considered clinically important. The authors assessed study quality through reporting of allocation concealment, blinding, and withdrawals. Eleven trials representing 12,068 women were included in the review. Relative and absolute risk reductions for the 10-mg dose were as follows. For vertebral fractures, a 45 percent relative risk reduction was found (relative risk [RR] = 0.55; 95% confidence interval [CI], 0.45 to 0.67). This was significant for primary prevention, with a 45 percent relative risk reduction (RR = 0.55; 95% CI, 0.38 to 0.80) and 2 percent absolute risk reduction; and for secondary prevention, with 45 percent relative risk reduction (RR = 0.55; 95% CI, 0.43 to 0.69) and 6 percent absolute risk reduction. For nonvertebral fractures, a 16 percent relative risk reduction was found (RR = 0.84; 95% CI, 0.74 to 0.94). This was significant for secondary prevention, with a 23 percent relative risk reduction (RR = 0.77; 95% CI, 0.64 to 0.92) and a 2 percent absolute risk reduction, but not for primary prevention (RR = 0.89; 95% CI, 0.76 to 1.04). There was a 40 percent relative risk reduction in hip fractures (RR = 0.60; 95% CI, 0.40 to 0.92), but only secondary prevention was significant, with a 53 percent relative risk reduction (RR = 0.47; 95% CI

Enhanced anti-tumor activity and safety profile of targeted nano-scaled HPMA copolymer-alendronate-TNP-470 conjugate in the treatment of bone malignances

PubMed Central

Segal, Ehud; Pan, Huaizhong; Benayoun, Liat; Kopečková, Pavla; Shaked, Yuval; Kopeček, Jindčrich; Satchi-Fainaro, Ronit

2015-01-01

Bone neoplasms, such as osteosarcoma, exhibit a propensity for systemic metastases resulting in adverse clinical outcome. Traditional treatment consisting of aggressive chemotherapy combined with surgical resection, has been the mainstay of these malignances. Therefore, bone-targeted non-toxic therapies are required. We previously conjugated the aminobisphosphonate alendronate (ALN), and the potent anti-angiogenic agent TNP-470 with N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer. HPMA copolymer-ALN-TNP-470 conjugate exhibited improved anti-angiogenic and anti-tumor activity compared with the combination of free ALN and TNP-470 when evaluated in a xenogeneic model of human osteosarcoma. The immune system has major effect on toxicology studies and on tumor progression. Therefore, in this manuscript we examined the safety and efficacy profiles of the conjugate using murine osteosarcoma syngeneic model. Toxicity and efficacy evaluation revealed superior anti-tumor activity and decreased organ-related toxicities of the conjugate compared with the combination of free ALN plus TNP-470. Finally, comparative anti-angiogenic activity and specificity studies, using surrogate biomarkers of circulating endothelial cells (CEC), highlighted the advantage of the conjugate over the free agents. The therapeutic platform described here may have clinical translational relevance for the treatment of bone-related angiogenesis-dependent malignances. PMID:21429572

Inhibition of particulate debris-induced osteolysis by alendronate in a rat model.

PubMed

Thadani, Peter J; Waxman, Bryan; Sladek, Eduard; Barmada, Riad; Gonzalez, Mark H

2002-01-01

A rat model was used to study the efficacy of alendronate therapy in inhibition of particle-induced periprosthetic osteolysis. A prosthesis was simulated by inserting a cylindrical polymethylmethacrylate plug into the distal femur of 24 rats allowing the plug to communicate with the joint space. Intra-articular injections of irregularly-shaped ultra-high molecular weight polyethylene particles of 20-200 pm in diameter were administered at 2-week intervals. The rats were randomized into two groups (n=12 each). Group A rats received twice weekly subcutaneous injections of alendronate sodium while group B rats received injections of saline vehicle only. At 10 weeks all rats were sacrificed. The distal femurs were harvested and axial sections were prepared for histologic analysis. Each section was graded on a scale of 1-4, quantifying the degree of osteolysis surrounding the polymethylmethacrylate plug. Microscopic examination showed a significant (P<.0001) difference in the amount of periprosthetic bone. Femurs from group A treated with alendronate demonstrated mostly normal or near-normal periprosthetic trabeculations, whereas femurs from group B treated with saline showed extensive bone resorption. There was no qualitative difference in the inflammatory cellular response between the groups. This study established the ability of alendronate to inhibit the osteoclastic-mediated osteolysis around joint implants.

Pharmacokinetics of coadministration of levothyroxine sodium and alendronate sodium new effervescent formulation.

PubMed

Bone, H G; Walter, M A; Hurley, M E; Epstein, S

2017-05-01

No clinically important pharmacokinetic interference of alendronate occurred between a new effervescent formulation of alendronate and levothyroxine when coadministered. The combination does not materially affect levothyroxine absorption. Concurrent treatment of osteoporosis with alendronate (Aln) and hypothyroidism with levothyroxine (LT4) may be problematic because both drugs are to be taken separately after fasting overnight. The primary objective was to assess pharmacokinetic interactions between a new effervescent formulation of Aln (Aln-NEF) and LT4. A randomized, open-label, 3-way crossover study was conducted in 30 healthy adults (15 women). Subjects were dosed 3 times, separated by 35 days, after overnight fasts, with Aln-NEF alone (70 mg), LT4 alone (600 μg), or Aln-NEF and LT4 concurrently. Samples were analyzed for plasma Aln and serum LT4. Pharmacokinetic drug-drug interaction was assessed using 90% confidence intervals (CIs) for the test/reference ratio of the geometric means for area under the concentration-time curve from time zero to last measureable time point (AUC 0-t ) and maximum concentration (C max ). Results were compared to the default no-effect boundaries of 80 to 125% for the ratio Aln-NEF and LT4 concurrently/Aln-NEF alone and the ratio Aln-NEF and LT4 concurrently/LT4 alone. Geometric mean ratios (Aln-NEF with LT4/Aln-NEF alone) were 0.927 (90% CI 0.795-1.081) for AUC 0-8 and 0.912 (90% CI 0.773-1.077) for C max , demonstrating LT4 does not appreciably affect the pharmacokinetics of Aln. Geometric mean ratios (LT4 with Aln-NEF/LT4 alone) were 1.049 (90% CI 0.983-1.119) for AUC 0-48 and 1.075 (90% CI 1.006-1.148) for C max , demonstrating LT4 is bioequivalent between the 2 treatments. Coadministration of Aln-NEF and LT4 was well tolerated. There was no clinically important pharmacokinetic interference between the Aln-NEF formulation and LT4. Aln-NEF does not materially affect LT4 absorption.

Treatment dynamics of newly marketed drugs and implications for comparative effectiveness research.

PubMed

Gagne, Joshua J; Bykov, Katsiaryna; Willke, Richard J; Kahler, Kristijan H; Subedi, Prasun; Schneeweiss, Sebastian

2013-01-01

Clinicians and payers require rapid comparative effectiveness (CE) evidence generation to inform decisions for new drugs. We empirically assessed treatment dynamics of newly marked drugs and their implications for conducting CE research. We used claims data to evaluate five drug-outcome pairs: 1) raloxifene (vs. alendronate) and fracture; 2) risedronate (vs. alendronate) and fracture; 3) simvastatin plus ezetimibe fixed-dose combination (simvastatin + ezetimibe) (vs. simvastatin alone) and cardiovascular events; 4) rofecoxib (vs. nonselective nonsteroidal anti-inflammatory drugs [ns-NSAIDs]) and myocardial infarction; and 5) rofecoxib (vs. ns-NSAIDS) and gastrointestinal bleed. We examined utilization dynamics in the early marketing period, including evolving utilization patterns, outcome risk among those treated with new versus established drugs, and prior treatment patterns that may indicate treatment resistance or intolerance. We addressed these challenges by replicating active CE monitoring with sequential matched cohort analysis. Patients initiating new drugs were more likely to have used other drugs for the same indication in the past, but the majority of patients in all new drug cohorts were treatment naive (82.0% overall). Patients initiating rofecoxib had higher predicted baseline risk of gastrointestinal bleed than did patients initiating ns-NSAIDs. Patients initiating risedronate and alendronate had similar predicted baseline risks of fracture, while those initiating raloxifene and simvastatin + ezetimibe had lower risks of outcomes of interest relative to their comparators. Prospective monitoring yielded results consistent with expectation for each example. Many challenges to assessing the CE of new drugs are borne out in empirical data. Attention to these challenges can yield valid CE results. Copyright © 2013, International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc.

Effect of low-magnitude whole-body vibration combined with alendronate in ovariectomized rats: a random controlled osteoporosis prevention study.

PubMed

Chen, Guo-Xian; Zheng, Shuai; Qin, Shuai; Zhong, Zhao-Ming; Wu, Xiu-Hua; Huang, Zhi-Ping; Li, Wei; Ding, Ruo-Ting; Yu, Hui; Chen, Jian-Ting

2014-01-01

Alendronate (ALE) is a conventional drug used to treat osteoporosis. Low-magnitude whole-body vibration (WBV) exercise has been developed as a potential treatment for osteoporosis. The aim of this study was to investigate whether low-magnitude WBV could enhance the protective effect of ALE on bone properties in ovariectomized rats. A total of 128 Sprague-Dawley rats were randomly divided into five groups (SHAM, OVX+VEH, OVX+WBV, OVX + ALE, OVX+WBV+ALE). The level of WBV applied was 0.3 g at 45-55 Hz for 20 min/day, 5 day/week and for 3 months. ALE was administered in dose of 1 mg/Kg once a week. Every four weeks eight rats from each group were sacrificed and their blood and both tibiae were harvested. The expression of osteocalcin and CTX in serum was measured by enzyme-linked immunosorbent assay (ELISA) and the tibiae were subjected to metaphyseal three-point bending and μCT analysis. Osteocalcin rose after ovariectomy and was not appreciably changed by either alendronate or WBV alone or in combination. Alendronate treatment significantly prevented an increase in CTX. WBV alone treatment did not alter this effect. Compared with the OVX+WBV group, nearly all tested indices such as the BV/TV, TV apparent, Tb.N, Tb.Th, and Conn.D were higher in the OVX+ALE group at week 12.Compared with the OVX+WBV group, certain tested indices such as BV/TV, TV apparent, Tb.N, and Con.D, were higher in the OVX+WBV+ALE group at week 12. At week 12, tibiae treated with WBV+ALE exhibited a significantly higher Fmax compared to the OVX+VEH group, and a significant difference was also found in energy absorption between the OVX+WBV+ALE and OVX+VEH groups. Compared with the WBV, ALE was more effective at preventing bone loss and improved the trabecular architecture. However, WBV enhanced the effect of alendronate in ovariectomized rats by inducing further improvements in trabecular architecture.

Effect of Low-Magnitude Whole-Body Vibration Combined with Alendronate in Ovariectomized Rats: A Random Controlled Osteoporosis Prevention Study

PubMed Central

Zhong, Zhao-Ming; Wu, Xiu-Hua; Huang, Zhi-Ping; Li, Wei; Ding, Ruo-Ting; Yu, Hui; Chen, Jian-Ting

2014-01-01

Background Alendronate (ALE) is a conventional drug used to treat osteoporosis. Low-magnitude whole-body vibration (WBV) exercise has been developed as a potential treatment for osteoporosis. The aim of this study was to investigate whether low-magnitude WBV could enhance the protective effect of ALE on bone properties in ovariectomized rats. Methods A total of 128 Sprague-Dawley rats were randomly divided into five groups (SHAM, OVX+VEH, OVX+WBV, OVX + ALE, OVX+WBV+ALE). The level of WBV applied was 0.3 g at 45–55 Hz for 20 min/day, 5 day/week and for 3 months. ALE was administered in dose of 1 mg/Kg once a week. Every four weeks eight rats from each group were sacrificed and their blood and both tibiae were harvested. The expression of osteocalcin and CTX in serum was measured by enzyme-linked immunosorbent assay (ELISA) and the tibiae were subjected to metaphyseal three-point bending and μCT analysis. Results Osteocalcin rose after ovariectomy and was not appreciably changed by either alendronate or WBV alone or in combination. Alendronate treatment significantly prevented an increase in CTX. WBV alone treatment did not alter this effect. Compared with the OVX+WBV group, nearly all tested indices such as the BV/TV, TV apparent, Tb.N, Tb.Th, and Conn.D were higher in the OVX+ALE group at week 12.Compared with the OVX+WBV group, certain tested indices such as BV/TV, TV apparent, Tb.N, and Con.D, were higher in the OVX+WBV+ALE group at week 12. At week 12, tibiae treated with WBV+ALE exhibited a significantly higher Fmax compared to the OVX+VEH group, and a significant difference was also found in energy absorption between the OVX+WBV+ALE and OVX+VEH groups. Conclusions Compared with the WBV, ALE was more effective at preventing bone loss and improved the trabecular architecture. However, WBV enhanced the effect of alendronate in ovariectomized rats by inducing further improvements in trabecular architecture. PMID:24796785

[Role of bones in the physiopathology of idiopathic hypercalciuria: effect of amino-bisphosphonate alendronate].

PubMed

Weisinger, J R; Alonzo, E; Machado, C; Carlini, R; Martinis, R; Paz-Martínez, V; Bellorín-Font, E

1997-01-01

Previous studies from our laboratory demonstrated that bone mineral content is affected in patients with idiopathic hypercalciuria and that there is a correlation between bone mineral loss and in-vitro cytokine production. At the same time we found that short term treatment with alendronate decreased urinary calcium in these subjects. In the present study we have examined the long-term effects of alendronate treatment (10 mg/day for one year) on urinary calcium, urinary hydroxyproline and bone mineral content in 18 idiopathic hypercalciuric and 8 normocalciuric stone formers. Clinical characteristics, as well as gender and age distribution were similar in both groups. Urinary calcium and hydroxyproline, were measured monthly. Calcium excretion decreased significantly at the end of the first month, and remained lower thereafter (277 +/- 28, before vs. 202 +/- 26 mg/g creatinine, after 12 months on alendronate, p < 0.01). Urinary hydroxyproline decreased significantly during the study (125.5 +/- 32.1 vs. 39.66 +/- 17.5 mg/g creatinine, p < 0.05). Serum calcium, glomerular filtration rate, and urinary sodium, did not change during the study. Lumbar spine bone density (trabecular bone) obtained with X ray absorptiometry revealed a significant increase from 1.162 +/- 0.231 to 1.197 +/- 0.248 g/cm2 (p < 0.01). These changes were associated with a significant decrease in IL-1 alpha mRNA transcription by unstimulated and lipopolysaccharide stimulated blood mononuclear cells, as tested by the reverse transcriptase polymerase chain reaction. No changes were observed in bone cortical sites (femoral neck). Normocalciuric subjects showed no significant changes in urinary calcium. In summary, the changes observed in urinary calcium excretion and different bone metabolic parameters, suggest a role of bone in the pathophysiology of idiopathic hypercalciuria.

Impact of noncompliance with alendronate and risedronate on the incidence of nonvertebral osteoporotic fractures in elderly women

PubMed Central

Blouin, Julie; Dragomir, Alice; Moride, Yola; Ste-Marie, Louis-Georges; Fernandes, Julio Cesar; Perreault, Sylvie

2008-01-01

AIMS To evaluate the association between noncompliance with alendronate and risedronate and the risk of nonvertebral osteoporotic fracture in community-dwelling elderly women. METHODS A nested case–control study was conducted using the Quebec administrative health databases. To be included in the cohort, women needed to be aged ≥ 68 years and to have initiated treatment with alendronate or risedronate between 1 January 2002 and 31 March 2005. Cases consisted of all women with an incident nonvertebral osteoporotic fracture occurring ≥ 1 year after initiation of therapy. Each case was matched with up to 20 controls using incidence density sampling, according to age (± 1 year) and follow-up duration. A woman was noncompliant if she had a medication possession ratio (MPR) <80% for total follow-up duration. Rate ratios (RR) for fracture were estimated through conditional logistic regression analysis, adjusting for potential confounders. RESULTS Among the 30 259 women included in the cohort, 1036 nonvertebral fracture cases were identified and were matched to 20 069 controls. Compared with women with a MPR ≥ 80%, those with a MPR < 80% had a greater risk of nonvertebral fracture [adjusted RR 1.27, 95% confidence interval (CI) 1.12, 1.44]. Considering hip fracture only, the multivariate model yielded similar results, (adjusted RR 1.28, 95% CI 1.02, 1.61). CONCLUSIONS Among community-dwelling elderly women, noncompliance with alendronate or risedronate is associated with an increased risk of nonvertebral fracture. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Compliance with alendronate and risedronate is suboptimal.Few studies have specifically evaluated the impact of noncompliance with alendronate or risedronate on the incidence of osteoporotic fractures in community-dwelling elderly women. WHAT THIS STUDY ADDS Among community-dwelling elderly women, noncompliance [defined as medication possession ratio (MPR) < 80%] with alendronate or risedronate was associated with

Determination of pKa values of alendronate sodium in aqueous solution by piecewise linear regression based on acid-base potentiometric titration.

PubMed

Ke, Jing; Dou, Hanfei; Zhang, Ximin; Uhagaze, Dushimabararezi Serge; Ding, Xiali; Dong, Yuming

2016-12-01

As a mono-sodium salt form of alendronic acid, alendronate sodium presents multi-level ionization for the dissociation of its four hydroxyl groups. The dissociation constants of alendronate sodium were determined in this work by studying the piecewise linear relationship between volume of titrant and pH value based on acid-base potentiometric titration reaction. The distribution curves of alendronate sodium were drawn according to the determined pKa values. There were 4 dissociation constants (pKa 1 =2.43, pKa 2 =7.55, pKa 3 =10.80, pKa 4 =11.99, respectively) of alendronate sodium, and 12 existing forms, of which 4 could be ignored, existing in different pH environments.

Inhibited osteoclastic bone resorption through alendronate treatment in rats reduces severe osteoarthritis progression.

PubMed

Siebelt, M; Waarsing, J H; Groen, H C; Müller, C; Koelewijn, S J; de Blois, E; Verhaar, J A N; de Jong, M; Weinans, H

2014-09-01

Osteoarthritis (OA) is a non-rheumatoid joint disease characterized by progressive degeneration of extra-cellular cartilage matrix (ECM), enhanced subchondral bone remodeling, osteophyte formation and synovial thickening. Alendronate (ALN) is a potent inhibitor of osteoclastic bone resorption and results in reduced bone remodeling. This study investigated the effects of pre-emptive use of ALN on OA related osteoclastic subchondral bone resorption in an in vivo rat model for severe OA. Using multi-modality imaging we measured effects of ALN treatment within cartilage and synovium. Severe osteoarthritis was induced in left rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with subcutaneous ALN injections and compared to twenty untreated controls. Animals were longitudinally monitored for 12weeks with in vivo μCT to measure subchondral bone changes and SPECT/CT to determine synovial macrophage activation using a folate-based radiotracer. Articular cartilage was analyzed at 6 and 12weeks with ex vivo contrast enhanced μCT and histology to measure sulfated-glycosaminoglycan (sGAG) content and cartilage thickness. ALN treatment successfully inhibited subchondral bone remodeling. As a result we found less subchondral plate porosity and reduced osteophytosis. ALN treatment did not reduce subchondral sclerosis. However, after the OA induction phase, ALN treatment protected cartilage ECM from degradation and reduced synovial macrophage activation. Surprisingly, ALN treatment also improved sGAG content of tibia cartilage in healthy joints. Our data was consistent with the hypothesis that osteoclastic bone resorption might play an important role in OA and may be a driving force for progression of the disease. However, our study suggest that this effect might not solely be effects on osteoclastic activity, since ALN treatment also influenced macrophage functioning. Additionally, ALN treatment and physical activity

Formulation and evaluation of Alendronate Sodium gel for the treatment of bone resorptive lesions in Periodontitis.

PubMed

Reddy, G Thirumal; Kumar, T M Pramod; Veena

2005-01-01

Alendronate sodium is formulated into gels and evaluated for the treatment of bone resorptive lesions in periodontitis. Carbopol 934P was used for the preparation of gels in three different concentrations. The prepared gel was evaluated for various properties such as preformulation, content uniformity, viscosity, compatibility, sterility, in vitro diffusion, and in vivo studies. The drug and the polymer were found to be compatible and confirmed by Fourier transform infrared spectroscopy. Viscosity of the gels increased with the increase in the polymer concentration. The formulations were found to be sterile. In vitro release study revealed that drug released from the gel follows non-Fickian diffusion followed by first-order release. In vivo studies were carried out for 6 months in patients. The results revealed a significant improvement in the clinical parameters such as gingival index, probing pocket depth, clinical attachment level, and potent inhibitory effect on bone resorption by inhibition of osteoclasts. In addition, there was increase in the new bone formation.

Impregnation of bone chips with alendronate and cefazolin, combined with demineralized bone matrix: a bone chamber study in goats

PubMed Central

2012-01-01

Background Bone grafts from bone banks might be mixed with bisphosphonates to inhibit the osteoclastic response. This inhibition prevents the osteoclasts to resorb the allograft bone before new bone has been formed by the osteoblasts, which might prevent instability. Since bisphosphonates may not only inhibit osteoclasts, but also osteoblasts and thus bone formation, we studied different bisphosphonate concentrations combined with allograft bone. We investigated whether locally applied alendronate has an optimum dose with respect to bone resorption and formation. Further, we questioned whether the addition of demineralized bone matrix (DBM), would stimulate bone formation. Finally, we studied the effect of high levels of antibiotics on bone allograft healing, since mixing allograft bone with antibiotics might reduce the infection risk. Methods 25 goats received eight bone conduction chambers in the cortical bone of the proximal medial tibia. Five concentrations of alendronate (0, 0.5 mg/mL, 1 mg/mL, 2 mg/mL, and 10 mg/mL) were tested in combination with allograft bone and supplemented with cefazolin (200 μg/mL). Allograft not supplemented with alendronate and cefazolin served as control. In addition, allograft mixed with demineralized bone matrix, with and without alendronate, was tested. After 12 weeks, graft bone area and new bone area were determined with manual point counting. Results Graft resorption decreased significantly (p < 0.001) with increasing alendronate concentration. The area of new bone in the 1 mg/mL alendronate group was significantly (p = 0.002) higher when compared to the 10 mg/mL group. No differences could be observed between the group without alendronate, but with demineralized bone, and the control groups. Conclusions A dose-response relationship for local application of alendronate has been shown in this study. Most new bone was present at 1 mg/mL alendronate. Local application of cefazolin had no effect on bone remodelling. PMID:22443362

Influence of Alendronate and Endplate Degeneration to Single Level Posterior Lumbar Spinal Interbody Fusion

PubMed Central

Rhee, Wootack; Ha, Seongil; Lim, Jae Hyeon; Jang, Il Tae

2014-01-01

Objective Using alendronate after spinal fusion is a controversial issue due to the inhibition of osteoclast mediated bone resorption. In addition, there are an increasing number of reports that the endplate degeneration influences the lumbar spinal fusion. The object of this retrospective controlled study was to evaluate how the endplate degeneration and the bisphosphonate medication influence the spinal fusion through radiographic evaluation. Methods In this study, 44 patients who underwent single-level posterior lumbar interbody fusion (PLIF) using cage were examined from April 2007 to March 2009. All patients had been diagnosed as osteoporosis and would be recommended for alendronate medication. Endplate degeneration is categorized by the Modic changes. The solid fusion is defined if there was bridging bone between the vertebral bodies, either within or external to the cage on the plain X-ray and if there is less than 5° of angular difference in dynamic X-ray. Results In alendronate group, fusion was achieved in 66.7% compared to 73.9% in control group (no medication). Alendronate did not influence the fusion rate of PLIF. However, there was the statistical difference of fusion rate between the endplate degeneration group and the group without endplate degeneration. A total of 52.4% of fusion rate was seen in the endplate degeneration group compared to 91.3% in the group without endplate degeneration. The endplate degeneration suppresses the fusion process of PLIF. Conclusion Alendronate does not influence the fusion process in osteoporotic patients. The endplate degeneration decreases the fusion rate. PMID:25620981

The Effect of Alendronate on Various Graft Materials Used in Maxillary Sinus Augmentation: A Rabbit Study.

PubMed

Ayranci, Ferhat; Gungormus, Metin; Omezli, Mehmet Melih; Gundogdu, Betul

2015-12-01

Increasing sinus pneumatization and the accompanying alveolar bone resorption complicate dental implant placement. This problem can be overcome today by raising the maxillary sinus floor with graft materials. Bisphosphonates are commonly used to accelerate the recovery of the graft materials and to prevent resorption. The purpose of this study is to investigate whether systemic administration of a bisphosphonate (alendronate) would improve new bone formation and reduce fibrous tissue formation over a 6-week follow-up in rabbits treated with two different grafting materials for maxillary sinus floor augmentation. This experimental animal study was conducted at the Experimental Medical Application and Research Center at Erzurum/ Turkey. Twelve New Zealand rabbits, each weighing between 2.7 and 3.3 kg, were used. Twenty-four maxillary sinus floor elevation operations were performed, two on each animal (n = 24). Each elevation was repaired with either deproteinized bovine bone (xenograft) or autogenous bone graft obtained from the iliac crest. Both groups were divided into 2 subgroups: saline-treated and alendronate-treated. All groups underwent the same surgical procedures and evaluation, and were sacrificed at the 6th postoperative week. Sinuses augmented with deproteinized bovine bone (xenograft) and autogenous bone graft were examined histopathologically and histomorphometrically. At 6 weeks, the bone area was significantly larger in the Xenograft-Alendronate group (33.0% ± 5.0%) than in the Xenograft-Saline group (20.8% ± 4.9%) and the bone area was significantly larger in the Autogenous-Alendronate group (43.3% ± 3.8%) than in the Autogenous-Saline group (37.5% ± 6.6%) (P = 0.001). The histomorphometric and histopathological results consistently showed that alendronate stimulated bone formation and reduced fibrous tissue formation in maxillary sinus augmentation grafts, especially in the deproteinized bovine bone group (xenograft). Alendronate may be

The Effect of Alendronate on Various Graft Materials Used in Maxillary Sinus Augmentation: A Rabbit Study

PubMed Central

Ayranci, Ferhat; Gungormus, Metin; Omezli, Mehmet Melih; Gundogdu, Betul

2015-01-01

Background: Increasing sinus pneumatization and the accompanying alveolar bone resorption complicate dental implant placement. This problem can be overcome today by raising the maxillary sinus floor with graft materials. Bisphosphonates are commonly used to accelerate the recovery of the graft materials and to prevent resorption. Objectives: The purpose of this study is to investigate whether systemic administration of a bisphosphonate (alendronate) would improve new bone formation and reduce fibrous tissue formation over a 6-week follow-up in rabbits treated with two different grafting materials for maxillary sinus floor augmentation. Materials and Methods: This experimental animal study was conducted at the Experimental Medical Application and Research Center at Erzurum/ Turkey. Twelve New Zealand rabbits, each weighing between 2.7 and 3.3 kg, were used. Twenty-four maxillary sinus floor elevation operations were performed, two on each animal (n = 24). Each elevation was repaired with either deproteinized bovine bone (xenograft) or autogenous bone graft obtained from the iliac crest. Both groups were divided into 2 subgroups: saline-treated and alendronate-treated. All groups underwent the same surgical procedures and evaluation, and were sacrificed at the 6th postoperative week. Sinuses augmented with deproteinized bovine bone (xenograft) and autogenous bone graft were examined histopathologically and histomorphometrically. Results: At 6 weeks, the bone area was significantly larger in the Xenograft-Alendronate group (33.0% ± 5.0%) than in the Xenograft-Saline group (20.8% ± 4.9%) and the bone area was significantly larger in the Autogenous-Alendronate group (43.3% ± 3.8%) than in the Autogenous-Saline group (37.5% ± 6.6%) (P = 0.001). The histomorphometric and histopathological results consistently showed that alendronate stimulated bone formation and reduced fibrous tissue formation in maxillary sinus augmentation grafts, especially in the deproteinized

Duration-dependent effects of clinically relevant oral alendronate doses on cortical bone toughness in beagle dogs

PubMed Central

Burr, David B.; Liu, Ziyue; Allen, Matthew R.

2014-01-01

Bisphosphonates (BPs) have been shown to significantly reduce bone toughness in vertebrae within one year when given at clinical doses to dogs. Although BPs also reduce toughness in cortical bone when given at high doses, their effect on cortical bone material properties when given at clinical doses is less clear. In part, this may be due to the use of small sample sizes that were powered to demonstrate differences in bone mineral density rather than bone’s material properties. Our lab has conducted several studies in which dogs were treated with alendronate at a clinically relevant dose. The goal of this study was to examine these published and unpublished data collectively to determine whether there is a significant time-dependent effect of alendronate on toughness of cortical bone. This analysis seemed particularly relevant given the recent occurrence of atypical femoral fractures in humans. Differences in the toughness of ribs taken from dogs derived from five separate experiments were measured. The dogs were orally administered saline (CON, 1 ml/kg/day) or alendronate (ALN) at a clinical dose (0.2 mg/kg/day). Treatment duration ranged from 3 months to 3 years. Groups were compared using ANOVA, and time trends analyzed with linear regression analysis. Linear regressions of the percent difference in toughness between CON and ALN at each time point revealed a significant reduction in toughness with longer exposure to ALN. The downward trend was primarily driven by a downward trend in post-yield toughness, whereas toughness in the pre-yield region was not changed relative to CON. These data suggest that a longer duration of treatment with clinical doses of ALN results in deterioration of cortical bone toughness in a time-dependent manner. As the duration of treatment is lengthened, the cortical bone exhibits increasingly brittle behavior. This may be important in assessing the role that long-term BP treatments play in the risk of atypical fractures of femoral

Evaluation of the topical effect of alendronate on the root surface of extracted and replanted teeth. Microscopic analysis on rats' teeth.

PubMed

Lustosa-Pereira, Adriana; Garcia, Roberto Brandão; de Moraes, Ivaldo Gomes; Bernardineli, Norberti; Bramante, Clovis Monteiro; Bortoluzzi, Eduardo Antunes

2006-02-01

The treatment of choice for tooth avulsion is replantation. The ideal replantation should be realized as quickly as possible, or at least, the avulsed tooth should be kept in an adequate solution to preserve the periodontal ligament attached to the root. If that is not possible, treatment of the radicular surface should be done in order to prevent radicular resorption. The purpose of this study was to test sodium alendronate as a substance for topical treatment of the radicular surface of avulsed teeth in an attempt to prevent the occurrence of dental resorptions. Fifty-four rat maxillary right central incisors were extracted and replanted. Group I--extra-alveolar dry period of 15 min, intracanal dressing with calcium hydroxide (CALEN, S.S. White, Artigos Dentários LTDA, Rio de Janeiro, Brazil) and replantation; Groups II and III - extra-alveolar dry periods of 30 and 60 min, respectively, immersion in 1% sodium hypochlorite for 30 min for removal of the periodontal ligament, washing in saline solution for 5 min, and treatment of the radicular surface with 3.2 mg/l sodium alendronate solution for 10 min. Intracanal dressing with calcium hydroxide and replantation followed. At 15, 60, and 90 days post-reimplantation, the animals were killed and the samples obtained and processed for microscopic analysis. The results indicated that sodium alendronate was able to reduce the incidence of radicular resorption, but not of dental ankylosis. No significant differences were observed regarding variations in the extra-alveolar periods among the groups.

Effect of topical alendronate on root resorption of dried replanted dog teeth.

PubMed

Levin, L; Bryson, E C; Caplan, D; Trope, M

2001-06-01

Alendronate (ALN) is a third generation bisphosphonate with demonstrated osteoclast inhibitory activity that may slow down the resorptive process after severe traumatic injuries. Eighty-two premolar roots of five mongrel dogs were endodontically treated and restored, extracted and treated as follows: 70 roots were bench dried for either 40 or 60 min. Thirty-eight of these roots were then soaked for 5 min in a 1 mM solution of ALN in Hanks' Balanced Salt Solution (HBSS) and replanted. Thirty-two roots were soaked for 5 min in HBSS and replanted. In the remaining 12 roots which were not exposed to the bench drying procedure, a 0.5 mM deep lingual mid-root cemental defect was made. Six of these roots were soaked in a 1 mM solution of ALN in HBSS for 5 min and replanted. The other six roots were soaked for 5 min in HBSS and replanted. Historical negative and positive controls were used from similarly treated teeth in our previous studies. After 4 months the dogs were killed and the roots prepared for histological evaluation. Five-microm-thick cross-sections of the root and surrounding tissue taken every 70 microm were evaluated for healing according to the criteria of Andreasen. In the 12 roots with cemental defects, healing with cementum of the damaged root surface was evaluated. In addition, residual root mass was also measured to determine the extent of root structure loss for each soaking method. Cemental healing took place in all 12 artificially damaged roots, indicating that these soaking media did not inhibit cementogenesis. The alendronate-soaked roots had statistically significantly more healing than the roots soaked in HBSS without alendronate. This improvement in healing was seen in all dogs except one and in all teeth except the first premolar. Soaking in alendronate also resulted in significantly less loss in root mass due to resorption compared to those teeth soaked in HBSS without alendronate.

Effects of long-term alendronate treatment on postmenopausal osteoporosis bone material properties.

PubMed

Hassler, N; Gamsjaeger, S; Hofstetter, B; Brozek, W; Klaushofer, K; Paschalis, E P

2015-01-01

Raman microspectroscopic analysis of iliac crest from patients that were treated with alendronate (ALN) for 10 years revealed minimal, transient alterations in bone material properties confined to actively forming bone surfaces compared to patients that were on ALN for 5 years. These changes were not encountered in the bulk tissue. Alendronate (ALN) and other bisphosphonates (BPs) are the most widely prescribed therapy for postmenopausal osteoporosis. Despite their overall excellent safety record and efficacy in reducing fractures, questions have been raised regarding potential detrimental effects that may be related to prolonged bone turnover reduction, although no definite cause-effect relationship has been established to date. The purpose of the present study was to evaluate bone material properties in patients that were receiving ALN for 5 or 10 years. Raman microspectroscopic analysis was used to analyze iliac crest biopsies from postmenopausal women with osteoporosis who had been treated with ALN for 5 years and were then re-randomized to placebo (PBO, N = 14), 5 mg/day ALN (N = 10), or 10 mg/day ALN (N = 6) for another 5 years. The parameters monitored and expressed as a function of tissue age were (i) the mineral/matrix ratio (MM), (ii) the relative proteoglycan content (PG), (iii) the relative lipid content (LPD), (iv) the mineral maturity/crystallinity (MMC), and (v) the relative pyridinoline content (PYD). The obtained data indicate that 10-year ALN use results in minimal, transient bone tissue composition changes compared to use for 5 years, confined to actively forming trabecular surfaces, implying potential differences in bone matrix maturation that nevertheless did not result in differences of these values in bulk tissue. The data suggest that prolonged reduction in bone turnover during 10 years of therapy with ALN by itself is unlikely to be associated with adverse effects on bone material properties.

In vitro disintegration studies of weekly generic alendronate sodium tablets (70 mg) available in the US.

PubMed

Dansereau, Richard J; Crail, Debbie J; Perkins, Alan C

2009-02-01

Bisphosphonates as a class have the potential to cause upper gastrointestinal irritation. Although the generic alendronate sodium tablets are bioequivalent to the branded product, a potential concern is that the pharmaceutical attributes of the various generic formulations my affect the potential for local irritation and tolerability. The in vitro disintegration times were determined using the method described in the US Pharmacopeia 30 (USP 30). The disintegration of three generic alendronate sodium tablets 70 mg available in the United States was compared to that of the branded product. The mean disintegration times of the generic alendronate sodium tablets ranged from 9 to 10 s for the Barr lots to 108 s for the Watson lot. The disintegration time of the branded product (Fosamax) was 53 s. The three Barr lots and one Teva lot had rapid disintegration times which were similar to the disintegration standards (< 30 s) for orally disintegrating tablets. Since there is no established disintegration time for alendronate sodium tablets there can be no assurance that the generic tablets are equivalent to the branded product in terms of esophageal exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration performance. Copies of generic alendronate sodium tablets are approved based on the results of single-dose bioavailability studies in healthy subjects and this is not considered adequate to establish similar disintegration characteristics.

Estimating the Time to Benefit for Preventive Drugs with the Statistical Process Control Method: An Example with Alendronate.

PubMed

van de Glind, Esther M M; Willems, Hanna C; Eslami, Saeid; Abu-Hanna, Ameen; Lems, Willem F; Hooft, Lotty; de Rooij, Sophia E; Black, Dennis M; van Munster, Barbara C

2016-05-01

For physicians dealing with patients with a limited life expectancy, knowing the time to benefit (TTB) of preventive medication is essential to support treatment decisions. The aim of this study was to investigate the usefulness of statistical process control (SPC) for determining the TTB in relation to fracture risk with alendronate versus placebo in postmenopausal women. We performed a post hoc analysis of the Fracture Intervention Trial (FIT), a randomized, controlled trial that investigated the effect of alendronate versus placebo on fracture risk in postmenopausal women. We used SPC, a statistical method used for monitoring processes for quality control, to determine if and when the intervention group benefited significantly more than the control group. SPC discriminated between the normal variations over time in the numbers of fractures in both groups and the variations that were attributable to alendronate. The TTB was defined as the time point from which the cumulative difference in the number of clinical fractures remained greater than the upper control limit on the SPC chart. For the total group, the TTB was defined as 11 months. For patients aged ≥70 years, the TTB was 8 months [absolute risk reduction (ARR) = 1.4%]; for patients aged <70 years, it was 19 months (ARR = 0.7%). SPC is a clear and understandable graphical method to determine the TTB. Its main advantage is that there is no need to define a prespecified time point, as is the case in traditional survival analyses. Prescribing alendronate to patients who are aged ≥70 years is useful because the TTB shows that they will benefit after 8 months. Investigators should report the TTB to simplify clinical decision making.

Role of Prostaglandin Pathway and Alendronate-Based Carriers to Enhance Statin-induced Bone

PubMed Central

Lee, Yeonju; Liu, Xinming; Nawshad, Ali; Marx, David B.; Wang, Dong; Reinhardt, Richard A.

2011-01-01

Objective This study investigated the role of the prostaglandin (PG) pathway in locally-applied, simvastatin-induced oral bone growth. The possibility of enhancing long-term bone augmentation with an alendronate-based carrier was initiated. Methods Mandibles of 44 mature female rats were treated bilaterally with the following combinations: 2 mg simvastatin in ethanol (SIM-EtOH), EtOH, 2 mg simvastatin acid complexed with alendronate-beta-cyclodextrin conjugate (SIM/ALN-CD), ALN-CD, or ALN. Bone wash technology (injection of PBS and recollection by suction) was used to sample injection sites at baseline (day 0), and 3, 7, 14 and 21 days post-treatment. After 21-24 or 48 days, histomorphometric analysis was done. The amount of PGE2 in bone wash fluid was measured by ELISA, normalized by total protein, and compared between high and low bone growth groups (ANOVA) and correlated with subsequent bone histology at 21 days (Spearman). SIM-stimulated PGE2 synthase and EP4 receptor mRNA in murine osteoblast and fibroblast cell lines were evaluated with real-time PCR. Results Single injections of 2 mg SIM-EtOH induced significantly more new bone than control side after 21 days. PGE2/protein ratios peaked at day 7 and were correlated with the subsequent 21-day new bone width. The correlations at day 14 between PGE2 and new bone width changed to a negative relationship in the test group. SIM-stimulated osteoblasts expressed increased mRNA levels of PGE receptor EP4, while SIM activated PGE synthesis in fibroblasts. SIM/ALN-CD tended to preserve bone long-term. Conclusion Findings suggest that PGE pathway activation and higher levels of PGE2 during the first week following SIM-induced bone growth are desirable, and alendronate-beta-cyclodextrin conjugates not only act as tissue-specific carriers, but preserve new bone. PMID:21438610

Alendronate treatment alters bone tissues at multiple structural levels in healthy canine cortical bone.

PubMed

Acevedo, Claire; Bale, Hrishikesh; Gludovatz, Bernd; Wat, Amy; Tang, Simon Y; Wang, Mingyue; Busse, Björn; Zimmermann, Elizabeth A; Schaible, Eric; Allen, Matthew R; Burr, David B; Ritchie, Robert O

2015-12-01

Bisphosphonates are widely used to treat osteoporosis, but have been associated with atypical femoral fractures (AFFs) in the long term, which raises a critical health problem for the aging population. Several clinical studies have suggested that the occurrence of AFFs may be related to the bisphosphonate-induced changes of bone turnover, but large discrepancies in the results of these studies indicate that the salient mechanisms responsible for any loss in fracture resistance are still unclear. Here the role of bisphosphonates is examined in terms of the potential deterioration in fracture resistance resulting from both intrinsic (plasticity) and extrinsic (shielding) toughening mechanisms, which operate over a wide range of length-scales. Specifically, we compare the mechanical properties of two groups of humeri from healthy beagles, one control group comprising eight females (oral doses of saline vehicle, 1 mL/kg/day, 3 years) and one treated group comprising nine females (oral doses of alendronate used to treat osteoporosis, 0.2mg/kg/day, 3 years). Our data demonstrate treatment-specific reorganization of bone tissue identified at multiple length-scales mainly through advanced synchrotron x-ray experiments. We confirm that bisphosphonate treatments can increase non-enzymatic collagen cross-linking at molecular scales, which critically restricts plasticity associated with fibrillar sliding, and hence intrinsic toughening, at nanoscales. We also observe changes in the intracortical architecture of treated bone at microscales, with partial filling of the Haversian canals and reduction of osteon number. We hypothesize that the reduced plasticity associated with BP treatments may induce an increase in microcrack accumulation and growth under cyclic daily loadings, and potentially increase the susceptibility of cortical bone to atypical (fatigue-like) fractures. Published by Elsevier Inc.

Synthesis and evaluation of alendronate-modified gelatin biopolymer as a novel osteotropic nanocarrier for gene therapy.

PubMed

Mekhail, George M; Kamel, Amany O; Awad, Gehanne As; Mortada, Nahed D; Rodrigo, Rowena L; Spagnuolo, Paul A; Wettig, Shawn D

2016-09-01

To synthesize an osteotropic alendronate functionalized gelatin (ALN-gelatin) biopolymer for nanoparticle preparation and targeted delivery of DNA to osteoblasts for gene therapy applications. Alendronate coupling to gelatin was confirmed using Fourier transform IR, (31)PNMR, x-ray diffraction (XRD) and differential scanning calorimetry. ALN-gelatin biopolymers prepared at various alendronate/gelatin ratios were utilized to prepare nanoparticles and were optimized in combination with DNA and gemini surfactant for transfecting both HEK-293 and MG-63 cell lines. Gelatin functionalization was confirmed using the above methods. Uniform nanoparticles were obtained from a nanoprecipitation technique. ALN-gelatin/gemini/DNA complexes exhibited higher transfection efficiency in MG-63 osteosarcoma cell line compared with the positive control. ALN-gelatin is a promising biopolymer for bone targeting of either small molecules or gene therapy applications.

Process analytical technology to understand the disintegration behavior of alendronate sodium tablets.

PubMed

Xu, Xiaoming; Gupta, Abhay; Sayeed, Vilayat A; Khan, Mansoor A

2013-05-01

Various adverse events including esophagus irritations have been reported with the use of alendronate tablets, likely attributed to the rapid tablet disintegration in the mouth or esophagus. Accordingly, the disintegration of six alendronate tablet drug products was studied using a newly developed testing device equipped with in-line sensors, in addition to the official compendial procedure for measuring the disintegration time. The in-line sensors were used to monitor the particle count and solution pH change to assess the onset and duration of disintegration. A relatively large variation was observed in the disintegration time of the tested drug products using the compendial method. The data collected using the in-line sensors suggested that all tested drug products exhibited almost instantaneous onset of disintegration, under 2 s, and a sharp drop in solution pH. The drop in pH was slower for tablets with slower disintegration. The in-house prepared alendronate test tablets also showed similar trends suggesting rapid solubilization of the drug contributed to the fast tablet disintegration. This research highlights the usefulness of the newly developed in-line analytical method in combination with the compendial method in providing a better understanding of the disintegration and the accompanying drug solubilization processes for fast disintegrating tablet drug products. Copyright © 2013 Wiley Periodicals, Inc.

The role of counselling and other factors in compliance of postmenopausal osteoporotic patients to alendronate 70 therapy

PubMed Central

Horst-Sikorska, Hanna; Stępień-Kłos, Wioletta; Antkowiak, Agnieszka; Janik, Małgorzata; Cieślak, Karol; Marcinkowska, Michalina; Cegłowska, Agnieszka; Stuss, Michał

2013-01-01

Introduction The aim of the study was to assess the role of patient counselling, nurse assistance and effects of biochemical examinations in adherence of women with postmenopausal osteoporosis to alendronate 70 administration over 12 months of therapy. Material and methods Compliance and persistence to alendronate 70 therapy were assessed in a prospective study of 123 postmenopausal women, followed up for one year. The patients were divided into 4 groups (controls, counselled group, biochemical group and nurse assisted group) with monitoring every 6 months; in the nurse assisted group, additional phone contacts were made after 3 and 9 months of treatment. After 12 months, compliance and persistence were analysed. The medication possession ratio (MPR) was regarded as optimal when its value exceeded 80%. Results The compliance to alendronate 70 therapy was 54.03% in the control group and the mean persistence with medication was 197 days. The MPR above 80% was observed in 37.5%, and, after 1 year, 43.75% of patients were found persistent with the therapy. In the remaining groups, both compliance and persistence were higher but not statistically significantly, compared to the control group. Neither patient's age, education, diet, nor physical activity influenced the compliance with prescribed therapy. The most common reason to discontinue therapy was either its side effects or smoking. Conclusions The obtained results suggest that better adherence with medical recommendations is observed in patients who receive additional attention, e.g. counselling, biochemical tests or nursing care. The critical elements for therapy discontinuation were side effects and smoking. PMID:23671440

Effect of bisphosphonate use on risk of postmenopausal breast cancer: results from the randomized clinical trials of alendronate and zoledronic acid.

PubMed

Hue, Trisha F; Cummings, Steven R; Cauley, Jane A; Bauer, Douglas C; Ensrud, Kristine E; Barrett-Connor, Elizabeth; Black, Dennis M

2014-10-01

Studies have shown that bisphosphonates may have antitumor and antimetastatic properties. Recently, observational studies have suggested a possible protective effect of bisphosphonates on breast cancer, but the effect of bisphosphonate use on risk of breast cancer has not been tested in randomized trials. To assess the relationship of postmenopausal breast cancer incidence and bisphosphonate use using data from 2 randomized (1:1), double-blind, placebo-controlled trials. The Fracture Intervention Trial (FIT) randomly assigned 6459 women aged 55 to 81 years to alendronate or placebo for a mean follow-up of 3.8 years. The Health Outcomes and Reduced Incidence With Zoledronic Acid Once Yearly-Pivotal Fracture Trial (HORIZON-PFT) randomly assigned 7765 women aged 65 to 89 years to annual intravenous zoledronic acid or placebo for a mean follow-up of 2.8 years. Data were collected at clinical centers in the United States (FIT and HORIZON-PFT) and in Asia and the Pacific, Europe, North America, and South America (HORIZON-PFT). Women, in either study, with recurrent breast cancer or who reported a history of breast cancer were excluded from analyses. In each trial, a blinded review was conducted of each cancer adverse event report to verify incident invasive breast cancer cases. The primary analysis compared events in the active vs placebo group using a log-rank test. Alendronate vs placebo (FIT) or zoledronic acid vs placebo (HORIZON-PFT). Hazard ratio for incident breast cancer in the bisphosphonate treatment group compared to the placebo group. There was no significant difference in the rate of breast cancer in FIT: 1.5% (n = 46) in the placebo group and 1.8% (n = 57) in the alendronate group (hazard ratio [HR], 1.24 [95% CI, 0.84-1.83]). In HORIZON-PFT, there was also no significant difference: 0.8% (n = 29) in the placebo group and 0.9% (n = 33) in the zoledronic acid group (HR, 1.15 [95% CI, 0.70-1.89]). There was also no significant difference when

Modulation of adhesion-dependent cAMP signaling by echistatin and alendronate

NASA Technical Reports Server (NTRS)

Fong, J. H.; Ingber, D. E.

1996-01-01

We measured intracellular cAMP levels in cells during attachment and spreading on different extracellular matrix (ECM) proteins. Increases in cAMP were observed within minutes when cells attached to fibronectin, vitronectin, and a synthetic RGD-containing fibronectin peptide (Petite 2000), but not when they adhered to another integrin alpha nu beta 3 ligand, echistatin. Because echistatin also inhibits bone resorption, we measured the effects of adding another osteoporosis inhibitor, alendronate, in this system. Alendronate inhibited the cAMP increase induced by ligands that primarily utilize integrin alpha nu beta 3 (vitronectin, Peptite 2000), but not by fibronectin which can also use integrin alpha 5 beta 1. These results show that cell adhesion to ECM can increase intracellular cAPM levels and raise the possibility that inhibitors of osteoporosis may act, in part, by preventing activation of this pathway by integrins.

Synergistic antiosteoporotic effect of Lepidium sativum and alendronate in glucocorticoid-induced osteoporosis in Wistar rats.

PubMed

Elshal, Mohamed F; Almalki, Abdulrahman L; Hussein, Hussein K; Khan, Jalal A

2013-01-01

Alendronate belongs to a class of drugs called bisphosphonates. Bisphosphonates (BP) therapy is a vital option to reduce the risk of bone fracture in people who suffer from osteoporosis. Yet, bisphosphonate have displayed several side effects. Lepidium sativum (LS) seeds have been used in traditional folk medicine to heal fractured bones. However, there is a dearth of information on the impact of LS on bone metabolism especially in cases of glucocorticoids induced osteoporosis. Therefore, the aim of the study was to compare the biochemical bone markers and histological responses of LS alone (6 g of LS seeds in diet daily, n=8), ALD (alendronate, 70 mg/kg s.c.; n=8) alone, or LS and ALD combined in a rat model of glucocorticoid-induced osteoporosis (GIO) by injecting rats with methylprednisolone 3.5 mg/kg per day for 4 weeks. Serum calcium (Ca), albumin, phosphorus (P), bone-specific alkaline phosphatase (b-ALP), and tartrate-resistant acid phosphatase (TRAP) were measured 4 weeks after induction of GIO. GIO-group showed significantly increased serum TRAP and decreased b-ALP. GIO-group also showed significantly decreased serum P and unaltered Ca concentrations. Histological examination of GIO-group tibia bones indicated an osteoporotic change and a concomitant decrease in percentage of trabecular area or bone marrow area (PTB) in the proximal femoral epiphysis. Treatment with either LS and/or ALD ameliorated the above mentioned changes with variable degrees, with a net results of enhanced serum calcium, bone architecture, PTB, b-ALP and decreased TRAP in LS and LS+ALD groups compared to that of animals treated with alendronate alone. In conclusion, our findings present evidence supporting the potential benefits of LS in reducing the burden of GCs on bone health.

In vitro disintegration and dissolution studies of once-weekly copies of alendronate sodium tablets (70 mg) and in vivo implications.

PubMed

Dansereau, Richard J; Crail, Debbie J; Perkins, Alan C

2008-04-01

The aim of this study was to evaluate the in vitro disintegration and dissolution of 26 alendronic acid tablets (70 mg) on the market in Canada, Germany, the Netherlands, and the United Kingdom compared to the branded product (Fosamax). The disintegration and dissolution times were determined using the methods described in the United States Pharmacopeia 30 (USP 30). The disintegration of four orally disintegrating tablets (non-bisphosphonates) and branded film-coated risedronate sodium tablets were included for comparison. The mean disintegration times of the alendronic acid tablets ranged from 14 s for Pharmachemie (Netherlands) to 342 s (5.7 min) for Betapharm (Germany). The mean disintegration time of the branded product tablets ranged from 43 to 78 s. Six of the 26 companies market alendronic acid tablets with very rapid disintegration times which are similar to those of orally disintegrating tablets (non-bisphosphonates). The alendronic acid tablets with very rapid mean disintegration times are as follows: Pharmachemie (Netherlands), 14 s; Novopharm (Canada), 13-24 s; GRY-Pharma (Germany), 21 s; Juta Pharma (Germany), 30 s; APS/Teva (United Kingdom), 26 and 37 s; and Teva (UK), 14-29 s. Since there is no established disintegration time for alendronic acid tablets there can be no assurance that the copy tablets are equivalent to the branded product in terms of esophageal drug exposure. However, the in vitro disintegration times have not been correlated with in vivo disintegration and performance. The dissolution of all the bisphosphonate tablets was rapid with greater than 80% dissolved in 15 min and all products conformed to the USP 30 specification. The dissolution of all alendronic acid tablets was rapid and complete and conformed to the established USP 30 specifications which should ensure adequate drug absorption from the copy products. However, copies of alendronic acid tablets are approved based on the results of single-dose bioavailability studies in

Alveolar bone dynamics in osteoporotic rats treated with raloxifene or alendronate: confocal microscopy analysis

NASA Astrophysics Data System (ADS)

Ramalho-Ferreira, Gabriel; Faverani, Leonardo Perez; Grossi-Oliveira, Gustavo Augusto; Okamoto, Tetuo; Okamoto, Roberta

2015-03-01

In this study, the characteristics of the alveolar bone of rats with induced osteoporosis were examined. Thirty-two rats were divided into four groups according to the induction of osteoporosis and drugs administered: OG, osteoporotic rats without treatment (negative control); SG, rats which underwent sham surgery ovariectomy (SHAM); alendronate (AG), osteoporotic rats treated with alendronate; and RG, osteoporotic rats treated with raloxifene (RG). On the 8th day after ovariectomy and SHAM surgeries, drug therapy was started with AG or RG. On the 52nd day, 20 mg/kg calcein was administered to all of the rats, and on the 80th day, 20 mg/kg alizarin red was administered. Euthanasia was performed on the 98th day. The bone area marked by fluorochromes was calculated and data were subjected to two-way ANOVA test and Tukey's post-hoc test (p<0.05). The comparison of the induced osteoporosis groups showed no statistically significant differences in bone turnover only between RG and SG (p=0.074) and AG and OG (p=0.138). All other comparisons showed significant differences (p<0.001). The largest bone turnover was observed in RG and SG groups. RG was the medication that improved the dynamics of the alveolar bone of rats with induced osteoporosis, resembling that of healthy rats.

Effect of Sequential Treatment with Bisphosphonates After Teriparatide in Ovariectomized Rats: A Direct Comparison Between Risedronate and Alendronate.

PubMed

Yano, Tetsuo; Yamada, Mei; Inoue, Daisuke

2017-07-01

Teriparatide (TPTD), a recombinant human parathyroid hormone N-terminal fragment (1-34), is a widely used bone anabolic drug for osteoporosis. Sequential treatment with antiresorptives such as bisphosphonates after TPTD discontinuation is generally recommended. However, relative effects of bisphosphonates have not been determined. In the present study, we directly compared effects of risedronate (RIS) and alendronate (ALN) on bone mineral density (BMD), bone turnover, structural property and strength in ovariectomized (OVX) rats, when administered after TPTD. Female Sprague Dawley rats were divided into one sham-operated and eight ovariectomized groups. TPTD, RIS, and ALN were given subcutaneously twice per week for 4 or 8 weeks after 4 week treatment with TPTD. TPTD significantly increased BMD (+9.6%) in OVX rats after 4 weeks of treatment. 8 weeks after TPTD withdrawal, vehicle-treated group showed a blunted BMD increase of +8.4% from the baseline. In contrast, 8 weeks of treatment with RIS and ALN significantly increased BMD to 17.4 and 21.8%, respectively. While ALN caused a consistently larger increase in BMD, sequential treatment with RIS resulted in lower Tb.Sp compared to ALN in the fourth lumbar vertebra as well as in greater stiffness in compression test. In conclusion, the present study demonstrated that sequential therapy with ALN and RIS after TPTD both improved bone mass and structure. Our results further suggest that RIS may have a greater effect on improving bone quality and stiffness than ALN despite less prominent effect on BMD. Further studies are necessary to determine clinical relevance of these findings to fracture rate.

Cytotoxicity analysis of alendronate on cultured endothelial cells and subcutaneous tissue. a pilot study.

PubMed

Moreira, Maria Stella; Katayama, Emilio; Bombana, Antonio Carlos; Marques, Márcia Martins

2005-12-01

The use of alendronate, a bisphosphonate which is able to inhibit bone resorption, in order to prevent dental root resorption after tooth replantation would be of clinical relevance. However, this drug must be biocompatible to the periapical tissues. The aim of this study was to analyze the effect of an alendronate paste in polyethyleneglycol (2 g ml(-1)) on endothelial cells in culture (in vitro) and on rat subcutaneous tissue (in vivo). For the in vitro study the paste was applied on round glass coverslips that were immersed into confluent cell cultures (clone Cips). The cell viability percentages of these cultures were obtained 0, 6 and 12 h after contact with the substance. As control, cultures that received plain coverslips were used. This analysis was carried out in triplicate using the Trypan blue dye exclusion assay. For the in vivo study the paste was introduced into polyethylene tubes that were placed into the rat subcutaneous tissue. The rats were killed 7 and 14 days later; then, the tissue sections stained with hematoxylin-eosin were analyzed. In vitro, the alendronate caused a significant decrease in the cell viability in 6 h (P < 0.05) and 12 h (P < 0.01), when compared with the control cultures. In vivo the tissue response was exuberant and similar at the two experimental times. There was a necrosis in a comprehensive area in contact with the open end of the tube. Presence of micro-abscesses and intense inflammatory infiltrate in the hypoderm permeating the muscle fibers and fat lobules were observed. In conclusion, the alendronate paste in polyethylene glycol as used showed to be highly cytotoxic in vitro as well as in vivo.

Mutual augmentation of the induction of the histamine-forming enzyme, histidine decarboxylase, between alendronate and immuno-stimulants (IL-1, TNF, and LPS), and its prevention by clodronate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng Xue; Department of Oral Diagnosis, Graduate School of Dentistry, Tohoku University, Seiryo-machi, Aoba-ku, Sendai 980-8575; Yu Zhiqian

2006-05-15

Nitrogen-containing bisphosphonates (N-BPs), powerful anti-bone-resorptive drugs, have inflammatory side effects, while histamine is not only an inflammatory mediator, but also an immuno-modifier. In murine models, a single intraperitoneal injection of an N-BP induces various inflammatory reactions, including the induction of the histamine-forming enzyme histidine decarboxylase (HDC) in tissues important in immune responses (such as liver, lungs, spleen, and bone marrow). Lipopolysaccharide (LPS) and the proinflammatory cytokines IL-1 and TNF are also capable of inducing HDC. We reported previously that in mice (i) the inflammatory actions of N-BPs depend on IL-1 (ii) N-BP pretreatment augments both LPS-stimulated IL-1 production and HDCmore » induction, and (iii) the co-administration of clodronate (a non-N-BP) with an N-BP inhibits the latter's inflammatory actions (including HDC induction). Here, we add the new findings that (a) pretreatment with alendronate (a typical N-BP) augments both IL-1- and TNF-induced HDC elevations, (b) LPS pretreatment augments the alendronate-induced HDC elevation, (c) co-administration of clodronate with alendronate abolishes these augmentations, (d) alendronate does not induce HDC in IL-1-deficient mice even if they are pretreated with LPS, and (e) alendronate increases IL-1{beta} in all tissues tested, but not in the serum. These results suggest that (1) there are mutual augmentations between alendronate and immuno-stimulants (IL-1, TNF, and LPS) in HDC induction, (2) tissue IL-1{beta} is important in alendronate-stimulated HDC induction, and (3) combination use of clodronate may have the potential to reduce the inflammatory effects of alendronate (we previously found that clodronate, conveniently, does not inhibit the anti-bone-resorptive activity of alendronate)« less

Formulation, characterization and cytotoxicity studies of alendronate sodium-loaded solid lipid nanoparticles.

PubMed

Ezzati Nazhad Dolatabadi, Jafar; Hamishehkar, Hamed; Eskandani, Morteza; Valizadeh, Hadi

2014-05-01

Solid lipid nanoparticles (SLNs) are novel drug delivery system for drug targeting in various routs of administration such as parenteral, oral, ophthalmic and topical. These carriers have some advantages such as high drug payload, increased drug stability, the possibility of incorporation of lipophilic and hydrophilic drugs, and low biotoxicity. In this study, alendronate sodium was used as a hydrophilic model drug and was incorporated into SLNs. Hot homogenization method was used for preparation of alendronate sodium-loaded SLN formulations and the encapsulation efficiency of drug in SLNs was determined by ultrafiltration method using centrifugal devices. Scanning electron microscopy (SEM) was carried out to study the morphological behaviors of prepared SLNs like sphericity. Several cytotoxicity studies including MTT, DAPI staining and DNA fragmentation assays were used for biocompatibility assays. High drug encapsulation efficiency (70-85%) was achieved by drug determination through derivatization with o-phthalaldehyde. The physical stability of drug-loaded SLNs in aqueous dispersions was assessed in terms of size and drug leakage during two weeks. Scanning electron microscopy images showed spherical particles in the nanometer range confirming the obtained data from size analyzer. Several cytotoxicity studies including MTT, DAPI staining and DNA fragmentation assays as well as flow cytometry analysis confirmed the low toxicity of alendronate-loaded SLNs. The cost-efficient procedure, the avoidance of organic solvents application, acceptable reproducibility, ease of manufacturing under mild preparation conditions, high level of drug encapsulation, desirable physical stability and biocompatibility are the advantages of the proposed SLN formulations. Copyright © 2014 Elsevier B.V. All rights reserved.

Histological comparison of alendronate, calcium hydroxide and formocresol in amputated rat molar.

PubMed

Cengiz, S Burcak; Batirbaygil, Yildiz; Onur, Mehmet Ali; Atilla, Pergin; Asan, Esin; Altay, Nil; Cehreli, Zafer C

2005-10-01

The purpose of this study was to evaluate the potential of alendronate sodium (ALN), a biphosohonate to stimulate hard tissue formation in pulpotomized (amputated) rat molars. Two commonly used pulpotomy materials, calcium hydroxide (CH) and formocresol (FC) were utilized for comparisons. Histological evaluations were performed by observers blinded to treatment allocation on days 7, 15, 30 and 60, followed by statistical analysis of selected histological criteria. In all evaluation periods, hard tissue deposition was evident along the radicular dentin in ALN and CH groups. In days 30 and 60, the latter two groups showed no differences in inflammatory cell response and hard tissue deposition scores (P > 0.05). ALN appears to be capable of maintaining pulpal vitality, while promoting hard tissue formation, similar to CH.

Antiresorption implant coatings based on calcium alendronate and octacalcium phosphate deposited by matrix assisted pulsed laser evaporation.

PubMed

Boanini, Elisa; Torricelli, Paola; Forte, Lucia; Pagani, Stefania; Mihailescu, Natalia; Ristoscu, Carmen; Mihailescu, Ion N; Bigi, Adriana

2015-12-01

The integration of an implant material with bone tissue depends on the chemistry and physics of the implant surface. In this study we applied matrix assisted pulsed laser evaporation (MAPLE) in order to synthesize calcium alendronate monohydrate (a bisphosphonate obtained by calcium sequestration from octacalcium phosphate by alendronate) and calcium alendronate monohydrate/octacalcium phosphate composite thin films on titanium substrates. Octacalcium phosphate coatings were prepared as reference material. The powders, which were synthesized in aqueous medium, were suspended in deionised water, frozen at liquid nitrogen temperature and used as targets for MAPLE experiments. The transfer was conducted with a KrF* excimer laser source (λ = 248 nm, τFWHM ≤ 25 ns) in mild conditions of temperature and pressure. XRD, FTIR and SEM analyses confirmed that the coatings contain the same crystalline phases as the as-prepared powder samples. Osteoblast derived from stem cells and osteoclast derived from monocytes of osteoporotic subjects were co-cultured on the coatings up to 14 days. Osteoclast displayed significantly reduced proliferation and differentiation in the presence of calcium alendronate monohydrate, pointing to a clear role of the coatings containing this bisphosphonate on inhibiting excessive bone resorption. At variance, osteoblast production of alkaline phosphatase and type I pro-collagen were promoted by the presence of bisphosphonate, which also decreased the production of interleukin 6. The positive influence towards osteoblast differentiation was even more enhanced in the composite coatings, thanks to the presence of octacalcium phosphate. Copyright © 2015 Elsevier B.V. All rights reserved.

Improvement of cancellous bone microstructure in patients on teriparatide following alendronate pretreatment.

PubMed

Fahrleitner-Pammer, Astrid; Burr, David; Dobnig, Harald; Stepan, Jan J; Petto, Helmut; Li, Jiliang; Krege, John H; Pavo, Imre

2016-08-01

An increase in procollagen type I amino-terminal propeptide (PINP) early after teriparatide initiation was shown to correlate with increased lumbar spine areal BMD and is a good predictor of the anabolic response to teriparatide. Few data exist correlating PINP and bone microstructure, and no data exist in patients on teriparatide following prior potent antiresorptive treatment. This exploratory analysis aimed to investigate the effects of teriparatide on cancellous bone microstructure and correlations of bone markers with microstructure in alendronate-pretreated patients. This was a post hoc analysis of changes in bone markers and three-dimensional indices of bone microstructure in paired iliac crest biopsies from a prospective teriparatide treatment study in postmenopausal women with osteoporosis who were either treatment-naïve (TN, n=16) or alendronate-pretreated (ALN, n=29) at teriparatide initiation. Teriparatide (20μg/day) was given for 24months; biopsies were taken at baseline and endpoint, and serum concentrations of PINP and type 1 collagen cross-linked C-telopeptide (βCTX) were measured at intervals up to 24months. In the TN and ALN groups, respectively, mean (SD) increases in three-dimensional bone volume/tissue volume were 105 (356)% (P=0.039) and 55 (139)% (P<0.005) and trabecular thickness 30.4 (30)% (P<0.001) and 30.8 (53)% (P<0.001). No significant changes were observed in trabecular number or separation. In the ALN patients, 3-month change of neither PINP nor βCTX correlated with indices of cancellous bone microstructure. However, 12-month changes in biochemical bone markers correlated significantly with improvements in bone volume/tissue volume, r=0.502 (P<0.01) and r=0.378 (P<0.05), trabecular number, r=0.559 (P<0.01) and r=0.515 (P<0.01), and reduction of trabecular separation, r=-0.432 (P<0.05) and r=-0.530 (P<0.01), for PINP and βCTX, respectively. We conclude that cancellous bone microstructure improved with teriparatide therapy

Role of 1% alendronate gel as adjunct to mechanical therapy in the treatment of chronic periodontitis among smokers.

PubMed

Sharma, Anuj; Raman, Achala; Pradeep, Avani Raju

2017-01-01

Alendronate (ALN) inhibits osteoclastic bone resorption and triggers osteostimulative properties both in vivo and in vitro, as shown by increase in matrix formation. This study aimed to explore the efficacy of 1% ALN gel as local drug delivery (LDD) in adjunct to scaling and root planing (SRP) for the treatment of chronic periodontitis among smokers. 75 intrabony defects were treated in 46 male smokers either with 1% ALN gel or placebo gel. ALN gel was prepared by adding ALN into carbopol-distilled water mixture. Clinical parameters [modified sulcus bleeding index, plaque index, probing depth (PD), and periodontal attachment level (PAL)] were recorded at baseline, at 2 months, and at 6 months, while radiographic parameters were recorded at baseline and at 6 months. Defect fill at baseline and at 6 months was calculated on standardized radiographs by using the image analysis software. Mean PD reduction and mean PAL gain were found to be greater in the ALN group than in the placebo group, both at 2 and 6 months. Furthermore, a significantly greater mean percentage of bone fill was found in the ALN group (41.05±11.40%) compared to the placebo group (2.5±0.93%). The results of this study showed 1% ALN stimulated a significant increase in PD reduction, PAL gain, and an improved bone fill compared to placebo gel in chronic periodontitis among smokers. Thus, 1% ALN, along with SRP, is effective in the treatment of chronic periodontitis in smokers.

Self-assembled monolayers of alendronate on Ti6Al4V alloy surfaces enhance osteogenesis in mesenchymal stem cells

NASA Astrophysics Data System (ADS)

Rojo, Luis; Gharibi, Borzo; McLister, Robert; Meenan, Brian J.; Deb, Sanjukta

2016-07-01

Phosphonates have emerged as an alternative for functionalization of titanium surfaces by the formation of homogeneous self-assembled monolayers (SAMs) via Ti-O-P linkages. This study presents results from an investigation of the modification of Ti6Al4V alloy by chemisorption of osseoinductive alendronate using a simple, effective and clean methodology. The modified surfaces showed a tailored topography and surface chemistry as determined by SEM microscopy and RAMAN spectroscopy. X-ray photoelectron spectroscopy revealed that an effective mode of bonding is created between the metal oxide surface and the phosphate residue of alendronate, leading to formation of homogenous drug distribution along the surface. In-vitro studies showed that alendronate SAMs induce differentiation of hMSC to a bone cell phenotype and promote bone formation on modified surfaces. Here we show that this novel method for the preparation of functional coatings on titanium-based medical devices provides osseoinductive bioactive molecules to promote enhanced integration at the site of implantation.

Self-assembled monolayers of alendronate on Ti6Al4V alloy surfaces enhance osteogenesis in mesenchymal stem cells

PubMed Central

Rojo, Luis; Gharibi, Borzo; McLister, Robert; Meenan, Brian J.; Deb, Sanjukta

2016-01-01

Phosphonates have emerged as an alternative for functionalization of titanium surfaces by the formation of homogeneous self-assembled monolayers (SAMs) via Ti-O-P linkages. This study presents results from an investigation of the modification of Ti6Al4V alloy by chemisorption of osseoinductive alendronate using a simple, effective and clean methodology. The modified surfaces showed a tailored topography and surface chemistry as determined by SEM microscopy and RAMAN spectroscopy. X-ray photoelectron spectroscopy revealed that an effective mode of bonding is created between the metal oxide surface and the phosphate residue of alendronate, leading to formation of homogenous drug distribution along the surface. In-vitro studies showed that alendronate SAMs induce differentiation of hMSC to a bone cell phenotype and promote bone formation on modified surfaces. Here we show that this novel method for the preparation of functional coatings on titanium-based medical devices provides osseoinductive bioactive molecules to promote enhanced integration at the site of implantation. PMID:27468811

The influence of alendronate on the healing of extraction sockets of ovariectomized rats assessed by in vivo micro-computed tomography.

PubMed

Jee, Jeong-Hyun; Lee, Wan; Lee, Byung Do

2010-08-01

Many dental patients take bisphosphonates to reduce the risk of hip and vertebral fractures. In vivo micro-computed tomography (micro-CT) was used to examine the longitudinal inhibitory effect of alendronate on the healing of extraction sockets in ovariectomized rats. Twenty 5-week-old Sprague-Dawley rats were assigned randomly to 1 of 3 groups: sham-operated (n = 5), and 2 ovariectomized (OVX) groups: saline treated (0.1 mL/100 g/d, n = 7) and alendronate treated (1 mg/kg/d, n = 8). Before micro-CT scanning, the left maxillary first molars of the rats were extracted. In vivo micro-CT (spatial resolution 50 x 50 mum) of the jaw was performed at baseline and at 2-week intervals for 6 weeks. Alveolar-bone radiographic densities and dimensions were analyzed with repeated measures analysis of variance. The bony healing patterns of the extraction sockets were also evaluated in each group. The radiographic socket densities of the sham-treated and OVX-alendronate groups significantly increased during the first 4 weeks after extraction (P < .05). At 2 weeks, the radiographic densities of the sockets in the OVX-saline group increased, but the increase was significantly lower than for the other groups at 4 weeks (P < .05). Newly formed bone was identified in the extraction sockets in all groups 2 to 6 weeks after extraction. There was a significant loss of alveolar ridge height at the second week postextraction compared with baseline, and at the fourth week compared with the second week (P < .05) except in the alendronate group. Alendronate appears to promote the healing of extraction sockets in estrogen-deficient rats and helps resist the loss of alveolar bone adjacent to extraction sockets. Copyright 2010 Mosby, Inc. All rights reserved.

Morphometric and microscopic evaluation of the effect of a solution of alendronate as an intracanal therapeutic agent in rat teeth submitted to late reimplantation.

PubMed

Mori, Graziela Garrido; Garcia, Roberto Brandão; Gomes de Moraes, Ivaldo; Bramante, Clóvis Monteiro; Bernardineli, Norberti

2007-08-01

The use of substances that inhibit root resorption may be an alternative for cases of unsuccessful reimplants. Hence, the purpose of this study was to test a solution of alendronate, a resorption inhibitor, as an intracanal therapeutic agent for teeth submitted to late reimplantation. Thirty rat maxillary right central incisors were avulsed and kept dry for 30 min. The teeth were instrumented, and the root surfaces treated with 1% hypochlorite solution followed by application of 2% sodium fluoride. Thereafter, the teeth were divided in two groups according to the intracanal dressing: (i) group I, solution of alendronate and (ii) group II, calcium hydroxide paste. Teeth were then reimplanted in their respective sockets. The animals were killed at 15, 30 and 60 days after reimplantation and the samples processed for morphometric and microscopic analysis. The results demonstrated that the solution of alendronate and the calcium hydroxide paste limited the root resorption, yet did not impair its occurrence. It may be concluded that alendronate and calcium hydroxide paste demonstrated similar behavior.

The Effect of Local Delivery Doxycycline and Alendronate on Bone Repair.

PubMed

Limirio, Pedro Henrique Justino Oliveira; Rocha, Flaviana Soares; Batista, Jonas Dantas; Guimarães-Henriques, João César; de Melo, Geraldo Batista; Dechichi, Paula

2016-08-01

The aim of the present study was to investigate the local effect of 10% doxycycline and 1% alendronate combined with poly(lactic-co-glycolic acid) (PLGA) on bone repair. Thirty rats were divided into three groups, as follows: control group (CG), drug group (DG), and vehicle-PLGA group (VG). Bone defect was created in the right femur and filled with the following: blood clot (CG); PLGA gel, 10% doxycycline and 1% alendronate (DG); or vehicle-PLGA (VG). The animals were euthanized 7 or 15 days after surgery. Bone density, bone matrix and number of osteoclasts were quantified. At 7 days, the findings showed increased density in DG (177.75 ± 76.5) compared with CG (80.37 ± 27.4), but no difference compared with VG (147.1 ± 41.5); no statistical difference in bone neoformation CG (25.6 ± 4.8), VG (27.8 ± 4), and DG (18.9 ± 7.8); and decrease osteoclasts in DG (4.6 ± 1.9) compared with CG (26.7 ± 7.4) and VG (17.3 ± 2.7). At 15 days, DG (405.1 ± 63.1) presented higher density than CG (213.2 ± 60.9) and VG (283.4 ± 85.8); there was a significant increase in percentage of bone neoformation in DG (31.5 ± 4.2) compared with CG (23 ± 4), but no difference compared with VG (25.1 ± 2.9). There was a decreased number of osteoclasts in DG (20.7 ± 4.7) and VG (29.5 ± 5.4) compared with CG (40 ± 9.4). The results suggest that the association of 10% doxycycline and 1% alendronate with PLGA-accelerated bone repair.

The inhibitory effect of alendronate, a nitrogen-containing bisphosphonate on the PI3K-Akt-NFkappaB pathway in osteosarcoma cells.

PubMed

Inoue, Ryosuke; Matsuki, Nori-aki; Jing, Gao; Kanematsu, Takashi; Abe, Kihachiro; Hirata, Masato

2005-11-01

1 Bisphosphonates are inhibitors of tumor cell growth as well as of bone resorption by inducing cell apoptosis. However, little is known regarding the mechanisms by which the drug induces cell apoptosis. The aim of the present study was to determine the effect of alendronate, one of the nitrogen-containing bisphosphonates on the phoshoinositide 3-kinase (PI3K)-Akt-NFkappaB pathway, the major cell survival pathway. 2 The PI3K-Akt-NFkappaB pathway was activated in the osteosarcoma cell line MG-63 treated with tumor necrosis factor-alpha or insulin. Saos-2 was also used in some experiments. This was assessed by the production of phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)), increased PI3K activity, phosphorylation of Akt at serine 473 and threonine 308, increase in activity of the inhibitor of nuclear factor kappaB (IkappaB) kinase (IKK) and finally phosphorylation of IkappaB and its subsequent degradation. 3 Pretreatment with alendronate at 100 microM for 24 h prior to the stimulation with tumor necrosis factor-alpha or insulin partially inhibited the IkappaB phosphorylation and degradation. These events were more clearly observed in the presence of inhibitors of proteasomes, which are responsible for the degradation of IkappaB. The drug also partially inhibited the activity of IKK, but almost fully inhibited the phosphorylation of Akt and the production of PtdIns(3,4,5)P(3). 4 The inhibitory effect of alendronate on IkappaB phosphorylation and degradation was not attenuated by the exogenous addition of geranylgeraniol to replenish the cytosolic isoprenyl lipid substrate. 5 The present findings demonstrate that alendronate inhibited the PI3K-Akt-NFkappaB cell survival pathway at the point of PI3K activation, thus indicating the presence of new targets of alendronate.

Role of 1% alendronate gel as adjunct to mechanical therapy in the treatment of chronic periodontitis among smokers

PubMed Central

SHARMA, Anuj; RAMAN, Achala; PRADEEP, Avani Raju

2017-01-01

Abstract Objective Alendronate (ALN) inhibits osteoclastic bone resorption and triggers osteostimulative properties both in vivo and in vitro, as shown by increase in matrix formation. This study aimed to explore the efficacy of 1% ALN gel as local drug delivery (LDD) in adjunct to scaling and root planing (SRP) for the treatment of chronic periodontitis among smokers. Material and Methods 75 intrabony defects were treated in 46 male smokers either with 1% ALN gel or placebo gel. ALN gel was prepared by adding ALN into carbopol-distilled water mixture. Clinical parameters [modified sulcus bleeding index, plaque index, probing depth (PD), and periodontal attachment level (PAL)] were recorded at baseline, at 2 months, and at 6 months, while radiographic parameters were recorded at baseline and at 6 months. Defect fill at baseline and at 6 months was calculated on standardized radiographs by using the image analysis software. Results Mean PD reduction and mean PAL gain were found to be greater in the ALN group than in the placebo group, both at 2 and 6 months. Furthermore, a significantly greater mean percentage of bone fill was found in the ALN group (41.05±11.40%) compared to the placebo group (2.5±0.93%). Conclusions The results of this study showed 1% ALN stimulated a significant increase in PD reduction, PAL gain, and an improved bone fill compared to placebo gel in chronic periodontitis among smokers. Thus, 1% ALN, along with SRP, is effective in the treatment of chronic periodontitis in smokers. PMID:28678942

Disintegration/dissolution profiles of copies of Fosamax (alendronate).

PubMed

Epstein, S; Cryer, B; Ragi, S; Zanchetta, J R; Walliser, J; Chow, J; Johnson, M A; Leyes, A E

2003-01-01

Poor quality has been reported for some generics and other copies of original products. We performed a pilot study to compare the disintegration/dissolution profiles of FOSAMAX (alendronate) 70 mg tablets with those of copies of FOSAMAX that were manufactured outside the United States. We used the standard United States Pharmacopeia (USP) disintegration method to evaluate FOSAMAX 70 mg tablets and 13 copies. At least 12 (n = 12) dosage units were tested for each product (except Fosmin, n = 10). The dissolution profiles of FOSAMAX and one representative copy were also compared. Nine copies (Osteomax, Defixal, Fosmin, Endronax, Osteomix, Genalmen, Fixopan, Osteoplus, and Fosval) disintegrated two- to ten-fold faster than FOSAMAX. Three other copies (Neobon, Regenesis, and Ostenan) disintegrated at least five-fold slower than FOSAMAX. Neobon is a softgel capsule, so special consideration was given to this different dosage form. One copy (Arendal) did not fall into either category but exhibited potentially large inter- and intra-lot variability. Dissolution of alendronate from Regenesis lagged behind that from FOSAMAX. Slower disintegration may reduce efficacy because bisphosphonates must be taken in the fasting state and contact with food or even certain beverages severely reduces bioavailability. Faster disintegration (or the use of gel-caps or other alterations to the drug formulation) could increase the risk of esophagitis, an adverse event associated with prolonged contact of the esophagus with bisphosphonates. These disintegration and dissolution results suggest that important differences may exist between FOSAMAX and its copies with regard to bioavailability, pharmacokinetics, and clinical efficacy and safety profiles. Additional testing is warranted to evaluate the pharmacokinetics and clinical safety of these copies.

Hydrophobically Modified Glycol Chitosan Nanoparticles for Targeting Breast Cancer Microcalcification Using Alendronate Probes

NASA Astrophysics Data System (ADS)

Vishnu, Kamalakannan

In 2016, invasive breast cancer was diagnosed in about 246,660 women and 2,600 men. An additional 61,000 new cases of in situ breast cancer was diagnosed in women. Microcalcifications are most common abnormalities detected by mammography for breast cancer, present in about 30% of all malignant breast lesions. Tumor specific biomarkers are used for targeting these abnormalities. Nanoparticles with multimodal and combinatorial therapies and conjunction of bio-ligands for specific molecular targeting using surface modifications effectually deliver a variety of drugs and are simultaneously used to image tumor progression. Alendronate, a germinal bisphosphonate conjugation as a targeting ligand would improve the nanoparticle's direct binding to hydroxyapatite (HA) mimicking calcified spots in breast cancer lesions. In this study, the hydrophobically modified glycol chitosan (HGC) micelle was modified with alendronate surface functionalization using a biotin-avidin interaction to improve the nanomicelle's calcification targeting ability. Biotinylated, avidinlyated hydrophobically modified iv glycol chitosan particles were linked to biotinylated alendronate via a strong biotin-avidin linkage. Cyanine 3, a red fluorescent dye was conjugated to the amine groups on HGC for visualization of micelles. The size of the nanoparticles measured was 254.0 +/- 0.43 nm and 209.7 +/- 1.0 nm for Cy3- BHGCA and Cy3-BHGCA-BALN nanoparticles respectively. The average surface charge was measured to be +26.9 +/- 0.19 mV and +27.68 +/- 0.20 mV for Cy3-BHGCA and Cy3-BHGCA- BALN nanoparticles respectively. Binding affinity using hydroxyapatite (HA) revealed that both Cy3 BHGCA BALN and Cy3 BHGCA nanoparticles displayed 95% binding in 24 hours. However, the biotin quenched nanoparticle Cy3 BHGCAB displayed 68% binding in 24 hours. The synthesis and binding chemistry was verified using Fourier transform infrared spectroscopy (FTIR).

Anti-osteoporotic treatments in France: initiation, persistence and switches over 6 years of follow-up.

PubMed

Belhassen, M; Confavreux, C B; Cortet, B; Lamezec, L; Ginoux, M; Van Ganse, E

2017-03-01

Limited information is available on anti-osteoporotic treatment initiation patterns in France. In 2006-2013, the most frequently prescribed first-line treatment class for osteoporosis was represented by bisphosphonates (alendronic acid and risedronic acid), followed by strontium ranelate. Persistence with anti-osteoporotic treatment was low, with high proportions of treatment discontinuations and switches. This epidemiological, longitudinal study described first-line treatment initiation, persistence, switches to second-line treatment, and medical care consumption in osteoporotic patients in France during the 2007-2013 period. Patients aged ≥50 years, who were recorded in a French claims database and did not die during the observation period, were included if they met ≥1 inclusion criteria for osteoporosis in 2007 (≥1 reimbursement for anti-osteoporotic treatment, hospitalisation for osteoporotic fracture (spine, hip, femur, forearm bones, humerus, wrist), or ≥1 reimbursement for long-term osteoporosis-associated status). We collected data on consumption of anti-osteoporotic treatment (alendronic acid, ibandronic acid, risedronic acid, zoledronic acid, raloxifene, strontium ranelate, teriparatide) and of osteoporosis-related medical care after the date of first reimbursement for anti-osteoporotic treatment. We obtained 2219 patients with a 6-year follow-up and 1387 who initiated an anti-osteoporotic treatment in 2007 and who can be selected for the treatment regimen analysis. The most frequently used first-line treatments were alendronic acid (32.7 %), risedronic acid (22.4 %), strontium ranelate (19.3 %), ibandronic acid (13.1 %) and raloxifene (12.2 %). Among patients who received these treatments, the highest persistence after 6 years was observed for raloxifene (37.3 %), alendronic acid (35.1 %) and risedronic acid (32.3 %). Treatment discontinuations were reported for 35.5 % (raloxifene) to 53.4 % (strontium ranelate) and treatment switches

OPG, RANKL, and RANK gene polymorphisms and the bone mineral density response to alendronate therapy in postmenopausal Chinese women with osteoporosis or osteopenia.

PubMed

Zheng, Hui; Wang, Chun; He, Jin-Wei; Fu, Wen-Zhen; Zhang, Zhen-Lin

2016-01-01

The aim of the study was to explore the association between OPG, RANKL, and RANK gene variations and the bone mineral density (BMD) response to alendronate therapy in postmenopausal Chinese women with osteoporosis or osteopenia. In the present study, 40 single-nucleotide polymorphisms (SNPs) in the OPG, RANKL, and RANK genes were genotyped in 501 postmenopausal Chinese women with osteoporosis or osteopenia who were given alendronate (70 mg weekly) orally for 1 year. The BMD at the lumbar spine 1-4 (L1-L4), femoral neck, and total hip was measured. A total of 442 patients completed 1 year of alendronate therapy. The rs7239261 SNP of the RANK gene was significantly associated with baseline L1-L4 BMD (P=0.0004) after correction for age and BMI. Participants with the SNP A allele (C/A and A/A) had a higher BMD than those with the C/C genotype (C/A vs. C/C, P=0.001; A/A vs. C/C, P=0.025). Haplotypes AG of rs7239261-rs12969154, GG of rs3826619-rs11877530, and CACG of rs1805034-rs8083511-rs17069895-rs7231887 in the RANK gene were genetic protective factors toward a higher baseline L1-L4 BMD. No association was observed between any SNP or haplotype of the OPG, RANKL, and RANK genes and the response of BMD to alendronate therapy. The RANK gene might contribute to genetic variability in L1-L4 BMD in postmenopausal Chinese women with osteoporosis or osteopenia. No evidence of an association between any SNP or haplotype of the OPG, RANKL, and RANK genes and the response of BMD to alendronate therapy was found in postmenopausal Chinese women with osteoporosis or osteopenia.

Mouse macrophages primed with alendronate down-regulate monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) production in response to Toll-like receptor (TLR) 2 and TLR4 agonist via Smad3 activation.

PubMed

Masuda, Takahiro; Deng, Xue; Tamai, Riyoko

2009-08-01

Alendronate is one of the nitrogen-containing bisphosphonates (NBPs) used as anti-bone resorptive drugs. However, NBPs have inflammatory side effects including osteomyelitis and osteonecrosis of the jaw. In the present study, we examined the effects of alendronate on chemokine production by the macrophage-like cell line, J774.1, when incubated with Pam(3)CSK(4) (a Toll-like receptor (TLR) 2 agonist) and Lipid A (a TLR4 agonist). Pretreatment of J774.1 cells with alendronate decreased the production of TLR ligand-induced monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) but did not influence nuclear factor-kappaB (NF-kappaB) activation. While this agent induced caspase-8 activation, a caspase-8 inhibitor did not affect the decrease in MCP-1 production by alendronate and TLR ligands. Thus, the alendronate-mediated decrease in chemokine production was independent of NF-kappaB and caspase-8 activation. Although transforming growth factor-beta1 (TGF-beta1) is known to inhibit chemokine production by various cell types via Smad3 activation, pretreatment with alendronate did not increase TGF-beta1 production by J774.1 cells incubated in the presence or absence of TLR ligands. However, alendronate directly activated Smad3. These results suggest that by down-regulating MCP-1 and MIP-1alpha production via Smad3, long-term use of alendronate might inhibit normal activation and migration of osteoclasts and cause osteonecrosis.

Two-way crossover bioequivalence study of alendronate sodium tablets in healthy, non-smoking male volunteers under fasted conditions.

PubMed

Thudi, Nageshwar Rao; Gagnon, Stéphanie; Hussain, Saleh; Abolfathi, Zohreh; Singla, Ajay; Pai, Raveendra; Kumar, Sudershan; Monif, Tausif

2009-01-01

This study was conducted in order to assess the bioequivalence of two different formulations containing 70 mg alendronate sodium (CAS 121268-17-5) under fasted conditions. One hundred twenty-two healthy male volunteers were enrolled in an open label, randomized, crossover design with a wash-out period of 20 days in one study center. Urine samples were collected up to 36 h post-dose, and the concentrations of alendronic acid were determined using a high performance liquid chromatographic method with pre-derivatization and fluorescence detection (HPLC/FL) method. The mean Ae(0-t) were 604.24 +/- 348.73 microg and 627.36 +/- 327.99 microg, while the mean R(max) were 193.87 +/- 114.68 microg/h and 202.00 +/- 107.83 microg/h for the test and reference formulations, respectively. The T(max) of the test and reference tablets were 1.26 +/- 0.58 h and 1.26 +/- 0.51 h, respectively. No significant differences of pharmacokinetic parameters between the two studied formulations were found. The 90% confidence intervals for the primary target parameters, intra-individual ratios for Ae(0-t) and R(max) of alendronic acid, were between 0.86-1.00 and 0.85-1.01, respectively, and thus within the acceptance range for bioequivalence criteria. In the light of the present study it can be concluded that the test formulation is bioequivalent to the reference formulation.

Cost-utility and budget impact analysis of primary prevention with alendronate of osteoporotic hip fractures in Catalonia.

PubMed

Pueyo, María J; Larrosa, Marta; Surís, Xavier; Garcia-Ruiz, Antonio J

2012-01-01

To determine whether primary drug prevention of osteoporotic hip fracture is a useful measure in Catalonia and what would be their budgetary impact. We performed a cost-utility social perspective study with a time horizon of 10 to 20 years. Univariate sensitivity analysis was performed. Doing nothing is compared with an intervention that includes screening for osteoporosis in women> 64 years and in those diagnosed and who received treatment with generic alendronate for 10 years. Decision trees are developed for groups of 65-69, 70-74 and 75-79. HF data is from 2009 hospital discharges .Costs are derived from fees paid by public insurance. In 2009 there were 9262 HF. The direct cost was € 55 million (€ 5,943.4/patient). The total cost was € 227 million for 10 years. The intervention dominates in all age groups in a 20 year perspective. In any horizon and age group, the different scenario puts the value per QALY below or within the proposed values for Spain. The budgetary impact is estimated at € 8.9 million which increased by 31% the actual direct cost, and 0.5% of the public pharmacy budget. Considering the total costs and the prospect of 20 years, annual savings of 7.4 million € were seen. The prevention of HF with alendronate in osteoporotic women>64 years is cost-useful in the long term (20 years) with a low budgetary impact in the 75-79 year group. Copyright © 2011 Elsevier España, S.L. All rights reserved.

Validated spectrophotometric methods for determination of Alendronate sodium in tablets through nucleophilic aromatic substitution reactions

PubMed Central

2012-01-01

Background Alendronate (ALD) is a member of the bisphosphonate family which is used for the treatment of osteoporosis, bone metastasis, Paget's disease, hypocalcaemia associated with malignancy and other conditions that feature bone fragility. ALD is a non-chromophoric compound so its determination by conventional spectrophotometric methods is not possible. So two derivatization reactions were proposed for determination of ALD through the reaction with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) and 2,4-dinitrofluorobenzene (DNFB) as chromogenic derivatizing reagents. Results Three simple and sensitive spectrophotometric methods are described for the determination of ALD. Method I is based on the reaction of ALD with NBD-Cl. Method II involved heat-catalyzed derivatization of ALD with DNFB, while, Method III is based on micellar-catalyzed reaction of the studied drug with DNFB at room temperature. The reactions products were measured at 472, 378 and 374 nm, for methods I, II and III, respectively. Beer's law was obeyed over the concentration ranges of 1.0-20.0, 4.0-40.0 and 1.5-30.0 μg/mL with lower limits of detection of 0.09, 1.06 and 0.06 μg/mL for Methods I, II and III, respectively. The proposed methods were applied for quantitation of the studied drug in its pure form with mean percentage recoveries of 100.47 ± 1.12, 100.17 ± 1.21 and 99.23 ± 1.26 for Methods I, II and III, respectively. Moreover the proposed methods were successfully applied for determination of ALD in different tablets. Proposals of the reactions pathways have been postulated. Conclusion The proposed spectrophotometric methods provided sensitive, specific and inexpensive analytical procedures for determination of the non-chromophoric drug alendronate either per se or in its tablet dosage forms without interference from common excipients. Graphical abstract PMID:22472190

Validated spectrophotometric methods for determination of Alendronate sodium in tablets through nucleophilic aromatic substitution reactions.

PubMed

Walash, Mohamed I; Metwally, Mohamed E-S; Eid, Manal; El-Shaheny, Rania N

2012-04-02

Alendronate (ALD) is a member of the bisphosphonate family which is used for the treatment of osteoporosis, bone metastasis, Paget's disease, hypocalcaemia associated with malignancy and other conditions that feature bone fragility. ALD is a non-chromophoric compound so its determination by conventional spectrophotometric methods is not possible. So two derivatization reactions were proposed for determination of ALD through the reaction with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) and 2,4-dinitrofluorobenzene (DNFB) as chromogenic derivatizing reagents. Three simple and sensitive spectrophotometric methods are described for the determination of ALD. Method I is based on the reaction of ALD with NBD-Cl. Method II involved heat-catalyzed derivatization of ALD with DNFB, while, Method III is based on micellar-catalyzed reaction of the studied drug with DNFB at room temperature. The reactions products were measured at 472, 378 and 374 nm, for methods I, II and III, respectively. Beer's law was obeyed over the concentration ranges of 1.0-20.0, 4.0-40.0 and 1.5-30.0 μg/mL with lower limits of detection of 0.09, 1.06 and 0.06 μg/mL for Methods I, II and III, respectively. The proposed methods were applied for quantitation of the studied drug in its pure form with mean percentage recoveries of 100.47 ± 1.12, 100.17 ± 1.21 and 99.23 ± 1.26 for Methods I, II and III, respectively. Moreover the proposed methods were successfully applied for determination of ALD in different tablets. Proposals of the reactions pathways have been postulated. The proposed spectrophotometric methods provided sensitive, specific and inexpensive analytical procedures for determination of the non-chromophoric drug alendronate either per se or in its tablet dosage forms without interference from common excipients. GRAPHICAL

Prolonged use of alendronate alters the biology of cranial repair in estrogen-deficient rats' associated simultaneous immunohistochemical expression of TGF-β1+, α-ER+, and BMPR1B.

PubMed

Giovanini, Allan Fernando; de Sousa Passoni, Giuliene Nunes; Göhringer, Isabella; Deliberador, Tatiana Miranda; Zielak, João Cesar; Storrer, Carmem Lucia Muller; Costa-Casagrande, Thais Andrade; Scariot, Rafaela

2018-06-01

TGF-β1 is a cytokine that may induce both osteoneogenesis through Runx-2 or fibrosis via the transcription of α-smooth muscle actin (α-SMA). Because it has been previously known that alendronate increases the level of TGF-β1 and that under the usual condition of bone metabolism the estrogen may prevent the fibrotic effect of TGF-β1, the aim of this study was to evaluate if alendronate alters the cellular differentiation process post calvarial surgery in estrogen-deficient specimens. A transosseous defect that was 5 mm in diameter was created on the calvarium of each of 32 female rats with previous ovarian-salpingo-oophorectomy. All defects were treated with autografts, and 16 rats received the administration of 1 mg/kg of alendronate three times a week until euthanasia on the 15th and 60th day post surgery. Histomorphometric and immunohistochemical analyses of the expression of TGF-β1, estrogen receptor alpha nuclear (α-ER), α-SMA, BMPR1B, and Runx-2 were performed, and ELISA was used to measure the level of estrogen. All animals demonstrated low levels of estrogen post ovarian-salpingo-oophorectomy. The histological results demonstrated larger bone matrix deposition in specimens treated with alendronate on the 15th day post surgery. The result was associated with a higher co-expression of TGF-β1, BMPR1B, and Runx-2 when compared with the control group. In addition, on the 60th day post surgery, the increase of bone matrix deposition from 15th to 60th day was discrete in specimens treated with alendronate compared with the control group. This result coincided with the intense simultaneous expression of TGF-β1, α-ER, and α-SMA, whereas the expression of BMPR1B and Runx-2 decreased. The prolonged administration of alendronate altered the cranial repair in ovarian-salpingo-oophorectomized specimens due to the simultaneous occurrence of low estrogen and the presence of TGF-β1+/α-ER+ inducing the presence of α-SMA + , whereas BMPR1B and Runx-2 were

Effects of combined elcatonin and alendronate treatment on the architecture and strength of bone in ovariectomized rats.

PubMed

Ogawa, Koko; Hori, Masayuki; Takao, Ryoko; Sakurada, Toyozo

2005-01-01

We examined the combined effects of elcatonin (ECT) and alendronate (ALN) on bone mass, architecture, and strength in ovariectomized (OVX) rats. Fifty female Sprague Dawley rats, aged 13 weeks, were divided into Sham, OVX, OVX+ECT, OVX+ALN, and OVX+ECT+ALN groups (n = 10). Immediately after ovariectomy, ECT was administered at a dose of 15 units (U)/kg three times a week, and ALN was administered daily at a dose of 2.0 microg/kg, subcutaneously for 12 weeks. The three-dimensional architecture of the bone in the distal femoral metaphysis was analyzed using a microfocus X-ray computed tomography system (microCT), and bone strength was measured using a material-testing machine. Trabecular bone volume (BV/TV) and number (Tb.N) were significantly greater in the OVX+ECT and OVX+ALN groups than in the OVX group. In the OVX+ECT+ALN group, BV/TV and Tb.N were significantly greater when compared with those in the OVX+ECT and OVX+ALN groups. Trabecular thickness (Tb.Th) was significantly greater in the OVX+ECT+ALN group than in the OVX+ALN group. With regard to bone strength, the compression strength in the femoral metaphysis was significantly lower in the OVX group than in the Sham group. The reduction of compression strength was slightly lower in the OVX+ECT and OVX+ALN groups. In the OVX+ECT+ALN group, the compression strength in the femoral metaphysis significantly increased when compared with the OVX and OVX+ECT groups. These results suggest that the combined treatment of ECT and ALN does not alter the individual effects of each drug and that it exerts an additive effect on trabecular architecture and bone strength in OVX rats.

Effects of the bisphosphonate alendronate on molars of young rats after lateral luxation.

PubMed

Rothbarth, Cláudia Pires; Bradaschia-Correa, Vivian; Ferreira, Lorraine Braga; Arana-Chavez, Victor Elias

2014-12-01

The bisphosphonate alendronate (ALN) was employed with the aim of investigating its effects on dental and periodontal tissues after lateral luxation of developing molars. Twenty-one-day-old Wistar rats had their second upper molars laterally luxated. Daily 2.5 mg kg(-1) ALN injections started at the day of the luxation; controls received sterile saline solution. The teeth were analyzed 7, 14, and 21 days after the procedure. On the days cited, the maxillae were fixed, decalcified, and embedded in paraffin or Spurr resin. The paraffin sections were stained with H&E, incubated for TRAP histochemistry or immunolabeled for osteopontin (OPN). Spurr ultrathin sections were examined in a transmission electron microscope. After 21 days, the root apex of luxated molars without ALN was wide open and disorganized and also covered by an irregular layer of cellular cementum, which was not observed in ALN-treated animals. Ankylosis sites were observed in ALN rats in both luxated and non-luxated teeth. The TRAP-positive osteoclasts were more numerous in ALN group, despite their latent ultrastructural appearance without the presence of resorption apparatus compared to controls. OPN immunolabeling revealed a thick immunopositive line in the dentin that must be resultant from the moment of the luxation, while ALN-treated specimens did not present alterations in dentin. The present findings indicate that alendronate inhibits some alterations in dentin and cementum formation induced by dental trauma. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Bone loss from Wnt inhibition mitigated by concurrent alendronate therapy.

PubMed

Madan, Babita; McDonald, Mitchell J; Foxa, Gabrielle E; Diegel, Cassandra R; Williams, Bart O; Virshup, David M

2018-01-01

Dysregulated Wnt signaling is associated with the pathogenesis of cancers, fibrosis, and vascular diseases. Inhibition of Wnt signaling has shown efficacy in various pre-clinical models of these disorders. One of the key challenges in developing targeted anti-cancer drugs is to balance efficacy with on-target toxicity. Given the crucial role Wnts play in the differentiation of osteoblasts and osteoclasts, acute inhibition of Wnt signaling is likely to affect bone homeostasis. In this study, we evaluated the skeletal effect of small molecule inhibitor of an o-acyl transferase porcupine (PORCN) that prevents Wnt signaling by blocking the secretion of all Wnts. Micro-computed tomography and histomorphometric evaluation revealed that the bones of mice treated with two structurally distinct PORCN inhibitors LGK974 and ETC-1922159 (ETC-159) had loss-of-bone volume and density within 4 weeks of exposure. This decreased bone mass was associated with a significant increase in adipocytes within the bone marrow. Notably, simultaneous administration of a clinically approved anti-resorptive, alendronate, a member of the bisphosphonate family, mitigated loss-of-bone mass seen upon ETC-159 treatment by regulating activity of osteoclasts and blocking accumulation of bone marrow adipocytes. Our results support the addition of bone protective agents when treating patients with PORCN inhibitors. Mitigation of bone toxicity can extend the therapeutic utility of Wnt pathway inhibitors.

Therapist perception of treatment outcome: Evaluating treatment outcomes among youth with antisocial behavior problems.

PubMed

Crandal, Brent R; Foster, Sharon L; Chapman, Jason E; Cunningham, Phillippe B; Brennan, Patricia A; Whitmore, Elizabeth A

2015-06-01

Effective evaluation of treatment requires the use of measurement tools producing reliable scores that can be used to make valid decisions about the outcomes of interest. Therapist-rated treatment outcome scores that are obtained within the context of empirically supported treatments (ESTs) could provide clinicians and researchers with data that are easily accessible and complimentary to existing instrumentation. We examined the psychometric properties of scores from the Therapist Perception of Treatment Outcome: Youth Antisocial Behavior (TPTO:YAB), an instrument developed to assess therapist judgments of treatment success among families participating in an EST, Multisystemic Therapy (MST), for youth with antisocial behavior problems. Data were drawn from a longitudinal study of MST. The initial 20-item TPTO:YAB was completed by therapists of 111 families at midtreatment and 163 families at treatment termination. Rasch model dimensionality analyses provided evidence for 2 dimensions reflecting youth- and caregiver-related aspects of treatment outcome, although a bifactor analyses suggested that these dimensions reflected a single more general construct. Rasch analyses were also used to assess item and rating scale characteristics and refine the number of items. These analyses suggested items performed similarly across time and that scores reflect treatment outcome in similar ways at mid and posttreatment. Multilevel and zero-order analyses provided evidence for the validity of TPTO:YAB scores. TPTO:YAB scores were moderately correlated with scores of youth and caregiver behaviors targeted in treatment, adding support to its use as a treatment outcome measurement instrument. (c) 2015 APA, all rights reserved).

Low Doses of Simvastatin Potentiate the Effect of Sodium Alendronate in Inhibiting Bone Resorption and Restore Microstructural and Mechanical Bone Properties in Glucocorticoid-Induced Osteoporosis.

PubMed

Sequetto, Priscila L; Gonçalves, Reggiani V; Pinto, Aloísio S; Oliveira, Maria G A; Maldonado, Izabel R S C; Oliveira, Tânia T; Novaes, Rômulo D

2017-10-01

By using an experimental model of dexamethasone-induced osteoporosis we investigated the effects of different therapeutic schemes combining sodium alendronate (SA) and simvastatin on bone mineral and protein composition, microstructural and mechanical remodeling. Wistar rats were randomized into eight groups: G1: non-osteoporotic; G2: osteoporotic; G3, G4, and G5: osteoporotic+SA (0.2, 0.4, and 0.8 mg/kg, respectively); G6, G7, and G8: osteoporotic+SA (0.2, 0.4, and 0.8 mg/kg, respectively)+simvastatin (0.4, 0.6, and 1 mg/kg, respectively). Osteoporosis was induced by dexamethasone (7 mg/kg, i.m.) once a week for 5 weeks. All treatments were administered for 8 weeks. Dexamethasone increased serum levels of alkaline phosphatase, calcium, phosphorus, and urea, especially in non-treated animals, which showed severe osteoporosis. Dexamethasone also induced bone microstructural fragility and reduced mechanical resistance, which were associated with a marked depletion in mineral mass, collagenous and non-collagenous protein levels in cortical and cancellous bone. Although SA has attenuated osteoporosis severity, the effectiveness of drug therapy was enhanced combining alendronate and simvastatin. The restoration in serum parameters, organic and inorganic bone mass, and mechanical behavior showed a dose-dependent effect that was potentially related to the complementary mechanisms by which each drug acts to induce bone anabolism, accelerating tissue repair.

Predicting in-treatment performance and post-treatment outcomes in methamphetamine users.

PubMed

Hillhouse, Maureen P; Marinelli-Casey, Patricia; Gonzales, Rachel; Ang, Alfonso; Rawson, Richard A

2007-04-01

This study examines the utility of individual drug use and treatment characteristics for predicting in-treatment performance and post-treatment outcomes over a 1-year period. Data were collected from 420 adults who participated in the Methamphetamine Treatment Project (MTP), a multi-site study of randomly assigned treatment for methamphetamine dependence. Interviews were conducted at baseline, during treatment and during three follow-up time-points: treatment discharge and at 6 and 12 months following admission. The Addiction Severity Index (ASI); the Craving, Frequency, Intensity and Duration Estimate (CFIDE); and laboratory urinalysis results were used in the current study. Analyses addressed both in-treatment performance and post-treatment outcomes. The most consistent finding is that pre-treatment methamphetamine use predicts in-treatment performance and post-treatment outcomes. No one variable predicted all in-treatment performance measures; however, gender, route of administration and pre-treatment methamphetamine use were significant predictors. Similarly, post-treatment outcomes were predicted by a range of variables, although pre-treatment methamphetamine use was significantly associated with each post-treatment outcome. These findings provide useful empirical information about treatment outcomes for methamphetamine abusers, and highlight the utility of assessing individual and in-treatment characteristics in the development of appropriate treatment plans.

Development and characterization of a gastroretentive dosage form composed of chitosan and hydroxyethyl cellulose for alendronate

PubMed Central

Chen, Ying-Chen; Ho, Hsiu-O; Chiu, Chiao-Chi; Sheu, Ming-Thau

2014-01-01

In this study, alendronate, the most commonly used biphosphonate for treating osteoporosis, was formulated as gastroretentive dosage form (GRDF) tablets to enhance its oral bioavailability. GRDF tablets were characterized with the effects of different molecular weights (MWs) of chitosan (CS) and hydroxyethyl cellulose (HEC) at various ratios on swelling, floating, and physical integrity. The CS component was formed using various acids: acetic, lactic, malic, succinic, and citric, and a high viscosity grade of HEC was selected. The results demonstrated that the swelling ratios of the formulations comprising high MW CS were lower than those of low or medium MW CS when salts were formed with any countering acids except for acetic acid. The decreasing ranking of the swelling rates was: CS-citrate > CS-malate > CS-lactate > CS-succinate > CS-acetate. A negative correlation was found between the pKa of the respective countering acid and the swelling rate. The swelling rate was promoted if an acidic salt of CS with a lower water content was incorporated, while it became slower when tablet hardness was higher or the compression force to form tablets was increased. Although HEC did not contribute to swelling or floating, it played a role in maintaining structural integrity. A prolonged dissolution profile of alendronate GRDF tablets developed in this study was observed. PMID:24403821

Therapies for treatment of osteoporosis in US women: cost-effectiveness and budget impact considerations.

PubMed

Tosteson, Anna N A; Burge, Russel T; Marshall, Deborah A; Lindsay, Robert

2008-09-01

To evaluate the cost-effectiveness of osteoporosis treatments for women at high fracture risk and estimate the population-level impact of providing bisphosphonate therapy to all eligible high-risk US women. Fractures, healthcare costs, and quality-adjusted life-years (QALYs) were estimated over 10 years using a Markov model. No therapy, risedronate, alendronate, ibandronate, and teriperatide (PTH) were compared among 4 risk groups. Sensitivity analyses examined the robustness of model results for 65-year-old women with low bone density and previous vertebral fracture. Women treated with a bisphosphonate experienced fewer fractures and more QALYs compared with no therapy or PTH. Total costs were lowest for the untreated cohort, followed by risedronate, alendronate, ibandronate, and PTH in all risk groups except women aged 75 years with previous fracture. The incremental cost-effectiveness of risedronate compared with no therapy ranged from cost saving for the base case to $66,722 per QALY for women aged 65 years with no previous fracture. Ibandronate and PTH were dominated in all risk groups. (A dominated treatment has a higher cost and poorer outcome.) Treating all eligible women with a bisphosphonate would cost an estimated additional $5563 million (21% total increase) and would result in 390,049 fewer fractures (35% decrease). In the highest risk group, the additional cost of therapy was offset by other healthcare cost savings. Osteoporosis treatment of high-risk women is cost-effective, with bisphosphonates providing the most benefit at lowest cost. For highest risk women, costs are offset by savings from fracture prevention.

Bisphosphonate-modified gold nanoparticles: a useful vehicle to study the treatment of osteonecrosis of the femoral head

NASA Astrophysics Data System (ADS)

Fanord, Fedena; Fairbairn, Korie; Kim, Harry; Garces, Amanda; Bhethanabotla, Venkat; Gupta, Vinay K.

2011-01-01

Legg-Calvé-Perthes disease (LCPD) is a juvenile form of osteonecrosis of the femoral head that presents in children aged 2-14 years. To date, there is no effective medical therapy for treating LCPD largely due to an inability to modulate the repair process, including the predominance of bone resorption. This investigation aims to evaluate the feasibility of using gold nanoparticles (GNPs) that are surface modified with a bisphosphonate compound for the treatment of osteonecrosis at the cellular level. Studies have found osteoclast-mediated resorption to be a process that contributes significantly to the pathogenesis of femoral head deformities arising from Perthes disease. Our in vitro model was designed to elucidate the effect of alendronate-(a bisphosphonate) modified GNPs, on osteoclastogenesis and osteoclast function. RAW 264.7 macrophage cells were cultured with recombinant mouse receptor activator of NF-κB ligand (RANKL), which stimulates osteoclastogenesis, and were then treated with alendronate-modified GNPs for 24, 48, and 72 h. Cell proliferation, osteoclast function, and osteoclast morphology were evaluated by trypan blue dye exclusion assay, tartrate-resistant acid phosphatase (TRAP) staining, and transmission electron microscopy (TEM) imaging. Comparative studies were performed with GNPs that were only stabilized with citrate ions and with alendronate alone. Neither osteoclastogenesis nor osteoclast function were adversely affected by the presence of the citrate-GNP. Alendronate-modified GNPs had an enhanced effect on inducing osteoclast apoptosis and impairing osteoclast function when compared to unbound alendronate populations.

Cost-effectiveness of osteoporosis treatments in postmenopausal women using FRAX™ thresholds for decision.

PubMed

Alzahouri, Kazem; Bahrami, Stéphane; Durand-Zaleski, Isabelle; Guillemin, Francis; Roux, Christian

2013-01-01

FRAX™ is a fracture prediction algorithm to determine a patient's absolute fracture risk. There is a growing consensus that osteoporosis treatment should be based on individual 10-year fracture probability, as calculated in the FRAX™ algorithm, rather than on T-scores alone. Our objective was to evaluate the cost-effectiveness of five years of branded alendronate therapy in postmenopausal French women with a known FRAX™ score. A Markov cohort state transition model using FRAX™ values and whenever possible population-specific data and probabilities. We estimated the incremental cost-effectiveness ratio (ICER) of alendronate versus no treatment in postmenopausal women with FRAX™ ranging from 10 to 3%. Number of women to treat (NNT) for preventing hip fracture, costs, quality-adjusted life-years, incremental cost-effectiveness ratios. The incremental cost-effectiveness ratios (ICER) compared to no treatment at age 70 ranged from €104,183 to €413,473 per QALY when FRAX™ decreased from 10 to 3%. The NNTs for preventing one hip fracture ranged from 97 to 388 according to age (50-80 years) and FRAX™. Sensitivity analyses showed that the main determinants of cost-effectiveness were adherence to therapy and cost of treatment. Using French costs of branded drug and current estimates of treatment efficacy, alendronate therapy for 70-year-old women with 10-year probability of hip fracture of 10% just meets the accepted cost-effectiveness threshold. Improving treatment adherence and/or decreasing treatment cost lowers the ICER. The model however underestimates the potential benefit by excluding other fractures. Copyright © 2012 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Systematic Outcomes Research for Corrections-Based Treatment: Implications from the Criminal Justice Kentucky Treatment Outcome Study

ERIC Educational Resources Information Center

Staton-Tindall, Michele; McNees, Erin; Leukefeld, Carl G.; Walker, Robert; Thompson, LaDonna; Pangburn, Kevin; Oser, Carrie B.

2009-01-01

Over the last four years, the Kentucky correctional system has expanded corrections-based modified therapeutic community treatment from 6 programs to 24 programs. To examine the effectiveness of these programs, the state initiated a systematic treatment outcome study known as the Criminal Justice Kentucky Treatment Outcome Study (CJKTOS). The…

Low concentrations of alendronate increase the local invasive potential of osteoblastic sarcoma cell lines via connexin 43 activation.

PubMed

Yoshitani, Kazuhiro; Kido, Akira; Honoki, Kanya; Akahane, Manabu; Fujii, Hiromasa; Tanaka, Yasuhito

2011-07-15

Bisphosphonates (BPs) are agents used for treating disorders of excessive bone resorption. In addition, due to their cell-killing activity, BPs were potent candidates for adjuvant cancer therapy. On the other hand, low-concentrations of BPs have been reported to increase cellular viability in several types of tumor cells. Therefore, we focused on the effect of BPs on cellular aggressiveness of malignant bone tumors at low concentrations. MTS assay was performed using osteosarcoma cell lines MG63 and HOS, fibrosarcoma cell line HT1080, and prostate cancer cell line PC3. All the cell lines showed toxicity at high concentrations. On the other hand, at lower concentrations, the cellular viabilities of HOS and MG63 were rather higher than those of untreated controls. Since this tendency was most evident, HOS was used for further assays, including cellular motility, bone resorption activity, and cathepsin K activity. The low-concentration of alendronate enhanced cellular viability and motility, which correlated with the expression of connexin 43 at the mRNA and protein levels. Interestingly, oleamide, a potent connexin 43 inhibitor, had an inhibitory effect on the enhanced proliferation. Our data suggest that alendronate may enhance the proliferation of osteoblastic cell line through connexin 43 activation. Copyright © 2011 Elsevier GmbH. All rights reserved.

Magnetic resonance imaging of osteosarcoma using a bis(alendronate)-based bone-targeted contrast agent.

PubMed

Ge, Pingju; Sheng, Fugeng; Jin, Yiguang; Tong, Li; Du, Lina; Zhang, Lei; Tian, Ning; Li, Gongjie

2016-12-01

Magnetic resonance (MR) is currently used for diagnosis of osteosarcoma but not well even though contrast agents are administered. Here, we report a novel bone-targeted MR imaging contrast agent, Gd 2 -diethylenetriaminepentaacetate-bis(alendronate) (Gd 2 -DTPA-BA) for the diagnosis of osteosarcoma. It is the conjugate of a bone cell-seeking molecule (i.e., alendronate) and an MR imaging contrast agent (i.e., Gd-DTPA). Its physicochemical parameters were measured, including pK a , complex constant, and T 1 relaxivity. Its bone cell-seeking ability was evaluated by measuring its adsorption on hydroxyapatite. Hemolysis was investigated. MR imaging and biodistribution of Gd 2 -DTPA-BA and Gd-DTPA were studied on healthy and osteosarcoma-bearing nude mice. Gd 2 -DTPA-BA showed high adsorption on hydroxyapatite, the high MR relaxivity (r 1 ) of 7.613mM -1 s -1 (2.6 folds of Gd-DTPA), and no hemolysis. The MR contrast effect of Gd 2 -DTPA-BA was much higher than that of Gd-DTPA after intravenous injection to the mice. More importantly, the MR imaging of osteosarcoma was significantly improved by Gd 2 -DTPA-BA. The signal intensity of Gd 2 -DTPA-BA reached 120.3% at 50min, equal to three folds of Gd-DTPA. The bone targeting index (bone/blood) of Gd 2 -DTPA-BA in the osteosarcoma-bearing mice was very high to 130 at 180min. Furthermore, the contrast enhancement could also be found in the lung due to metastasis of osteosarcoma. Gd 2 -DTPA-BA plays a promising role in the diagnoses of osteosacomas, including the primary bone tumors and metastases. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Alendronate-Eluting Biphasic Calcium Phosphate (BCP) Scaffolds Stimulate Osteogenic Differentiation

PubMed Central

Kim, Sung Eun; Lee, Deok-Won; Kang, Eun Young; Jeong, Won Jae; Lee, Boram; Jeong, Myeong Seon; Kim, Hak Jun; Park, Kyeongsoon; Song, Hae-Ryong

2015-01-01

Biphasic calcium phosphate (BCP) scaffolds have been widely used in orthopedic and dental fields as osteoconductive bone substitutes. However, BCP scaffolds are not satisfactory for the stimulation of osteogenic differentiation and maturation. To enhance osteogenic differentiation, we prepared alendronate- (ALN-) eluting BCP scaffolds. The coating of ALN on BCP scaffolds was confirmed by scanning electron microscopy (FE-SEM), energy-dispersive X-ray spectroscopy (EDS), and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). An in vitro release study showed that release of ALN from ALN-eluting BCP scaffolds was sustained for up to 28 days. In vitro results revealed that MG-63 cells grown on ALN-eluting BCP scaffolds exhibited increased ALP activity and calcium deposition and upregulated gene expression of Runx2, ALP, OCN, and OPN compared with the BCP scaffold alone. Therefore, this study suggests that ALN-eluting BCP scaffolds have the potential to effectively stimulate osteogenic differentiation. PMID:26221587

Understanding Treatment Effect Estimates When Treatment Effects Are Heterogeneous for More Than One Outcome.

PubMed

Brooks, John M; Chapman, Cole G; Schroeder, Mary C

2018-06-01

Patient-centred care requires evidence of treatment effects across many outcomes. Outcomes can be beneficial (e.g. increased survival or cure rates) or detrimental (e.g. adverse events, pain associated with treatment, treatment costs, time required for treatment). Treatment effects may also be heterogeneous across outcomes and across patients. Randomized controlled trials are usually insufficient to supply evidence across outcomes. Observational data analysis is an alternative, with the caveat that the treatments observed are choices. Real-world treatment choice often involves complex assessment of expected effects across the array of outcomes. Failure to account for this complexity when interpreting treatment effect estimates could lead to clinical and policy mistakes. Our objective was to assess the properties of treatment effect estimates based on choice when treatments have heterogeneous effects on both beneficial and detrimental outcomes across patients. Simulation methods were used to highlight the sensitivity of treatment effect estimates to the distributions of treatment effects across patients across outcomes. Scenarios with alternative correlations between benefit and detriment treatment effects across patients were used. Regression and instrumental variable estimators were applied to the simulated data for both outcomes. True treatment effect parameters are sensitive to the relationships of treatment effectiveness across outcomes in each study population. In each simulation scenario, treatment effect estimate interpretations for each outcome are aligned with results shown previously in single outcome models, but these estimates vary across simulated populations with the correlations of treatment effects across patients across outcomes. If estimator assumptions are valid, estimates across outcomes can be used to assess the optimality of treatment rates in a study population. However, because true treatment effect parameters are sensitive to correlations

Magnetic resonance imaging in the evaluation of clinical treatment of otospongiosis: a pilot study.

PubMed

de Oliveira Vicente, Andy; Chandrasekhar, Sujana S; Yamashita, Helio K; Cruz, Oswaldo Laercio M; Barros, Flavia A; Penido, Norma O

2015-06-01

To evaluate the applicability of magnetic resonance imaging (MRI) as a method for monitoring the activity of otospongiotic lesions before and after clinical treatment. Prospective, randomized, controlled, double-blind study. One single tertiary care institution in a large, cosmopolitan city. Twenty-six patients (n = 42 ears) with clinical, audiometric, and tomographic diagnosis of otosclerosis were enrolled. If computed tomography (CT) demonstrated active lesions, these patients underwent MRI to detect otospongiotic foci, seen as areas of gadolinium enhancement. Patients were divided into 3 groups and received treatment with placebo, sodium alendronate, or sodium fluoride for 6 months. After this period, clinical and audiometric evaluations and a second MRI were performed. Each MRI was evaluated by both a neuroradiologist and an otolaryngologist in a subjective (visual) and objective (using specific eFilm Workstation software) manner. Otospongiosis was most predominantly identified in the region anterior to the oval window, and this site was reliable for comparing pre- and posttreatment scans. The patients in the alendronate and sodium fluoride groups had MRI findings that suggested a decrease in activity of otospongiotic lesions, more relevant in the alendronate group. These findings were statistically significant for both subjective and objective MRI evaluations. MRI shows higher sensitivity than clinical or audiometric assessment for detecting reduction in activity of otospongiosis. The objective MRI evaluation based on software analysis was the most accurate method of monitoring clinical treatment response in otospongiosis. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Comparative gastrointestinal safety of weekly oral bisphosphonates

PubMed Central

Katz, J. N.; Brookhart, M. A.; Stürmer, T.; Stedman, M. R.; Levin, R.; Solomon, D. H.

2012-01-01

Summary Weekly bisphosphonates are the primary agents used to treat osteoporosis. Although these agents are generally well tolerated, serious gastrointestinal adverse events, including hospitalization for gastrointestinal bleed, may arise. We compared the gastrointestinal safety between weekly alendronate and weekly risedronate and found no important difference between new users of these agents. Introduction Weekly bisphosphonates are the primary agents prescribed for osteoporosis. We examined the comparative gastrointestinal safety between weekly bisphosphonates. Methods We studied new users of weekly alendronate and weekly risedronate from June 2002 to August 2005 among enrollees in a state-wide pharmaceutical benefit program for seniors. Our primary outcome was hospitalization for upper gastrointestinal bleed. Secondary outcomes included outpatient diagnoses for upper gastrointestinal disease, symptoms, endoscopic procedures, use of gastroprotective agents, and switching between therapies. We used Cox proportional hazard models to compare outcomes between agents within 120 days of treatment initiation, adjusting for propensity score quintiles. We also examined composite safety outcomes and stratified results by age and prior gastrointestinal history. Results A total of 10,420 new users were studied, mean age=79 years (SD, 6.9), and 95% women. We observed 31 hospitalizations for upper gastrointestinal bleed (0.91 per 100 person-years) within 120 days of treatment initiation. Adjusting for covariates, there was no difference in hospitalization for upper gastrointestinal bleed among those treated with risedronate compared with alendronate (HR, 1.12; 95%CI, 0.55 to 2.28). Risedronate switching rates were lower; otherwise, no differences were observed for secondary or composite outcomes. Conclusions We found no important difference in gastrointestinal safety between weekly oral bisphosphonates. PMID:19266138

The absorption of (99m)Tc-alendronate given by rectal route in rabbits.

PubMed

Asikoğlu, Makbule; Ozguney, Isik; Ozcan, Ipek; Orumlu, Oya; Guneri, Tamer; Koseoğlu, Kamil; Ozkilic, Hayal

2008-01-01

Alendronate sodium (ALD) is a bisphosphonate medication used in the treatment and prevention of osteoporosis. Absorption of ALD as oral formulation is very poor (0.5%-1%). Its bioavailability can decrease with food effect. It has some gastrointestinal adverse effects such as gastritis, gastric ulcer, and esophagitis. The aim of this study was to develop a rectal formulation of ALD as an alternative to oral route and to investigate the absorption of it by using gamma scintigraphy. For this reason, ALD was labeled with Technetium-99m ((99m)Tc) by direct method. The radiochemical characterization of the (99m)Tc-ALD was carried out by paper chromatography, thin layer chromatography, and electrophoresis methods. The labeling efficiency of (99m)Tc-ALD was found 99% without significant changes until 6 h postlabeling at room temperature. The rectal suppositories containing (99m)Tc-ALD were prepared by fusion method using polyethylene glycol (PEG) 1500. The (99m)Tc-labeled ALD suppositories were administrated to rabbits by rectal route. Serial scintigrams over all bodies of the rabbits were obtained at different time intervals using a gamma camera. We found that the rectal absorption of (99m)Tc-ALD from suppository formulation was possible. According to our results, this formulation of ALD can be suggested for the therapy of osteoporosis as an alternative route.

Treatment Outcomes in an Adolescent Chemical Dependency Program.

ERIC Educational Resources Information Center

Ralph, Norbert; McMenamy, Carol

1996-01-01

Investigates treatment outcomes for all admissions to an adolescent chemical dependency program over a 10-month period. Interviews with parents of patients were conducted. The effect of various pretreatment and treatment factors on outcomes were investigated. Better treatment outcome was associated with older adolescents, greater participation in…

Alendronate promotes bone formation by inhibiting protein prenylation in osteoblasts in rat tooth replantation model.

PubMed

Komatsu, Koichiro; Shimada, Akemi; Shibata, Tatsuya; Wada, Satoshi; Ideno, Hisashi; Nakashima, Kazuhisa; Amizuka, Norio; Noda, Masaki; Nifuji, Akira

2013-11-01

Bisphosphonates (BPs) are a major class of antiresorptive drug, and their molecular mechanisms of antiresorptive action have been extensively studied. Recent studies have suggested that BPs target bone-forming cells as well as bone-resorbing cells. We previously demonstrated that local application of a nitrogen-containing BP (N-BP), alendronate (ALN), for a short period of time increased bone tissue in a rat tooth replantation model. Here, we investigated cellular mechanisms of bone formation by ALN. Bone histomorphometry confirmed that bone formation was increased by local application of ALN. ALN increased proliferation of bone-forming cells residing on the bone surface, whereas it suppressed the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts in vivo. Moreover, ALN treatment induced more alkaline phosphatase-positive and osteocalcin-positive cells on the bone surface than PBS treatment. In vitro studies revealed that pulse treatment with ALN promoted osteocalcin expression. To track the target cells of N-BPs, we applied fluorescence-labeled ALN (F-ALN) in vivo and in vitro. F-ALN was taken into bone-forming cells both in vivo and in vitro. This intracellular uptake was inhibited by endocytosis inhibitors. Furthermore, the endocytosis inhibitor dansylcadaverine (DC) suppressed ALN-stimulated osteoblastic differentiation in vitro and it suppressed the increase in alkaline phosphatase-positive bone-forming cells and subsequent bone formation in vivo. DC also blocked the inhibition of Rap1A prenylation by ALN in the osteoblastic cells. These data suggest that local application of ALN promotes bone formation by stimulating proliferation and differentiation of bone-forming cells as well as inhibiting osteoclast function. These effects may occur through endocytic incorporation of ALN and subsequent inhibition of protein prenylation.

Treatment Outcomes and Efficacy in the Schools.

ERIC Educational Resources Information Center

Logemann, Jeri A.

1998-01-01

Introduces six articles which address treatment outcomes and efficacy in audiology and speech-language pathology in the schools. Stresses the importance of practitioners participating in studies of treatment outcomes and efficacy to demonstrate that their evaluations and treatments make a significant difference to individuals served. (DB)

Outcome expectations and associated treatment outcomes in motivational enhancement therapy delivered in English and Spanish.

PubMed

Serafini, Kelly; Decker, Suzanne; Kiluk, Brian D; Añez, Luis; Paris, Manuel; Frankforter, Tami; Carroll, Kathleen M

2015-12-01

The relationship between patients' baseline expectations regarding treatment outcome and actual outcomes has not been widely studied within the field of substance use disorders. We hypothesized that outcome expectations would be unrelated to outcomes in a study investigating motivational enhancement therapy delivered in English (MET-E) consistent with our earlier work, and conducted exploratory analyses in a separate study that investigated the same treatment delivered in Spanish (MET-S). These secondary analyses compared patient outcome expectations and substance use treatment outcomes in two large, multisite randomized controlled clinical trials that evaluated three sessions of MET-E or MET-S. The MET-E sample included 461 participants and the MET-S sample included 405 participants. Outcome expectations were measured by a single item regarding expectations about abstinence prior to initiating treatment. Outcome expectations were strongly associated with most substance use outcomes in the MET-S trial (but not in MET-E), even after controlling for severity of substance use at baseline. In MET-S, those who indicated that they were "unsure" that they would achieve abstinence during treatment submitted a greater percentage of drug-positive urine toxicology screens during the treatment period than those who were 'sure' they would achieve abstinence (F = 18.83, p < .001). Patients' outcome expectations regarding the likelihood of abstinence may be an important predictor of drug use treatment outcomes among Spanish-speakers, but not necessarily for English-speakers. Individual differences and cultural factors may play a role in the association between outcome expectations and treatment outcomes. © American Academy of Addiction Psychiatry.

Outcome Expectations and Associated Treatment Outcomes in Motivational Enhancement Therapy Delivered in English and Spanish

PubMed Central

Serafini, Kelly; Decker, Suzanne; Kiluk, Brian D.; Añez, Luis; Paris, Manuel; Frankforter, Tami; Carroll, Kathleen M.

2016-01-01

Background and Objectives The relationship between patients’ baseline expectations regarding treatment outcome and actual outcomes has not been widely studied within the field of substance use disorders. We hypothesized that outcome expectations would be unrelated to outcomes in a study investigating Motivational Enhancement Therapy delivered in English (MET-E) consistent with our earlier work, and conducted exploratory analyses in a separate study that investigated the same treatment delivered in Spanish (MET-S). Methods These secondary analyses compared patient outcome expectations and substance use treatment outcomes in two large, multisite randomized controlled clinical trials that evaluated three sessions of MET-E or MET-S. The MET-E sample included 461 participants and the MET-S sample included 405 participants. Outcome expectations were measured by a single item regarding expectations about abstinence prior to initiating treatment. Results Outcome expectations were strongly associated with most substance use outcomes in the MET-S trial (but not in MET-E), even after controlling for severity of substance use at baseline. In MET-S, those who indicated that they were ‘unsure’ that they would achieve abstinence during treatment submitted a greater percentage of drug-positive urine toxicology screens during the treatment period than those who were ‘sure’ they would achieve abstinence (F = 18.83, p <.001). Discussion and Conclusions Patients’ outcome expectations regarding the likelihood of abstinence may be an important predictor of drug use treatment outcomes among Spanish-speakers, but not necessarily for English-speakers. Scientific Significance Individual differences and cultural factors may play a role in the association between outcome expectations and treatment outcomes. PMID:26541501

Collagenase-3 (MMP-13) and its activators in rheumatoid arthritis: localization in the pannus-hard tissue junction and inhibition by alendronate.

PubMed

Konttinen, Y T; Salo, T; Hanemaaijer, R; Valleala, H; Sorsa, T; Sutinen, M; Ceponis, A; Xu, J W; Santavirta, S; Teronen, O; López-Otín, C

1999-08-01

The hypothesis of the present work was that the pannus tissue overlying the articular hard tissues has an aggressive phenotype and contains the newly discovered collagenase-3 and its endogenous inducers and activators. We therefore analyzed the eventual presence of collagenase-3 and its regulation at the pannus-cartilage junction. Collagenase-3 mRNA (in situ hybridization) and enzyme protein (ABC and immunofluorescence staining) were found in the pannocytes in the pannus-hard tissue junction. Inflammatory round cells associated with the critical interface contained TNF-alpha and IL-1beta. These cytokines induced collagenase-3 secretion in cultured rheumatoid synovial fibroblasts. Procollagenase-3 activators, stromelysin-1, 72 kDa type IV collagenase/gelatinase and membrane-type 1-MMP, were also found in the pannus-hard tissue junction. Active collagenase-3 was inhibited with alendronate (IC50 = 500-750 microM). Collagenase-3, due to its substrate profile and local synthesis in a milieu favoring its activation, might play a major role in the degradation of cartilage type II and bone type I collagens. Alendronate, at concentrations attainable in vivo, is able to inhibit collagenase-3. This might offer an option to control collagenase-3-mediated tissue destruction in rheumatoid arthritis.

Treatment outcomes of temporal bone osteoradionecrosis.

PubMed

Kammeijer, Quinten; van Spronsen, Erik; Mirck, Piet G B; Dreschler, Wouter A

2015-04-01

To investigate the clinical relevance of the classification systems used for temporal bone osteoradionecrosis (ORN) and to define a treatment protocol for temporal bone ORN. Retrospective case series. Amsterdam, department of otorhinolaryngology and head and neck surgery. Classification of temporal bone ORN was performed through use of clinical data and radiologic imaging. Outcomes of conservative and surgical treatment were investigated and compared for different grades of ORN. Of the 49 ears included in this study, 35 were primarily treated conservatively. At start of conservative treatment, 23 were classified as a localized and 8 as a diffuse form of ORN; 4 could not be classified. There was a significant difference in clinical outcome between the localized and diffuse forms of ORN (χ(2) = 5.862, P = .015), and mastoid air cell destruction on preoperative computed tomography scan was found to be a significant predictor for a negative outcome of conservative treatment (χ(2) = 4.34, P = .037). Fourteen ears with diffuse ORN were primarily treated surgically, and 11 were secondarily treated surgically following a period of conservative treatment. Twenty-two patients were treated with subtotal petrosectomy, of which 20 were cured. Three patients were treated with canal wall down mastoidectomy, and 2 had recurrence of disease. Ramsden's classification system is clinically relevant in predicting conservative treatment outcomes. Mastoid air cell destruction on computed tomography differentiates between the localized and diffuse forms of ORN. Given our results and experience with treating temporal bone ORN, we propose a treatment protocol. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

Hazelden's model of treatment and its outcome.

PubMed

Stinchfield, R; Owen, P

1998-01-01

Although the Minnesota Model of treatment for alcohol and drug addiction is a common treatment approach, there are few published reports of its effectiveness. This study describes the Minnesota Model treatment approach as practiced at Hazelden, a private residential alcohol and drug abuse treatment center located in Center City, Minnesota (a founding program of the Minnesota Model) and presents recent outcome results from this program. This study includes 1,083 male and female clients admitted to Hazelden for treatment of a psychoactive substance-use disorder between 1989 and 1991. The outcome study is a one group pretest/posttest design. Data collection occurred at admission to treatment and at 1-month, 6-month, and 12-month posttreatment. At 1-year follow-up, 53% reported that they remained abstinent during the year following treatment and an additional 35% had reduced their alcohol and drug use. These results are similar to those reported by other private treatment programs. The Minnesota Model has consistently yielded satisfactory outcome results, and future research needs to focus on the therapeutic process of this common treatment approach.

Prediction of antiepileptic drug treatment outcomes using machine learning.

PubMed

Colic, Sinisa; Wither, Robert G; Lang, Min; Zhang, Liang; Eubanks, James H; Bardakjian, Berj L

2017-02-01

Antiepileptic drug (AED) treatments produce inconsistent outcomes, often necessitating patients to go through several drug trials until a successful treatment can be found. This study proposes the use of machine learning techniques to predict epilepsy treatment outcomes of commonly used AEDs. Machine learning algorithms were trained and evaluated using features obtained from intracranial electroencephalogram (iEEG) recordings of the epileptiform discharges observed in Mecp2-deficient mouse model of the Rett Syndrome. Previous work have linked the presence of cross-frequency coupling (I CFC ) of the delta (2-5 Hz) rhythm with the fast ripple (400-600 Hz) rhythm in epileptiform discharges. Using the I CFC to label post-treatment outcomes we compared support vector machines (SVMs) and random forest (RF) machine learning classifiers for providing likelihood scores of successful treatment outcomes. (a) There was heterogeneity in AED treatment outcomes, (b) machine learning techniques could be used to rank the efficacy of AEDs by estimating likelihood scores for successful treatment outcome, (c) I CFC features yielded the most effective a priori identification of appropriate AED treatment, and (d) both classifiers performed comparably. Machine learning approaches yielded predictions of successful drug treatment outcomes which in turn could reduce the burdens of drug trials and lead to substantial improvements in patient quality of life.

Effects of adding alendronate to ongoing hormone therapy on bone mineral density in postmenopausal Korean women: a randomized, double-blind, placebo-controlled clinical trial.

PubMed

Min, Yong-Ki; Lee, Dong-Yun; Choi, Suk-Joo; Kim, Joo Han; Choi, DooSeok; Yoon, Byung-Koo

2013-07-01

This study was conducted to evaluate the effects of adding the bisphosphonate alendronate (ALEN) to ongoing hormone therapy (HT) on bone mineral density (BMD) in postmenopausal Korean women. This randomized, double-blind, placebo-controlled clinical trial at a university hospital included a total of 139 postmenopausal women who had low BMD after HT lasting at least 1 year. Women received either ALEN (10 mg/d) or placebo in combination with HT for 1 year. Changes in BMD and biochemical markers of bone turnover were evaluated. Lumbar spine and total hip BMDs increased significantly in both treatment groups after 1 year. The addition of ALEN, when compared with HT alone, did not produce a significant change in BMD at the lumbar spine (3.7% vs 4.3%) and total hip (2.2% vs 3.2%) after adjusting for controllable variables. Serum osteocalcin showed a similar change, but urinary deoxypyridinoline response differed between treatment groups. Compared with HT alone, the addition of ALEN to ongoing HT for 1 year does not make a difference in BMD among postmenopausal Korean women with low BMD.

Estimating scaled treatment effects with multiple outcomes.

PubMed

Kennedy, Edward H; Kangovi, Shreya; Mitra, Nandita

2017-01-01

In classical study designs, the aim is often to learn about the effects of a treatment or intervention on a single outcome; in many modern studies, however, data on multiple outcomes are collected and it is of interest to explore effects on multiple outcomes simultaneously. Such designs can be particularly useful in patient-centered research, where different outcomes might be more or less important to different patients. In this paper, we propose scaled effect measures (via potential outcomes) that translate effects on multiple outcomes to a common scale, using mean-variance and median-interquartile range based standardizations. We present efficient, nonparametric, doubly robust methods for estimating these scaled effects (and weighted average summary measures), and for testing the null hypothesis that treatment affects all outcomes equally. We also discuss methods for exploring how treatment effects depend on covariates (i.e., effect modification). In addition to describing efficiency theory for our estimands and the asymptotic behavior of our estimators, we illustrate the methods in a simulation study and a data analysis. Importantly, and in contrast to much of the literature concerning effects on multiple outcomes, our methods are nonparametric and can be used not only in randomized trials to yield increased efficiency, but also in observational studies with high-dimensional covariates to reduce confounding bias.

Prediction of antiepileptic drug treatment outcomes using machine learning

NASA Astrophysics Data System (ADS)

Colic, Sinisa; Wither, Robert G.; Lang, Min; Zhang, Liang; Eubanks, James H.; Bardakjian, Berj L.

2017-02-01

Objective. Antiepileptic drug (AED) treatments produce inconsistent outcomes, often necessitating patients to go through several drug trials until a successful treatment can be found. This study proposes the use of machine learning techniques to predict epilepsy treatment outcomes of commonly used AEDs. Approach. Machine learning algorithms were trained and evaluated using features obtained from intracranial electroencephalogram (iEEG) recordings of the epileptiform discharges observed in Mecp2-deficient mouse model of the Rett Syndrome. Previous work have linked the presence of cross-frequency coupling (I CFC) of the delta (2-5 Hz) rhythm with the fast ripple (400-600 Hz) rhythm in epileptiform discharges. Using the I CFC to label post-treatment outcomes we compared support vector machines (SVMs) and random forest (RF) machine learning classifiers for providing likelihood scores of successful treatment outcomes. Main results. (a) There was heterogeneity in AED treatment outcomes, (b) machine learning techniques could be used to rank the efficacy of AEDs by estimating likelihood scores for successful treatment outcome, (c) I CFC features yielded the most effective a priori identification of appropriate AED treatment, and (d) both classifiers performed comparably. Significance. Machine learning approaches yielded predictions of successful drug treatment outcomes which in turn could reduce the burdens of drug trials and lead to substantial improvements in patient quality of life.

Treatment outcomes of drug-resistant tuberculosis patients in Kenya.

PubMed

Mibei, D J; Kiarie, J W; Wairia, A; Kamene, M; Okumu, M E

2016-11-01

Successful treatment of drug-resistant tuberculosis (DR-TB) is crucial in preventing disease transmission and reducing related morbidity and mortality. A standardised DR-TB treatment regimen is used in Kenya. Although patients on treatment are monitored, no evaluation of factors affecting treatment outcomes has yet been performed. To analyse treatment outcomes of DR-TB patients in Kenya and factors associated with successful outcome. Retrospective analysis of secondary data from Kenya's National Tuberculosis, Leprosy and Lung disease programme. DR-TB data from the national database for January to December 2012 were reviewed. Of 205 DR-TB patients included in the analysis, 169 (82.4%) had a successful treatment outcome, 18 (9%) died and 18 (9%) were lost to follow-up. Only sex (P = 0.006) and human immunodeficiency virus (HIV) status (P = 0.008) were predictors of successful treatment. Females were more likely to attain treatment success (OR 3.86, 95%CI 1.47-10.12), and HIV-negative status increased the likelihood of successful treatment (OR 3.53, 95%CI 1.4-8.9). Treatment success rates were higher than World Health Organization targets. Targeted policies for HIV-positive patients and males will improve treatment outcomes in these groups.

Predictors of anger treatment outcomes.

PubMed

Mackintosh, Margaret-Anne; Morland, Leslie A; Kloezeman, Karen; Greene, Carolyn J; Rosen, Craig S; Elhai, Jon D; Frueh, B Christopher

2014-10-01

This study investigated predictors of therapeutic outcomes for veterans who received treatment for dysregulated anger. Data are from a randomized controlled trial investigating the effectiveness of video teleconferencing compared to in-person delivery of anger management therapy (AMT) among 125 military veterans. Multilevel modeling was used to assess 2 types of predictors (demographic characteristics and mental health factors) of changes in anger symptoms after treatment. Results showed that while veterans benefited similarly from treatment across modalities, veterans who received two or more additional mental health services and who had longer commutes to care showed the greatest improvement on a composite measure of self-reported anger symptoms. Results highlight that veterans with a range of psychosocial and mental health characteristics benefited from AMT, while those receiving the most additional concurrent mental health services had better outcomes. © 2014 Wiley Periodicals, Inc.

Management and treatment outcomes of patients enrolled in MDR-TB treatment in Viet Nam.

PubMed

Phuong, N T M; Nhung, N V; Hoa, N B; Thuy, H T; Takarinda, K C; Tayler-Smith, K; Harries, A D

2016-03-21

The programmatic management of drug-resistant tuberculosis (TB) in Viet Nam has been rapidly scaled up since 2009. To document the annual numbers of patients enrolled for multidrug-resistant tuberculosis (MDR-TB) treatment during 2010-2014 and to determine characteristics and treatment outcomes of patients initiating treatment during 2010-2012. A retrospective cohort study using national reports and data from the national electronic data system for drug-resistant TB. The number of patients enrolled annually for MDR-TB treatment increased from 97 in 2010 to 1522 in 2014. The majority of patients were middle-aged men who had pulmonary disease and had failed a retreatment regimen; 77% had received ⩾2 courses of TB treatment. Favourable outcomes (cured and treatment completed) were attained in 73% of patients. Unfavourable outcomes included loss to follow-up (12.5%), death (8%) and failure (6.3%). Having had ⩾2 previous treatment courses and being human immunodeficiency virus-positive were associated with unfavourable outcomes. Increasing numbers of patients are being treated for MDR-TB each year with good treatment outcomes under national programme management in Viet Nam. However, there is a need to increase case detection-currently at 30% of the estimated 5100 MDR-TB cases per year, reduce adverse outcomes and improve monitoring and evaluation.

Effect of depression treatment on chronic pain outcomes.

PubMed

Teh, Carrie Farmer; Zaslavsky, Alan M; Reynolds, Charles F; Cleary, Paul D

2010-01-01

To examine the effect of depression treatment on medical and social outcomes for individuals with chronic pain and depression. People with chronic pain and depression have worse health outcomes than those with chronic pain alone. Little is known about the effectiveness of depression treatment for this population. Propensity score-weighted analyses, using both waves (1997-1998 and 2000-2001) of the National Survey of Alcohol, Drug, and Mental Health Problems, were used to examine the effect of a) any depression treatment and b) minimally adequate depression treatment on persistence of depression symptoms, depression severity, pain severity, overall health, mental health status, physical health status, social functioning, employment status, and number of workdays missed. Analyses were limited to those who met Composite International Diagnostic Interview Short-Form criteria for major depressive disorder, reported having at least one chronic pain condition, and completed both interviews (n = 553). Receiving any depression treatment was associated with higher scores on the mental component summary of the Medical Outcomes Study Short Form-12, indicating better mental health (difference = 2.65 points, p = .002) and less interference of pain on work (odds ratio = 0.57, p = .02). Among those receiving treatment, minimal adequacy of treatment was not significantly associated with better outcomes. Depression treatment improves mental health and reduces the effects of pain on work among those with chronic pain and depression. Understanding the effect of depression treatment on outcomes for this population is important for employers, healthcare providers treating this population, and policymakers working in this decade of pain control and research to improve care for chronic pain sufferers.

Preparation and Biological Study of (68)Ga-DOTA-alendronate.

PubMed

Fakhari, Ashraf; Jalilian, Amir R; Johari-Daha, Fariba; Shafiee-Ardestani, Mehdi; Khalaj, Ali

2016-01-01

In line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, DOTA-conjugated alendronate (DOTA-ALN) was synthesized and evaluated after labeling with gallium-68 ((68)Ga). DOTA-ALN was synthesized and characterized, followed by (68)Ga-DOTA-ALN preparation, using DOTA-ALN and (68)GaCl3 (pH: 4-5) at 92-95° C for 10 min. Stability tests, hydroxyapatite assay, partition coefficient calculation, biodistribution studies, and imaging were performed on the developed agent in normal rats. The complex was prepared with high radiochemical purity (>99% as depicted by radio thin-layer chromatography; specific activity: 310-320 GBq/mmol) after solid phase purification and was stabilized for up to 90 min with a log P value of -2.91. Maximum ligand binding (65%) was observed in the presence of 50 mg of hydroxyapatite; a major portion of the activity was excreted through the kidneys. With the exception of excretory organs, gastrointestinal tract organs, including the liver, intestine, and colon, showed significant uptake; however, the bone uptake was low (<1%) at 30 min after the injection. The data were also confirmed by sequential imaging at 30-90 min following the intravenous injection. The high solubility and anionic properties of the complex led to major renal excretion and low hydroxyapatite uptake; therefore, the complex failed to demonstrate bone imaging behaviors.

Personality disorder and treatment outcome in alcohol use disorder.

PubMed

Newton-Howes, Giles; Foulds, James

2018-01-01

As personality disorder impacts the outcome of most major mental disorders, it would be consistent for it to impact negatively on the outcome of alcohol use disorders (AUDs). This update is to provide an up-to-date overview of the recent literature examining the impact of personality disorder and personality traits on the treatment outcome of AUDs. Comorbidity between personality disorder and AUD is significant and approaches 50%. Patients with AUD and comorbid personality disorder are substantially less likely to remain in treatment, drink more per drinking day and drink more frequently. If retained in treatment, comorbidity does not, however, lead to poorer outcomes. Relapse to drinking is more common in patient with high novelty seeking and lower reward dependence and persistence. Reporting from most studies is of moderate-to-poor quality and a single high-quality study may alter these findings. Landmark alcohol studies are notably quiet on the impact of personality on AUD treatment outcome. Both personality disorder and higher novelty seeking impact negatively on the treatment outcome of AUD. As personality disorder is common in this group, clinicians engaged in AUD treatment should screen for personality disturbance, either disorder or high novelty seeking.

Management and treatment outcomes of patients enrolled in MDR-TB treatment in Viet Nam

PubMed Central

Nhung, N. V.; Hoa, N. B.; Thuy, H. T.; Takarinda, K. C.; Tayler-Smith, K.; Harries, A. D.

2016-01-01

Setting: The programmatic management of drug-resistant tuberculosis (TB) in Viet Nam has been rapidly scaled up since 2009. Objectives: To document the annual numbers of patients enrolled for multidrug-resistant tuberculosis (MDR-TB) treatment during 2010–2014 and to determine characteristics and treatment outcomes of patients initiating treatment during 2010–2012. Design: A retrospective cohort study using national reports and data from the national electronic data system for drug-resistant TB. Results: The number of patients enrolled annually for MDR-TB treatment increased from 97 in 2010 to 1522 in 2014. The majority of patients were middle-aged men who had pulmonary disease and had failed a retreatment regimen; 77% had received ⩾2 courses of TB treatment. Favourable outcomes (cured and treatment completed) were attained in 73% of patients. Unfavourable outcomes included loss to follow-up (12.5%), death (8%) and failure (6.3%). Having had ⩾2 previous treatment courses and being human immunodeficiency virus-positive were associated with unfavourable outcomes. Conclusion: Increasing numbers of patients are being treated for MDR-TB each year with good treatment outcomes under national programme management in Viet Nam. However, there is a need to increase case detection—currently at 30% of the estimated 5100 MDR-TB cases per year, reduce adverse outcomes and improve monitoring and evaluation. PMID:27051608

Involuntary admission may support treatment outcome and motivation in patients receiving assertive community treatment.

PubMed

Kortrijk, Hans Erik; Staring, A B P; van Baars, A W B; Mulder, C L

2010-02-01

Patients with severe mental illness who are treated in assertive community treatment (ACT) teams are sometimes involuntarily admitted when they are dangerous to themselves or others, and are not motivated for treatment. However, the consequences of involuntary admission in terms of psychosocial outcome and treatment motivation are largely unknown. We hypothesized that involuntary admission would improve psychosocial outcome and not adversely affect their treatment motivation. In the context of routine 6-monthly outcome monitoring in the period January 2003-March 2008, we used the Health of the Nation Outcome Scales (HoNOS) and a motivation-for-treatment scale to assess 260 severely mentally ill patients at risk for involuntary admission. Mixed models with repeated measures were used for data analyses. During the observation period, 77 patients (30%) were involuntarily admitted. Relative to patients who were not involuntarily admitted, these patients improved significantly in HoNOS total scores (F = 17,815, df = 1, p < 0.001) and in motivation for treatment (F = 28.139, df = 1, p < 0.001). Patients who were not involuntarily admitted had better HoNOS and motivation scores at baseline, but did not improve. Involuntary admission in the context of ACT was associated with improvements in psychosocial outcome and motivation for treatment. There are no indications that involuntary admission leads to deterioration in psychosocial outcome or worsening of motivation for treatment.

Combination therapy with ONO-KK1-300-01, a cathepsin K inhibitor, and parathyroid hormone results in additive beneficial effect on bone mineral density in ovariectomized rats.

PubMed

Ochi, Yasuo; Yamada, Hiroyuki; Mori, Hiroshi; Kawada, Naoki; Tanaka, Makoto; Imagawa, Akira; Ohmoto, Kazuyuki; Kawabata, Kazuhito

2016-01-01

This study examined the effects of a novel cathepsin K inhibitor, ONO-KK1-300-01 (KK1-300), used concurrently with parathyroid hormone (PTH) in ovariectomized (OVX) rats. KK1-300 (3 mg/kg, twice daily), alendronate (1 mg/kg, once daily) or vehicle were orally administered to OVX rats for 56 days, starting the day after ovariectomy, followed by combination treatment with or without PTH (3 μg/kg, subcutaneously three times a week) for another 28 days. OVX control animals exhibited a significant increase in both bone resorption (urinary deoxypyridinoline; DPD) and formation markers (serum osteocalcin) as well as microstructural changes associated with decreased bone mineral density (BMD). Combination treatment with KK1-300 and PTH significantly decreased urinary DPD and increased serum osteocalcin, indicating a sustained beneficial effect compared to the effect of each mono-therapy. On the other hand, combination therapy with alendronate and PTH weakened the PTH-induced increase in osteocalcin. In proximal tibia, combination treatment with KK1-300 and PTH increased BMD to a level significantly higher than that achieved following single treatment with KK1-300 or PTH alone. On the other hand, combination treatment with alendronate and PTH failed to produce any significant additive effect on BMD following single treatment with alendronate or PTH alone. Microstructural analysis revealed that the PTH-induced increase in bone formation (MS/BS and BFR/BS) was fully maintained following combination treatment with KK1-300 and PTH, but not following combination treatment with alendronate and PTH. These findings indicate that KK1-300, unlike alendronate, has an additive effect on the preventive action of PTH on bone loss in OVX rats.

Barriers to Implementing Treatment Integrity Procedures: Survey of Treatment Outcome Researchers

ERIC Educational Resources Information Center

Perepletchikova, Francheska; Hilt, Lori M.; Chereji, Elizabeth; Kazdin, Alan E.

2009-01-01

Treatment integrity refers to implementing interventions as intended. Treatment integrity is critically important for experimental validity and for drawing valid inferences regarding the relationship between treatment and outcome. Yet, it is rarely adequately addressed in psychotherapy research. The authors examined barriers to treatment integrity…

General practitioners' treatment orientations towards low back pain: influence on treatment behaviour and patient outcome.

PubMed

Sieben, Judith M; Vlaeyen, Johan W S; Portegijs, Piet J M; Warmenhoven, Franca C; Sint, Ageeth G; Dautzenberg, Nadine; Romeijnders, Arnold; Arntz, Arnoud; Knottnerus, J André

2009-04-01

In low back pain (LBP) treatment and research attention has shifted from a biomedical towards a biopsychosocial approach. Patients' LBP beliefs and attitudes were found to predict long-term outcome, and recently it has been suggested that the health care providers' ideas about LBP are also important predictors of treatment behaviour and outcome. In the present study we examined whether (1) differences in General Practitioners' (GP) LBP treatment orientation are associated with differences in actual treatment behaviour and (2) whether treatment orientation is related to LBP outcome in patients. Two hundred twenty two patients consulting their GP with a new episode of LBP were recruited and completed questionnaires on (among others) LBP outcome (graded chronic pain scale) at baseline, during 12 months of follow-up and at the end of the study. Data on treatment were collected from the GPs. The GPs also completed a set of questionnaires on LBP treatment orientation. Associations between measures of treatment orientation, treatment recommendations, treatment behaviour and LBP outcome were analysed. A biomedical treatment orientation was found to be associated with more concern about tissue damage and the effect of physical activity on pain and recovery in vignettes. No associations were found between treatment orientation measures, actual treatment behaviour and LBP outcome. Associations were not found as expected. Still these findings are relevant and may feed a clinically important debate on widely accepted assumptions about the role and influence of health care providers in changing patients' pain behaviours.

Post-treatment Stage of Change Predicts 12-month Outcome of Treatment for Alcohol Problems

PubMed Central

Heather, Nick; McCambridge, Jim

2013-01-01

Aims: To evaluate relationships between clients' self-reported ‘stage of change’ and outcomes after treatment for alcohol problems. Methods: Using data from the ‘United Kingdom Alcohol Treatment Trial’, clients who had received at least one session of treatment and who had complete data (n = 392) entered the analysis. Two continuous measures of drinking behaviour (% days abstinent (PDA) and drinks per drinking day (DDD)) and categorical outcomes at the 12-month follow-up were compared between clients in Pre-action and Action stages of change at either pre- or post-treatment assessment. Multiple and logistic regression analyses examined the relationships between stage of change and treatment outcomes, evaluating the strength of these relationships by controlling for likely confounders. Results: Pre-treatment stage of change did not predict outcome but post-treatment stage of change predicted PDA and DDD at the 12-month follow-up. In unadjusted and adjusted analyses, clients in Action at post-treatment were two to three times more likely to show a favourable categorical outcome, variously defined, than those in Pre-action. There were no differences between clients who had received Motivational Enhancement Therapy and those who had received Social Behaviour and Network Therapy in proportions maintaining or moving towards Action from before to after treatment. Conclusions: These findings confirm previous reports that motivational variables predict outcome of treatment but add that such a relationship is seen for post-treatment stage of change. For therapists, it would seem important to monitor the client's stage of change—which in good clinical practice often occurs in informal ways—and have strategies to deal with low motivation to change whenever it occurs throughout treatment. The findings are also consistent with a ‘common factors’ perspective on effective treatment for alcohol problems. PMID:23408241

Surrogate markers for time-varying treatments and outcomes

PubMed Central

Hsu, Jesse Y; Kennedy, Edward H; Roy, Jason A; Stephens-Shields, Alisa J; Small, Dylan S; Joffe, Marshall M

2015-01-01

Background A surrogate marker is a variable commonly used in clinical trials to guide treatment decisions when the outcome of ultimate interest is not available. A good surrogate marker is one where the treatment effect on the surrogate is a strong predictor of the effect of treatment on the outcome. We review the situation when there is one treatment delivered at baseline, one surrogate measured at one later time point and one ultimate outcome of interest, and discuss new issues arising when variables are time-varying. Methods Most of the literature on surrogate markers has only considered simple settings with one treatment, one surrogate, and one outcome of interest at a fixed time point. However, more complicated time-varying settings are common in practice. In this paper, we describe the unique challenges in two settings, time-varying treatments and time-varying surrogates, while relating the ideas back to the causal-effects and causal-association paradigms. Conclusions In addition to discussing and extending popular notions of surrogacy to time-varying settings, we give examples illustrating that one can be misled by not taking into account time-varying information about the surrogate or treatment. We hope this paper has provided some motivation for future work on estimation and inference in such settings. PMID:25948621

Effect of alendronate on post-traumatic osteoarthritis induced by anterior cruciate ligament rupture in mice.

PubMed

Khorasani, Mohammad S; Diko, Sindi; Hsia, Allison W; Anderson, Matthew J; Genetos, Damian C; Haudenschild, Dominik R; Christiansen, Blaine A

2015-02-16

Previous studies in animal models of osteoarthritis suggest that alendronate (ALN) has antiresorptive and chondroprotective effects, and can reduce osteophyte formation. However, these studies used non-physiologic injury methods, and did not investigate early time points during which bone is rapidly remodeled prior to cartilage degeneration. The current study utilized a non-invasive model of knee injury in mice to investigate the effect of ALN treatment on subchondral bone changes, articular cartilage degeneration, and osteophyte formation following injury. Non-invasive knee injury via tibial compression overload or sham injury was performed on a total of 90 mice. Mice were treated with twice weekly subcutaneous injections of low-dose ALN (40 μg/kg/dose), high-dose ALN (1,000 μg/kg/dose), or vehicle, starting immediately after injury until sacrifice at 7, 14 or 56 days. Trabecular bone of the femoral epiphysis, subchondral cortical bone, and osteophyte volume were quantified using micro-computed tomography (μCT). Whole-joint histology was performed at all time points to analyze articular cartilage and joint degeneration. Blood was collected at sacrifice, and serum was analyzed for biomarkers of bone formation and resorption. μCT analysis revealed significant loss of trabecular bone from the femoral epiphysis 7 and 14 days post-injury, which was effectively prevented by high-dose ALN treatment. High-dose ALN treatment was also able to reduce subchondral bone thickening 56 days post-injury, and was able to partially preserve articular cartilage 14 days post-injury. However, ALN treatment was not able to reduce osteophyte formation at 56 days post-injury, nor was it able to prevent articular cartilage and joint degeneration at this time point. Analysis of serum biomarkers revealed an increase in bone resorption at 7 and 14 days post-injury, with no change in bone formation at any time points. High-dose ALN treatment was able to prevent early trabecular

Group Treatment of Depression: Individual Predictors of Outcome.

ERIC Educational Resources Information Center

Hoberman, Harry M.; And Others

1988-01-01

Identified patient characteristics predictive of individual outcome in psychoeducational group treatment for unipolar depression, a coping with depression course. After treatment, 85 percent of the subjects no longer met diagnostic criteria for depressive disorders. Found the most robust predictors of outcome to be pretreatment depression level,…

The association between patient-therapist MATRIX congruence and treatment outcome.

PubMed

Mendlovic, Shlomo; Saad, Amit; Roll, Uri; Ben Yehuda, Ariel; Tuval-Mashiah, Rivka; Atzil-Slonim, Dana

2018-03-14

The present study aimed to examine the association between patient-therapist micro-level congruence/incongruence ratio and psychotherapeutic outcome. Nine good- and nine poor-outcome psychodynamic treatments (segregated by comparing pre- and post-treatment BDI-II) were analyzed (N = 18) moment by moment using the MATRIX (total number of MATRIX codes analyzed = 11,125). MATRIX congruence was defined as similar adjacent MATRIX codes. the congruence/incongruence ratio tended to increase as the treatment progressed only in good-outcome treatments. Progression of MATRIX codes' congruence/incongruence ratio is associated with good outcome of psychotherapy.

Treatment outcomes of using inhalation sedation for comprehensive dental care.

PubMed

Madouh, M; BaniHani, A; Tahmassebi, J F

2018-02-01

To assess the outcomes of dental treatment under inhalation sedation within a UK specialist hospital setting. This was a retrospective cohort study of the case notes of patients under 17 years of age who received dental treatment using inhalation sedation at a UK specialist setting during the period 2006-2011. Treatment outcomes were categorised into five groups: (1) treatment completed as planned, (2) modified treatment completed, (3) treatment abandoned in sedation unit and patient referred for treatment under general analgesia (GA), (4) treatment abandoned in sedation unit and patient referred for treatment under local analgesia (LA), (5) child failed to return to complete treatment. In total, the case notes of 453 patients were evaluated. The mean age of the patients was 10.3 ± 2.9 years. Treatment was completed successfully in 63.6% of the cases, 15.9% were referred for treatment under GA, 11.2% failed to return to complete the treatment, 7.1% received modified treatment completed, and only 2.2% were referred for treatment under LA. Treatment outcomes were significantly associated with patient`s age (p = 0.002). The treatment outcome "treatment abandoned and child referred to be treated under GA" had significantly lower mean patient ages than the other outcomes. The majority of children referred for inhalation sedation, completed their course of treatment. A significantly higher proportion of those in the younger age group required GA to complete their treatment.

Paediatric forearm fractures: functional outcome of conservative treatment.

PubMed

Tarmuzi, Nazari Ahmad; Abdullah, Shalimar; Osman, Zulkiflee; Das, Srijit

2009-01-01

Forearm fractures are common in the paediatric age group. Closed reduction and casting are the primary means of treatment in over 90% of these fractures. Resultant deformities are usually a product of indirect trauma involving angular loading combined with rotational deformity and fragment displacement. Retrospectively, 48 patients aged between 4 to 12 years with forearm fractures, were treated conservatively with closed reduction and a cast during a 2-year period. Functional outcomes were measured in terms of pronation and supination. All fractures united before the final visit. Most forearm bone fractures were complete fractures at the mid shaft. Eighty-six percent of the patients had excellent functional outcomes and none had poor outcomes. There were significantly reduced angles of deformities before and after treatment (p < 0.05). Radiographically, in the frontal plane, 57.1% of radius and 73.9% of ulnar fractures achieved perfect reduction (i.e. a degree of deformity of less than 5 degrees). However, in the lateral plane, there were fewer perfect reductions for the radius and ulna, at 14.6% and 54.3%, respectively. All except for one patient were satisfied with the outcomes. The level of fracture did not influence the outcomes. Conservative treatment is still an acceptable form of treatment especially for stable forearm fractures in children achieving excellent outcomes (Tab. 1, Fig. 7, Ref. 20).

The resistance of cortical bone tissue to failure under cyclic loading is reduced with alendronate.

PubMed

Bajaj, Devendra; Geissler, Joseph R; Allen, Matthew R; Burr, David B; Fritton, J C

2014-07-01

Bisphosphonates are the most prescribed preventative treatment for osteoporosis. However, their long-term use has recently been associated with atypical fractures of cortical bone in patients who present with low-energy induced breaks of unclear pathophysiology. The effects of bisphosphonates on the mechanical properties of cortical bone have been exclusively studied under simple, monotonic, quasi-static loading. This study examined the cyclic fatigue properties of bisphosphonate-treated cortical bone at a level in which tissue damage initiates and is accumulated prior to frank fracture in low-energy situations. Physiologically relevant, dynamic, 4-point bending applied to beams (1.5 mm × 0.5 mm × 10 mm) machined from dog rib (n=12/group) demonstrated mechanical failure and micro-architectural features that were dependent on drug dose (3 groups: 0, 0.2, 1.0mg/kg/day; alendronate [ALN] for 3 years) with cortical bone tissue elastic modulus (initial cycles of loading) reduced by 21% (p<0.001) and fatigue life (number of cycles to failure) reduced in a stress-life approach by greater than 3-fold with ALN1.0 (p<0.05). While not affecting the number of osteons, ALN treatment reduced other features associated with bone remodeling, such as the size of osteons (-14%; ALN1.0: 10.5±1.8, VEH: 12.2±1.6, ×10(3) μm2; p<0.01) and the density of osteocyte lacunae (-20%; ALN1.0: 11.4±3.3, VEH: 14.3±3.6, ×10(2) #/mm2; p<0.05). Furthermore, the osteocyte lacunar density was directly proportional to initial elastic modulus when the groups were pooled (R=0.54, p<0.01). These findings suggest that the structural components normally contributing to healthy cortical bone tissue are altered by high-dose ALN treatment and contribute to reduced mechanical properties under cyclic loading conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Relationships between Treatment Expectations and Treatment Outcomes among Outpatients with Substance Use Problems

ERIC Educational Resources Information Center

Raylu, Namrata; Kaur, Inderjit

2012-01-01

Currently, studies exploring the relationship between treatment expectations (TE) and outcome among individuals with substance use problems are significantly lacking. This is important as relapse and attrition rates among this group are greater than those with other psychological problems. Understanding how TE impact treatment outcomes among this…

Predictors of multidisciplinary treatment outcome in fibromyalgia:a systematic review.

PubMed

de Rooij, Aleid; Roorda, Leo D; Otten, René H J; van der Leeden, Marike; Dekker, Joost; Steultjens, Martijn P M

2013-03-01

To identify outcome predictors for multidisciplinary treatment in patients with chronic widespread pain (CWP) or fibromyalgia (FM). A systematic literature search in PubMed, PsycINFO, CINAHL, Cochrane Library, EMBASE and Pedro. Selection criteria included: age over 18; diagnosis CWP or FM; multidisciplinary treatment; longitudinal study design; original research report. Outcome domains: pain, physical functioning, emotional functioning, global treatment effect and 'others'. Methodological quality of the selected articles was assessed and a qualitative data synthesis was performed to identify the level of evidence. Fourteen studies (all with FM patients) fulfilled the selection criteria. Six were of high quality. Poorer outcome (pain, moderate evidence; physical functioning and quality of life, weak evidence) was predicted by depression. Similarly, poorer outcome was predicted by the disturbance and pain profile of the Minnesota Multiphasic Personality Inventory (MMPI), strong beliefs in fate and high disability (weak evidence). A better outcome was predicted by a worse baseline status, the dysfunctional and the adaptive copers profile of the Multidimensional Pain Inventory (MPI), and high levels of pain (weak evidence). Some predictors were related to specific multidisciplinary treatment (weak evidence). Inconclusive evidence was found for other demographic and clinical factors, cognitive and emotional factors, symptoms and physical functioning as predictors of outcome. It was found that a higher level of depression was a predictor of poor outcome in FM (moderate evidence). In addition, it was found that the baseline status, specific patient profiles, belief in fate, disability, and pain were predictors of the outcome of multidisciplinary treatment. Our results highlight the lack of high quality studies for evaluating predictors of the outcome of multidisciplinary treatment in FM. Further research on predictors of multidisciplinary treatment outcome is needed.

Preparation and Biological Study of 68Ga-DOTA-alendronate

PubMed Central

Fakhari, Ashraf; Jalilian, Amir R.; Johari-Daha, Fariba; Shafiee-Ardestani, Mehdi; Khalaj, Ali

2016-01-01

Objective(s): In line with previous research on the development of conjugated bisphosphonate ligands as new bone-avid agents, in this study, DOTA-conjugated alendronate (DOTA-ALN) was synthesized and evaluated after labeling with gallium-68 (68Ga). Methods: DOTA-ALN was synthesized and characterized, followed by 68Ga-DOTA-ALN preparation, using DOTA-ALN and 68GaCl3 (pH: 4-5) at 92-95° C for 10 min. Stability tests, hydroxyapatite assay, partition coefficient calculation, biodistribution studies, and imaging were performed on the developed agent in normal rats. Results: The complex was prepared with high radiochemical purity (>99% as depicted by radio thin-layer chromatography; specific activity: 310-320 GBq/mmol) after solid phase purification and was stabilized for up to 90 min with a log P value of -2.91. Maximum ligand binding (65%) was observed in the presence of 50 mg of hydroxyapatite; a major portion of the activity was excreted through the kidneys. With the exception of excretory organs, gastrointestinal tract organs, including the liver, intestine, and colon, showed significant uptake; however, the bone uptake was low (<1%) at 30 min after the injection. The data were also confirmed by sequential imaging at 30-90 min following the intravenous injection. Conclusion: The high solubility and anionic properties of the complex led to major renal excretion and low hydroxyapatite uptake; therefore, the complex failed to demonstrate bone imaging behaviors. PMID:27408898

Predictors of outcome in residential cognitive and interpersonal treatment for social phobia: do cognitive and social dysfunction moderate treatment outcome?

PubMed

Borge, Finn-Magnus; Hoffart, Asle; Sexton, Harold

2010-09-01

The predictors of residential cognitive (RCT) and residential interpersonal Treatment (RIPT) for social phobia were explored. (1) Sotsky et al. (1991) found differential effects of CT and IPT for depression, suggesting that the level of cognitive or social dysfunction predicted differential outcome. We examined whether an analogous effect could be demonstrated in 10 weeks of residential treatment of 80 social phobia subjects. (2) We also included expectations, age of onset, severity of illness, concurrent anxiety, mood, avoidant personality disorder, and body dysmorphic disorder as predictors in this exploratory study. Main outcome was the social phobia subscale of Social Phobia and Anxiety Inventory (SPAI SP). DSM-IV axis I and II interviews were completed. (1) Sotsky et al. (1991) findings were not reproduced. However, RIPT subjects with poor general functioning were less improved following treatment. Subjects with concurrent agoraphobia responded better with RCT than subjects without agoraphobia. (2) Age of onset and expectations were the most powerful predictors of post treatment outcome. Some patient characteristics appear to impact outcome with RIPT and RCT differentially. The findings are discussed. (c) 2010 Elsevier Ltd. All rights reserved.

Hispanic Subgroups, Acculturation, and Substance Abuse Treatment Outcomes

PubMed Central

Chartier, Karen G.; Carmody, Tom; Akhtar, Maleeha; Stebbins, Mary B.; Walters, Scott T.; Warden, Diane

2015-01-01

This study explored Hispanic subgroup differences in substance use treatment outcomes, and the relationship of acculturation characteristics to these outcomes. Data were from a multisite randomized clinical trial of motivational enhancement therapy versus treatment as usual in a sample of Spanish-speaking substance abusers. Participants were Cuban American (n=34), Mexican American (n=209), Puerto Rican (n=78), and other Hispanic American (n=54). Results suggested that Cuban Americans and individuals with more connection to Hispanic culture had lower treatment retention. Hispanics born in the U.S and those who spoke English at home had a lower percentage of days abstinent during weeks 5-16, although Puerto Ricans born in the U.S. and Cuban Americans living more years in the U.S. had a higher percentage of days abstinent in weeks 1-4 and 5-16, respectively. Results may inform future hypothesis-driven studies in larger Hispanic treatment seeking samples of the relationship between acculturation and treatment outcome. PMID:26362001

Vitamin D, osteoprotegerin/receptor activator of nuclear factor-kappaB ligand (OPG/RANKL) and inflammation with alendronate treatment in HIV-infected patients with reduced bone mineral density.

PubMed

Natsag, J; Kendall, M A; Sellmeyer, D E; McComsey, G A; Brown, T T

2016-03-01

The aim of the study was to determine the effect of alendronate (ALN) on inflammatory markers and osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL), and to explore the associations of baseline systemic inflammation and vitamin D status on the bone mineral density (BMD) response to ALN. Eighty-two HIV-positive patients with lumbar spine T-score ≤ -1.5 were randomized to ALN 70 mg weekly or placebo for 48 weeks; all received calcium carbonate 500 mg/vitamin D3 200 IU twice daily. Serum C-telopeptide (CTx) and BMD were assessed at baseline and week 48. Stored plasma samples in 70 subjects were assayed for levels of 25-hydroxyvitamin D (25(OH)D), OPG, RANKL, interleukin (IL)-6 and soluble receptors for tumour necrosis factor (TNF)-α 1 and 2 (sTNFR 1 and 2). ALN increased BMD more than placebo at both the lumbar spine (difference ALN - placebo 2.64%; P = 0.011) and the total hip (difference 2.27%; P = 0.016). No within- or between-arm differences in OPG, RANKL or inflammatory markers were observed over 48 weeks. High baseline CTx and sTNFR2 were associated with a more robust BMD response to ALN over 48 weeks at the lumbar spine [difference 5.66%; 95% confidence interval (CI) 3.50, 7.82; P < 0.0001] and total hip (difference 4.99%; 95% CI 2.40, 7.57; P = 0.0002), respectively. Baseline 25(OH)D < 32 ng/mL was associated with larger increases in total hip BMD over 48 weeks, independent of ALN treatment (P = 0.014). Among HIV-positive patients, higher baseline bone resorption and TNF-α activity were associated with an increased BMD response to ALN. The greater BMD response in those with lower vitamin D reinforces the importance of vitamin D supplementation with bisphosphonate treatment. © 2015 British HIV Association.

The Tennessee study: factors affecting treatment outcome and healing time following nonsurgical root canal treatment.

PubMed

Azim, A A; Griggs, J A; Huang, G T-J

2016-01-01

To determine factors that may influence treatment outcome and healing time following root canal treatment. Root filled and restored teeth by pre-doctoral students were included in this study. Teeth/roots were followed-up regularly, and treatment outcome was evaluated at every follow-up appointment (healed, healing, uncertain or unsatisfactory). Host (age, immune condition, pulp/periapical diagnosis, tooth/root type, location and anatomy) and treatment factors (master apical file size, apical extension, voids and density of root filling) were recorded from patient dental records. Univariate, bivariate and multivariate analyses were performed to determine the impact of the factors on treatment outcomes and healing times. A total of 422 roots from 291 teeth met the inclusion criteria with a mean follow-up period of 2 years. The preoperative pulp condition, procedural errors during treatment, apical extension and density of root fillings significantly affected the treatment outcome. The average time required for a periapical lesion to heal was 11.78 months. The healing time increased in patients with compromised healing, patients older than 40 years, roots with Weine type II root canal systems, root canal systems prepared to a master apical file size <35, and roots with overextended fillings (P < 0.1). Multiple host and treatment factors affected the healing time and outcome of root canal treatment. Follow-up protocols should consider these factors before concluding the treatment outcome: patient's age, immune condition, as well as roots with overextended fillings, root canal systems with smaller apical preparations (size <35) or roots with complex canal systems. Intervention may be recommended if the treatment quality was inadequate or if patients became symptomatic. © 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Alendronate (ALN) combined with Osteoprotegerin (OPG) significantly improves mechanical properties of long bone than the single use of ALN or OPG in the ovariectomized rats

PubMed Central

2011-01-01

Background Alendronate (ALN) is the most common form of bisphosphonates used for the treatment of osteoporosis. Osteoprotegerin (OPG) has also been shown to reduce osteoporotic changes in both humans and experimental animals after systemic administration. The aim of this current study was to test if the anti-resorption effects of ALN may be enhanced when used in combination with OPG. Objectives To investigate the effects of ALN, OPG or combined on bone mass and bone mechanical properties in ovariectomized (OVX) rats. Methods OVX rats were treated with ALN, OPG-Fc, or OPG-Fc and ALN. Biochemical markers, trabecular bone mass, biomechanics, histomorphometry and RANKL expression in the bone tissues were examined following the treatments. Results The treatment of ALN, OPG-Fc and ALN+OPG-Fc all prevented bone loss in the OVX-rats, there was no statistical difference among the three treatment groups in terms of vertebrae BMD, mineralizing surfaces, mineral apposition rate, BFR/BS. The ALN+OPG-Fc treatment group had significantly increased the mechanical strength of lumber vertebral bodies and femoral shafts when compared to the ALN and OPG-Fc treatment groups. The RANKL protein expression in the vertebral bones was significantly decreased in the ALN and ALN+OPG-Fc treatment groups, suggesting the combined use of OPG-Fc and ALN might have amplified inhibition of bone resorption through inhibiting RANKL-dependent osteoclastogenesis. Conclusion The combined use of OPG-Fc and ALN may be a new treatment strategy for reversing bone loss and restoring bone quality in osteoprotic disorders. PMID:21752290

Treatment agreement, adherence, and outcome in cognitive behavioral treatments for insomnia.

PubMed

Dong, Lu; Soehner, Adriane M; Bélanger, Lynda; Morin, Charles M; Harvey, Allison G

2018-03-01

Patient adherence has been identified as an important barrier to the implementation of evidence-based psychological treatments. In cognitive behavioral treatments (CBT) for insomnia, the current study examined (a) the validity of therapist ratings of patient agreement and adherence against an established behavioral measure of adherence, and (b) the relationship between treatment agreement, adherence, and outcome. Participants were 188 adults meeting DSM-IV-TR criteria for chronic insomnia who were randomized to receive behavior therapy, cognitive therapy, or CBT for insomnia. Treatment agreement/adherence was measured by (a) weekly therapist ratings of patient agreement and homework completion, and (b) adherence to behavioral strategies (ABS) derived from patient-reported sleep diary. Outcome measures were Insomnia Severity Index and insomnia remission (Insomnia Severity Index <8). Therapist ratings of patient agreement as well as homework completion were significantly associated with sleep diary-derived global ABS. Therapist-rated patient agreement and homework completion as well as global ABS predicted greater insomnia symptoms reduction from pretreatment to posttreatment. Patient agreement also predicted insomnia symptoms reduction from pretreatment to 6-month follow-up. Patient agreement, adherence, and ABS measures during treatment significantly predicted insomnia remission at posttreatment, and all but therapist rating of homework completion predicted remission at 6-month follow-up. Greater patient agreement and adherence (therapist ratings and ABS) during treatment predicted better treatment outcome. Therapist-rated treatment agreement and adherence correspond well with patient-reported sleep diary-derived adherence measure. These simple, deployable therapist-rated patient agreement and adherence can potentially be useful for treatments for other disorders. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Effect of Depression Treatment on Chronic Pain Outcomes

PubMed Central

Teh, Carrie Farmer; Zaslavsky, Alan; Reynolds, Charles F.; Cleary, Paul D.

2011-01-01

Objective People with chronic pain and depression have worse health outcomes than those with chronic pain alone. Little is known about the effectiveness of depression treatment for this population. We examined the effect of depression treatment on medical and social outcomes for individuals with chronic pain and depression Methods Propensity score weighted analyses using both waves (1997-1998 and 2000-2001) of the National Survey of Alcohol, Drug, and Mental Health Problems were used to examine the effect of (1) any depression treatment and (2) minimally adequate depression treatment on persistence of depression symptoms, depression severity, pain severity, overall health, mental health status, physical health status, social functioning, employment status, and number of work days missed. Analyses were limited to those who met CIDI-SF criteria for major depressive disorder, reported having at least one chronic pain condition, and completed both interviews (n=553). Results Receiving any depression treatment was associated with higher scores on the mental component summary of the MOS SF-12, indicating better mental health (difference = 2.65 points, p=0.002) and less interference of pain on work (OR=0.57, p=0.02). Among those receiving treatment, minimal adequacy of treatment was not significantly associated with better outcomes. Conclusions Depression treatment improves mental health and reduces the effects of pain on work among those with chronic pain and depression. Understanding the effect of depression treatment on outcomes for this population is important for employers, healthcare providers treating this population, and policymakers working in this Decade of Pain Control and Research to improve care for chronic pain sufferers. PMID:19875633

[Headache case that responded to alendronate treatment in Paget's disease].

PubMed

Bozkurt, Dilek; Hiz, Fazilet; Çinar, Meral; Can, Meltem

2012-01-01

Paget's disease of the bone is a chronic, focal skeletal disease characterized by bone pain and deformity, pathological fractures and neurological symptoms such as headache, hearing loss and tinnitus, etc. The frequency of the disease increases in later ages. Viral and genetical factors play a role in the etiology. The majority of cases are asymptomatic. It is often diagnosed with an incidental finding on radiography or with an unexpected high serum alkaline phosphatase level. Bone fractures or neurological complications can negatively affect the quality of life. Early diagnosis and treatment are thus very important. Bisphosphonates are the most frequently used medication in the treatment. We present a case who sought medical help because of headache and was diagnosed as Paget's disease. Neurological complications and the diagnosis and treatment of Paget's disease are reviewed in the literature.

Treatment outcome of patients with isoniazid mono-resistant tuberculosis.

PubMed

Chien, J-Y; Chen, Y-T; Wu, S-G; Lee, J-J; Wang, J-Y; Yu, C-J

2015-01-01

Isoniazid mono-resistance is the most common first-line drug resistance in tuberculosis (TB), but its treatment outcome remains unclear. From January 2004 to October 2011, 425 (5.1%) of 8414 patients with culture-confirmed pulmonary TB from four hospitals in Taiwan were identified as having isoniazid mono-resistant TB. Among them, 395 (92.9%) were included and followed up for 2 years after complete treatment. Although 328 (83.0%) patients were successfully treated, 67 (17.0%) had unfavourable outcomes, including death in 56 (14.2%) and treatment failure in 11 (2.8%). The treatment success rate was similar in patients with high-level and low-level isoniazid-resistant TB (82.2% versus 83.4%, p 0.785) and among those taking anti-TB treatment with and without isoniazid (83.1% versus 83.0%, p 1.000). Patients without rifampicin interruption had lower risk of unfavourable outcome (14.3% versus 37.0%, p <0.001), especially those with low-level isoniazid resistance (11.5% versus 56.5%, p <0.001). Supplementation with a new-generation fluoroquinolone improved treatment success (60.0% versus 12.5%, p 0.003). The presence of cavitary lesions was significantly associated with a higher relapse rate (4.1% versus 0.0%, p 0.006) and extended treatment of 7-9, 10-12 and >12 months had less relapse than 6-month treatment (3.2%, 0%, 3.7% and 25.0%, respectively, p 0.037). Multivariate Cox proportional hazards analysis revealed that co-morbidity with cancer (hazard ratio, 2.43) and rifampicin interruption (hazard ratio 1.91) were independent factors associated with unfavourable outcomes. Treatment throughout with rifampicin and extended treatment for cavitary disease are crucial for improving outcomes in patients with isoniazid mono-resistant TB. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Do treatment quality indicators predict cardiovascular outcomes in patients with diabetes?

PubMed

Sidorenkov, Grigory; Voorham, Jaco; de Zeeuw, Dick; Haaijer-Ruskamp, Flora M; Denig, Petra

2013-01-01

Landmark clinical trials have led to optimal treatment recommendations for patients with diabetes. Whether optimal treatment is actually delivered in practice is even more important than the efficacy of the drugs tested in trials. To this end, treatment quality indicators have been developed and tested against intermediate outcomes. No studies have tested whether these treatment quality indicators also predict hard patient outcomes. A cohort study was conducted using data collected from >10.000 diabetes patients in the Groningen Initiative to Analyze Type 2 Treatment (GIANTT) database and Dutch Hospital Data register. Included quality indicators measured glucose-, lipid-, blood pressure- and albuminuria-lowering treatment status and treatment intensification. Hard patient outcome was the composite of cardiovascular events and all-cause death. Associations were tested using Cox regression adjusting for confounding, reporting hazard ratios (HR) with 95% confidence intervals. Lipid and albuminuria treatment status, but not blood pressure lowering treatment status, were associated with the composite outcome (HR = 0.77, 0.67-0.88; HR = 0.75, 0.59-0.94). Glucose lowering treatment status was associated with the composite outcome only in patients with an elevated HbA1c level (HR = 0.72, 0.56-0.93). Treatment intensification with glucose-lowering but not with lipid-, blood pressure- and albuminuria-lowering drugs was associated with the outcome (HR = 0.73, 0.60-0.89). Treatment quality indicators measuring lipid- and albuminuria-lowering treatment status are valid quality measures, since they predict a lower risk of cardiovascular events and mortality in patients with diabetes. The quality indicators for glucose-lowering treatment should only be used for restricted populations with elevated HbA1c levels. Intriguingly, the tested indicators for blood pressure-lowering treatment did not predict patient outcomes. These results question whether all treatment

TB treatment in a chronic complex emergency: treatment outcomes and experiences in Somalia.

PubMed

Liddle, Karin Fischer; Elema, Riekje; Thi, Sein Sein; Greig, Jane; Venis, Sarah

2013-11-01

Médecins Sans Frontières (MSF) provides TB treatment in Galkayo and Marere in Somalia. MSF international supervisory staff withdrew in 2008 owing to insecurity but maintained daily communication with Somali staff. In this paper, we aimed to assess the feasibility of treating TB in a complex emergency setting and describe the programme adaptations implemented to facilitate acceptable treatment outcomes. Routinely collected treatment data from 2005-2012 were retrospectively analysed. In multivariate analyses, factors associated with successful outcome (cure or completion versus failure, death and default) were assessed, including the presence of international supervisory staff. Informal interviews were conducted with Somali staff regarding programmatic factors affecting patient management and perceived reasons for default. In total, 6167 patients were admitted (34.8% female; median age 24.0 years [IQR 13.0-38.0 years]). Treatment success was 79% (programme range 69-87%). Presence of international staff did not improve outcomes (adjusted OR 0.85, 95% CI 0.66-1.09; p=0.27). Perceived reasons for default included being away from family, nomadic group, insecurity, travel cost, need to return to grazing land or feeling better. Despite the challenges, a high percentage of patients were successfully treated. Treatment outcomes were not adversely affected by withdrawal of international supervisory staff.

Systematic Review of Treatment Outcome Measures for Vulvodynia.

PubMed

Sadownik, Leslie A; Yong, Paul J; Smith, Kelly B

2018-07-01

To systematically evaluate the literature regarding vulvodynia treatment outcome measures. A systematic literature search on OVID, PubMed, and PsycINFO databases was conducted from inception until May 2016. Studies were included/excluded based on prespecified criteria. Reported outcome measures were organized into 6 core outcome domains recommended by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT): pain; physical functioning, emotional functioning, participant ratings of global improvement and satisfaction with treatment, symptoms and adverse events, and participant disposition. Of the 206 articles identified for full-text screening, 33 met our criteria. One study adhered to all IMMPACT recommendations. The number of outcomes measured per study ranged from 1 to greater than 20. Patient-reported pain outcomes were found in the majority (27/33; 82%) of studies. Pain severity with intercourse was reported by 24 (73%) of 33 studies-9 different scales were used to measure this outcome. Clinician-reported outcomes were present in 14 (42%) of 33 studies. Methods of measuring vestibular sensitivity by "cotton swab" test were different in 8 of 10 studies. Other domains reported included; physical function (8/33 studies; 24%), sexual function (23/33 studies; 70%), and emotional function (13/33 studies; 39%). Symptoms and adverse events were reported by 15 (45%) of 33 studies. One study formally reported participant disposition using all the information recommended by CONSORT. Comparison of clinical trial results in vulvodynia is not possible because of a lack of standard treatment outcome measures. Vulvodynia researchers should apply the IMMPACT criteria to guide the development of a minimum core set of standard outcome measures that measure holistic health.

Outcomes associated with a negotiated asthma treatment plan.

PubMed

Clark, Noreen M; Ko, Yi-An; Gong, Z Molly; Johnson, Timothy R

2012-08-01

Negotiated treatment plans are increasingly recommended in asthma clinical care. However, limited data are available to indicate whether this more patient-engaged process results in improved health outcomes. The aim of this study was to determine the associations between the presence of a negotiated treatment plan and the outcomes related to adherence to the medical regimen, symptom control, and health care use. The focus of the study was on women, the subgroup of adult patients, who are most vulnerable for negative asthma outcomes. Data were collected by telephone interview and medical record review from 808 women diagnosed with asthma at baseline, first year, and second year follow-up. Associations were examined between the presence of a negotiated treatment plan at baseline and subsequent asthma outcomes. Women with a negotiated treatment plan reported more adherent to prescribed asthma medicines (odds ratio (OR) = 2.41, 95% confidence interval (CI) = (1.82, 3.19)) and those with a plan and using oral steroids at baseline had less oral steroid use at follow-up (OR = 0.21, 95% CI = (0.05, 0.93)). Women with a negotiated plan also had more days (17%, 95% CI = (8, 27)) and nights (31%, 95% CI = (16, 48)) with symptoms than those without such a plan. No differences in hospitalizations, emergency department visits, or urgent physician office visits were noted between the groups. Patients with higher education levels were more likely to have a negotiated treatment plan. Negotiated treatment plans appear to have achieved greater adherence to prescribed asthma medicines and less need for oral steroids but were not related to fewer symptoms of asthma or reductions in urgent health care use. Additional strategies may be needed to reduce symptom and health services utilization outcomes.

Prompted to treatment by the criminal justice system: Relationships with treatment retention and outcome among cocaine users.

PubMed

Kiluk, Brian D; Serafini, Kelly; Malin-Mayor, Bo; Babuscio, Theresa A; Nich, Charla; Carroll, Kathleen M

2015-04-01

A substantial portion of individuals entering treatment for substance use have been referred by the criminal justice system, yet there are conflicting reports regarding treatment engagement and outcome differences compared to those not referred. This study examined baseline characteristic and treatment outcome differences among cocaine-dependent individuals participating in cocaine treatment randomized trials. This secondary analysis pooled samples across five completed randomized controlled trials, resulting in 434 participants. Of these, 67 (15%) were prompted to treatment by the criminal justice system. This subsample of criminal justice prompted (CJP) individuals did not differ from those not prompted by the criminal justice system in terms of gender, race/ethnicity, marital status, or age. However, the CJP group reported more years of regular cocaine use, more severe employment and legal problems, as well as less readiness to change prior to treatment. Treatment outcomes did not differ significantly from those without a criminal justice prompt, and on some measures the outcomes for CJP group were better (e.g., percentage of days cocaine abstinent, number of therapy sessions attended). These findings suggest that being prompted to treatment by the criminal justice system may not lead to poorer treatment engagement or substance use outcomes for individuals participating in randomized controlled treatment trials. Despite some baseline indicators of poorer treatment prognosis, individuals who have been prompted to treatment by the criminal justice system have similar treatment outcomes as those presenting to treatment voluntarily. © American Academy of Addiction Psychiatry.

Pediatric malignancies, treatment outcomes and abandonment of pediatric cancer treatment in Zambia.

PubMed

Slone, Jeremy S; Chunda-Liyoka, Catherine; Perez, Marta; Mutalima, Nora; Newton, Robert; Chintu, Chifumbe; Kankasa, Chipepo; Chipeta, James; Heimburger, Douglas C; Vermund, Sten H; Friedman, Debra L

2014-01-01

There exist significant challenges to the receipt of comprehensive oncologic treatment for children diagnosed with cancer in sub-Saharan Africa. To better define those challenges, we investigated treatment outcomes and risk factors for treatment abandonment in a cohort of children diagnosed with cancer at the University Teaching Hospital (UTH), the site of the only pediatric oncology ward in Zambia. Using an established database, a retrospective cohort study was conducted of children aged 0-15 years admitted to the pediatric oncology ward between July 2008 and June 2010 with suspected cancer. Diagnosis, mode of diagnosis, treatment outcome, and risk factors for abandonment of treatment were abstracted from this database and clinical medical records. Among 162 children treated at the UTH during the study time period that met inclusion criteria, only 8.0% completed a treatment regimen with most of the patients dying during treatment or abandoning care. In multivariable analysis, shorter distance from home to the UTH was associated with a lower risk of treatment abandonment (Adjusted Odds Ratio [aOR]  = 0.48 (95% confidence interval [CI] 0.23-0.97). Conversely maternal education less than secondary school was associated with increased risk for abandonment (aOR = 1.65; 95% CI 1.05-2.58). Despite availability of dedicated pediatric oncology treatment, treatment completion rates are poor, due in part to the logistical challenges faced by families, low educational status, and significant distance from the hospital. Alternative treatment delivery strategies are required to bring effective pediatric oncology care to the patients in need, as their ability to come to and remain at a central tertiary care facility for treatment is limited. We suggest that the extensive system now in place in most of sub-Saharan Africa that sustains life-long antiretroviral therapy for children with human immunodeficiency virus (HIV) infection be adapted for pediatric cancer treatment to

The effects of bone remodeling inhibition by alendronate on three-dimensional microarchitecture of subchondral bone tissues in guinea pig primary osteoarthrosis.

PubMed

Ding, Ming; Danielsen, Carl Christian; Hvid, Ivan

2008-01-01

We assessed whether increase of subchondral bone density enhances cartilage stress during impact loading, leading to progressive cartilage degeneration and accelerated osteoarthrosis (OA) progression. Sixty-six male guinea pigs were randomly divided into six groups. During a 9-week treatment period, four groups received twice-weekly subcutaneous injections of alendronate (ALN) in two doses: two groups received 10 microg/kg and two groups received 50 microg/kg. The two control groups received vehicle. After 9 weeks, one 10 microg/kg ALN group, one 50 microg/kg ALN group, and one control group were killed. The remaining three groups (17-week groups) were left for an additional 8 weeks, receiving the same treatment regimen before death. The left proximal tibiae were scanned by micro-computed tomography to quantify the microarchitecture of subchondral bone, followed by mechanical testing and determination of collagen and mineral. The control groups had typical OA-related cartilage degeneration at 9 and 17 weeks, whereas the 50 microg/kg ALN group had even worse degeneration in the medial condyle. It is unclear whether there is a direct or a secondary effect of ALN on the cartilage. The 9-week ALN group had significantly greater subchondral plate thickness. The 9- and 17-week groups had similar changes of cancellous bone microarchitecture, with greater volume fraction and connectivity and an extremely plate-like structure. The 9-week ALN group had greater bone mineral concentration, and the 17-week ALN group had reduced collagen concentration and greater mineral concentration. Treatment with ALN did not significantly change the mechanical properties of the cancellous bone.

Brief dynamic psychotherapy : patient suitability, treatment length, and outcome.

PubMed

Høglend, P; Sørlie, T; Heyerdahl, O; Sørbye, O; Amlo, S

1993-01-01

Forty-three neurotic outpatients were treated according to common practice with dynamic psychotherapy of brief to moderate length. Suitability for brief dynamic psychotherapy, measured by quality of interpersonal relations, was independent of DSM-III diagnoses. Suitability was a significant direct predictor of symptomatic and dynamic change 2 and 4 years after therapy. Treatment length added no explained outcome variance over patient characteristics. However, patients with high suitability had a relatively more favorable dynamic outcome with a brief, focused treatment approach, whereas patients with low suitability had relatively more favorable outcome with a longer, less focused treatment of more than 1 year's duration. The significant interaction emerged at 4-year follow-up.

Development of a core set of outcome measures for OAB treatment.

PubMed

Foust-Wright, Caroline; Wissig, Stephanie; Stowell, Caleb; Olson, Elizabeth; Anderson, Anita; Anger, Jennifer; Cardozo, Linda; Cotterill, Nikki; Gormley, Elizabeth Ann; Toozs-Hobson, Philip; Heesakkers, John; Herbison, Peter; Moore, Kate; McKinney, Jessica; Morse, Abraham; Pulliam, Samantha; Szonyi, George; Wagg, Adrian; Milsom, Ian

2017-12-01

Standardized measures enable the comparison of outcomes across providers and treatments giving valuable information for improving care quality and efficacy. The aim of this project was to define a minimum standard set of outcome measures and case-mix factors for evaluating the care of patients with overactive bladder (OAB). The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group (WG) of leading clinicians and patients to engage in a structured method for developing a core outcome set. Consensus was determined by a modified Delphi process, and discussions were supported by both literature review and patient input. The standard set measures outcomes of care for adults seeking treatment for OAB, excluding residents of long-term care facilities. The WG focused on treatment outcomes identified as most important key outcome domains to patients: symptom burden and bother, physical functioning, emotional health, impact of symptoms and treatment on quality of life, and success of treatment. Demographic information and case-mix factors that may affect these outcomes were also included. The standardized outcome set for evaluating clinical care is appropriate for use by all health providers caring for patients with OAB, regardless of specialty or geographic location, and provides key data for quality improvement activities and research.

Predictors of treatment outcome among Asian pathological gamblers (PGs): clinical, behavioural, demographic, and treatment process factors.

PubMed

Guo, Song; Manning, Victoria; Thane, Kyaw Kyaw Wai; Ng, Andrew; Abdin, Edimansyah; Wong, Kim Eng

2014-03-01

Research on predictors of treatment outcome among pathological gamblers (PGs) is inconclusive and dominated by studies from Western countries. Using a prospective longitudinal design, the current study examined demographic, clinical, behavioural and treatment programme predictors of gambling frequency at 3, 6 and 12-months, among PGs treated at an addiction clinic in Singapore. Measures included the Hospital anxiety and depression scale, gambling symptom assessment scale (GSAS), personal well-being index (PWI), treatment perception questionnaire and gambling readiness to change scale. Treatment response in relation to changes in symptom severity, personal wellbeing and abstinence were also assessed. Abstinence rates were 38.6, 46.0 and 44.4 % at 3, 6 and 12-months respectively. Significant reductions in gambling frequency, GSAS, and improvement in PWI were reported between baseline and subsequent outcome assessments, with the greatest change occurring in the initial three months. No demographic, clinical, behavioural or treatment programme variable consistently predicted outcome at all three assessments, though treatment satisfaction was the most frequent significant predictor. However, being unemployed, having larger than average debts, poor treatment satisfaction and attending fewer sessions at the later stages of treatment were associated with significantly poorer outcomes, up to 1-year after initiating treatment. These findings show promise for the effectiveness of a CBT-based treatment approach for the treatment of predominantly Chinese PGs. Clinical implications and suggestions for future research are discussed. Taken together, the findings suggest early treatment satisfaction is paramount in improving short-term outcomes, with baseline gambling behaviour and treatment intensity playing a more significant role in the longer term.

Denosumab is really effective in the treatment of osteoporosis secondary to hypogonadism in prostate carcinoma patients? A prospective randomized multicenter international study.

PubMed

Doria, Carlo; Leali, Paolo Tranquilli; Solla, Federico; Maestretti, Gianluca; Balsano, Massimo; Scarpa, Robero Mario

2016-01-01

alendronate (P<0.001). New vertebral fractures developed in fewer patients in the denosumab group than in the alendronate group during the 24-month period, although this difference was not significant (P=0.10). Back pain significantly (P<0.001) improved from baseline at all time points during the study in both study groups. SF-8 health survey scores significantly improved following treatment with both drugs. Incidence of adverse drug reactions were similar in both groups. In our study denosumab and alendronate showed similar clinical efficacy in the therapy of ADT-related osteoporosis in men with prostate carcinoma; both drugs provided significant improvements in back pain and general health conditions. Denosumab showed significant increase of BTMs and BMD than alendronate with lower rate of new vertebral fractures.

Denosumab is really effective in the treatment of osteoporosis secondary to hypogonadism in prostate carcinoma patients? A prospective randomized multicenter international study

PubMed Central

Doria, Carlo; Leali, Paolo Tranquilli; Solla, Federico; Maestretti, Gianluca; Balsano, Massimo; Scarpa, Robero Mario

2016-01-01

months were 5.6% with denosumab vs −1.1% with alendronate (P<0.001). New vertebral fractures developed in fewer patients in the denosumab group than in the alendronate group during the 24-month period, although this difference was not significant (P=0.10). Back pain significantly (P<0.001) improved from baseline at all time points during the study in both study groups. SF-8 health survey scores significantly improved following treatment with both drugs. Incidence of adverse drug reactions were similar in both groups. Conclusion In our study denosumab and alendronate showed similar clinical efficacy in the therapy of ADT-related osteoporosis in men with prostate carcinoma; both drugs provided significant improvements in back pain and general health conditions. Denosumab showed significant increase of BTMs and BMD than alendronate with lower rate of new vertebral fractures. PMID:28228781

Update on long-term treatment with bisphosphonates for postmenopausal osteoporosis: a systematic review.

PubMed

Eriksen, Erik F; Díez-Pérez, Adolfo; Boonen, Steven

2014-01-01

Osteoporosis is a progressive skeletal disorder that requires long-term treatment. However, there is little guidance regarding optimal treatment duration and what the treatment discontinuation and retreatment criteria should be. Given that bisphosphonates are the most commonly prescribed class of agent for the treatment of osteoporosis, we reviewed the long-term data relating to these therapies and discussed the considerations for using bisphosphonates in postmenopausal women with osteoporosis. A PubMed search, using the search terms 'bisphosphonate', 'postmenopausal osteoporosis' and 'long term' and/or 'extension' was conducted in January 2013. Results from nine controlled studies that prospectively assessed alendronate, risedronate, ibandronate or zoledronic acid in women with postmenopausal osteoporosis were reviewed. Clinical studies in postmenopausal women with osteoporosis showed that long-term use of bisphosphonates resulted in persistent antifracture and bone mineral density (BMD) increasing effects beyond 3 years of treatment. No unexpected adverse events were identified in these studies and the long-term tolerability profiles of bisphosphonates remain favorable. Data from the withdrawal extension studies of alendronate and zoledronic acid also showed that residual fracture benefits were seen in patients who discontinued treatment for 3 to 5 years after an initial 3- to 5-year treatment period. BMD monitoring and fracture risk assessments should be conducted regularly to determine whether treatment could be stopped or should be reinitiated. Patients exhibiting T-scores<-2.5 or who have suffered a new fracture while on treatment should continue treatment, while patients with T-scores>-2.5 could be considered for discontinuation of active treatment while undergoing continued monitoring of their bone health. The duration and potential discontinuation of treatment should be personalized for individual patients based on their response to treatment, fracture

[Treatment outcomes for tuberculosis patients in FBIH during 1998-2003].

PubMed

Ustamujić, Aida; Dizdarević, Zehra; Zutić, Hasan

2007-01-01

To evaluate treatment outcome data for all new pulmonary sputum smear positive cases and treatment outcome data for all new pulmonary culture positive cases. To evaluate re-treatment outcome data for all retreated pulmonary sputum smear positive Tb cases and re-treatment outcome data for all retreated pulmonary culture positive TB cases,in FB&H, in the period 1998-2003. Achieving WHO aims of 85% success on new found TB cases. Retrospective cohort analysis for new pulmonary smear positive cases, new pulmonary culture positive cases. Retrospective cohort analysis for retreated pulmonary smear-positive cases; retreated pulmonary culture positive cases, registered in FB&H in the period 1998-2003. A recording and reporting system used standardized registers according to WHO. Results are presented in four tables and four graphs. Middle rate of success (cured or completed treatment) was 84%, middle value of failed (5%), defaulted (5%) and transferred (2%). Results of success in newfound TB cases are achiived according to WHO aims (85-90,7%). Success NTP in control of TB is concern on ability to hold high rate of cured or completed treatment.

Treatment outcomes of saddle nose correction.

PubMed

Hyun, Sang Min; Jang, Yong Ju

2013-01-01

Many valuable classification schemes for saddle nose have been suggested that integrate clinical deformity and treatment; however, there is no consensus regarding the most suitable classification and surgical method for saddle nose correction. To present clinical characteristics and treatment outcome of saddle nose deformity and to propose a modified classification system to better characterize the variety of different saddle nose deformities. The retrospective study included 91 patients who underwent rhinoplasty for correction of saddle nose from April 1, 2003, through December 31, 2011, with a minimum follow-up of 8 months. Saddle nose was classified into 4 types according to a modified classification. Aesthetic outcomes were classified as excellent, good, fair, or poor. Patients underwent minor cosmetic concealment by dorsal augmentation (n = 8) or major septal reconstruction combined with dorsal augmentation (n = 83). Autologous costal cartilages were used in 40 patients (44%), and homologous costal cartilages were used in 5 patients (6%). According to postoperative assessment, 29 patients had excellent, 42 patients had good, 18 patients had fair, and 2 patients had poor aesthetic outcomes. No statistical difference in surgical outcome according to saddle nose classification was observed. Eight patients underwent revision rhinoplasty, owing to recurrence of saddle, wound infection, or warping of the costal cartilage for dorsal augmentation. We introduce a modified saddle nose classification scheme that is simpler and better able to characterize different deformities. Among 91 patients with saddle nose, 20 (22%) had unsuccessful outcomes (fair or poor) and 8 (9%) underwent subsequent revision rhinoplasty. Thus, management of saddle nose deformities remains challenging. 4.

Relationship between Nutritional Support and Tuberculosis Treatment Outcomes in West Bengal, India.

PubMed

Samuel, Blesson; Volkmann, Tyson; Cornelius, Sushma; Mukhopadhay, Sugata; MejoJose; Mitra, Kaushik; Kumar, Ajay M V; Oeltmann, John E; Parija, Sidhajyoti; Prabhakaran, Aslesh Ottapura; Moonan, Patrick K; Chadha, Vineet K

2016-12-01

Poverty and poor nutrition are associated with the risk of developing tuberculosis (TB). Socioeconomic factors may interfere with anti-tuberculosis treatment compliance and its outcome. We examined whether providing nutritional support (monthly supply of rice and lentil beans) to TB patients who live below the poverty line was associated with TB treatment outcome. This was a retrospective cohort study of sputum smear-positive pulmonary TB patients living below the poverty line (income of <$1.25 per day) registered for anti-tuberculosis treatment in two rural districts of West Bengal, India during 2012 to 2013. We compared treatment outcomes among patients who received nutritional support with those who did not. A log-binomial regression model was used to assess the relation between nutritional support and unsuccessful treatment outcome (loss-to-follow-up, treatment failure and death). Of 173 TB patients provided nutritional support, 15 (9%) had unsuccessful treatment outcomes, while 84 (21%) of the 400 not provided nutrition support had unsuccessful treatment outcomes (p < 0.001). After adjusting for age, sex and previous treatment, those who received nutritional support had a 50% reduced risk of unsuccessful treatment outcome than those who did not receive nutritional support (Relative Risk: 0.51; 95% Confidence Intervals: 0.30 - 0.86). Under programmatic conditions, monthly rations of rice and lentils were associated with lower risk of unsuccessful treatment outcome among impoverished TB patients. Given the relatively small financial commitment needed per patient ($10 per patient per month), the national TB programme should consider scaling up nutritional support among TB patients living below the poverty line.

In vivo microfocal computed tomography and micro-magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat.

PubMed

Jones, Michael D; Tran, Charles W; Li, Guang; Maksymowych, Walter P; Zernicke, Ronald F; Doschak, Michael R

2010-09-01

To determine whether treatment with an antiresorptive drug in combination with an antiinflammatory drug reduces periarticular bone and soft tissue adaptations associated with the progression of posttraumatic secondary osteoarthritis (OA). We used in vivo microfocal computed tomography (micro-CT) to map bony adaptations and in vivo micro-magnetic resonance imaging (micro-MRI) to examine joint inflammation in a rat model of surgically induced OA secondary to knee triad injury. We examined the arthroprotective effects of the bisphosphonates alendronate and risedronate and the nonsteroidal antiinflammatory drug (NSAID) meloxicam. Micro-CT revealed reduced levels of periarticular trabecular bone loss in animals with knee triad injury treated with the bisphosphonate drugs alendronate or risedronate, or the NSAID meloxicam, compared with untreated animals. Alendronate treatment reduced bony osteophyte development. While risedronate as a monotherapy did not positively impact osteophytogenesis, combination therapy with risedronate and meloxicam reduced osteophyte severity somewhat. Micro-MRI revealed an increased, diffuse water signal in the epiphyses of untreated rats with knee triad injury 8 weeks after surgery, suggestive of a bone marrow lesion-like stimulus. In contrast, meloxicam-treated rats showed a significant reduction in fluid signal compared with both bisphosphonate-treated groups 8 weeks after surgery. Histologic analysis qualitatively confirmed the chondroprotective effect of both bisphosphonate treatments, showing fewer degradative changes compared with untreated rats with knee triad injury. Our findings indicate that select combinations of bisphosphonate and NSAID drug therapy in the early stages of secondary OA preserve trabecular bone mass and reduce the impact of osteophytic bony adaptations and bone marrow lesion-like stimulus. Bisphosphonate and NSAID therapy may be an effective disease-modifying drug regimen if administered early after the initial

Cognitive-behavioral therapy for persistent pain: does adherence after treatment affect outcome?

PubMed

Curran, Charlotte; Williams, Amanda C de C; Potts, Henry W W

2009-02-01

It is a tenet of cognitive behavioral treatment of persistent pain problems that ex-patients should adhere to treatment methods over the longer term, in order to maintain and to extend treatment gains. However, no research has quantified the causal influence of adherence on short-term outcome in this field. The aims of this study are to assess determinants of adherence to treatment recommendations in several domains, and to examine the extent to which cognitive and behavioral adherence predicts better outcome of cognitive behavioral treatment for persistent pain. Longitudinal data from a sample of 2345 persistent pain patients who attended a multicomponent treatment programme were subjected to structural equation modeling. Adherence emerged as a mediating factor linking post-treatment and follow-up treatment outcome, but contributed only 3% unique variance to follow-up outcomes. Combined end-of-treatment outcomes and adherence factors accounted for 72% of the variance in outcome at one-month follow-up. Notwithstanding shortcomings in the measurement of adherence, these findings question the emphasis normally given to adherence in the maintenance of behavioral and cognitive change, and clinical implications are discussed.

Predictors of outcomes of psychological treatments for disordered gambling: A systematic review.

PubMed

Merkouris, S S; Thomas, S A; Browning, C J; Dowling, N A

2016-08-01

This systematic review aimed to synthesise the evidence relating to pre-treatment predictors of gambling outcomes following psychological treatment for disordered gambling across multiple time-points (i.e., post-treatment, short-term, medium-term, and long-term). A systematic search from 1990 to 2016 identified 50 articles, from which 11 socio-demographic, 16 gambling-related, 21 psychological/psychosocial, 12 treatment, and no therapist-related variables, were identified. Male gender and low depression levels were the most consistent predictors of successful treatment outcomes across multiple time-points. Likely predictors of successful treatment outcomes also included older age, lower gambling symptom severity, lower levels of gambling behaviours and alcohol use, and higher treatment session attendance. Significant associations, at a minimum of one time-point, were identified between successful treatment outcomes and being employed, ethnicity, no gambling debt, personality traits and being in the action stage of change. Mixed results were identified for treatment goal, while education, income, preferred gambling activity, problem gambling duration, anxiety, any psychiatric comorbidity, psychological distress, substance use, prior gambling treatment and medication use were not significantly associated with treatment outcomes at any time-point. Further research involving consistent treatment outcome frameworks, examination of treatment and therapist predictor variables, and evaluation of predictors across long-term follow-ups is warranted to advance this developing field of research. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Fidelity and outcomes in six integrated dual disorders treatment programs.

PubMed

Chandler, Daniel W

2011-02-01

Fidelity scores and outcomes were measured in six outpatient programs in California which implemented Integrated Dual Disorders Treatment (IDDT). Outcomes were measured for 1 year in four sites and 2 years in two sites; fidelity was assessed at 6 month intervals. Three of the six sites achieved high fidelity (at least a 4 on a 5 point fidelity scale) and three moderate fidelity (at least a 3). Retention in treatment, mental health functioning, stage of substance abuse treatment, abstinence, and psychiatric hospitalization were measured. Outcomes for individual programs were generally positive but not consistent within programs or across programs. Using pooled data in a longitudinal regression model with random effects at person level and adjustment of standard errors for clustering by site, change over time was not statistically significant for the primary outcomes. Fidelity scores had limited association with positive outcomes.

Improving Outcome for Mental Disorders by Enhancing Memory for Treatment

PubMed Central

Harvey, Allison G.; Lee, Jason; Smith, Rita L.; Gumport, Nicole B.; Hollon, Steven D.; Rabe-Hesketh, Sophia; Hein, Kerrie; Dolsen, Michael R.; Hamen, Kristen; Kanady, Jennifer C.; Thompson, Monique A.; Abrons, Deidre

2017-01-01

Summary Patients exhibit poor memory for treatment. A novel Memory Support Intervention, derived from basic science in cognitive psychology and education, is tested with the goal of improving patient memory for treatment and treatment outcome. Adults with major depressive disorder (MDD) were randomized to 14 sessions of cognitive therapy (CT)+Memory Support (n = 25) or CT-as-usual (CTMS; n = 23). Outcomes were assessed at baseline, post-treatment and 6 months later. Memory support was greater in CT+Memory Support compared to the CT-as-usual. Compared to CT-as-usual, small to medium effect sizes were observed for recall of treatment points at post-treatment. There was no difference between the treatment arms on depression severity (primary outcome). However, the odds of meeting criteria for ‘response’ and ‘remission’ were higher in CT+Memory Support compared with CT-as-usual. CT+Memory Support also showed an advantage on functional impairment. While some decline was observed, the advantage of CT+Memory Support was evident through 6-month follow-up. Patients with less than 16 years of education experience greater benefits from memory support than those with 16 or more years of education. Memory support can be manipulated, may improve patient memory for treatment and may be associated with an improved outcome. PMID:27089159

Treatment Outcomes for Extensively Drug-Resistant Tuberculosis and HIV Co-infection

PubMed Central

Padayatchi, Nesri; Kvasnovsky, Charlotte; Werner, Lise; Master, Iqbal; Horsburgh, C. Robert

2013-01-01

High mortality rates have been reported for patients co-infected with extensively drug-resistant tuberculosis (XDR-TB) and HIV, but treatment outcomes have not been reported. We report treatment outcomes for adult XDR TB patients in KwaZulu-Natal Province, South Africa. Initial data were obtained retrospectively, and outcomes were obtained prospectively during 24 months of treatment. A total of 114 XDR TB patients were treated (median 6 drugs, range 3–9 drugs); 82 (73%) were HIV positive and 50 (61%) were receiving antiretroviral therapy. After receiving treatment for 24 months, 48 (42%) of 114 patients died, 25 (22%) were cured or successfully completed treatment, 19 (17%) withdrew from the study, and 22 (19%) showed treatment failure. A higher number of deaths occurred among HIV-positive patients not receiving antiretroviral therapy and among patients who did not show sputum culture conversion. Culture conversion was a major predictor of survival but was poorly predictive (51%) of successful treatment outcome. PMID:23622055

Personality disorder and alcohol treatment outcome: systematic review and meta-analysis.

PubMed

Newton-Howes, Giles M; Foulds, James A; Guy, Nicola H; Boden, Joseph M; Mulder, Roger T

2017-07-01

Background Personality disorders commonly coexist with alcohol use disorders (AUDs), but there is conflicting evidence on their association with treatment outcomes. Aims To determine the size and direction of the association between personality disorder and the outcome of treatment for AUD. Method We conducted a systematic review and meta-analysis of randomised trials and longitudinal studies. Results Personality disorders were associated with more alcohol-related impairment at baseline and less retention in treatment. However, during follow-up people with a personality disorder showed a similar amount of improvement in alcohol outcomes to that of people without such disorder. Synthesis of evidence was hampered by variable outcome reporting and a low quality of evidence overall. Conclusions Current evidence suggests the pessimism about treatment outcomes for this group of patients may be unfounded. However, there is an urgent need for more consistent and better quality reporting of outcomes in future studies in this area. © The Royal College of Psychiatrists 2017.

Relationship between Nutritional Support and Tuberculosis Treatment Outcomes in West Bengal, India

PubMed Central

Samuel, Blesson; Volkmann, Tyson; Cornelius, Sushma; Mukhopadhay, Sugata; MejoJose; Mitra, Kaushik; Kumar, Ajay M. V.; Oeltmann, John E.; Parija, Sidhajyoti; Prabhakaran, Aslesh Ottapura; Moonan, Patrick K.; Chadha, Vineet K.

2016-01-01

Introduction Poverty and poor nutrition are associated with the risk of developing tuberculosis (TB). Socioeconomic factors may interfere with anti-tuberculosis treatment compliance and its outcome. We examined whether providing nutritional support (monthly supply of rice and lentil beans) to TB patients who live below the poverty line was associated with TB treatment outcome. Methods This was a retrospective cohort study of sputum smear-positive pulmonary TB patients living below the poverty line (income of <$1.25 per day) registered for anti-tuberculosis treatment in two rural districts of West Bengal, India during 2012 to 2013. We compared treatment outcomes among patients who received nutritional support with those who did not. A log-binomial regression model was used to assess the relation between nutritional support and unsuccessful treatment outcome (loss-to-follow-up, treatment failure and death). Results Of 173 TB patients provided nutritional support, 15 (9%) had unsuccessful treatment outcomes, while 84 (21%) of the 400 not provided nutrition support had unsuccessful treatment outcomes (p < 0.001). After adjusting for age, sex and previous treatment, those who received nutritional support had a 50% reduced risk of unsuccessful treatment outcome than those who did not receive nutritional support (Relative Risk: 0.51; 95% Confidence Intervals: 0.30 - 0.86). Conclusion Under programmatic conditions, monthly rations of rice and lentils were associated with lower risk of unsuccessful treatment outcome among impoverished TB patients. Given the relatively small financial commitment needed per patient ($10 per patient per month), the national TB programme should consider scaling up nutritional support among TB patients living below the poverty line. PMID:28042591

A test of faith in God and treatment: the relationship of belief in God to psychiatric treatment outcomes.

PubMed

Rosmarin, David H; Bigda-Peyton, Joseph S; Kertz, Sarah J; Smith, Nasya; Rauch, Scott L; Björgvinsson, Thröstur

2013-04-25

Belief in God is very common and tied to mental health/illness in the general population, yet its relevance to psychiatric patients has not been adequately studied. We examined relationships between belief in God and treatment outcomes, and identified mediating mechanisms. We conducted a prospective study with n=159 patients in a day-treatment program at an academic psychiatric hospital. Belief in God, treatment credibility/expectancy, emotion regulation and congregational support were assessed prior to treatment. Primary outcomes were treatment response as well as degree of reduction in depression over treatment. Secondary outcomes were improvements in psychological well-being and reduction in self-harm. Belief in God was significantly higher among treatment responders than non-responders F(1,114)=4.81, p<.05. Higher levels of belief were also associated with greater reductions in depression (r=.21, p<.05) and self-harm (r=.24, p<.01), and greater improvements in psychological well-being (r=.19, p<.05) over course of treatment. Belief remained correlated with changes in depression and self-harm after controlling for age and gender. Perceived treatment credibility/expectancy, but not emotional regulation or community support, mediated relationships between belief in God and reductions in depression. No variables mediated relationships to other outcomes. Religious affiliation was also associated with treatment credibility/expectancy but not treatment outcomes. Belief in God, but not religious affiliation, was associated with better treatment outcomes. With respect to depression, this relationship was mediated by belief in the credibility of treatment and expectations for treatment gains. Copyright © 2012 Elsevier B.V. All rights reserved.

Depression-Specific Outcomes After Treatment of Chronic Rhinosinusitis

PubMed Central

Schlosser, Rodney J.; Hyer, J. Madison; Smith, Timothy L.; Mace, Jess C.; Cortese, Bernadette M.; Uhde, Thomas W.; Rudmik, Luke; Soler, Zachary M.

2016-01-01

IMPORTANCE Depression is frequently undiagnosed in patients with chronic rhinosinusitis (CRS) and affects quality of life, productivity, and health care use. OBJECTIVE To examine depression-specific outcomes after medical or surgical treatment of CRS. DESIGN, SETTING, AND PARTICIPANTS A multi-institutional, prospective study of patients with refractory CRS treated at tertiary academic rhinology centers was performed from March 1, 2011, to November 1, 2015. Data analysis was performed from October 1, 2015, to November 1, 2015. INTERVENTIONS Patients self-selected to undergo continued medical management or endoscopic sinus surgery for refractory CRS. MAIN OUTCOMES AND MEASURES Patients completed the 22-item Sinonasal Outcome Test (SNOT22), Rhinosinusitis Disability Index (RSDI), Pittsburgh Sleep Quality Index (PSQI), and missed productivity and medication use questionnaires before and at least 6 months after treatment. Computed tomography and endoscopy scoring were performed with reviewers masked to patient-reported data. Depression-specific outcomes were recorded using the 2-item Patient Health Questionnaire (PHQ2). RESULTS Baseline data were available on 685 patients, with 167 (24.4%) having depression according to the PHQ2 scores. The mean (SD) age of the patients was 50.5 (15.0) years, and 332 (48.4%) were male. Revision surgery status was the only baseline factor associated with depression (53.9%vs 38.0%, P < .001). Patients with depression had worse baseline SNOT22 (mean, 64.5 vs 47.6), PSQI (mean, 12.8 vs 8.4), productivity (mean, 22.8 vs 5.2 days missed), and medication use scores for oral antibiotics (mean, 23.8 vs 14.8) and oral corticosteroids (mean, 17.8 vs 9.9) (P < .001 for all). Medical and surgical treatments had similar outcomes for patients with depression with mean improvement in the PHQ2 scores from 3.96 to 1.91 (P < .001), and 110 of 167 patients (65.9%) categorized as having depression at baseline were categorized as not having depression after

The Association between Outpatient Buprenorphine Detoxification Duration and Clinical Treatment Outcomes: A Review

PubMed Central

Sigmon, Stacey C.; Strain, Eric C.; Heil, Sarah H.; Higgins, Stephen T.

2011-01-01

Background The association between buprenorphine taper duration and treatment outcomes is not well understood. This review evaluated whether duration of outpatient buprenorphine taper is significantly associated with treatment outcomes. Methods Studies that were published in peer-reviewed journals, administered buprenorphine as an outpatient taper to opioid-dependent participants, and provided data on at least one of three primary treatment outcome measures (opioid abstinence, retention, peak withdrawal severity) were reviewed. Primary treatment outcomes were evaluated as a function of taper duration using hierarchical linear regressions using pre-taper maintenance as a cofactor. Results Twenty-eight studies were reviewed. Taper duration significantly predicted percent of opioid-negative samples provided during treatment, however pre-taper maintenance period predicted percent participants abstinent on the final day of treatment. High rates of relapse were reported. No significant association between taper duration and retention in treatment or peak withdrawal severity was observed. Conclusion The data reviewed here suggest taper duration is associated with opioid abstinence achieved during detoxification but not with other markers of treatment outcome. The reviewed studies varied widely on several parameters (e.g., frequency of urinalysis testing, provision of ancillary medications) that may influence treatment outcome and thus could have interfered with the ability to identify relationships between taper duration and outcomes. Future studies evaluating opioid detoxification should utilize rigorous experimental methods and report a wider range of outcome measures in order to help advance our understanding of the association between taper duration and treatment outcomes. PMID:21741781

Mental health indicator interaction in predicting substance abuse treatment outcomes in nevada.

PubMed

Greenfield, Lawrence; Wolf-Branigin, Michael

2009-01-01

Indicators of co-occurring mental health and substance abuse problems routinely collected at treatment admission in 19 State substance abuse treatment systems include a dual diagnosis and a State mental health (cognitive impairment) agency referral. These indicators have yet to be compared as predictors of treatment outcomes. 1. Compare both indices as outcomes predictors individually and interactively. 2. Assess relationship of both indices to other client risk factors, e.g., physical/sexual abuse. Client admission and discharge records from the Nevada substance abuse treatment program, spanning 1995-2001 were reviewed (n = 17,591). Logistic regression analyses predicted treatment completion with significant improvement (33%) and treatment readmission following discharge (21%). Using Cox regression, the number of days from discharge to treatment readmission was predicted. Examined as predictors were two mental health indicators and their interaction with other admission and treatment variables controlled. Neither mental health indicator alone significantly predicted any of the three outcomes; however, the interaction between the two indicators significantly predicted each outcome (p < .05). Having both indices was highly associated with physical/sexual abuse, domestic violence, homelessness, out of labor force and prior treatment. Indicator interactions may help improve substance abuse treatment outcomes prediction.

Social support is associated with gambling treatment outcomes in pathological gamblers.

PubMed

Petry, Nancy M; Weiss, Lindsay

2009-01-01

Poor social support is a contributory factor in development of addictive disorders, but it has rarely been evaluated in pathological gamblers. This study examined social support in pathological gamblers and its relationship with treatment outcomes. Low baseline social support was associated with increased severity of gambling, family, and psychiatric problems and poorer post-treatment outcomes. Further, social support assessed post-treatment was significantly related to severity of gambling problems at the 12-month follow-up. These findings demonstrate that social support plays an important role in moderating outcomes, and enhancing social support may be an important aspect of effective gambling treatments.

Treatment outcome of new smear positive pulmonary tuberculosis patients in Penang, Malaysia

PubMed Central

2014-01-01

Background According to the World Health Organization’s recent report, in Malaysia, tuberculosis (TB) treatment success rate for new smear positive pulmonary tuberculosis (PTB) patients is still below the global success target of 85%. In this study, we evaluated TB treatment outcome among new smear positive PTB patients, and identified the predictors of unsuccessful treatment outcome and longer duration of treatment (i.e., > 6 months). Methods The population in this study consisted of all new smear positive PTB patients who were diagnosed at the chest clinic of Penang General Hospital between March 2010 and February 2011. During the study period, a standardized data collection form was used to obtain socio-demographic, clinical and treatment related data of the patients from their medical charts and TB notification forms (Tuberculosis Information System; TBIS). These data sources were reviewed at the time of the diagnosis of the patients and then at the subsequent follow-up visits until their final treatment outcomes were available. The treatment outcomes of the patients were reported in line with six outcome categories recommended by World Health Organization. Multiple logistic regression analysis was used to find the independent risk factors for unsuccessful treatment outcome and longer treatment duration. Data were analyzed using the PASW (Predictive Analysis SoftWare, version 19.0. Armonk, NY: IBM Corp). Results Among the 336 PTB patients (236 male and 100 female) notified during the study period, the treatment success rate was 67.26% (n = 226). Out of 110 patients in unsuccessful outcome category, 30 defaulted from the treatment, 59 died and 21 were transferred to other health care facilities. The mean duration of TB treatment was 8.19 (SD 1.65) months. In multiple logistic regression analysis, risk factors for unsuccessful treatment outcome were foreign nationality, male gender and being illiterate. Similarly, risk factors for mortality due to TB

Effects of eight-month treatment with ONO-5334, a cathepsin K inhibitor, on bone metabolism, strength and microstructure in ovariectomized cynomolgus monkeys.

PubMed

Ochi, Yasuo; Yamada, Hiroyuki; Mori, Hiroshi; Nakanishi, Yasutomo; Nishikawa, Satoshi; Kayasuga, Ryoji; Kawada, Naoki; Kunishige, Akiko; Hashimoto, Yasuaki; Tanaka, Makoto; Sugitani, Masafumi; Kawabata, Kazuhito

2014-08-01

This study examined the effect of ONO-5334, a cathepsin K inhibitor, on bone turnover, mineral density (BMD), mechanical strength and microstructure in ovariectomized (OVX) cynomolgus monkeys. Vehicle, ONO-5334 (3, 10 or 30 mg/kg) or alendronate (0.5 mg/kg) was orally administered for eight months to sham- and OVX-operated monkeys. ONO-5334 dose-dependently suppressed OVX-induced increase in bone turnover markers (urinary C-terminal cross-linking telopeptide of type I collagen (CTX) and serum osteocalcin). At the dose of 30 mg/kg, ONO-5334 maintained urinary CTX at nearly zero level and kept serum osteocalcin around the level of the sham animals. Marker levels in the alendronate-treated animals were similar to those in the sham animals throughout the study. ONO-5334 dose-dependently reversed the effect of OVX on vertebral BMD as measured by dual-energy X-ray absorptiometry (DXA) with improvement of bone mechanical strength. Both ONO-5334 and alendronate suppressed OVX-induced changes in vertebral microstructure and turnover state. In the femoral neck, peripheral quantitative computed tomography (pQCT) analysis showed that ONO-5334 increased total and cortical BMD. In particular, ONO-5334 significantly increased cortical BMD with improvement of bone mechanical strength. In microstructural analysis, alendronate suppressed OVX-induced increase in femoral mid-shaft osteonal bone formation rate (BFR) to a level below that recorded in the sham group, whereas ONO-5334 at 30 mg/kg did not suppress periosteal, osteonal and endocortical BFR. This finding supports the significant effect of ONO-5334 on cortical BMD and mechanical strength in the femoral neck. The results of this study suggest that ONO-5334 has good therapeutic potential for the treatment of osteoporosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of psychotherapy attendance on buprenorphine treatment outcome

PubMed Central

Montoya, Iván D.; Schroeder, Jennifer R.; Preston, Kenzie L.; Covi, Lino; Umbricht, Annie; Contoreggi, Carlo; Fudala, Paul J.; Johnson, Rolley E.; Gorelick, David A.

2008-01-01

We evaluated the influence of psychotherapy attendance on treatment outcome in 90 dually (cocaine and heroin) dependent outpatients who completed 70 days of a controlled clinical trial of sublingual buprenorphine (16 mg, 8 mg, or 2 mg daily, or 16 mg every other day) plus weekly individual standardized interpersonal cognitive psychotherapy. Treatment outcome was evaluated by quantitative urine benzoylecgonine (BZE) and morphine levels (log-transformed), performed three times per week. Repeated-measures linear regression was used to assess the effects of psychotherapy attendance (percent of visits kept), medication group, and study week on urine drug metabolite levels. Mean psychotherapy attendance was 71% of scheduled visits. Higher psychotherapy attendance was associated with lower urine BZE levels, and this association grew more pronounced as the study progressed (p = 0.04). The inverse relationship between psychotherapy attendance and urine morphine levels varied by medication group, being most pronounced for subjects receiving 16 mg every other day (p = 0.02). These results suggest that psychotherapy can improve the outcome of buprenorphine maintenance treatment for patients with dual (cocaine and opioid) dependence. PMID:15857725

Outcome of multimodality treatment of Ewing's sarcoma of the extremities.

PubMed

Tiwari, Akshay; Gupta, Himesh; Jain, Sandeep; Kapoor, Gauri

2010-10-01

The management of Ewing's sarcoma family of tumors (ESFT, Ewing's sarcoma/primitive neuroectodermal tumor) has been established as a multimodality treatment. Advances in imaging and diagnostics, chemotherapy, surgical techniques, radiotherapy and prosthetic technology have resulted in drastic changes in the outcome of this disease, with most of the recent studies having 5-year survival rates of more than 60%. The Indian patients present at a more advanced stage and the compliance of treatment is suboptimal. While there is plenty of data in the world literature on the outcome of Ewing's sarcoma, there is paucity of data in Indian patients. Therefore, we conducted the present study to analyze the outcome of multimodality treatment of ESFT of the extremities at a tertiary nonprofit institute over a decade. 34 patients who had histopathologically proven diagnosis of Ewing's sarcoma of the extremities and had received treatment at our institute from 1997 through 2007 were included for analysis. The majority of patients had involvement of the femur (35%), followed by tibia (17%), fibula and foot (15% each), humerus (12%) and soft tissue of thigh (6%). Twenty-nine patients presented with localized disease (Enneking stage II B) while five patients presented with metastases (Enneking stage III). All patients received Vincristine, Actinomycin D, Cyclofosfamide + Ifosfamide and Etoposide (VAC+IE)-based chemotherapy and local treatment was offered to all but three patients having multicentric disease. The local treatment offered were, radiation (n= 15), surgery (n= 12) both surgery and radiation (n=4). All patients were analyzed for oncological outcome (event-free and overall survival, local and systemic relapses) by clinical and imaging evaluation and functional outcome by using the musculoskeletal tumor society (MSTS) score. These outcomes were correlated with age, sex, size of tumor, stage at presentation, modality of local treatment and site of relapse. At the final follow

Neuroblastoma: treatment outcome after incomplete resection of primary tumors.

PubMed

Moon, Suk-Bae; Park, Kwi-Won; Jung, Sung-Eun; Youn, Woong-Jae

2009-09-01

For International Neuroblastoma Staging System (INSS) stages III or IV neuroblastoma (intermediate or high risk), complete excision of the primary tumor is not always feasible. Most current studies on the treatment outcome of these patients have reported on the complete excision status. The aim of this study is to review the treatment outcome after the incomplete resection. The medical records of 37 patients that underwent incomplete resection between January 1986 and December 2005 were reviewed retrospectively. Incomplete resection was assessed by review of the operative notes and postoperative computerized tomography. Age, gender, tumor location, INSS stage, N-myc gene copy number, pre- and postoperative therapy, and treatment outcome were reviewed. The treatment outcome was evaluated according to the postoperative treatment protocol in the high-risk group. Intermediate-risk patients were treated with conventional chemotherapy, isotretinoin (ITT) and interleukin-2 (IL-2). High-risk patients were treated with peripheral blood stem cell transplantation (PBSCT), ITT, and IL-2 (N = 11). Before the introduction of PBSCT, the high-risk patients were also treated with the conventional chemotherapy (N = 19). Intermediate-risk patients (N = 5) currently have no evidence of disease (NED). For the high-risk patients (N = 32), 19 patients were treated with chemotherapy alone; 15 patients died of their disease while four patients currently have an NED status. Eight of 11 patients that underwent PBSCT are currently alive. For intermediate risk, conventional chemotherapy appears to be acceptable treatment. However, for high-risk patients, every effort should be made to control residual disease including the use of myeloablative chemotherapy, differentiating agents and immune-modulating agents.

Prioritizing treatment outcomes: How people with acne vulgaris decide if their treatment is working.

PubMed

Layton, Alison M; Whitehouse, Heather; Eady, E Anne; Cowdell, Fiona; Warburton, Katharine L; Fenton, Mark

2017-08-01

To collect information about how people with acne make day-to-day decisions concerning the effectiveness of their treatment. Between May and August 2013, an optional question was embedded in the James Lind Alliance Acne Priority Setting Partnership's online survey to collect treatment uncertainties. The question asked people with acne to "Tell us in your own words how you decide if your treatment has been effective." A total of 742 respondents specified at least one outcome or means of assessing change (outcome measure). Fewer spots were the most commonly cited outcome, identified by 272 respondents (36.7%). Other frequently mentioned outcomes were in descending order: less redness (19.4%), reduction in spot size (12.1%), and less pain/discomfort (11.4%). Signs were much more commonly used than symptoms and surrogate outcomes such as changes in aspects of life quality were infrequently mentioned. Visual inspection of the skin was the most widely adopted outcome measure (16.3%). Although the most frequently used methods map well onto the outcome measures adopted in the majority of acne trials, namely physician-assessed changes in lesion counts and global acne severity, people with acne often take into account several factors that cannot be assessed by a third party at a single point in time. The minimal use of changes in psychosocial wellbeing and mood may reflect that these are regarded as secondary consequences of improvements in appearance. The robustness of these findings now requires independent evaluation. If confirmed, they could form the basis of a new patient-reported outcome measure. © 2017 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.

Brain mu-opioid receptor binding predicts treatment outcome in cocaine-abusing outpatients

PubMed Central

Ghitza, Udi E.; Preston, Kenzie L.; Epstein, David H.; Kuwabara, Hiroto; Endres, Christopher J.; Bencherif, Badreddine; Boyd, Susan J.; Copersino, Marc L.; Frost, J. James; Gorelick, David A.

2010-01-01

Background Cocaine users not seeking treatment have increased regional brain mu-opioid receptor (mOR) binding that correlates with cocaine craving and tendency to relapse. In cocaine-abusing outpatients in treatment, the relationship of mOR binding and treatment outcome is unknown. Methods We determined whether regional brain mOR binding before treatment correlates with outcome and compared it to standard clinical predictors of outcome. Twenty-five individuals seeking outpatient treatment for cocaine abuse or dependence (DSM-IV) received up to 12 weeks of cognitive-behavioral therapy and cocaine-abstinence reinforcement whereby each cocaine-free urine was reinforced with vouchers redeemable for goods. Regional brain mOR binding was measured before treatment using positron emission tomography (PET) with [11C] carfentanil (a selective mOR agonist). Main outcome measures were: 1) overall percentage of urines positive for cocaine during first month of treatment, 2) longest duration (weeks) of abstinence from cocaine during treatment, all verified by urine toxicology. Results Elevated mOR binding in the medial frontal and middle frontal gyri before treatment correlated with greater cocaine use during treatment. Elevated mOR binding in the anterior cingulate, medial frontal, middle frontal, middle temporal, and sub-lobar insular gyri correlated with shorter duration of cocaine abstinence during treatment. Regional mOR binding contributed significant predictive power for treatment outcome beyond that of standard clinical variables such as baseline drug and alcohol use. Conclusions Elevated mOR binding in brain regions associated with reward sensitivity is a significant independent predictor of treatment outcome in cocaine-abusing outpatients, suggesting a key role for the brain endogenous opioid system in cocaine addiction. PMID:20579973

Determinants of unsuccessful tuberculosis treatment outcomes in Malaysian HIV-infected patients.

PubMed

Ismail, Ismawati; Bulgiba, Awang

2013-01-01

To determine predictors of unsuccessful treatment in HIV-infected tuberculosis (TB) patients. We reviewed medical records at the time of TB diagnosis and subsequent follow-up of all registered TB patients with HIV co-infection at TB clinics in the Institute of Respiratory Medicine and three public hospitals in Malaysia between January 2010 and September 2010. We reviewed these medical records again twelve months after their initial diagnosis to determine treatment outcomes. Multiple logistic regression was conducted to identify risk factors for unsuccessful TB treatment. Among the 219 patients analyzed, 53.4% achieved successful outcomes (cure, completed treatment) while 46.6% of patients had unsuccessful outcomes (default, treatment failure, died). After adjusting for other factors, unsuccessful outcome was associated with intravenous drug use (OR 2.72; 95% CI 1.44-5.16), not receiving antiretroviral therapy (OR 5.10; 95% CI 2.69-9.69), lymphadenopathy (OR 2.01; 95% CI 1.09-3.72) and low serum albumin (OR 4.61; 95% CI 1.73-12.27). Anti-retroviral treatment must be provided to all HIV-infected tuberculosis patients. Good immune and nutritional status needs to be assured in all HIV-infected tuberculosis patients. More studies are required in intravenous drug users to understand why tuberculosis treatment outcomes are poor in this group. Copyright © 2013 Elsevier Inc. All rights reserved.

Cost effectiveness of denosumab compared with oral bisphosphonates in the treatment of post-menopausal osteoporotic women in Belgium.

PubMed

Hiligsmann, Mickaël; Reginster, Jean-Yves

2011-10-01

Denosumab has recently been shown to be well tolerated, to increase bone mineral density (BMD) and to significantly reduce the risk of hip, vertebral and non-vertebral fractures in the FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial. It is becoming increasingly important to evaluate not only the therapeutic value of a new drug but also the cost effectiveness compared with the most relevant treatment alternatives. The objective of this study was to estimate the cost effectiveness of denosumab compared with oral bisphosphonates (branded and generic drugs) in the treatment of post-menopausal osteoporotic women in Belgium. Cost effectiveness of 3 years of treatment with denosumab was compared with branded risedronate and branded and generic alendronate using an updated version of a previously validated Markov microsimulation model. The model was populated with relevant cost, adherence and epidemiological data for Belgium from a payer perspective and the results were presented as costs per QALY gained (&U20AC;, year 2009 values). Analyses were performed in populations (aged ≥60 years) in which osteoporosis medications are currently reimbursed in many European countries, i.e. those with BMD T-score of -2.5 or less or prevalent vertebral fracture. Patients receiving denosumab were assumed to have a 46% lower risk of discontinuation than those receiving oral bisphosphonates, and the effect of denosumab after treatment cessation was assumed to decline linearly to zero over a maximum of 1 year. Denosumab was cost effective compared with all other therapies, assuming a willingness to pay of &U20AC;40 000 per QALY gained. In particular, denosumab was found to be cost effective compared with branded alendronate and risedronate at a threshold value of &U20AC;30 000 per QALY and denosumab was dominant (i.e. lower cost and greater effectiveness) compared with risedronate from the age of 70 years in women with a T-score of -2.5 or

Treatment outcomes of multidrug-resistant tuberculosis patients in Zhejiang, China, 2009-2013.

PubMed

Zhang, L; Meng, Q; Chen, S; Zhang, M; Chen, B; Wu, B; Yan, G; Wang, X; Jia, Z

2018-04-01

To examine treatment outcomes and factors associated with poor outcome of multidrug-resistant (MDR) tuberculosis (TB) in China. We conducted a prospective observational cohort study including consecutive patients with MDR-TB between 2009 and 2013 in six regions of Zhejiang province. Patients were prescribed treatments by infectious disease specialists, and treatment outcomes were recorded. Sociodemographic characteristics were obtained through a structured questionnaire. The primary endpoint was poor treatment outcomes, defined as treatment failure based on microbiologic persistence, default (lost to follow-up) or death at 24 months. We assessed risk factors for poor treatment outcomes using a Cox proportional hazards model. A total of 820 MDR-TB patients were observed, and 537 with known treatment outcomes were included in our study. Overall, the treatment success rate was 40.2 per 100 years (374/537 participants, 69.6%), while treatment failure, death and default rates were 10.0 per 100 years (101 participants, 18.8%), 3.4 per 100 years (36 participants, 6.7%) and 2.7 per 100 years (26 participants, 4.8%) respectively. Independent predictors of poor treatment outcomes included age >60 years (hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.2-4.2), patients registered as experiencing relapse (HR 2.2, 95% CI 1.1-4.4), patients registered as receiving treatment after failure (HR 2.4, 95% CI 1.2-4.9), use of standardized MDR-TB regimens (HR 0.6, 95% CI 0.4-1.0), cavitary disease (HR 4.9, 95% CI 2.8-8.6) and adverse events (HR 2.5, 95% CI 1.2-5.5). Under well-designed treatment and management scheme, high treatment success rates were achieved in a high-MDR-TB-burden country. Antimicrobial susceptibility testing for all second-line drugs should be conducted to further assist in the treatment of MDR-TB. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Childhood Sexual Abuse Patterns, Psychosocial Correlates, and Treatment Outcomes among Adults in Drug Abuse Treatment

ERIC Educational Resources Information Center

Boles, Sharon M.; Joshi, Vandana; Grella, Christine; Wellisch, Jean

2005-01-01

This study reports on the effects of having a history of childhood sexual abuse (CSA) on treatment outcomes among substance abusing men and women (N = 2,434) in a national, multisite study of drug treatment outcomes. A history of CSA was reported by 27.2% of the women and 9.2% of the men. Controlling for gender, compared to patients without CSA,…

Combining clinical variables to optimize prediction of antidepressant treatment outcomes.

PubMed

Iniesta, Raquel; Malki, Karim; Maier, Wolfgang; Rietschel, Marcella; Mors, Ole; Hauser, Joanna; Henigsberg, Neven; Dernovsek, Mojca Zvezdana; Souery, Daniel; Stahl, Daniel; Dobson, Richard; Aitchison, Katherine J; Farmer, Anne; Lewis, Cathryn M; McGuffin, Peter; Uher, Rudolf

2016-07-01

The outcome of treatment with antidepressants varies markedly across people with the same diagnosis. A clinically significant prediction of outcomes could spare the frustration of trial and error approach and improve the outcomes of major depressive disorder through individualized treatment selection. It is likely that a combination of multiple predictors is needed to achieve such prediction. We used elastic net regularized regression to optimize prediction of symptom improvement and remission during treatment with escitalopram or nortriptyline and to identify contributing predictors from a range of demographic and clinical variables in 793 adults with major depressive disorder. A combination of demographic and clinical variables, with strong contributions from symptoms of depressed mood, reduced interest, decreased activity, indecisiveness, pessimism and anxiety significantly predicted treatment outcomes, explaining 5-10% of variance in symptom improvement with escitalopram. Similar combinations of variables predicted remission with area under the curve 0.72, explaining approximately 15% of variance (pseudo R(2)) in who achieves remission, with strong contributions from body mass index, appetite, interest-activity symptom dimension and anxious-somatizing depression subtype. Escitalopram-specific outcome prediction was more accurate than generic outcome prediction, and reached effect sizes that were near or above a previously established benchmark for clinical significance. Outcome prediction on the nortriptyline arm did not significantly differ from chance. These results suggest that easily obtained demographic and clinical variables can predict therapeutic response to escitalopram with clinically meaningful accuracy, suggesting a potential for individualized prescription of this antidepressant drug. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Bioequivalence of generic alendronate sodium tablets (70 mg) to Fosamax® tablets (70 mg) in fasting, healthy volunteers: a randomized, open-label, three-way, reference-replicated crossover study

PubMed Central

Zhang, Yifan; Chen, Xiaoyan; Tang, Yunbiao; Lu, Youming; Guo, Lixia; Zhong, Dafang

2017-01-01

Purpose The aim of this study was to evaluate the bioequivalence of a generic product 70 mg alendronate sodium tablets with the reference product Fosamax® 70 mg tablet. Materials and methods A single-center, open-label, randomized, three-period, three-sequence, reference-replicated crossover study was performed in 36 healthy Chinese male volunteers under fasting conditions. In each study period, the volunteers received a single oral dose of the generic or reference product (70 mg). Blood samples were collected at pre-dose and up to 8 h after administration. The bioequivalence of the generic product to the reference product was assessed using the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) reference-scaled average bioequivalence (RSABE) methods. Results The average maximum concentrations (Cmax) of alendronic acid were 64.78±43.76, 56.62±31.95, and 60.15±37.12 ng/mL after the single dose of the generic product and the first and second doses of the reference product, respectively. The areas under the plasma concentration–time curves from time 0 to the last timepoint (AUC0–t) were 150.36±82.90, 148.15±85.97, and 167.11±110.87 h⋅ng/mL, respectively. Reference scaling was used because the within-subject standard deviations of the reference product (sWR) for Cmax and AUC0–t were all higher than the cutoff value of 0.294. The 95% upper confidence bounds were −0.16 and −0.17 for Cmax and AUC0–t, respectively, and the point estimates for the generic/reference product ratio were 1.08 and 1.00, which satisfied the RSABE acceptance criteria of the FDA. The 90% CIs for Cmax and AUC0–t were 90.35%–129.04% and 85.31%–117.15%, respectively, which were within the limits of the EMA for the bioequivalence of 69.84%–143.19% and 80.00%–125.00%. Conclusion The generic product was bioequivalent to the reference product in terms of the rate and extent of alendronate absorption after a single 70 mg oral dose under fasting

ECT treatment outcomes following performance improvement changes.

PubMed

Pulia, Kathy; Vaidya, Punit; Jayaram, Geetha; Hayat, Matthew J; Reti, Irving M

2013-11-01

Differences in electroconvulsive therapy (ECT) outcomes were explored following changes in ECT administration at our institution. Two changes were introduced: (a) switching the anesthetic agent from propofol to methohexital, and (b) using a more aggressive ECT charge dosing regimen for right unilateral (RUL) electrode placement. Length of stay (LOS) and number of treatments administered per patient were monitored. A retrospective analysis was performed of two inpatient groups treated on our Mood Disorders Unit: those who underwent ECT in the 12 months prior to the changes (n = 40) and those who underwent treatment in the 12 months after the changes (n = 38). Compared with patients receiving ECT with RUL placement prior to the changes, patients who received RUL ECT after the changes had a significantly shorter inpatient LOS (27.4 versus 18 days, p = 0.028). Treatment efficacy monitored by the Montgomery Asberg Depression Rating Scale was not impacted. The change in anesthetic agent and charge dosing each accounted for 11% of the variance in LOS among patients receiving RUL ECT. The implemented changes in ECT administration positively impacted outcome for patients receiving treatment with RUL electrode placement. Copyright 2013, SLACK Incorporated.

Experiential acceptance, motivation for recovery, and treatment outcome in eating disorders.

PubMed

Espel, Hallie M; Goldstein, Stephanie P; Manasse, Stephanie M; Juarascio, Adrienne S

2016-06-01

This study sought to test whether the relationship between experiential acceptance (EA) and treatment outcome among eating disorder (ED) patients was mediated by motivation. Upon admission to a residential ED treatment facility, female patients completed measures of EA, motivation, and baseline ED symptom severity (covariate); symptom severity was reassessed at discharge. Higher levels of baseline EA predicted significantly greater symptom reduction during treatment. Moreover, results from bootstrapped mediation analyses indicated that the relationship between EA and treatment outcome was partially mediated by motivation: increased EA was associated with greater motivation to give up ED behaviors at the beginning of treatment, and this led to greater symptom reduction from admission to discharge. Motivation appears to be one mechanism by which EA facilitates improved treatment outcomes in EDs. Further development of interventions that promote EA as a means for improving motivation and subsequent ED treatment response may be warranted.

In Vitro and In Vivo Evaluation of Commercially Available Fibrin Gel as a Carrier of Alendronate for Bone Tissue Engineering.

PubMed

Kim, Beom Su; Shkembi, Feride; Lee, Jun

2017-01-01

Alendronate (ALN) is a bisphosphonate drug that is widely used for the treatment of osteoporosis. Furthermore, local delivery of ALN has the potential to improve the bone regeneration. This study was designed to investigate an ALN-containing fibrin (fibrin/ALN) gel and evaluate the effect of this gel on both in vitro cellular behavior using human mesenchymal stem cells (hMSCs) and in vivo bone regenerative capacity. Fibrin hydrogels were fabricated using various ALN concentrations (10 -7 -10 -4  M) with fibrin glue and the morphology, mechanical properties, and ALN release kinetics were characterized. Proliferation and osteogenic differentiation of and cytotoxicity in fibrin/ALN gel-embedded hMSCs were examined. In vivo bone formation was evaluated using a rabbit calvarial defect model. The fabricated fibrin/ALN gel was transparent with Young's modulus of ~13 kPa, and these properties were not affected by ALN concentration. The in vitro studies showed sustained release of ALN from the fibrin gel and revealed that hMSCs cultured in fibrin/ALN gel showed significantly increased proliferation and osteogenic differentiation. In addition, microcomputed tomography and histological analysis revealed that the newly formed bone was significantly enhanced by implantation of fibrin/ALN gel in a calvarial defect model. These results suggest that fibrin/ALN has the potential to improve bone regeneration.

In Vitro and In Vivo Evaluation of Commercially Available Fibrin Gel as a Carrier of Alendronate for Bone Tissue Engineering

PubMed Central

Kim, Beom Su; Shkembi, Feride

2017-01-01

Alendronate (ALN) is a bisphosphonate drug that is widely used for the treatment of osteoporosis. Furthermore, local delivery of ALN has the potential to improve the bone regeneration. This study was designed to investigate an ALN-containing fibrin (fibrin/ALN) gel and evaluate the effect of this gel on both in vitro cellular behavior using human mesenchymal stem cells (hMSCs) and in vivo bone regenerative capacity. Fibrin hydrogels were fabricated using various ALN concentrations (10−7–10−4 M) with fibrin glue and the morphology, mechanical properties, and ALN release kinetics were characterized. Proliferation and osteogenic differentiation of and cytotoxicity in fibrin/ALN gel-embedded hMSCs were examined. In vivo bone formation was evaluated using a rabbit calvarial defect model. The fabricated fibrin/ALN gel was transparent with Young's modulus of ~13 kPa, and these properties were not affected by ALN concentration. The in vitro studies showed sustained release of ALN from the fibrin gel and revealed that hMSCs cultured in fibrin/ALN gel showed significantly increased proliferation and osteogenic differentiation. In addition, microcomputed tomography and histological analysis revealed that the newly formed bone was significantly enhanced by implantation of fibrin/ALN gel in a calvarial defect model. These results suggest that fibrin/ALN has the potential to improve bone regeneration. PMID:28210623

Trends in treatment and outcomes of pediatric craniopharyngioma, 1975-2011.

PubMed

Cohen, Michal; Bartels, Ute; Branson, Helen; Kulkarni, Abhaya V; Hamilton, Jill

2013-06-01

Craniopharyngioma tumors and their treatment can lead to significant long-term morbidity due to their proximity to vital structures. The optimal treatment has been debated for many years. We aimed to review the long-term outcomes of children treated for craniopharyngioma in our institution over the past decade and describe trends in treatment and outcomes over the past 3 decades. Charts of children with craniopharyngioma treated and followed at The Hospital for Sick Children between 2001 and 2011 were reviewed. Data regarding findings at diagnosis, treatment, and long-term outcomes were analyzed. Comparison was made with previously published data from our institution. Data from 33 patients are included; mean age at treatment, 10.7 ± 4.8 years. In 18 children (55%), the initial surgical approach was tumor cyst decompression with or without adjuvant therapy, compared with only 0-2% in the preceding decades (P < .01). Diabetes insipidus occurred in 55% of children and panhypopituitarism in 58% compared with 88% (P < .01) and 86% (P < .01), respectively, in the previous 10 years. Overall, there was a 36% reduction in the number of children who developed severe obesity compared with the preceding decade. Body mass index at follow-up was associated with body mass index at diagnosis (P = .004) and tumor resection as an initial treatment approach (P = .028). A shift in surgical treatment approach away from gross total resection has led to improved endocrine outcomes. This may have beneficial implications for quality of life in survivors.

Improved Binocular Outcomes Following Binocular Treatment for Childhood Amblyopia

PubMed Central

Kelly, Krista R.; Jost, Reed M.; Wang, Yi-Zhong; Dao, Lori; Beauchamp, Cynthia L.; Leffler, Joel N.; Birch, Eileen E.

2018-01-01

Purpose Childhood amblyopia can be treated with binocular games or movies that rebalance contrast between the eyes, which is thought to reduce depth of interocular suppression so the child can experience binocular vision. While visual acuity gains have been reported following binocular treatment, studies rarely report gains in binocular outcomes (i.e., stereoacuity, suppression) in amblyopic children. Here, we evaluated binocular outcomes in children who had received binocular treatment for childhood amblyopia. Methods Data for amblyopic children enrolled in two ongoing studies were pooled. The sample included 41 amblyopic children (6 strabismic, 21 anisometropic, 14 combined; age 4–10 years; ≤4 prism diopters [PD]) who received binocular treatment (20 game, 21 movies; prescribed 9–10 hours treatment). Amblyopic eye visual acuity and binocular outcomes (Randot Preschool Stereoacuity, extent of suppression, and depth of suppression) were assessed at baseline and at 2 weeks. Results Mean amblyopic eye visual acuity (P < 0.001) and mean stereoacuity improved (P = 0.045), and mean extent (P = 0.005) and depth of suppression (P = 0.003) were reduced from baseline at the 2-week visit (87% game adherence, 100% movie adherence). Depth of suppression was reduced more in children aged <8 years than in those aged ≥8 years (P = 0.004). Worse baseline depth of suppression was correlated with a larger depth of suppression reduction at 2 weeks (P = 0.001). Conclusions After 2 weeks, binocular treatment in amblyopic children improved visual acuity and binocular outcomes, reducing the extent and depth of suppression and improving stereoacuity. Binocular treatments that rebalance contrast to overcome suppression are a promising additional option for treating amblyopia. PMID:29625442

Improved Binocular Outcomes Following Binocular Treatment for Childhood Amblyopia.

PubMed

Kelly, Krista R; Jost, Reed M; Wang, Yi-Zhong; Dao, Lori; Beauchamp, Cynthia L; Leffler, Joel N; Birch, Eileen E

2018-03-01

Childhood amblyopia can be treated with binocular games or movies that rebalance contrast between the eyes, which is thought to reduce depth of interocular suppression so the child can experience binocular vision. While visual acuity gains have been reported following binocular treatment, studies rarely report gains in binocular outcomes (i.e., stereoacuity, suppression) in amblyopic children. Here, we evaluated binocular outcomes in children who had received binocular treatment for childhood amblyopia. Data for amblyopic children enrolled in two ongoing studies were pooled. The sample included 41 amblyopic children (6 strabismic, 21 anisometropic, 14 combined; age 4-10 years; ≤4 prism diopters [PD]) who received binocular treatment (20 game, 21 movies; prescribed 9-10 hours treatment). Amblyopic eye visual acuity and binocular outcomes (Randot Preschool Stereoacuity, extent of suppression, and depth of suppression) were assessed at baseline and at 2 weeks. Mean amblyopic eye visual acuity (P < 0.001) and mean stereoacuity improved (P = 0.045), and mean extent (P = 0.005) and depth of suppression (P = 0.003) were reduced from baseline at the 2-week visit (87% game adherence, 100% movie adherence). Depth of suppression was reduced more in children aged <8 years than in those aged ≥8 years (P = 0.004). Worse baseline depth of suppression was correlated with a larger depth of suppression reduction at 2 weeks (P = 0.001). After 2 weeks, binocular treatment in amblyopic children improved visual acuity and binocular outcomes, reducing the extent and depth of suppression and improving stereoacuity. Binocular treatments that rebalance contrast to overcome suppression are a promising additional option for treating amblyopia.

Smoking Status and Substance Use Treatment Outcomes Among Spanish Speakers Enrolled in Substance Abuse Treatment.

PubMed

de Dios, Marcel A; Cano, Miguel Ángel; Childress, Sarah; Vaughan, Ellen; Cerna, Yohanna; Niaura, Raymond

2016-10-01

Smoking is highly prevalent among individuals with drug and alcohol disorders. Concurrent tobacco dependence treatment during substance use disorder (SUD) treatment is supported, yet the association between SUD treatment outcomes and smoking status has been understudied in minorities, including Latinos. Participants were 322 Spanish-speaking Latinos enrolled in a SUD treatment study in 5 U.S. cities. Logistic regression examined associations between baseline smoking status and treatment outcomes for nontobacco substance use at follow-up. Covariates included age, gender, level of education, marital status, treatment group, and mandated treatment status. Results indicated smokers had a reduced likelihood of abstinence for all nontobacco substances (p = .001) and their primary drug of use (p = .007). Findings contribute to the growing literature indicating a possible beneficial effect of smoking cessation services on SUD treatment, specifically among Latinos. Further research is needed to identify ideal smoking cessation treatments for Latinos. © 2016 Wiley Periodicals, Inc.

Tc-99m Radiolabeled Alendronate Sodium Microemulsion: Characterization and Permeability Studies Across Caco-2 Cells.

PubMed

Elitez, Yetkin; Ekinci, Meliha; Ilem-Ozdemir, Derya; Gundogdu, Evren; Asikoglu, Makbule

2018-01-01

Alendronate sodium (ALD) is used orally but it is poorly absorbed from the gastrointestinal (GI) tract. For this reason, microemulsion system was chosen to evaluate ALD from the GI tract after oral delivery. This study was aimed to prepare water-in-oil (w/o) microemulsion formulation of ALD and evaluate the permeability of ALD microemulsion from Caco-2 cell lines with radioactive and nonradioactive studies. The ALD microemulsion was developed by using pseudo-ternary phase diagram and composed of Soybean oil, Colliphor EL, Tween 80, Transcutol and distilled water. The prepared ALD microemulsion was characterized by physical appearance, droplet size, viscosity, pH, electrical conductivity and refractive index. The stability of the formulation was investigated for 6 months at 25±2°C/60±5% of relative humidity (RH) as well as at 40±2°C/75±5% RH. After that 1 mg of ALD was radiolabeled with 99mTc and added to microemulsion. The permeability studies were performed with both 99mTc-ALD microemulsion and ALD microemulsion. The experimental results suggested that ALD microemulsion presented adequate stability with droplet size varying from 37.8±0.9 to 39.9±1.2 nm during incubation time. In addition, ALD microemulsion was radiolabeled with high labeling efficiency (>95%). In a non-radioactive study, ALD permeability was found to be 45 µg.mL-1 and microemulsion has high permeability percentage when compared to another study. The novel w/o microemulsion formulation has been developed for oral delivery of ALD. Based on the results, permeability of ALD could be significantly improved by the microemulsion formulation. In addition, 99mTc-ALD microemulsion in capsule can be used for bone disease treatment and diagnosis. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Change in expressed emotion and treatment outcome in adolescent anorexia nervosa.

PubMed

Moskovich, Ashley A; Timko, C Alix; Honeycutt, Lisa K; Zucker, Nancy L; Merwin, Rhonda M

2017-01-01

Expressed emotion (EE) has been associated with poor outcomes in anorexia nervosa (AN); however, whether changes in EE predict superior treatment outcomes is unknown. The current study examined whether decreases in EE during an open trial of a novel family-based treatment for AN predicted symptoms at end of treatment. Forty-seven adolescents (12-18 years of age) with AN or sub-threshold AN and their parents (mothers: n = 47, fathers: n = 39) participated in 6 months of family treatment. Measures of AN symptomatology (Eating Disorder Examination completed by adolescent and end of treatment recovery status) and parental EE (Family Questionnaire completed by parents which measures two facets of EE: critical communication [CC] and emotional over-involvement [EOI]) were collected at baseline and end of treatment. Parental EOI, but not CC, significantly decreased during the course of treatment. Change in mothers', but not fathers', EE accounted for additional variance in AN symptomatology at end of treatment above baseline EE and baseline AN symptom levels. Findings suggest a greater emphasis on parent support during treatment may improve outcomes.

Experiential acceptance, motivation for recovery, and treatment outcome in eating disorders

PubMed Central

Espel, Hallie M.; Goldstein, Stephanie P.; Manasse, Stephanie M.; Juarascio, Adrienne S.

2016-01-01

Purpose This study sought to test whether the relationship between experiential acceptance (EA) and treatment outcome among eating disorder (ED) patients was mediated by motivation. Methods Upon admission to a residential ED treatment facility, female patients completed measures of EA, motivation, and baseline ED symptom severity (covariate); symptom severity was reassessed at discharge. Results Higher levels of baseline EA predicted significantly greater symptom reduction during treatment. Moreover, results from bootstrapped mediation analyses indicated that the relationship between EA and treatment outcome was partially mediated by motivation: increased EA was associated with greater motivation to give up ED behaviors at the beginning of treatment, and this led to greater symptom reduction from admission to discharge. Conclusions Motivation appears to be one mechanism by which EA facilitates improved treatment outcomes in EDs. Further development of interventions that promote EA as a means for improving motivation and subsequent ED treatment response may be warranted. PMID:26511501

A model-based cost-effectiveness analysis of osteoporosis screening and treatment strategy for postmenopausal Japanese women.

PubMed

Yoshimura, M; Moriwaki, K; Noto, S; Takiguchi, T

2017-02-01

Although an osteoporosis screening program has been implemented as a health promotion project in Japan, its cost-effectiveness has yet to be elucidated fully. We performed a cost-effectiveness analysis and found that osteoporosis screening and treatment would be cost-effective for Japanese women over 60 years. The purpose of this study was to estimate the cost-effectiveness of osteoporosis screening and drug therapy in the Japanese healthcare system for postmenopausal women with no history of fracture. A patient-level state transition model was developed to predict the outcomes of Japanese women with no previous fracture. Lifetime costs and quality-adjusted life years (QALYs) were estimated for women who receive osteoporosis screening and alendronate therapy for 5 years and those who do not receive the screening and treatments. The incremental cost-effectiveness ratio (ICER) of the screening option compared with the no screening option was estimated. Sensitivity analyses were performed to examine the influence of parameter uncertainty on the base case results. The ICERs of osteoporosis screening and treatments for Japanese women aged 50-54, 55-59, 60-64, 65-69, 70-74, and 75-79 years were estimated to be $89,242, $64,010, $40,596, $27,697, $17,027, and $9771 per QALY gained, respectively. Deterministic sensitivity analyses showed that several parameters such as the disutility due to vertebral fracture had a significant influence on the base case results. Applying a willingness to pay of $50,000 per QALY gained, the probability that the screening option became cost-effectiveness estimated to 50.9, 56.3, 59.1, and 64.7 % for women aged 60-64, 65-69, 70-74, and 75-79 years, respectively. Scenario analyses showed that the ICER for women aged 55-59 years with at least one clinical risk factor was below $50,000 per QALY. In conclusion, dual energy X-ray absorptiometry (DXA) screening and alendronate therapy for osteoporosis would be cost-effective for

Adverse pregnancy outcomes following syphilis treatment in pregnancy in the UK.

PubMed

Wallace, Harriet E; Isitt, Catherine E; Broomhall, Harriet M; Perry, Alison E; Wilson, Janet D

2016-10-01

Syphilis infection in pregnancy is known to cause a number of severe adverse pregnancy outcomes, including second-trimester miscarriage, stillbirth, very pre-term delivery and neonatal death, in addition to congenital syphilis. A retrospective review of women with positive syphilis serology and a pregnancy outcome between 2005 and 2012 in Leeds, UK, was performed. In all, 57 cases of positive syphilis serology in pregnancy were identified: 24 with untreated syphilis treated in the current pregnancy (Group 1); seven with reported but unconfirmed prior treatment who were retreated (Group 2); and 26 adequately treated prior to pregnancy (Group 3). The rate of severe adverse pregnancy outcomes in Group 1 at 21% was significantly higher than the 0% outcome of Group 3 (p = 0.02). The severe adverse pregnancy outcomes were two second-trimester miscarriages, two pre-term births at 25 and 28 weeks and one stillbirth at 32 weeks. There were no cases of term congenital syphilis or term neonatal death, but we observed high rates of other adverse pregnancy outcomes despite treatment during pregnancy. Rapid referral for treatment is needed before 18 weeks in order to minimise adverse pregnancy outcomes. © The Author(s) 2016.

Tuberculosis treatment outcome and predictors in northern Ethiopian prisons: a five-year retrospective analysis.

PubMed

Adane, Kelemework; Spigt, Mark; Dinant, Geert-Jan

2018-02-20

The prison situations are notorious for causing interruptions of tuberculosis (TB) treatment and occurrence of unfavorable outcomes. In Ethiopian prisons, though TB treatment programs exist, treatment outcome results and factors contributing to unsuccessful outcome are not well documented. In this study, we assessed the treatment outcome of TB cases and identified risk factors for unsuccessful outcome in northern Ethiopian prisons. A retrospective record review was conducted for all prisoners diagnosed with TB between September 2011 and August 2015. Outcome variables were defined following WHO guidelines. Out of the 496 patients, 11.5% were cured, 68% completed treatment, 2.5% were lost to follow-up, 1.6% were with a treatment failure, 1.4% died, and 15% were transferred out. All transferred out or released prisoners were not appropriately linked to health facilities and might be lost to treatment follow-up. The overall treatment success rate (TSR) of the 5 years was 94% among the patients who were not transferred out. The odds of unsuccessful outcome were 4.68 times greater among re-treatment cases compared to the newly treated cases. The year of treatment was also associated with variations in TSR; those treated during the earlier year were more likely to have unsuccessful outcome. Sputum non-conversion at the second-month check-up was strongly associated with unsuccessful outcome among the smear-positive cases. The mean TSR of the prisoners in the study prisons was quite satisfactory when gauged against the target level set by the End TB Strategy. However, the lack of appropriate linkage and tracking systems for those prisoners transferred or released before their treatment completion would have a negative implication for the national TB control program as such patients might interrupt their treatment and develop drug-resistant TB. Being in a re-treatment regimen and sputum non-conversion at the second-month check-up were significantly associated with

Comparison of treatment outcomes of transnasal vocal fold polypectomy versus microlaryngoscopic surgery.

PubMed

Wang, Chi-Te; Liao, Li-Jen; Huang, Tsung-Wei; Lo, Wu-Chia; Cheng, Po-Wen

2015-05-01

Office-based procedures have been proposed for the treatment of vocal polyps, including indirect laryngoscopic surgery and angiolytic laser photocoagulation. Our previous report documented good treatment outcomes by combining the two aforementioned procedures. This study was intended to further compare the treatment outcomes of office transnasal vocal fold polypectomy (VFP) with those of microlaryngoscopic surgery (MLS). A matched cohort study. This study retrospectively enrolled 50 age-, gender-, and size-matched patients with vocal polyps treated by VFP or MLS at a tertiary teaching hospital from January 2012 to October 2013. Treatment outcomes were evaluated before, 2 weeks, and 6 weeks after the procedures via perceptual rating of voice quality, acoustic measurement of the speech signal, 10-item voice-handicap index, maximal phonation time, subjective rating of voice quality, and videolaryngostroboscopic evaluation. Both VFP and MLS resulted in significant clinical improvements 2 and 6 weeks postoperatively. Study results exhibited similar objective outcomes between VFP and MLS, whereas patients who received VFP reported higher subjective voice quality than those receiving MLS 2 weeks postoperatively. Six weeks after the procedures, the objective and subjective treatment outcomes were not significantly different between the two treatment groups. This study shows that transnasal VFP may be used as an effective alternative treatment for small vocal polyps. Patients who received office VFP experienced rapid symptomatic relief with a higher degree of subjective effectiveness than MLS 2 weeks postoperatively, whereas the overall treatment outcomes showed a comparable level of effectiveness for both modalities. 3B. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Design, Synthesis, and Pharmacokinetics of a Bone-Targeting Dual-Action Prodrug for the Treatment of Osteoporosis.

PubMed

Xie, Haibo; Chen, Gang; Young, Robert N

2017-08-24

A dual-action bone-targeting prodrug has been designed, synthesized, and evaluated for in vitro and in vivo metabolic stability, in vivo tissue distribution, and rates of release of the active constituents after binding to bones through the use of differentially double-labeled derivatives. The conjugate (general structure 7) embodies the merger of a very potent and proven anabolic selective agonist of the prostaglandin EP4 receptor, compound 5, and alendronic acid, a potent inhibitor of bone resorption, optimally linked through a differentially hydrolyzable linker unit, N-4-carboxymethylphenyl-methyloxycarbonyl-leucinyl-argininyl-para-aminophenylmethylalcohol (Leu-Arg-PABA). Optimized conjugate 16 was designed so that esterase activity will liberate 5 and cathepsin K cleavage of the Leu-Arg-PABA element will liberate alendronic acid. Studies with doubly radiolabeled 16 provide a proof-of-concept for the use of a cathepsin K cleavable peptide-linked conjugate for targeting of bisphosphonate prodrugs to bone and slow release liberation of the active constituents in vivo. Such conjugates are potential therapies for the treatment of bone disorders such as osteoporosis.

Novel Methods of Determining Urinary Calculi Composition: Petrographic Thin Sectioning of Calculi and Nanoscale Flow Cytometry Urinalysis

PubMed Central

Gavin, Carson T; Ali, Sohrab N; Tailly, Thomas; Olvera-Posada, Daniel; Alenezi, Husain; Power, Nicholas E; Hou, Jinqiang; St. Amant, Andre H; Luyt, Leonard G; Wood, Stephen; Wu, Charles; Razvi, Hassan; Leong, Hon S

2016-01-01

Accurate determination of urinary stone composition has significant bearing on understanding pathophysiology, choosing treatment modalities and preventing recurrence. A need exists for improved methods to determine stone composition. Urine of 31 patients with known renal calculi was examined with nanoscale flow cytometry and the calculi collected during surgery subsequently underwent petrographic thin sectioning with polarized and fluorescent microscopy. Fluorescently labeled bisphosphonate probes (Alendronate-fluorescein/Alendronate-Cy5) were developed for nanoscale flow cytometry to enumerate nanocrystals that bound the fluorescent probes. Petrographic sections of stones were also imaged by fluorescent and polarized light microscopy with composition analysis correlated to alendronate +ve nanocrystal counts in corresponding urine samples. Urine samples from patients with Ca2+ and Mg2+ based calculi exhibited the highest alendronate +ve nanocrystal counts, ranging from 100–1000 nm in diameter. This novel urine based assay was in agreement with composition determined by petrographic thin sections with Alendronate probes. In some cases, high alendronate +ve nanocrystal counts indicated a Ca2+ or Mg2+ composition, as confirmed by petrographic analysis, overturning initial spectrophotometric diagnosis of stone composition. The combination of nanoscale flow cytometry and petrographic thin sections offer an alternative means for determining stone composition. Nanoscale flow cytometry of alendronate +ve nanocrystals alone may provide a high-throughput means of evaluating stone burden. PMID:26771074

Effect of Treatment Modality on Long-Term Outcomes in Attention-Deficit/Hyperactivity Disorder: A Systematic Review

PubMed Central

Arnold, L. Eugene; Hodgkins, Paul; Caci, Hervé; Kahle, Jennifer; Young, Susan

2015-01-01

Background Evaluation of treatments for attention-deficit/hyperactivity disorder (ADHD) previously focused on symptom control, but attention has shifted to functional outcomes. The effect of different ADHD treatment periods and modalities (pharmacological, non-pharmacological, and combination) on long-term outcomes needs to be more comprehensively understood. Methods A systematic search of 12 literature databases using Cochrane’s guidelines yielded 403 English-language peer-reviewed, primary studies reporting long-term outcomes (≥2 years). We evaluated relative effects of treatment modalities and durations and effect sizes of outcomes reported as statistically significantly improved with treatment. Results The highest proportion of improved outcomes was reported with combination treatment (83% of outcomes). Among significantly improved outcomes, the largest effect sizes were found for combination treatment. The greatest improvements were associated with academic, self-esteem, or social function outcomes. A majority of outcomes improved regardless of age of treatment initiation (60%–75%) or treatment duration (62%–72%). Studies with short treatment duration had shorter follow-up times (mean 3.2 years total study length) than those with longer treatment durations (mean 7.1 years total study length). Studies with follow-up times <3 years reported benefit with treatment for 93% of outcomes, whereas those with follow-up times ≥3 years reported treatment benefit for 57% of outcomes. Post-hoc analysis indicated that this result was related to the measurement of outcomes at longer periods (3.2 versus 0.4 years) after treatment cessation in studies with longer total study length. Conclusions While the majority of long-term outcomes of ADHD improve with all treatment modalities, the combination of pharmacological and non-pharmacological treatment was most consistently associated with improved long-term outcomes and large effect sizes. Older treatment initiation age

Substance use disorder patients who are mandated to treatment: characteristics, treatment process, and 1- and 5-year outcomes.

PubMed

Kelly, John F; Finney, John W; Moos, Rudolf

2005-04-01

A substantial number of patients with substance use disorders (SUDs) are mandated to treatment by the justice system. However, little is known about their characteristics and how they fare during treatment and in the longer term compared with nonmandated, justice-system-involved patients and patients not involved in the justice system. This prospective study (n=2,095) examined differences in pretreatment characteristics, treatment perceptions and satisfaction, during-treatment changes, and 1- and 5-year outcomes among these three types of patients and tested whether differences in pretreatment characteristics or during-treatment changes could help explain posttreatment outcome similarities or differences. Mandated patients had a less severe clinical profile at treatment intake, yet this did not account for their observed similar/better outcomes, which appeared because of the similar therapeutic gains made during treatment. Treatment perceptions and satisfaction were also comparable across groups. These findings appear to support the idea that judicial mandates can provide an opportunity for offenders with SUDs to access and benefit from needed treatment.

Risk factors for poor multidrug-resistant tuberculosis treatment outcomes in Kyiv Oblast, Ukraine.

PubMed

Aibana, Omowunmi; Bachmaha, Mariya; Krasiuk, Viatcheslav; Rybak, Natasha; Flanigan, Timothy P; Petrenko, Vasyl; Murray, Megan B

2017-02-07

Ukraine is among ten countries with the highest burden of multidrug- resistant TB (MDR-TB) worldwide. Treatment success rates for MDR-TB in Ukraine remain below global success rates as reported by the World Health Organization. Few studies have evaluated predictors of poor MDR-TB outcomes in Ukraine. We conducted a retrospective analysis of patients initiated on MDR-TB treatment in the Kyiv Oblast of Ukraine between January 01, 2012 and March 31st, 2015. We defined good treatment outcomes as cure or completion and categorized poor outcomes among those who died, failed treatment or defaulted. We used logistic regression analyses to identify baseline patient characteristics associated with poor MDR-TB treatment outcomes. Among 360 patients, 65 (18.1%) achieved treatment cure or completion while 131 (36.4%) died, 115 (31.9%) defaulted, and 37 (10.3%) failed treatment. In the multivariate analysis, the strongest baseline predictors of poor outcomes were HIV infection without anti-retroviral therapy (ART) initiation (aOR 10.07; 95% CI 1.20-84.45; p 0.03) and presence of extensively-drug resistant TB (aOR 9.19; 95% CI 1.17-72.06; p 0.03). HIV-positive patients initiated on ART were not at increased risk of poor outcomes (aOR 1.43; 95% CI 0.58-3.54; p 0.44). There was no statistically significant difference in risk of poor outcomes among patients who received baseline molecular testing with Gene Xpert compared to those who were not tested (aOR 1.31; 95% CI 0.63-2.73). Rigorous compliance with national guidelines recommending prompt initiation of ART among HIV/TB co-infected patients and use of drug susceptibility testing results to construct treatment regimens can have a major impact on improving MDR-TB treatment outcomes in Ukraine.

Dimensional personality traits and alcohol treatment outcome: a systematic review and meta-analysis.

PubMed

Foulds, James; Newton-Howes, Giles; Guy, Nicola H; Boden, Joseph M; Mulder, Roger T

2017-08-01

To identify dimensional personality traits associated with treatment outcome for patients with an alcohol use disorder (AUD). Systematic review and meta-analysis of clinical trials and longitudinal studies of ≥ 8 weeks in patients receiving treatment for AUD, in which the association between personality dimensions and treatment outcome was reported. Primary outcomes were relapse and alcohol consumption measures. Treatment retention was a secondary outcome. Eighteen studies, including 4783 subjects, were identified. Twelve studies used Cloninger's Temperament and Personality Questionnaire (TPQ) or Temperament and Character Inventory (TCI). Remaining studies used a broad range of other personality measures. Compared with non-relapsers, patients who relapsed had higher novelty-seeking [standardized mean difference in novelty-seeking score 0.28; 95% confidence interval (CI) = 0.12, 0.44], lower persistence (-0.30, 95% = CI -0.48, -0.12), lower reward dependence (-0.16, 95% CI = -0.31, -0.01) and lower cooperativeness (-0.23, 95% CI = -0.41, -0.04). Few studies reported on alcohol consumption outcomes, therefore findings for those outcomes were inconclusive. Lower novelty-seeking predicted better retention in treatment in two of three studies. Most studies reported findings only for those retained in treatment, and did not attempt to account for missing data; therefore, findings for the primary outcomes cannot be generalized to patients who dropped out of treatment. Studies using personality instruments other than the TCI or TPQ reported no consistent findings on the association between personality variables and treatment outcome. Among patients receiving treatment for an alcohol use disorder, those who relapse during follow-up have higher novelty-seeking, lower persistence, lower reward dependence and lower cooperativeness than those who do not relapse. © 2017 Society for the Study of Addiction.

ENGAGEMENT IN OUTPATIENT SUBSTANCE ABUSE TREATMENT AND EMPLOYMENT OUTCOMES

PubMed Central

Dunigan, Robert; Acevedo, Andrea; Campbell, Kevin; Garnick, Deborah W.; Horgan, Constance M.; Huber, Alice; Lee, Margaret T.; Panas, Lee; Ritter, Grant A.

2013-01-01

This study, a collaboration between an academic research center and Washington State’s health, employment and correction departments, investigates the extent to which treatment engagement, a widely adopted performance measure, is associated with employment, an important outcome for individuals receiving treatment for substance use disorders. Two-stage Heckman probit regressions were conducted using 2008 administrative data for 7,570 adults receiving publicly-funded treatment. The first stage predicted employment in the year following the first treatment visit and three separate second stages models predicted number of quarters employed, wages, and hours worked. Engagement as a main effect was not significant for any of the employment outcomes. However, for clients with prior criminal justice involvement, engagement was associated with both employment and higher wages following treatment. Clients with criminal justice involvement face greater challenge regarding employment, so the identification of any actionable step which increases the likelihood of employment or wages is an important result. PMID:23686216

Alendronate and Resistive Exercise Countermeasures Against Bed Rest-Induced Bone Loss: Biochemical Markers of Bone and Calcium Metabolism

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Nillen, Jeannie L.; Davis-Street, Janis E.; DeKerlegand, Diane E.; LeBlanc, Adrian; Shackelford, Linda C.

2001-01-01

Weightlessness-induced bone loss must be counteracted to ensure crew health during extendedduration space missions. Studies were conducted to assess two bone loss countermeasures in a ground-based model: horizontal bed rest. Following a 3-wk ambulatory adaptation period, male and female subjects (aged 21-56 y) completed a 17-wk bed rest protocol. Subjects were assigned to one of three treatments: alendronate (ALEN; 10 mg/d, n=6), resistive exercise (RE; 1.5 h/d, 6 d/wk, n=8), or control (CN; no countermeasure, n=8). Dietary intake was adjusted to maintain body weight. Endocrine and biochemical indices were measured in blood and urine using standard laboratory methods. All data reported are expressed as percent change from individual pre-bedrest data. Serum calcium changed little during bed rest, and tended to decrease (4-8%) in ALEN subjects. In RE subjects, bone alkaline phosphatase and osteocalcin were increased >65 and >30%, respectively, during bed rest, while these were unchanged or decreased in ALEN and CN subjects. Urinary calcium was increased 50% in CN subjects, but was unchanged or decreased in both ALEN and RE groups. Urinary n-telopeptide excretion was increased 40-50% in CN and RE subjects, but decreased 20% in ALEN subjects. Pyridinium crosslink and deoxypyridinoline excretion were increased 20-50% during bed rest. These data suggest that RE countermeasures are effective at increasing markers of bone formation in an analog of weightlessness, while ALEN reduces markers of bone resorption. Counteracting the bone loss of space flight may require both pharmacologic and exercise countermeasures.

Brainstem encephalitis: etiologies, treatment, and predictors of outcome

PubMed Central

Tan, Ik Lin; Mowry, Ellen M.; Steele, Sonya U.; Pardo, Carlos A.; McArthur, Justin C.; Nath, Avindra

2016-01-01

Brainstem encephalitis (BE) is an uncommon condition. We sought to characterize clinical presentations, etiologies, response to treatment, and predictors of outcome. We performed a retrospective review of non–HIV infected patients diagnosed with BE at Johns Hopkins Hospital (January 1997–April 2010). We characterized clinical and paraclinical features, and used regression models to assess associations with poor outcome. BE was diagnosed in 81 patients. An etiology was identified in 58 of 81 (71.6 %) of cases, most of which were confirmed or probable inflammatory/autoimmune conditions. Of the remaining 23 cases in which a specific diagnosis remained undefined, clinical presentation, CSF, neuroimaging studies, and outcomes were similar to the inflammatory/autoimmune group. Brain biopsy identified a specific diagnosis in 7 of 14 patients (50 %). Fifteen patients (18.5 %) either died or had a poor outcome. In multivariate logistic regression models, a higher CSF protein (per 5 mg/dl, OR = 1.11, 95 % CI: 1.03–1.20), a higher CSF glucose (per 5 mg/dl, OR = 1.36, 95 % CI: 1.09–1.70), and higher serum glucose (per 5 mg/dl, OR = 1.27, 95 % CI: 1.06–1.52) were independently associated with increased odds of poor outcome. Inflammatory and non-infectious conditions accounted for most cases of BE. Higher CSF protein and glucose were independently associated with poor outcome. In immunocompetent patients with BE of undefined etiology despite extensive investigation, a trial of immunosuppressive treatment may be warranted, though deterioration clinically or on magnetic resonance imaging should prompt a brain biopsy. PMID:23749332

High payload nanostructured lipid carriers fabricated with alendronate/polyethyleneimine ion complexes.

PubMed

Abd El-Hamid, Basma N; Swarnakar, Nitin K; Soliman, Ghareb M; Attia, Mohamed A; Pauletti, Giovanni M

2018-01-15

Oral bioavailability of the anti-osteoporotic drug alendronate (AL) is limited to ≤ 1% due to unfavorable physicochemical properties. To augment absorption across the gastrointestinal mucosa, an ion pair complex between AL and polyethyleneimine (PEI) was formed and incorporated into nanostructured lipid carriers (NLCs) using a modified solvent injection method. When compared to free AL, ion pairing with PEI increased drug encapsulation efficiency in NLCs from 10% to 87%. Drug release from NLCs measured in vitro using fasted state simulated intestinal fluid, pH 6.5 (FaSSIF-V2) was significantly delayed after PEI complexation. Stability of AL/PEI was pH-dependent resulting in 10-fold faster dissociation of AL in FaSSIF-V2 than measured at pH 7.4. Intestinal permeation properties estimated in vitro across Caco-2 cell monolayers revealed a 3-fold greater flux of AL encapsulated as hydrophobic ion complex in NLCs when compared to AL solution (P app  = 8.43 ± 0.14 × 10 -6 cm/s and vs. 2.76 ± 0.42 × 10 -6 cm/s). Cellular safety of AL/PEI-containing NLCs was demonstrated up to an equivalent AL concentration of 2.5 mM. These results suggest that encapsulation of AL/PEI in NLCs appears a viable drug delivery strategy for augmenting oral bioavailability of this clinically relevant bisphosphonate drug and, simultaneously, increase gastrointestinal safety. Copyright © 2017 Elsevier B.V. All rights reserved.

Posttreatment Factors Influencing Outcome of Adolescent Chemical Dependency Treatment.

ERIC Educational Resources Information Center

Shoemaker, Ruth H.; Sherry, Patrick

1991-01-01

Adolescents (n=144) in in-patient chemical dependency treatment completed questionnaires designed to determine pre- and posttreatment environmental, psychological, and problem severity influences on outcome of treatment. Results indicated that posttreatment psychosocial environment measures and pretreatment problem severity indicators consistently…

Eleven years of experience with bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I

PubMed Central

Iwamoto, Jun; Sato, Yoshihiro; Uzawa, Mitsuyoshi; Matsumoto, Hideo

2013-01-01

We report the 11-year follow-up of a man with osteogenesis imperfecta type I who was treated with bisphosphonates and alfacalcidol. A 36-year-old Japanese man with osteogenesis imperfecta type I who had frequently experienced painful fragility fractures consulted our clinic because of chronic back pain. The patient had multiple morphometric vertebral fractures and a low bone mineral density (BMD) at the lumbar spine. The patient was treated with cyclical etidronate 200 mg, for 2 weeks every 3 months, plus alfacalcidol 1 μg daily, for 2 years; and alendronate 5 mg daily or 35 mg weekly, plus alfacalcidol 1 μg daily for 9 years. After 11 years of treatment, BMD at the lumbar spine increased by 6.4%, following a 20.3% reduction in serum alkaline phosphatase. Serum calcium, phosphorus, and intact parathyroid hormone levels remained within the normal ranges. Three clinical fractures occurred at two ribs and the metacarpus, and two morphometric vertebral fractures occurred at the thoracic spine during the 11-year treatment period, but the patient experienced no adverse effects. Thus, the present case report shows the long-term outcome and safety of bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I. PMID:23293527

Does adherence to treatment mediate the relationship between patients' treatment outcome expectancies and the outcomes of pain intensity and recovery from acute low back pain?

PubMed

Haanstra, Tsjitske M; Kamper, Steven J; Williams, Christopher M; Spriensma, Alette S; Lin, Chung-Wei Christine; Maher, Christopher G; de Vet, Henrica C W; Ostelo, Raymond W J G

2015-08-01

It is believed that patients' expectancies about the effectiveness of treatment influence their treatment outcomes, but the working mechanism is rarely studied in patients with low back pain. Theoretical models suggest that adherence to treatment may be an important pathway. The aim of this study was to assess the mediating role of adherence to treatment in the relationship between expectancies and the outcomes of recovery and pain intensity in patients with acute low back pain. This study used data from a randomized placebo-controlled trial of paracetamol for acute low back pain. Expectancies were measured with the Credibility Expectancy Questionnaire. Adherence was measured with a medication diary. Pain intensity was recorded daily in a diary on a 0 to 10 pain scale, and recovery was defined as the first of 7 consecutive days scoring 0 or 1 on a 6-point pain scale. Cox regression (dependent variable: recovery) and linear mixed-model analyses (dependent variable: daily pain intensity scores) were performed. The "difference in coefficients" approach was used to establish mediation. A total of 1573 participants were included in current analyses. There was a small but highly significant relationship between expectancies and outcomes; 3.3% of the relationship between expectancies and recovery and 14.2% of the relationship between expectancies and pain intensity were mediated by adherence to treatment. This study does not convincingly support the theory that adherence is a key pathway in the relationship between treatment outcome expectancies and recovery and pain intensity in this acute low back pain population.

Client Engagement Characteristics Associated with Problem Gambling Treatment Outcomes

ERIC Educational Resources Information Center

Dowling, Nicki A.; Cosic, Sanja

2011-01-01

Previous research examining the factors associated with problem gambling treatment outcomes has examined client factors and to date, treatment characteristics, therapist factors, and client-therapist interactions have essentially remained unexplored. This study aimed to investigate how client engagement variables (client-rated therapeutic…

Measuring treatment outcomes in gambling disorders: a systematic review.

PubMed

Pickering, Dylan; Keen, Brittany; Entwistle, Gavin; Blaszczynski, Alex

2018-03-01

Considerable variation of outcome variables used to measure recovery in the gambling treatment literature has precluded effective cross-study evaluations and hindered the development of best-practice treatment methodologies. The aim of this systematic review was to describe current diffuse concepts of recovery in the gambling field by mapping the range of outcomes and measurement strategies used to evaluate treatments, and to identify more commonly accepted indices of recovery. A systematic search of six academic databases for studies evaluating treatments (psychological and pharmacological) for gambling disorders with a minimum 6-month follow-up. Data from eligible studies were tabulated and analysis conducted using a narrative approach. Guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) were adhered to. Thirty-four studies were reviewed systematically (RCTs = 17, comparative designs = 17). Sixty-three different outcome measures were identified: 25 (39.7%) assessed gambling-specific constructs, 36 (57.1%) assessed non-gambling specific constructs, and two instruments were used across both categories (3.2%). Self-report instruments ranged from psychometrically validated to ad-hoc author-designed questionnaires. Units of measurement were inconsistent, particularly in the assessment of gambling behaviour. All studies assessed indices of gambling behaviour and/or symptoms of gambling disorder. Almost all studies (n = 30; 88.2%) included secondary measures relating to psychiatric comorbidities, psychological processes linked to treatment approach, or global functioning and wellbeing. In research on gambling disorders, the incorporation of broader outcome domains that extend beyond disorder-specific symptoms and behaviours suggests a multi-dimensional conceptualization of recovery. Development of a single comprehensive scale to measure all aspects of gambling recovery could help to facilitate uniform reporting practices

Associations between therapists' occupational burnout and their patients' depression and anxiety treatment outcomes.

PubMed

Delgadillo, Jaime; Saxon, David; Barkham, Michael

2018-05-02

Occupational burnout is common in mental health professionals, but its impact on patient outcomes is as yet uncertain. This study aimed to investigate associations between therapist-level burnout and patient-level treatment outcomes after psychological therapy. We used multilevel modeling using depression (PHQ-9) and anxiety (GAD-7) outcomes data from 2,223 patients nested within 49 therapists. Therapists completed a survey including the Oldenburg Burnout Inventory (OLBI) and a job satisfaction scale (JDSS). After controlling for case-mix, around 5% of variability in treatment outcomes was explained by therapist effects (TE). Higher therapist OLBI-disengagement and lower JDSS scores were significantly associated with poorer treatment outcomes, explaining between 31 and 39% of the TE estimate. Higher OLBI scores were also correlated with lower job satisfaction ratings. Therapist burnout has a negative impact on treatment outcomes and could be the target of future preventive and remedial action. © 2018 Wiley Periodicals, Inc.

Reinforcement-Based Treatment Improves the Maternal Treatment and Neonatal Outcomes of Pregnant Patients Enrolled in Comprehensive Care Treatment

PubMed Central

Jones, Hendrée E.; O’Grady, Kevin E.; Tuten, Michelle

2011-01-01

This randomized clinical trial examined the efficacy of comprehensive Usual Care (UC) alone (n=42) or enhanced by Reinforcement-Based Treatment (RBT) (n=47) to produce improved treatment outcomes, maternal delivery, and neonatal outcomes in pregnant women with opioid and/or cocaine substance use disorders. RBT participants spent, on average, 32.6 days longer in treatment (p<.001) and almost six times longer in recovery housing than did UC participants (p=.01). There were no significant differences between the RBT and UC conditions in proportion of participants testing positive for any illegal substance. Neonates in the RBT condition spent 1.3 fewer days hospitalized after birth than UC condition neonates (p=.03), although the two conditions did not differ significantly in neonatal gestational age at delivery, birth weight, or number of days hospitalized. Integrating RBT into a rich array of comprehensive care treatment components may be a promising approach to increase maternal treatment retention and reduce neonatal length of hospital stay. PMID:21477047

Depression and treatment outcome in anorexia nervosa.

PubMed

Calugi, Simona; El Ghoch, Marwan; Conti, Maddalena; Dalle Grave, Riccardo

2014-08-15

The aim of this study was to compare the immediate and long-term effect of a cognitive-behavior therapy program for anorexia nervosa inpatients with and without concomitant Major Depressive Episodes (MDE). The program has been adapted from the "enhanced" form of Cognitive Behavior Therapy (CBT) for eating disorders. Sixty-three consecutive underweight adult patients with severe eating disorder were treated with inpatient CBT. MDE was assessed with the structured clinical interview for DSM-IV. The Eating Disorder Examination, and the Brief Symptom Inventory were recorded at entry, at the end of treatment, and 6 and 12 months later. MDE was present in 60.3% of participants. No significant differences were observed in the demographic and baseline clinical variables between patients with and without MDE. Significant improvements in weight, and in eating disorder and general psychopathology were showed. There were no differences between participants with and without MDE in terms of treatment outcome, and the severity of depression was not associated with changes in global Eating Disorder Examination score. These findings suggest that a diagnosis of MDE does not influence the outcome of inpatient treatment for anorexia nervosa patients, and that the severity of depression cannot be used to predict the success or failure of such treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Meta-Analysis of Treatment Outcomes Measured by the Y-OQ and Y-OQ-SR Comparing Wilderness and Non-Wilderness Treatment Programs

ERIC Educational Resources Information Center

Gillis, Harold L.; Speelman, Elizabeth; Linville, Noelle; Bailey, Emily; Kalle, Ashley; Oglesbee, Nathan; Sandlin, James; Thompson, Lauren; Jensen, Jennifer

2016-01-01

Background: Monitoring youth treatments requires outcome instruments sensitive to change. The Y-OQ and the Y-OQ-SR measure behavioral change during psychological treatment. Objective: The focus of this study was to compare treatment progress of youth in studies using the Youth Outcome Questionnaire (YOQ) or the Youth Outcome Questionnaire Self…

Relationship between LAAM-methadone preference and treatment outcomes.

PubMed

White, Jason M; Danz, Cath; Kneebone, Joanne; La Vincente, Sophie F; Newcombe, David A L; Ali, Robert L

2002-05-01

Studies of relative LAAM-methadone preference have indicated that a significant proportion of patients prefer levo-alpha-acetylmethadol (LAAM). The present study was designed to determine whether this preference is associated with better treatment outcomes. Sixty-two stable methadone patients participated in a randomised crossover clinical trial. They received LAAM (alternate days) and methadone (daily) for 3 months each, followed by a further 6-month period during which they were free to choose between the drugs. LAAM maintenance was associated with a lower rate of heroin use than methadone maintenance based on analysis of morphine concentration in hair and equivalent health outcomes. The majority of subjects showed a preference for LAAM (n=27, 69.2%) rather than methadone (n=12, 30.8%). The main reasons given for the LAAM preference were that it produced less withdrawal (39.3%), fewer side effects (28.5%), less craving for heroin (17.9%), and entailed fewer pick-up days (14.3%). Those who chose LAAM had lower levels of heroin use during LAAM maintenance, significantly better outcomes on two sub-scales of the SF-36 (Vitality and Mental Health), and reported that they felt more normal and that they were 'held' better when on LAAM. For those who chose methadone, there were no differences in outcomes between the LAAM and methadone maintenance periods. Preference for LAAM is associated with treatment outcomes as good or better than those with methadone.

Initial abstinence status and contingency management treatment outcomes: does race matter?

PubMed

Montgomery, LaTrice; Carroll, Kathleen M; Petry, Nancy M

2015-06-01

Limited research has evaluated African American substance users' response to evidence-based treatments. This study examined the efficacy of contingency management (CM) in African American and White cocaine users. A secondary analysis evaluated effects of race, treatment condition, and baseline cocaine urine sample results on treatment outcomes of African American (n = 444) and White (n = 403) cocaine abusers participating in one of six randomized clinical trials comparing CM to standard care. African American and White patients who initiated treatment with a cocaine-negative urine sample remained in treatment for similar durations and submitted a comparable proportion of negative samples during treatment regardless of treatment type; CM was efficacious in both races in terms of engendering longer durations of abstinence in patients who began treatment abstinent. Whites who began treatment with a cocaine positive sample remained in treatment longer and submitted a higher proportion of negative samples when assigned to CM than standard care. African Americans who initiated treatment with a cocaine positive sample, however, did not remain in treatment longer with CM compared with standard care, and gains in terms of drug use outcomes were muted in nature relative to Whites. This interaction effect persisted through the 9-month follow-up period. CM is not equally effective in reducing drug use among all subgroups, specifically African American patients who are using cocaine upon treatment entry. Future research on improving treatment outcomes in this population is needed. (c) 2015 APA, all rights reserved).

Concurrent Group Treatment for Hepatitis C: Implementation and Outcomes in a Methadone Maintenance Treatment Program

PubMed Central

Stein, Melissa R.; Soloway, Irene J.; Jefferson, Karen S.; Roose, Robert J.; Arnsten, Julia H.; Litwin, Alain H.

2012-01-01

Chronic hepatitis C virus (HCV) infection is highly prevalent among current and former drug users. However, the minority of patients enrolled in drug treatment programs have initiated HCV treatment. New models are needed to overcome barriers to care. In this retrospective study, we describe the implementation and outcomes of 42 patients treated in a Concurrent Group Treatment (CGT) program. Patients participated in weekly provider-led group treatment sessions which included review of side effects; discussion of adherence and side effect management; administration of interferon injections; brief physical exam; and ended with brief meditation. Of the first 27 patients who initiated CGT, 42% achieved a sustained viral response. Additionally, 87% (13/15) of genotype-1 infected patients treated with direct acting antiviral agent achieved an undetectable viral load at 24 weeks. The CGT model may be effective in overcoming barriers to treatment and improving adherence and outcomes among patients enrolled in drug treatment programs. PMID:23036920

Physical outcome measures for conductive and mixed hearing loss treatment: A systematic review.

PubMed

Johansson, M L; Tysome, J R; Hill-Feltham, P; Hodgetts, W E; Ostevik, A; McKinnon, B J; Monksfield, P; Sockalingam, R; Wright, T

2018-05-07

The number of potential options for rehabilitation of patients with conductive or mixed hearing loss is continually expanding. To be able to inform patients and other stakeholders there is a need to identify and develop patient-centred outcomes for treatment of hearing loss. To identify outcome measures in the physical core area used when reporting the outcome after treatment of conductive and mixed hearing loss in adult patients. Systematic review. Systematic review of literature related to reported physical outcome measures after treatment of mixed or conductive hearing loss without restrictions regarding type of intervention, treatment or device. Any measure reporting the physical outcome after treatment or intervention of mixed or conductive hearing loss was sought and categorised. The physical outcomes measures that had been extracted were then grouped into domains. The literature search resulted in the identification of 1,434 studies, of which 153 were selected for inclusion in the review. The majority (57%) of papers reported results from middle ear surgery, with the remainder reporting results from either bone conduction hearing devices or middle ear implants. Outcomes related to complications were categorised into 17 domains, whereas outcomes related to treatment success was categorised in 22 domains. The importance of these domains to patients and other stakeholders needs to be further explored in order to establish which of these domains are most relevant to interventions for conductive or mixed hearing loss. This will allow us to then assess which outcomes measures are most suitable for inclusion in the core set This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cluster analysis and prediction of treatment outcomes for chronic rhinosinusitis.

PubMed

Soler, Zachary M; Hyer, J Madison; Rudmik, Luke; Ramakrishnan, Viswanathan; Smith, Timothy L; Schlosser, Rodney J

2016-04-01

Current clinical classifications of chronic rhinosinusitis (CRS) have weak prognostic utility regarding treatment outcomes. Simplified discriminant analysis based on unsupervised clustering has identified novel phenotypic subgroups of CRS, but prognostic utility is unknown. We sought to determine whether discriminant analysis allows prognostication in patients choosing surgery versus continued medical management. A multi-institutional prospective study of patients with CRS in whom initial medical therapy failed who then self-selected continued medical management or surgical treatment was used to separate patients into 5 clusters based on a previously described discriminant analysis using total Sino-Nasal Outcome Test-22 (SNOT-22) score, age, and missed productivity. Patients completed the SNOT-22 at baseline and for 18 months of follow-up. Baseline demographic and objective measures included olfactory testing, computed tomography, and endoscopy scoring. SNOT-22 outcomes for surgical versus continued medical treatment were compared across clusters. Data were available on 690 patients. Baseline differences in demographics, comorbidities, objective disease measures, and patient-reported outcomes were similar to previous clustering reports. Three of 5 clusters identified by means of discriminant analysis had improved SNOT-22 outcomes with surgical intervention when compared with continued medical management (surgery was a mean of 21.2 points better across these 3 clusters at 6 months, P < .05). These differences were sustained at 18 months of follow-up. Two of 5 clusters had similar outcomes when comparing surgery with continued medical management. A simplified discriminant analysis based on 3 common clinical variables is able to cluster patients and provide prognostic information regarding surgical treatment versus continued medical management in patients with CRS. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All

Exposure and response prevention process predicts treatment outcome in youth with OCD.

PubMed

Kircanski, Katharina; Peris, Tara S

2015-04-01

Recent research on the treatment of adults with anxiety disorders suggests that aspects of the in-session exposure therapy process are relevant to clinical outcomes. However, few comprehensive studies have been conducted with children and adolescents. In the present study, 35 youth diagnosed with primary obsessive-compulsive disorder (OCD; M age = 12.9 years, 49% male, 63% Caucasian) completed 12 sessions of exposure and response prevention (ERP) in one of two treatment conditions as part of a pilot randomized controlled testing of a family focused intervention for OCD. Key exposure process variables, including youth self-reported distress during ERP and the quantity and quality of ERP completed, were computed. These variables were examined as predictors of treatment outcomes assessed at mid-treatment, post-treatment, and three-month follow-up, partialing treatment condition. In general, greater variability of distress during ERP and completing a greater proportion of combined exposures (i.e., exposures targeting more than one OC symptom at once) were predictive of better outcomes. Conversely, greater distress at the end of treatment was generally predictive of poorer outcomes. Finally, several variables, including within- and between-session decreases in distress during ERP, were not consistently predictive of outcomes. Findings signal potentially important facets of exposure for youth with OCD and have implications for treatment. A number of results also parallel recent findings in the adult literature, suggesting that there may be some continuity in exposure processes from child to adult development. Future work should examine additional measures of exposure process, such as psychophysiological arousal during exposure, in youth.

Treatment and outcomes of crisis resolution teams: a prospective multicentre study

PubMed Central

2011-01-01

Background Crisis resolution teams (CRTs) aim to help patients in acute mental health crises without admitting them to hospital. The aims of this study were to investigate content of treatment, service practice, and outcomes of crises of CRTs in Norway. Methods The study had a multicentre prospective design, examining routine data for 680 patients and 62 staff members of eight CRTs. The clinical staff collected data on the demographic, clinical, and content of treatment variables. The service practices of the staff were assessed on the Community Program Practice Scale. Information on each CRT was recorded by the team leaders. The outcomes of crises were measured by the changes in Global Assessment of Functioning scale scores and the total scores on the Health of the Nation Outcome Scales between admission and discharge. Regression analysis was used to predict favourable outcomes. Results The mean length of treatment was 19 days for the total sample (N = 680) and 29 days for the 455 patients with more than one consultation; 7.4% of the patients had had more than twice-weekly consultations with any member of the clinical staff of the CRTs. A doctor or psychologist participated in 55.5% of the treatment episodes. The CRTs collaborated with other mental health services in 71.5% of cases and with families/networks in 51.5% of cases. The overall outcomes of the crises were positive, with a small to medium effect size. Patients with depression received the longest treatments and showed most improvement of crisis. Patients with psychotic symptoms and substance abuse problems received the shortest treatments, showed least improvement, and were most often referred to other parts of the mental health services. Length of treatment, being male and single, and a team focus on out-of-office contact were predictors of favourable outcomes of crises in the adjusted model. Conclusions Our study indicates that, compared with the UK, the Norwegian CRTs provided less intensive and less

Prostate Cancer: A Contemporary Approach to Treatment and Outcomes.

PubMed

Weiner, Adam B; Kundu, Shilajit D

2018-03-01

Given the high incidence of prostate cancer and the need for shared decision-making before screening, it is imperative that primary care providers understand treatment options and treatment adverse effects. In this review article, the treatment options for the localized and metastatic prostate cancer are discussed, including the different modalities and their indications, adverse effects, oncologic outcomes, posttreatment monitoring, and potential treatment options following cancer recurrence. Copyright © 2017 Elsevier Inc. All rights reserved.

Predictors of unfavourable treatment outcome in patients with multidrug-resistant tuberculosis in India

PubMed Central

Velayutham, B.; Kannan, T.; Tripathy, J. P.; Harries, A. D.; Natrajan, M.; Swaminathan, S.

2017-01-01

Setting: India has one of the highest global rates of multidrug-resistant tuberculosis (MDR-TB), which is associated with poor treatment outcomes. A better understanding of the risk factors for unfavourable outcomes is needed. Objectives: To describe 1) the demographic and clinical characteristics of MDR-TB patients registered in three states of India during 2009–2011, 2) treatment outcomes, and 3) factors associated with unfavourable outcomes. Design: A retrospective cohort study involving a record review of registered MDR-TB patients. Results: Of 788 patients, 68% were male, 70% were aged 15–44 years, 90% had failed previous anti-tuberculosis treatment or were retreatment smear-positive, 60% had a body mass index < 18.5 kg/m2 and 72% had additional resistance to streptomycin and/or ethambutol. The median time from sputum collection to the start of MDR-TB treatment was 128 days (IQR 103–173). Unfavourable outcomes occurred in 40% of the patients, mostly from death or loss to follow-up. Factors significantly associated with unfavourable outcomes included male sex, age ⩾ 45 years, being underweight and infection with the human immunodeficiency virus. Adverse drug reactions were reported in 24% of patients, with gastrointestinal disturbance, psychiatric morbidity and ototoxicity the most common. Conclusion: Long delays from sputum collection to treatment initiation using conventional methods, along with poor treatment outcomes, suggest the need to scale up rapid diagnostic tests and shorter regimens for MDR-TB. PMID:28775941

Application of Certain π-Acceptors for the Spectrophotometric Determination of Alendronate Sodium in Pharmaceutical Bulk and Dosage Forms.

PubMed

Raza, Asad; Zia-Ul-Haq, Muhammad

2011-01-01

Two simple, fast, and accurate spectrophotometric methods for the determination of alendronate sodium are described. The methods are based on charge-transfer complex formation of the drug with two π-electron acceptors 7,7,7,8-tetracyanoquinodimethane (TCNQ) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in acetonitrile and methanol medium. The methods are followed spectrophotometrically by measuring the maximum absorbance at 840 nm and 465 nm, respectively. Under the optimized experimental conditions, the calibration curves showed a linear relationship over the concentration ranges of 2-10 μg mL(-1) and 2-12 μg mL(-1), respectively. The optimal reactions conditions values such as the reagent concentration, heating time, and stability of reaction product were determined. No significant difference was obtained between the results of newly proposed methods and the B.P. Titrimetric procedures. The charge transfer approach using TCNQ and DDQ procedures described in this paper is simple, fast, accurate, precise, and extraction-free.

Are Treatment Outcomes Determined by Type of Gambling? A UK Study.

PubMed

Ronzitti, Silvia; Soldini, Emiliano; Smith, Neil; Bayston, Andrew; Clerici, Massimo; Bowden-Jones, Henrietta

2018-01-30

One of the main difficulties faced in treating gambling disorder is compliance with psychological treatment. Gambling takes many forms and can differ greatly in its features such as speed of play and skill requirements. The type of gambling a pathological gambler opts for may play a key role in treatment compliance. The aim of the present study was to determine whether within treatment seeking sample of gambling disorder clients, gambling activity has any correlation with their resultant treatment outcomes. The study incorporated 524 treatment-seeking individuals who are clients of the National Problem Gambling Clinic in London. All of the clients were assessed prior to treatment and fulfilled the Problem Gambling Severity Index criteria for problem gambling. Data concerning clients' gambling behavior over the previous year was gathered using self-reports. Subsequently, the data was fitted to a multinomial logistic regression model, with the treatment outcome (i.e. pre-treatment dropouts, during treatment dropouts, and completed treatment) as the dependent variable and gambling behavior as the independent variable, whilst controlling for socio-demographic factors. The use of gaming machines was a significant predictor of dropping out pre-treatment (p < 0.05, RRR 1.616), whilst betting on sports events was a significant predictor of dropping out during treatment (p < 0.01, RRR 2.435). Treatment outcomes have been found to significantly differ based on participation in certain gambling activities. Further research into the salient features of these gambling activities may help to further explain pre-treatment and during treatment dropouts within this population.

Treatment outcomes and factors affecting unsuccessful outcome among new pulmonary smear positive and negative tuberculosis patients in Anqing, China: a retrospective study.

PubMed

Wen, Yufeng; Zhang, Zhiping; Li, Xianxiang; Xia, Dan; Ma, Jun; Dong, Yuanyuan; Zhang, Xinwei

2018-03-05

Monitoring the treatment outcomes of tuberculosis and determining the specific factors associated with unsuccessful treatment outcome are essential to evaluate the effectiveness of tuberculosis control program. This study aimed to assess treatment outcomes and explore the factors associated with unsuccessful outcomes among new pulmonary smear positive and negative tuberculosis patients in Anqing, China. A nine-year retrospective study was conducted using data from Anqing Center for Diseases Prevention and Control. New pulmonary tuberculosis patients treated with two six-month regimens were investigated. Non-conditional logistic regression was performed to calculate odds ratios and 95% confidence intervals for factors associated with unsuccessful outcomes. Among 22,998 registered patients (16,939 males, 6059 females), 64.54% were smear-positive patients. The treatment success rates was 95.02% for smear-positive patients and 95.00% for smear-negative patients. Characteristics associated with an higher risk of unsuccessful treatment among smear-positive patients included aged above 35 years, treatment management model of self-medication, full-course management and supervision in intensive phase, unchecked chest X-ray, cavity in chest X-ray, and miliary shadow in chest X-ray, while normal X-ray was negative factor. Unsuccessful treatment among smear-negative patients was significantly associated with age over 45 years, treatment management model of full-course management, unchecked chest X-ray, presence of miliary shadow in chest X-ray and delay over 51 days. Tuberculosis treatment in Anqing area was successful and independent of treatment regimens. Special efforts are required for patients with unsuccessful outcomes.

Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs.

PubMed

Cummings, Steven R; Karpf, David B; Harris, Fran; Genant, Harry K; Ensrud, Kristine; LaCroix, Andrea Z; Black, Dennis M

2002-03-01

To estimate how much the improvement in bone mass accounts for the reduction in risk of vertebral fracture that has been observed in randomized trials of antiresorptive treatments for osteoporosis. After a systematic search, we conducted a meta-analysis of 12 trials to describe the relation between improvement in spine bone mineral density and reduction in risk of vertebral fracture in postmenopausal women. We also used logistic models to estimate the proportion of the reduction in risk of vertebral fracture observed with alendronate in the Fracture Intervention Trial that was due to improvement in bone mineral density. Across the 12 trials, a 1% improvement in spine bone mineral density was associated with a 0.03 decrease (95% confidence interval [CI]: 0.02 to 0.05) in the relative risk (RR) of vertebral fracture. The reductions in risk were greater than predicted from improvement in bone mineral density; for example, the model estimated that treatments predicted to reduce fracture risk by 20% (RR = 0.80), based on improvement in bone mineral density, actually reduce the risk of fracture by about 45% (RR = 0.55). In the Fracture Intervention Trial, improvement in spine bone mineral density explained 16% (95% CI: 11% to 27%) of the reduction in the risk of vertebral fracture with alendronate. Improvement in spine bone mineral density during treatment with antiresorptive drugs accounts for a predictable but small part of the observed reduction in the risk of vertebral fracture.

Barriers to Implementing Treatment Integrity Procedures in School Psychology Research: Survey of Treatment Outcome Researchers

ERIC Educational Resources Information Center

Sanetti, Lisa M. Hagermoser; DiGennaro Reed, Florence D.

2012-01-01

Treatment integrity data are essential to drawing valid conclusions in treatment outcome studies. Such data, however, are not always included in peer-reviewed research articles in school psychology or related fields. To gain a better understanding of why treatment integrity data are lacking in the school psychology research, we surveyed the…

Does treatment of SDB in children improve cardiovascular outcome?

PubMed

Vlahandonis, Anna; Walter, Lisa M; Horne, Rosemary S C

2013-02-01

Sleep disordered breathing (SDB) is a common disorder in both adults and children and is caused by the obstruction of the upper airway during sleep. Unlike adults, most cases of paediatric SDB are due to the presence of enlarged tonsils and adenoids, thus the main treatment option is adenotonsillectomy (T&A). It is well known that obstructive sleep apnoea in adults increases the risk for hypertension, coronary artery disease and stroke, and there is now mounting evidence that SDB also has a significant impact on the cardiovascular system in children with reports of elevated blood pressure, endothelial dysfunction and altered autonomic cardiovascular control. As there is now substantial evidence that elevated blood pressure in childhood is carried on to adulthood it is important to know if treatment of SDB improves cardiovascular outcomes. Studies in adults have shown that treatment of SDB leads to improvements in cardiovascular function, including a reduction in pulmonary artery pressure, systemic blood pressure and endothelial dysfunction. However, studies exploring the outcomes of treatment of SDB in children on the cardiovascular system are limited and varied in their methodology and outcome measures. As a number of cardiovascular disturbances are sequelae of SDB, early detection and management could result in the reduction of elevated blood pressure in children, and consequently a reduction in cardiovascular morbidity in adulthood. The aim of this review is to summarise the findings of studies to date which have investigated the cardiovascular outcomes in children treated for SDB and to make recommendations for future management of this very common disease. Crown Copyright © 2012. Published by Elsevier Ltd. All rights reserved.

Treatment expectancy affects the outcome of cognitive-behavioral interventions in chronic pain.

PubMed

Goossens, Mariëlle E J B; Vlaeyen, Johan W S; Hidding, Alita; Kole-Snijders, Ank; Evers, Silvia M A A

2005-01-01

Patients' initial beliefs about the success of a given pain treatment are shown to have an important influence on the final treatment outcome. The aims of the paper are to assess determinants of patients' treatment expectancy and to examine the extent to which treatment expectancy predicts the short-term and long-term outcome of cognitive-behavioral treatment of chronic pain. This study employs the data of 2 pooled randomized clinical trials evaluating the effectiveness of cognitive-behavioral interventions for 171 patients with fibromyalgia and chronic low back pain. Pretreatment and posttreatment expectancy were measured by a short questionnaire, which was based on the procedure by Borkovec and Nau. Four composite outcome variables (pain coping and control, motoric behavior, negative affect, and quality of life) were measured before and after the intervention and at 12 months follow-up. Furthermore, several patient characteristics were taken into account. Patients with higher treatment expectancies significantly received less disability compensation and were less fearful. A regression model of 3 factors (better pain coping and control, active and positive interpretation of pain, and less disability compensation) significantly explained 10% of the variance in pretreatment expectancy. Pretreatment expectancy significantly predicted each of the 4 outcome measures immediately after treatment and at 12 months follow-up. This study corroborates the importance of treatment expectation before entering a cognitive-behavioral intervention in patients with chronic musculoskeletal pain.

How Much Is Too Much? Patterns of Drinking During Alcohol Treatment and Associations With Post-Treatment Outcomes Across Three Alcohol Clinical Trials.

PubMed

Witkiewitz, Katie; Roos, Corey R; Pearson, Matthew R; Hallgren, Kevin A; Maisto, Stephen A; Kirouac, Megan; Forcehimes, Alyssa A; Wilson, Adam D; Robinson, Charles S; McCallion, Elizabeth; Tonigan, J Scott; Heather, Nick

2017-01-01

This secondary data analysis examined patterns of drinking during alcohol treatment and associated drinking outcomes during the first year following treatment. The goal was to provide clinicians with guidance on which patients may be most at risk for negative long-term outcomes based on drinking patterns during treatment. This study was an analysis of existing data (N = 3,851) from three randomized clinical trials for alcohol use disorder: the COMBINE Study (n = 1,383), Project MATCH (n = 1,726), and the United Kingdom Alcohol Treatment Trial (n = 742). Indicators of abstinence, non-heavy drinking, and heavy drinking (defined as 4/5 or more drinks per day for women/men) were examined during each week of treatment using repeated-measures latent class analysis. Associations between drinking patterns during treatment and drinking intensity, drinking consequences, and physical and mental health 12 months following intake were examined. Seven drinking patterns were identified. Patients who engaged in persistent heavy drinking throughout treatment and those who returned to persistent heavy drinking during treatment had the worst long-term outcomes. Patients who engaged in some heavy drinking during treatment had better long-term outcomes than persistent heavy drinkers. Patients who reported low-risk drinking or abstinence had the best long-term outcomes. There were no differences in outcomes between low-risk drinkers and abstainers. Abstinence, low-risk drinking, or even some heavy drinking during treatment are associated with the best long-term outcomes. Patients who are engaging in persistent heavy drinking are likely to have the worst outcomes and may require a higher level of care.

Treatment outcomes for isoniazid-resistant tuberculosis under program conditions in British Columbia, Canada.

PubMed

Romanowski, Kamila; Chiang, Leslie Y; Roth, David Z; Krajden, Mel; Tang, Patrick; Cook, Victoria J; Johnston, James C

2017-09-04

Every year, over 1 million people develop isoniazid (INH) resistant tuberculosis (TB). Yet, the optimal treatment regimen remains unclear. Given increasing prevalence, the clinical efficacy of regimens used by physicians is of interest. This study aims to examine treatment outcomes of INH resistant TB patients, treated under programmatic conditions in British Columbia, Canada. Medical charts were retrospectively reviewed for cases of culture-confirmed INH mono-resistant TB reported to the BC Centre for Disease Control (BCCDC) from 2002 to 2014. Treatment regimens, patient and strain characteristics, and clinical outcomes were analysed. One hundred sixty five cases of INH mono-resistant TB were included in analysis and over 30 different treatment regimens were prescribed. Median treatment duration was 10.5 months (IQR 9-12 months) and treatment was extended beyond 12 months for 26 patients (15.8%). Fifty six patients (22.6%) experienced an adverse event that resulted in a drug regimen modification. Overall, 140 patients (84.8%) had a successful treatment outcome while 12 (7.2%) had an unsuccessful treatment outcome of failure (n = 2; 1.2%), relapse (n = 4; 2.4%) or all cause mortality (n = 6; 3.6%). Our treatment outcomes, while consistent with findings reported from other studies in high resource settings, raise concerns about current recommendations for INH resistant TB treatment. Only a small proportion of patients completed the recommended treatment regimens. High quality studies to confirm the effectiveness of standardized regimens are urgently needed, with special consideration given to trials utilizing fluoroquinolones.

Trends in treatment and outcomes of pediatric craniopharyngioma, 1975–2011

PubMed Central

Cohen, Michal; Bartels, Ute; Branson, Helen; Kulkarni, Abhaya V.; Hamilton, Jill

2013-01-01

Background Craniopharyngioma tumors and their treatment can lead to significant long-term morbidity due to their proximity to vital structures. The optimal treatment has been debated for many years. We aimed to review the long-term outcomes of children treated for craniopharyngioma in our institution over the past decade and describe trends in treatment and outcomes over the past 3 decades. Methods Charts of children with craniopharyngioma treated and followed at The Hospital for Sick Children between 2001 and 2011 were reviewed. Data regarding findings at diagnosis, treatment, and long-term outcomes were analyzed. Comparison was made with previously published data from our institution. Results Data from 33 patients are included; mean age at treatment, 10.7 ± 4.8 years. In 18 children (55%), the initial surgical approach was tumor cyst decompression with or without adjuvant therapy, compared with only 0–2% in the preceding decades (P < .01). Diabetes insipidus occurred in 55% of children and panhypopituitarism in 58% compared with 88% (P < .01) and 86% (P < .01), respectively, in the previous 10 years. Overall, there was a 36% reduction in the number of children who developed severe obesity compared with the preceding decade. Body mass index at follow-up was associated with body mass index at diagnosis (P = .004) and tumor resection as an initial treatment approach (P = .028). Conclusions A shift in surgical treatment approach away from gross total resection has led to improved endocrine outcomes. This may have beneficial implications for quality of life in survivors. PMID:23486689

Surgical treatment of gynecomastia: complications and outcomes.

PubMed

Li, Chun-Chang; Fu, Ju-Peng; Chang, Shun-Cheng; Chen, Tim-Mo; Chen, Shyi-Gen

2012-11-01

Gynecomastia is defined as the benign enlargement of the male breast. Multiple surgical options have been used to improve outcomes. The aim of this study was to analyze the surgical approaches to the treatment of gynecomastia and their outcomes over a 10-year period. All patients undergoing surgical correction of gynecomastia in our department between 2000 and 2010 were included for retrospective evaluation. The data were analyzed for etiology, stage of gynecomastia, surgical technique, complications, risk factors, and revision rate. The surgical result was evaluated with self-assessment questionnaires. A total of 41 patients with 75 operations were included. Techniques included subcutaneous mastectomy alone or with additional ultrasound-assisted liposuction (UAL) and isolated UAL. The surgical revision rate for all patients was 4.8%. The skin-sparing procedure gave good surgical results in grade IIb and grade III gynecomastia with low revision and complication rates. The self-assessment report revealed a good level of overall satisfaction and improvement in self-confidence (average scores 9.4 and 9.2, respectively, on a 10-point scale). The treatment of gynecomastia requires an individualized approach. Subcutaneous mastectomy combined with UAL could be used as the first choice for surgical treatment of grade II and III gynecomastia.

The National Treatment Outcomes Research Study (NTORS) and its influence on addiction treatment policy in the United Kingdom.

PubMed

Gossop, Michael

2015-07-01

This paper describes the political origins of the National Treatment Outcomes Research Study (NTORS) and the outputs and impacts of the study. NTORS was designed to meet the request of the Health Secretary and of a Government Task Force for evidence about the effectiveness of the national addiction treatment services. NTORS was a prospective cohort study which investigated outcomes over a 5-year period of drug users admitted to four major treatment modalities: in-patient treatment, residential rehabilitation, methadone reduction and methadone maintenance programmes. The study investigated treatments delivered under day-to-day operating conditions. Outcomes showed substantial reductions in illicit drug use and reduced injecting risk behaviours. These changes were accompanied by improved psychological and physical health and by reductions in criminal behaviour. However, not all outcomes were so positive. There was a continuing mortality rate in the cohort of about 1% per year, and many clients continued to drink heavily throughout the 5-year follow-up. NTORS findings informed and influenced UK addiction treatment policy both at the time and subsequently. The findings were influential in supporting an immediate increase in funding for treatment, and Government Ministers have repeatedly cited NTORS as evidence of the effectiveness of addiction treatment. One finding that received political attention was that of the cost savings provided by treatment through reductions in crime. This important finding led to an unanticipated consequence of NTORS; namely, the greater focus on crime reduction that has increasingly been promoted as a political and social priority for drug misuse treatment. © 2015 Society for the Study of Addiction.

Dental treatment and employment outcomes among social assistance recipients in Ontario, Canada.

PubMed

Singhal, Sonica; Mamdani, Muhammad; Mitchell, Andrew; Tenenbaum, Howard; Lebovic, Gerald; Quiñonez, Carlos

2016-10-01

Policy advocates continue to argue for the expansion of dental care services for people on social assistance in order to meet their health needs and to promote the move from welfare-to-work. However, there is little to no evidence to support the idea that receiving dental care ultimately improves employment outcomes. A retrospective cohort study was designed using administrative data from five Ontario regions and from the province's social assistance ministry. Employment outcomes among treatment and no-treatment cohorts were assessed at three, six and 12 months from baseline. Multivariable regression modeling was performed. We received data for 8742 people (2742 treatment, 6000 no-treatment). At one year, employment outcomes were not significantly different between the two groups (adjusted odds ratio=0.93; 95% CI: 0.83-1.03). Post-hoc analysis show that the change in proportion of individuals leaving social assistance for employment over time was significantly higher (p=0.0014) among those receiving treatment (13-29%; 124% increase) than those not receiving treatment (18-33%; 83% increase). At one year, dental treatment alone does not appear to be significantly associated with leaving assistance for employment in this population. However, this study suggests that people who received dental treatment may have been particularly disadvantaged and dental treatment may help to level them up in terms of employment outcomes over time. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Social capital and adverse treatment outcomes of tuberculosis: a case-control study.

PubMed

Deshmukh, P R; Mundra, A; Dawale, A

2017-08-01

'Social capital' refers to social norms, relationships, networks and values that affect the functioning and development of society. Social capital influences health positively, but its role in the treatment outcomes of tuberculosis (TB) is not known. To study the role of social capital in determining adverse TB treatment outcomes. Of 516 patients registered under the Revised National Tuberculosis Control Programme in 2014 in Wardha Tuberculosis Unit, Wardha, India, we included 88 patients with adverse treatment outcomes as cases and 187 controls from among those without adverse outcomes. Multiple logistic regression was used to compare standardised Z-scores. A greater proportion of controls than cases belonged to higher quartiles of social capital and its domains than cases, and the mean standardised Z-score was also consistently higher among controls than cases. Respectively 47% and 15% of cases and controls were in the poorest quartile of social capital, whereas respectively 10% and 33% of cases and controls were in the richest quartile. Each unit increase in Z-score of overall social capital reduced the odds of adverse treatment outcomes by 63.1%. Appropriate interventions for building social capital for TB patients and linking them with the programme would improve programme performance.

Facial dog bite injuries in children: treatment and outcome assessment.

PubMed

Eppley, Barry L; Schleich, Arno Rene

2013-03-01

Dog bite injuries to a child's face are not an infrequent occurrence. They may require primary and revisional surgery. All result in permanent facial scars. This report describes the treatment and outcomes of dog bites of the face, scalp, and neck based on a case series of 107 children over a 10-year period.The average children's age was 5.9 years. In cases where the dog was identified (95%), it was known to the victim and their family. The events leading to the dog bite were categorized as provoked (77%) in the majority of the cases.The majority of wounds could be closed primarily without a significant risk of wound infection. Complex reconstructions were required in more severe cases. The majority of families (77%) opted for scar revision between 9 and 18 months after initial treatment to improve the aesthetic outcome.Lawsuit actions resulted in 39 of the cases making good documentation an essential part of treatment. Dogbite injuries to the face in children frequently require multiple scar revisions to obtain the best possible aesthetic outcome, and the family should be so counseled at the onset of treatment.

The hydrogen sulfide donor, Lawesson's reagent, prevents alendronate-induced gastric damage in rats

PubMed Central

Nicolau, L.A.D.; Silva, R.O.; Damasceno, S.R.B.; Carvalho, N.S.; Costa, N.R.D.; Aragão, K.S.; Barbosa, A.L.R.; Soares, P.M.G.; Souza, M.H.L.P.; Medeiros, J.V.R.

2013-01-01

Our objective was to investigate the protective effect of Lawesson's reagent, an H2S donor, against alendronate (ALD)-induced gastric damage in rats. Rats were pretreated with saline or Lawesson's reagent (3, 9, or 27 µmol/kg, po) once daily for 4 days. After 30 min, gastric damage was induced by ALD (30 mg/kg) administration by gavage. On the last day of treatment, the animals were killed 4 h after ALD administration. Gastric lesions were measured using a computer planimetry program, and gastric corpus pieces were assayed for malondialdehyde (MDA), glutathione (GSH), proinflammatory cytokines [tumor necrosis factor (TNF)-α and interleukin (IL)-1β], and myeloperoxidase (MPO). Other groups were pretreated with glibenclamide (5 mg/kg, ip) or with glibenclamide (5 mg/kg, ip)+diazoxide (3 mg/kg, ip). After 1 h, 27 µmol/kg Lawesson's reagent was administered. After 30 min, 30 mg/kg ALD was administered. ALD caused gastric damage (63.35±9.8 mm2); increased levels of TNF-α, IL-1β, and MDA (2311±302.3 pg/mL, 901.9±106.2 pg/mL, 121.1±4.3 nmol/g, respectively); increased MPO activity (26.1±3.8 U/mg); and reduced GSH levels (180.3±21.9 µg/g). ALD also increased cystathionine-γ-lyase immunoreactivity in the gastric mucosa. Pretreatment with Lawesson's reagent (27 µmol/kg) attenuated ALD-mediated gastric damage (15.77±5.3 mm2); reduced TNF-α, IL-1β, and MDA formation (1502±150.2 pg/mL, 632.3±43.4 pg/mL, 78.4±7.6 nmol/g, respectively); lowered MPO activity (11.7±2.8 U/mg); and increased the level of GSH in the gastric tissue (397.9±40.2 µg/g). Glibenclamide alone reversed the gastric protective effect of Lawesson's reagent. However, glibenclamide plus diazoxide did not alter the effects of Lawesson's reagent. Our results suggest that Lawesson's reagent plays a protective role against ALD-induced gastric damage through mechanisms that depend at least in part on activation of ATP-sensitive potassium (KATP) channels. PMID:23969974

Do estrogen and alendronate improve metaphyseal fracture healing when applied as osteoporosis prophylaxis?

PubMed

Kolios, Leila; Hoerster, Ann Kristin; Sehmisch, Stephan; Malcherek, Marie Christin; Rack, Thomas; Tezval, Mohammed; Seidlova-Wuttke, Dana; Wuttke, Wolfgang; Stuermer, Klaus Michael; Stuermer, Ewa Klara

2010-01-01

Osteoporosis is accompanied by predominantly metaphyseal fractures with a delayed and qualitatively reduced healing process. This study addressed the question of whether fracture healing in the context of osteoporosis prophylaxis is improved with estrogen (E) or alendronate (ALN). Thirty-six ovariectomized and 12 sham-operated 12-week-old rats received soy-free (osteoporotic C, sham), E-, or ALN- supplemented diets. After 10 weeks, a metaphyseal tibia osteotomy and standardized T-plate fixation were performed. After a 5-week healing process, the fracture callus was evaluated qualitatively by biomechanical bending test and quantitatively in microradiographic sections. The time course of callus formation was examined using fluorochrome-labeled histological sections. Administration of E improved the biomechanical properties of callus (stiffness [N/mm]: sham: 110.2 + or - 76.07, C: 41.28 + or - 33.70, E: 85.72 + or - 47.24, ALN: 72.07 + or - 34.68). The resistance to microfracturing seen in E-treated animals was significantly enhanced and even superior to sham (yield load [N] sham: 27.44 + or - 9.72, C: 21.04 + or - 12.47, E: 42.85 + or - 13.74(Delta), ALN: 25.28 + or - 6.4(.)) (* P < 0.05 vs. sham group, (Delta) P < 0.05 vs. C group, (*) P < 0.05 vs. E group). Trabecular bone in particular was improved, indicating the presence of physiological endosteal bridging (Tr.Dn [%] sham: 10.53 + or - 18.9, C: 1.01 + or - 0.14, E: 24.13 + or - 34.09(Delta), ALN: 3.99 + or - 8.3(.)). ALN did not help bone healing, as shown by mechanical tests. Compared to the C group, statistically, ALN did not show worse properties. The induction of callus formation under ALN treatment was slightly delayed (Tt.Cl [mm(2)] sham: 3.68 + or - 0.66, C: 3.44 + or - 0.42, E: 3.69 + or - 0.58, ALN: 3.06 + or - 0.56). Osteoporotic metaphyseal fracture healing was qualitatively and quantitatively improved by E prophylaxis. The process of fracture healing occurred nearly physiologically (shamlike

Including a range of outcome targets offers a broader view of fibromyalgia treatment outcome: results from a retrospective review of multidisciplinary treatment.

PubMed

Marcus, Dawn A; Bernstein, Cheryl D; Haq, Adeel; Breuer, Paula

2014-06-01

Fibromyalgia is associated with substantial functional disability. Current drug and non-drug treatments result in statistically significant but numerically small improvements in typical numeric measures of pain severity and fibromyalgia impact. The aim of the present study was to evaluate additional measures of pain severity and functional outcome that might be affected by fibromyalgia treatment. This retrospective review evaluated outcomes from 274 adults with fibromyalgia who participated in a six-week, multidisciplinary treatment programme. Pain and function were evaluated on the first and final treatment visit. Pain was evaluated using an 11-point numerical scale to determine clinically meaningful pain reduction (decrease ≥ 2 points) and from a pain drawing. Function was evaluated by measuring active range of motion (ROM), walking distance and speed, upper extremity exercise repetitions, and self-reports of daily activities. Numerical rating scores for pain decreased by 10-13% (p < 0.01) and Fibromyalgia Impact Questionnaire (FIQ) scores decreased by 20% (p < 0.001). More substantial improvements were noted when using alternative measures. Clinically meaningful pain relief was achieved by 37% of patients, and the body area affected by pain decreased by 31%. ROM showed significant improvements in straight leg raise and cervical motion, without improvements in lumbar ROM. Daily walking distance increased fourfold and arm exercise repetitions doubled. Despite modest albeit statistically significant improvements in standard measures of pain severity and the FIQ, more substantial pain improvement was noted when utilizing alternative measures of pain and functional improvement. Alternative symptom assessment measures might be important outcome measures to include in drug and non-drug studies to better understand fibromyalgia treatment effectiveness. © 2013 John Wiley & Sons, Ltd.

Working memory capacity and addiction treatment outcomes in adolescents.

PubMed

Houck, Jon M; Feldstein Ewing, Sarah W

2018-01-01

Brief addiction treatments including motivational interviewing (MI) have shown promise with adolescents, but the factors that influence treatment efficacy in this population remain unknown. One candidate is working memory, the ability to hold a fact or thought in mind. This is relevant, as in therapy, a client must maintain and manipulate ideas while working with a clinician. Working memory depends upon brain structures and functions that change markedly during neurodevelopment and that can be negatively impacted by substance use. In a secondary analysis of data from a clinical trial for adolescent substance use comparing alcohol/marijuana education and MI, we evaluated the relationship between working memory and three-month treatment-outcomes with the hypothesis that the relationship between intervention conditions and outcome would be moderated by working memory. With a diverse sample of adolescents currently using alcohol and/or marijuana (N = 153, 64.7% male, 70.6% Hispanic), we examined the relationship between baseline measures of working memory and alcohol and cannabis-related problem scores measured at the three-month follow-up. The results showed that lower working memory scores were associated with poorer treatment response only for alcohol use, and only within the education group. No relationship was found between working memory and treatment outcomes in the MI group. The results suggest that issues with working memory capacity may interfere with adolescents' ability to process and implement didactic alcohol and marijuana content in standard education interventions. These results also suggest that MI can be implemented equally effectively across the range of working memory functioning in youth.

Posttreatment Motivation and Alcohol Treatment Outcome 9 Months Later: Findings From Structural Equation Modeling

PubMed Central

2014-01-01

Objective: To investigate the association between posttreatment motivation to change as measured by the Readiness to Change Questionnaire Treatment Version and drinking outcomes 9 months after the conclusion of treatment for alcohol problems. Method: Data from 392 participants in the United Kingdom Alcohol Treatment Trial were used to fit structural equation models investigating relationships between motivation to change pre- and posttreatment and 5 outcomes 9 months later. The models included pathways through changes in drinking behavior during treatment and adjustment for sociodemographic information. Results: Greater posttreatment motivation (being in action vs. preaction) was associated with 3 times higher odds of the most stringent definition of positive outcome (being abstinent or entirely a nonproblem drinker) 9 months later (odds ratio = 3.10, 95% confidence interval [1.83, 5.25]). A smaller indirect effect of pretreatment motivation on this outcome was seen from pathways through drinking behavior during treatment and posttreatment motivation (probit coefficient = 0.08, 95% confidence interval [0.03, 0.14]). A similar pattern of results was seen for other outcomes evaluated. Conclusion: Posttreatment motivation to change has hitherto been little studied and is identified here as a clearly important predictor of longer term treatment outcome. PMID:25244390

The impact of benzodiazepine use on methadone maintenance treatment outcomes.

PubMed

Brands, Bruna; Blake, Joan; Marsh, David C; Sproule, Beth; Jeyapalan, Renuka; Li, Selina

2008-01-01

The purposes of this study were to examine predictors of benzodiazepine use among methadone maintenance treatment patients, to determine whether baseline benzodiazepine use influenced ongoing use during methadone maintenance treatment, and to assess the effect of ongoing benzodiazepine use on treatment outcomes (i.e., opioid and cocaine use and treatment retention). A retrospective chart review of 172 methadone maintenance treatment patients (mean age = 34.6 years; standard deviation = 8.5 years; 64% male) from January 1997 to December 1999 was conducted. At baseline, 29% were "non-users" (past year) of benzodiazepine, 36% were "occasional users," and 35% were "regular/problem users." Regular/problem users were more likely to have started opioid use with prescription opioids, experienced more overdoses, and reported psychiatric comorbidity. Being female, more years of opioid use, and a history of psychiatric treatment were significant predictors of baseline benzodiazepine use. Ongoing benzodiazepine users were more likely to have opioid-positive and cocaine-positive urine screens during methadone maintenance treatment. Only ongoing cocaine use was negatively related to retention. Benzodiazepine use by methadone maintenance treatment patients is associated with a more complex clinical picture and may negatively influence treatment outcomes.

A Comparison of Preferred Treatment Outcomes between Children with ADHD and Their Parents

ERIC Educational Resources Information Center

Traywick, Tracey B.; Lamson, Angela L.; Diamond, John M.; Carawan, Sandra

2006-01-01

Objective: The newest guidelines for the treatment of ADHD call for the formation of an individualized treatment plan based on collaboration. Because the process of collaboration requires the communication of desired outcomes, the authors' goal is to examine the preferred outcomes of treatment for ADHD for children and parents. Method: A preferred…

How Much Is Too Much? Patterns of Drinking During Alcohol Treatment and Associations With Post-Treatment Outcomes Across Three Alcohol Clinical Trials

PubMed Central

Witkiewitz, Katie; Roos, Corey R.; Pearson, Matthew R.; Hallgren, Kevin A.; Maisto, Stephen A.; Kirouac, Megan; Forcehimes, Alyssa A.; Wilson, Adam D.; Robinson, Charles S.; McCallion, Elizabeth; Tonigan, J. Scott; Heather, Nick

2017-01-01

Objective: This secondary data analysis examined patterns of drinking during alcohol treatment and associated drinking outcomes during the first year following treatment. The goal was to provide clinicians with guidance on which patients may be most at risk for negative long-term outcomes based on drinking patterns during treatment. Method: This study was an analysis of existing data (N = 3,851) from three randomized clinical trials for alcohol use disorder: the COMBINE Study (n = 1,383), Project MATCH (n = 1,726), and the United Kingdom Alcohol Treatment Trial (n = 742). Indicators of abstinence, non-heavy drinking, and heavy drinking (defined as 4/5 or more drinks per day for women/men) were examined during each week of treatment using repeated-measures latent class analysis. Associations between drinking patterns during treatment and drinking intensity, drinking consequences, and physical and mental health 12 months following intake were examined. Results: Seven drinking patterns were identified. Patients who engaged in persistent heavy drinking throughout treatment and those who returned to persistent heavy drinking during treatment had the worst long-term outcomes. Patients who engaged in some heavy drinking during treatment had better long-term outcomes than persistent heavy drinkers. Patients who reported low-risk drinking or abstinence had the best long-term outcomes. There were no differences in outcomes between low-risk drinkers and abstainers. Conclusions: Abstinence, low-risk drinking, or even some heavy drinking during treatment are associated with the best long-term outcomes. Patients who are engaging in persistent heavy drinking are likely to have the worst outcomes and may require a higher level of care. PMID:27936365

Measuring Outcome in the Treatment of Cocaine Dependence

PubMed Central

Crits-Christoph, Paul; Gallop, Robert; Gibbons, Mary Beth Connolly; Sadicario, Jaclyn S.; Woody, George

2015-01-01

Background Little in known about the extent to which outcome measures used in studies of the treatment of cocaine dependence are associated with longer-term use and with broader measures of clinical improvement. The current study examined reductions in use, and abstinence-oriented measures, in relation to functioning and longer-term clinical benefits in the treatment of cocaine dependence. Methods Overall drug use, cocaine use, and functioning in a number of addiction-related domains for 487 patients diagnosed with DSM-IV cocaine dependence and treated with one of four psychosocial interventions in the NIDA Cocaine Collaborative Treatment Study were assessed monthly during 6 months of treatment and at 9, 12, 15, and 18 month follow-up. Results Measures of during-treatment reduction in use were moderately correlated with drug and cocaine use measures 12 months, but showed non-significant or small correlations with measures of functioning at 12 months. Highest correlations were evident for abstinence measures (maximum consecutive days abstinence and completely abstinent) during treatment in relation to sustained (3 month) abstinence at 12 months. Latent class analysis of patterns of change over time revealed that most patients initially (months 1 to 4 of treatment) either became abstinent immediately or continued to use every month. Over the couse of follow-up, patients either maintained abstinence or used regularly – intermittent use was less common. Conclusions There were generally small associations between various measures of cocaine use and longer-term clinical benefits, other than abstinence was associated with continued abstinence. No one method of measuring outcome of treatment of cocaine dependence appears superior to others. PMID:26366427

Predictors of prison-based treatment outcomes: a comparison of men and women participants.

PubMed

Messina, Nena; Burdon, William; Hagopian, Garo; Prendergast, Michael

2006-01-01

The purpose of this study was to examine differences between men and women entering prison-based therapeutic community (TC) treatment and to explore the relationship of those differences to posttreatment outcomes (i.e., aftercare participation and reincarceration rates). Extensive treatment-intake interview data for 4,386 women and 4,164 men from 16 prison-based TCs in California were compared using chi-square analyses and t-tests. Logistic regression analyses were then conducted separately for men and women to identify gender-specific factors associated with post-treatment outcomes. Prison intake data and treatment participation data come from a 5-year process and outcome evaluation of the California Department of Corrections' (CDC) Prison Treatment Expansion Initiative. The return-to-custody data came from the CDC's Offender Based Information System. Bivariate results showed that women were at a substantial disadvantage compared with their male counterparts with regard to histories of employment, substance abuse, psychological functioning, and sexual and physical abuse prior to incarceration. In contrast, men had more serious criminal justice involvement than women prior to incarceration. After controlling for these and other factors related to outcomes, regression findings showed that there were both similarities and differences with regard to gender-specific predictors of posttreatment outcomes. Time in treatment and motivation for treatment were similar predictors of aftercare participation for men and women. Psychological impairment was the strongest predictor of recidivism for both men and women. Substantial differences in background characteristics and the limited number of predictors related to posttreatment outcomes for women suggests the plausibility of gender-specific paths in the recovery process.

The association between interpersonal problems and treatment outcome in patients with eating disorders.

PubMed

Ung, Elise Meyn; Erichsen, Cecilie Birkmose; Poulsen, Stig; Lau, Marianne Engelbrecht; Simonsen, Sebastian; Davidsen, Annika Helgadóttir

2017-01-01

Interpersonal problems are thought to play an essential role in the development and maintenance of eating disorders. The aim of the current study was to investigate whether a specific interpersonal profile could be identified in a group of patients diagnosed with Bulimia Nervosa, Binge Eating Disorder, or Eating Disorders Not Otherwise Specified, and to explore if specific types of interpersonal problems were systematically related to treatment outcome in this group of patients. The participants were 159 patients who received systemic/narrative outpatient group psychotherapy. Interpersonal problems were measured at baseline, and eating disorder symptoms were measured pre- and post treatment. Data were analysed with the Structural Summary Method, a particular method for the analysis of the Inventory of Interpersonal Problems, and hierarchical regression analysis was conducted. The patients demonstrated a generally Non-assertive and Friendly-submissive interpersonal style. No significant association between the overall level of interpersonal problems and treatment outcome was identified. However, the results showed a correlation between being cold and hostile and poor treatment outcome, while being domineering showed a trend approaching significance in predicting better treatment outcome. The results indicate that patients with eating disorders show a specific interpersonal profile, and suggest that particular types of interpersonal problems are associated with treatment outcome.

The impact of the therapeutic alliance on treatment outcome in patients with dissociative disorders

PubMed Central

Cronin, Elisabeth; Brand, Bethany L.; Mattanah, Jonathan F.

2014-01-01

Background Research has shown that the therapeutic alliance plays an important role in enhancing treatment outcome among individuals with a variety of disorders, including posttraumatic stress disorder (PTSD). However, the therapeutic alliance and treatment outcome has not yet been studied in dissociative disorders (DD). Objectives The current study sought to investigate the impact of alliance on treatment outcome for DD patients. Methods Data from a naturalistic, longitudinal international treatment study of DD patients and their therapists were analyzed to determine if the alliance, as reported by patients and therapists, was associated with treatment outcome. Results Patients with higher self-rated alliance had fewer symptoms of dissociation, PTSD, and general distress, as well as higher levels of therapist-rated adaptive functioning. Over time, self-rated alliance scores predicted better outcomes, after controlling for patient adaptive capacities including symptom management at the time when the alliance ratings were made. Patient-rated alliance was more strongly associated with outcome than therapist-rated alliance. Conclusion Therapists who work with DD patients should understand the importance of the alliance on treatment outcome. These findings are consistent with previous literature demonstrating the importance of developing and maintaining a strong therapeutic alliance, although the effect sizes of individuals with DD were stronger than what has been found in many other patient groups. A greater understanding of the impact of the alliance in traumatized individuals may contribute to better outcomes for these individuals. PMID:24616755

Does impulsivity predict outcome in treatment for binge eating disorder? A multimodal investigation.

PubMed

Manasse, Stephanie M; Espel, Hallie M; Schumacher, Leah M; Kerrigan, Stephanie G; Zhang, Fengqing; Forman, Evan M; Juarascio, Adrienne S

2016-10-01

Multiple dimensions of impulsivity (e.g., affect-driven impulsivity, impulsive inhibition - both general and food-specific, and impulsive decision-making) are associated with binge eating pathology cross-sectionally, yet the literature on whether impulsivity predicts treatment outcome is limited. The present pilot study explored impulsivity-related predictors of 20-week outcome in a small open trial (n = 17) of a novel treatment for binge eating disorder. Overall, dimensions of impulsivity related to emotions (i.e., negative urgency) and food cues emerged as predictors of treatment outcomes (i.e., binge eating frequency and global eating pathology as measured by the Eating Disorders Examination), while more general measures of impulsivity were statistically unrelated to global eating pathology or binge frequency. Specifically, those with higher levels of negative urgency at baseline experienced slower and less pronounced benefit from treatment, and those with higher food-specific impulsivity had more severe global eating pathology at baseline that was consistent at post-treatment and follow-up. These preliminary findings suggest that patients high in negative urgency and with poor response inhibition to food cues may benefit from augmentation of existing treatments to achieve optimal outcomes. Future research will benefit from replication with a larger sample, parsing out the role of different dimensions of impulsivity in treatment outcome for eating disorders, and identifying how treatment can be improved to accommodate higher levels of baseline impulsivity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Influence of interpersonal traits on patient outcomes in the treatment of chronic rhinosinusitis.

PubMed

Levy, Joshua M; Mace, Jess C; Smith, Timothy L; Soler, Zachary M

2017-04-01

Patient-reported outcome measures (PROMs) measure health states in chronic rhinosinusitis (CRS) and have become the dominant metrics of treatment outcomes. Interpersonal traits (IPTs) are patient-specific factors that include personality type, perceived social support, and trust in physicians. The association of IPTs on treatment outcomes among patients with CRS has not been described previously, and IPTs may represent major clinical factors influencing treatment outcomes. Adult patients electing medical or surgical treatment for recalcitrant CRS were prospectively enrolled into a multi-institutional, observational outcomes study. Validated measures of IPTs, including the Big Five Inventory-10 Short Version (BFI-10), Multidimensional Scale of Perceived Social Support (MSPSS), and the Trust in Physician Scale (TPS), were completed and compared with PROMs, which included the 22-item SinoNasal Outcome Test (SNOT-22), the Medical Outcomes Study Short Form-6D (SF-6D), and the Patient Health Questionnaire-2 (PHQ-2). Three hundred fifty-four participants were included and followed for an average (± standard deviation) of 16.3 (±4.8) months. Significant within-subject improvement in mean PROM scores was reported (all p <0.001). No association was detected between PROM score improvement and baseline BFI-10 or MSPSS scores (p > 0.050). Significant, but weak, absolute correlations were reported between baseline TPS scores and improvement in SNOT-22, SF-6D, and PHQ-2 total scores (p < 0.050; r ≤ 0.138). Personality type and perceived social support do not associate with improvement after treatment for CRS. However, increased trust in physicians is weakly associated with greater posttreatment improvement. Further study is needed to examine the relationship between physician trust, patient satisfaction, and treatment outcomes among patients with CRS. © 2016 ARS-AAOA, LLC.

ADHD, Multimodal Treatment, and Longitudinal Outcome: Evidence, Paradox, and Challenge.

PubMed

Hinshaw, Stephen P; Arnold, L Eugene

2015-01-01

Given major increases in the diagnosis of attention-deficit hyperactivity disorder (ADHD) and in rates of medication for this condition, we carefully examine evidence for effects of single versus multimodal (i.e., combined medication and psychosocial/behavioral) interventions for ADHD. Our primary data source is the Multimodal Treatment Study of Children with ADHD (MTA), a 14-month, randomized clinical trial in which intensive behavioral, medication, and multimodal treatment arms were contrasted with one another and with community intervention (treatment-as-usual), regarding outcome domains of ADHD symptoms, comorbidities, and core functional impairments. Although initial reports emphasized the superiority of well-monitored medication for symptomatic improvement, reanalyses and reappraisals have highlighted (a) the superiority of combination treatment for composite outcomes and for domains of functional impairment (e.g., academic achievement, social skills, parenting practices); (b) the importance of considering moderator and mediator processes underlying differential patterns of outcome, including comorbid subgroups and improvements in family discipline style during the intervention period; (c) the emergence of side effects (e.g., mild growth suppression) in youth treated with long-term medication; and (d) the diminution of medication's initial superiority once the randomly assigned treatment phase turned into naturalistic follow-up. The key paradox is that whereas ADHD clearly responds to medication and behavioral treatment in the short term, evidence for long-term effectiveness remains elusive. We close with discussion of future directions and a call for greater understanding of relevant developmental processes in the attempt to promote optimal, generalized, and lasting treatments for this important and impairing neurodevelopmental disorder.

Assessment of treatment outcome in patients with craniomandibular dysfunction.

PubMed

de Leeuw, J R; Steenks, M H; Ros, W J; Lobbezoo-Scholte, A M; Bosman, F; Winnubst, J A

1994-11-01

Psychosocial, socio-demographic and symptom characteristics have been shown to be associated with treatment outcome in patients with craniomandibular dysfunction (CMD). This study was performed to assess to what extent symptoms and correlates of CMD change as a consequence of conservative treatment for CMD. Treatment outcome in a group of CMD patients treated with a stabilization splint (experimental group) was compared with that of a group of patients with CMD who were not treated for CMD (control group). Patients in the experimental group had fewer symptoms of CMD at the end of treatment. However, several symptoms and correlates of CMD also improved in the control group (severity of pain, joint noises, ear symptoms). It was therefore questioned whether all improvements in symptoms and correlates of CMD in the experimental group could be attributed to the treatment received. Results suggest that the main improvement that might be ascribed to therapy was a decrease in 'jaw symptoms'. There was a noticeable decrease in depression and an increased use of 'planned actions and rational thinking' as a coping style in the experimental group whereas these variables did not change in the control group. Implications and suggestions for further research are discussed.

Oral health-related quality of life, and satisfaction with treatment and treatment outcomes of adolescents/young adults with cleft lip/palate: an exploration.

PubMed

Munz, S M; Edwards, S P; Inglehart, M R

2011-08-01

The objectives of this correlational study were to explore whether the oral health-related quality of life (ohrqol) of adolescents/young adults with cleft lip/palate (CL/P) relates to their own and their parents' satisfaction with treatment and treatment outcomes. Data were collected using mailed surveys from 30 parents and 27 patients who completed CL/P treatment. Patients' ohrqol was assessed with the Michigan Oral Health-Related Quality of Life (MOHRQoL) Scale, treatment satisfaction with Kiyak's Post-Surgical Patient Satisfaction Questionnaire, and satisfaction with treatment outcomes with Noor and Musa's Cleft Evaluation Profile. Overall, patients reported a positive ohrqol. Their satisfaction scores ranged from low to high. Patient and parent treatment satisfaction was related, while their outcome satisfaction did not correlate. Patients' MOHRQoL scores correlated with parent and patient treatment satisfaction and parents' outcome satisfaction. Patients' MOHRQoL scores did not correlate with patients' outcome satisfaction. The patients' level of discomfort was strongly correlated with patients' and parents' treatment satisfaction and parents' outcome satisfaction. In conclusion, regardless of outcome satisfaction, young patients with CL/P report a quite positive ohrqol after treatment completion. There is a clear relationship between the ohrqol of these patients with CL/P and their own as well as their parents' treatment satisfaction assessments. Copyright © 2011 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Improved outcome of bacterial meningitis associated with use of corticosteroid treatment.

PubMed

Baunbæk-Knudsen, Gertrud; Sølling, Mette; Farre, Annette; Benfield, Thomas; Brandt, Christian T

2016-04-01

Background The aim of this study was to evaluate the clinical outcome of patients with bacterial meningitis following the introduction of dexamethasone treatment in Denmark. Methods Adult patients with bacterial meningitis, admitted from 2003-2010 to two different university hospitals, were included retrospectively. Data at clinical presentation, Glasgow outcome scale (GOS), cerebrospinal fluid and blood biochemistry were collected. Relative risk (RR) with 95% confidence interval (CI) was computed by Cox proportional hazard regression analysis. Results One hundred and forty-seven patients were included in the study. The population had a median age of 62 years and 31% had an immunosuppressive co-morbidity. Eighty-nine patients had an unfavourable outcome (GOS score = 1-4). Adjuvant treatment with corticosteroids (RR = 0.48; 95% CI = 0.30-0.76) was associated with a favourable outcome (GOS score = 5), while altered mental status (RR = 2.36; 95% CI = 1.17-4.78) and age (RR = 1.03; 95% CI = 1.01-1.04) per year increment was associated with an unfavourable outcome. Adjuvant corticosteroid treatment did not affect short- or long-term survival. Short-term mortality was influenced by age (RR = 1.06; 95% CI = 1.04-1.09). Long-term mortality was influenced by age (RR = 1.06; 95% CI = 1.03-1.08) and female sex (RR = 1.81; 95% CI = 1.05-3.14). Conclusion This study indicated that adjuvant corticosteroid treatment in acute bacterial meningitis improves the outcome and can safely be administered in an elderly population with high levels of immunosuppressive co-morbidity.

Outcomes of Treatment of Nonagenarians With Severe Aortic Stenosis.

PubMed

Mack, Molly Claire; Szerlip, Molly; Herbert, Morley A; Akram, Siddique; Worley, Christina; Kim, Rebeca J; Prince, Brandon A; Harrington, Katherine B; Mack, Michael J; Holper, Elizabeth M

2015-07-01

Because nonagenarians with aortic stenosis (AS) often present as frail with more comorbid conditions, long-term outcomes and quality of life are important treatment considerations. The aim of this report is to describe survival and functional outcomes of nonagenarians undergoing treatment for AS by surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR). This is a retrospective analysis of all patients aged 90 years or more undergoing treatment for AS between 2007 and 2013 at two centers. Outcomes were compared between SAVR and TAVR. Long-term survival was compared with an age- and sex-matched population from the Social Security Actuarial Life Table. In all, 110 patients underwent treatment for isolated AS (20 SAVR and 90 TAVR). Mean age was 91.85 ± 1.80 years, and 50.9% were female. The Society of Thoracic Surgeons mean predicted risk of mortality was 11.11% ± 5.74%. Operative mortality was 10.9% (10.0% SAVR; 11.1% TAVR); 2.7% of patients had a stroke. The TAVR patients were more likely to be discharged home (75.9% versus 55.6% for SAVR, p = 0.032). Mean follow-up was 1.8 ± 1.5 years, with a 1-year and 5-year survival of 78.7% and 45.3%, respectively, which approximated the US actuarial survival. There was a significant improvement in quality of life as measured by the Kansas City Cardiomyopathy Questionnaire at 1 year compared with baseline. Treatment of AS approximates natural life expectancy in select nonagenarians, with no significant difference in long-term survival between SAVR and TAVR. Importantly, patient quality of life improved at 1 year. With appropriate selection, nonagenarians with severe AS can benefit from treatment. Copyright © 2015 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

Treatment outcomes using CBT-IA with Internet-addicted patients.

PubMed

Young, Kimberly S

2013-12-01

Internet Gaming Disorder, a subtype of Internet Addiction, is now classified in Section 3 of the DSM-5. Cognitive behavioral therapy (CBT) has been suggested in treating Internet addiction as this modality has been shown to be an effective treatment for similar impulse control disorders. Given the daily and necessary use of the Internet and technology in general compared to other compulsive syndromes, a specialized form of CBT has been developed called Cognitive-Behavioral Therapy for Internet Addiction (CBT-IA). CBT-IA is a comprehensive three phase approach that includes behavior modification to control compulsive Internet use, cognitive restructuring to identify, challenge, and modify cognitive distortions that lead to addictive use, and harm reduction techniques to address and treat co-morbid issues associated with the disorder. As the first model of its kind, this study examines 128 clients to measure treatment outcomes using CBT-IA. Clients were evaluated using the Internet Addiction Test (IAT) to classify subjects and were administered twelve weekly sessions of CBT-IA. Treatment outcomes were measured at the end of the twelve weeks, one-month, three months and at six month post-treatment. RESULTS showed that over 95% of clients were able to manage symptoms at the end of the twelve weeks and 78% sustained recovery six months following treatment. RESULTS found that CBT-IA was effective at ameliorating symptoms associated with Internet addiction after twelve weekly sessions and consistently over one-month, three months, and six months after therapy. Further research implications such as investigating long-term outcome effects of the model with larger client populations and treatment differences among the subtypes of Internet addiction or with other cultural populations using CBT-IA are discussed.

Predictors of poor treatment outcomes in multidrug-resistant tuberculosis patients: a retrospective cohort study.

PubMed

Javaid, A; Ullah, I; Masud, H; Basit, A; Ahmad, W; Butt, Z A; Qasim, M

2018-06-01

We aimed to determine the characteristics, treatment outcomes and risk factors for poor treatment outcomes among multidrug-resistant (MDR) tuberculosis (TB) patients in Khyber Pakhtunkhwa province, Pakistan. A retrospective cohort study including all patients with MDR-TB who sought care at the MDR-TB unit in Peshawar was conducted between January 2012 and April 2014. Patients were followed until an outcome of TB treatment was recorded as successful (cured or completed) or unsuccessful. Binary logistic regression was used to identify predictors of poor outcome, i.e. unsuccessful treatment outcomes. Overall, 535 patients were included. The proportion of female subjects was relatively higher (n = 300, 56.1%) than male subjects. The mean (standard deviation) age of patients was 30.37 (14.09) years. Of 535 patients for whom treatment outcomes were available, 402 (75.1%) were cured, 4 (0.7%) completed therapy, 34 (6.4%) had disease that failed to respond to therapy, 93 (17.4%) died and two (0.4%) defaulted; in total, 129 (24.1%) had an unsuccessful outcome. We found three significant predictors of unsuccessful treatment during multivariate logistic regression: being married (odds ratio (OR) = 2.17, 95% confidence interval (CI) 1.01, 4.66), resistance to second-line drugs (OR = 2.61, 95% CI 1.61, 4.21) and presence of extensively drug-resistant TB (OR = 7.82, 95% CI 2.90, 21.07). Approximately 75% of the treatment success rate set by the Global Plan to Stop TB was achieved. Resistance to second-line drugs and presence of extensively drug-resistant TB are the main risk factors for poor treatment outcomes. Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

The Involvement of a Concerned Significant Other in Gambling Disorder Treatment Outcome.

PubMed

Jiménez-Murcia, Susana; Tremblay, Joël; Stinchfield, Randy; Granero, Roser; Fernández-Aranda, Fernando; Mestre-Bach, Gemma; Steward, Trevor; Del Pino-Gutiérrez, Amparo; Baño, Marta; Moragas, Laura; Aymamí, Neus; Gómez-Peña, Mónica; Tárrega, Salomé; Valenciano-Mendoza, Eduardo; Giroux, Isabelle; Sancho, Marta; Sánchez, Isabel; Mallorquí-Bagué, Núria; González, Vega; Martín-Romera, Virginia; Menchón, José M

2017-09-01

Interpersonal distress is a common feature in gambling disorder and adding a concerned significant other (CSO) to the recovery process could be an effective tool for improving treatment outcome. However, little empirical evidence is available regarding the effectiveness of including a CSO to interventions. We aimed to compare treatment outcomes (i.e. compliance with therapy guidelines, dropout from treatment, and relapse during treatment) in a CBT program involving a CSO to CBT treatment as usual (TAU) without a CSO. The sample comprised male gambling disorder patients (N = 675). The manualized CBT intervention consisted of 16 weekly outpatient group sessions and a 3-month follow-up period. Patient CSOs attended a predetermined number of sessions with the patient and were provided with resources to acquire a better understanding of the disorder, to manage risk situations, and to aid patients in adhering to treatment guidelines. Patients with a CSO had significant higher treatment attendance and reduced dropout compared to patients receiving TAU. Moreover, patients whose spouse was involved in the treatment program were less likely to relapse and adhered to the treatment guidelines more than those with a non-spousal CSO. Our results suggest that incorporating interpersonal support to gambling disorder interventions could potentially improve treatment outcomes.

Multiple Measures of Outcome in Assessing a Prison-Based Drug Treatment Program

ERIC Educational Resources Information Center

Prendergast, Michael L.; Hall, Elizabeth A.; Wexler, Harry K.

2003-01-01

Evaluations of prison-based drug treatment programs typically focus on one or two dichotomous outcome variables related to recidivism. In contrast, this paper uses multiple measures of outcomes related to crime and drug use to examine the impact of prison treatment. Crime variables included self-report data of time to first illegal activity,…

Tuberculosis treatment outcome monitoring in England, Wales and Northern Ireland for cases reported in 2001

PubMed Central

Antoine, Delphine; French, Clare E; Jones, Jane; Watson, John M

2007-01-01

Background Tuberculosis treatment outcome monitoring was introduced in England, Wales and Northern Ireland in 2002 based on cases reported in 2001. Objective To estimate the proportion of treatment success and to identify predictors of non‐completion for cases reported in 2001. Method At 12 months after the start of treatment, outcome was assessed according to a protocol based on standardised European recommendations. Results The proportion of cases completing treatment by 12 months was 79% if calculated for cases in whom outcome information was reported, and 62% of all cases regardless of whether information on outcome was reported or not. Of the new smear‐positive pulmonary cases for whom information on outcome was reported, 77% completed treatment. Non‐completion of treatment was associated with male sex, age ⩾65 years, recent entry into UK for those born abroad, residence outside London, pulmonary disease and drug resistance. Conclusions Despite the resources of an industrialised country with a low incidence of tuberculosis, the World Health Organization treatment success target of 85% was not achieved. This was partly due to the number of deaths in the elderly, and partly due to missing outcome information for 21% of the cases. As in other low‐incidence countries, additional outcome measures such as the proportion of those aged <65 years completing treatment would provide a more comparable indicator for assessment of treatment success. This first year of data collection has shown the importance of increasing the proportion of cases for whom outcome is ascertained, and of ensuring the validity of information provided. PMID:17372289

[Forensic (flexible) assertive community treatment: client characteristics and treatment outcomes].

PubMed

Neijmeijer, L; Verwoerd, J; van Vugt, M; Place, C; Kroon, H

(Flexible) Assertive community treatment ((f)act) is applied increasingly to forensic psychiatric clients. However, evidence about the effectiveness of forensic (f)act is scanty. To investigate to what extent (subgroups of) clients receiving care from forensic (f)act teams show, after a year, changes in their social and psychological functioning and are subjected to fewer justicial outcome measures. Between 2009 and 2011, eight forensic (f)act teams collected, at two measurement moments separated by an average of 12 months, data relating to client characteristics and outcomes of care. The study involved 202 clients. After a year clients showed significant improvements in psychological and social functioning, and had fewer confrontations with the police and the law. They were detained less often and for shorter periods and were considered to be less likely to reoffend. The number of admissions to mental health care and to addiction and forensic care remained constant. Clients with a psychiatric disorder and likely to display criminal behaviour showed improvement while being treated by forensic (f)act teams. Further research is needed to prove whether forensic (f)act treatment will have the desired effects in the longer term and will enjoy the status of being regarded as evidence based practice.

Effects of 24 months of treatment with romosozumab followed by 12 months of denosumab or placebo in postmenopausal women with low bone mineral density: A randomized, double-blind, phase 2, parallel group study.

PubMed

McClung, Michael R; Brown, Jacques P; Diez-Perez, Adolfo; Resch, Heinrich; Caminis, John; Meisner, Paul; Bolognese, Michael A; Goemaere, Stefan; Bone, Henry G; Zanchetta, Jose R; Maddox, Judy; Bray, Sarah; Grauer, Andreas

2018-04-25

Over 12 months, romosozumab increased bone formation and decreased bone resorption, resulting in increased BMD in postmenopausal women with low BMD (NCT00896532). Herein we report the study extension evaluating 24 months treatment with romosozumab, discontinuation of romosozumab, alendronate followed by romosozumab, and romosozumab followed by denosumab. Postmenopausal women age 55-85 years with a lumbar spine (LS), total hip (TH), or femoral neck T-score ≤-2.0 and ≥-3.5 were enrolled and randomly assigned to placebo, one of five romosozumab regimens (70mg, 140mg, 210mg monthly [QM]; 140mg Q3M; 210mg Q3M) for 24 months, or open-label alendronate for 12 months followed by romosozumab 140mg QM for 12 months. Eligible participants were then re-randomized 1:1 within original treatment groups to placebo or denosumab 60mg Q6M for an additional 12 months. Percentage change from baseline in BMD and bone turnover markers (BTMs) at months 24 and 36 and safety were evaluated. Of 364 participants initially randomized to romosozumab, placebo, or alendronate, 315 completed 24 months of treatment and 248 completed the extension. Romosozumab markedly increased LS and TH BMD through month 24, with largest gains observed with romosozumab 210mg QM (LS = 15.1%; TH = 5.4%). Women receiving romosozumab who transitioned to denosumab continued to accrue BMD, whereas BMD returned toward pretreatment levels with placebo. With romosozumab 210mg QM, bone formation marker P1NP initially increased following treatment initiation and gradually decreased to below baseline by month 12, remaining below baseline through month 24; and bone resorption marker β-CTX rapidly decreased following treatment, remaining below baseline through month 24. Transition to denosumab further decreased both BTMs, while after transition to placebo, P1NP returned to baseline and β-CTX increased above baseline. Adverse events were balanced between treatment groups through month 36. These data suggest that

Internet gaming disorder treatment: a review of definitions of diagnosis and treatment outcome.

PubMed

King, Daniel L; Delfabbro, Paul H

2014-10-01

Internet gaming disorder (IGD) is a new disorder currently positioned in the appendix of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. Few clinical studies report that psychological and pharmacological interventions can significantly reduce the severity of IGD symptomatology. The aim of this review was to assess current knowledge of the short- and long-term benefits of IGD interventions. This review presents a systematic evaluation of definitions of diagnosis and treatment outcomes employed in IGD treatment studies, including an assessment of goodness of fit with the DSM-5 classification. A computer database search of Academic Search Premier, PubMed, PsychINFO, ScienceDirect, Web of Science, and Google Scholar was conducted to identify all available research evidence on Internet gaming disorder treatment (N = 8 studies). Diagnostic and treatment outcome parameters were systematically evaluated. Several weaknesses of IGD treatment literature were identified. Only 2 treatment studies have employed an equivalent method of diagnosis for IGD. Studies have not assessed formative change in diagnostic status at posttreatment or follow-up. Duration of follow-up has been inadequate to assess relapse and remission. Posttreatment assessment has been predominantly limited to IGD symptomatology, comorbidity, and frequency of gaming behavior. Currently, there is insufficient evidence to warrant suggestion that trialled IGD interventions confer a long-term therapeutic benefit. Several improvements to study design and reporting are proposed to guide future studies of IGD. © 2014 Wiley Periodicals, Inc.

Patient or treatment centre? Where are efforts invested to improve cancer patients' psychosocial outcomes?

PubMed Central

Carey, ML; Clinton-McHarg, T; Sanson-Fisher, RW; Campbell, S; Douglas, HE

2011-01-01

The psychosocial outcomes of cancer patients may be influenced by individual-level, social and treatment centre predictors. This paper aimed to examine the extent to which individual, social and treatment centre variables have been examined as predictors or targets of intervention for psychosocial outcomes of cancer patients. Medline was searched to find studies in which the psychological outcomes of cancer patient were primary variables. Papers published in English between 1999 and 2009 that reported primary data relevant to psychosocial outcomes for cancer patients were included, with 20% randomly selected for further coding. Descriptive studies were coded for inclusion of individual, social or treatment centre variables. Intervention studies were coded to determine if the unit of intervention was the individual patient, social unit or treatment centre. After random sampling, 412 publications meeting the inclusion criteria were identified, 169 were descriptive and 243 interventions. Of the descriptive papers 95.0% included individual predictors, and 5.0% social predictors. None of the descriptive papers examined treatment centre variables as predictors of psychosocial outcomes. Similarly, none of the interventions evaluated the effectiveness of treatment centre interventions for improving psychosocial outcomes. Potential reasons for the overwhelming dominance of individual predictors and individual-focused interventions in psychosocial literature are discussed. PMID:20646035

Predictors of Stimulant Abuse Treatment Outcomes in Severely Mentally Ill Outpatients

PubMed Central

Angelo, Frank N.; McDonell, Michael G.; Lewin, Michael R.; Srebnik, Debra; Lowe, Jessica; Roll, John; Ries, Richard

2012-01-01

Background Severe mental illness is often exclusionary criteria for studies examining factors that influence addiction treatment outcome. Therefore, little is known about predictors of treatment response of individuals receiving psychosocial treatments for addictions who suffer from co-occurring severe mental illness. Methods The impact of demographic, substance abuse severity, psychiatric severity, and service utilization variables on in-treatment performance (i.e., longest duration of abstinence) in a 12-week contingency management (CM) intervention for stimulant abuse in 96 severely mentally ill adults was investigated. A 4-step linear regression was used to identify independent predictors of in-treatment abstinence. Results This model accounted for 37.4% of variance in the longest duration of abstinence outcome. Lower levels of stimulant use (i.e., stimulant-negative urine test) and psychiatric severity (i.e., lower levels of psychiatric distress), as well as higher rates of outpatient treatment utilization at study entry were independently associated with longer duration of drug abstinence. Conclusion These data suggest that individuals with low levels of stimulant use and psychiatric severity, as well as those actively engaged in services are most likely to succeed in a typical CM intervention. For others, modifications to CM interventions, such as increasing the value of reinforcement or adding CM to evidence based psychiatric interventions may improve treatment outcomes. PMID:23273776

3D printed alendronate-releasing poly(caprolactone) porous scaffolds enhance osteogenic differentiation and bone formation in rat tibial defects.

PubMed

Kim, Sung Eun; Yun, Young-Pil; Shim, Kyu-Sik; Kim, Hak-Jun; Park, Kyeongsoon; Song, Hae-Ryong

2016-09-29

The aim of this study was to evaluate the in vitro osteogenic effects and in vivo new bone formation of three-dimensional (3D) printed alendronate (Aln)-releasing poly(caprolactone) (PCL) (Aln/PCL) scaffolds in rat tibial defect models. 3D printed Aln/PCL scaffolds were fabricated via layer-by-layer deposition. The fabricated Aln/PCL scaffolds had high porosity and an interconnected pore structure and showed sustained Aln release. In vitro studies showed that MG-63 cells seeded on the Aln/PCL scaffolds displayed increased alkaline phosphatase (ALP) activity and calcium content in a dose-dependent manner when compared with cell cultures in PCL scaffolds. In addition, in vivo animal studies and histologic evaluation showed that Aln/PCL scaffolds implanted in a rat tibial defect model markedly increased new bone formation and mineralized bone tissues in a dose-dependent manner compared to PCL-only scaffolds. Our results show that 3D printed Aln/PCL scaffolds are promising templates for bone tissue engineering applications.

Development and validation of a Markov microsimulation model for the economic evaluation of treatments in osteoporosis.

PubMed

Hiligsmann, Mickaël; Ethgen, Olivier; Bruyère, Olivier; Richy, Florent; Gathon, Henry-Jean; Reginster, Jean-Yves

2009-01-01

Markov models are increasingly used in economic evaluations of treatments for osteoporosis. Most of the existing evaluations are cohort-based Markov models missing comprehensive memory management and versatility. In this article, we describe and validate an original Markov microsimulation model to accurately assess the cost-effectiveness of prevention and treatment of osteoporosis. We developed a Markov microsimulation model with a lifetime horizon and a direct health-care cost perspective. The patient history was recorded and was used in calculations of transition probabilities, utilities, and costs. To test the internal consistency of the model, we carried out an example calculation for alendronate therapy. Then, external consistency was investigated by comparing absolute lifetime risk of fracture estimates with epidemiologic data. For women at age 70 years, with a twofold increase in the fracture risk of the average population, the costs per quality-adjusted life-year gained for alendronate therapy versus no treatment were estimated at €9105 and €15,325, respectively, under full and realistic adherence assumptions. All the sensitivity analyses in terms of model parameters and modeling assumptions were coherent with expected conclusions and absolute lifetime risk of fracture estimates were within the range of previous estimates, which confirmed both internal and external consistency of the model. Microsimulation models present some major advantages over cohort-based models, increasing the reliability of the results and being largely compatible with the existing state of the art, evidence-based literature. The developed model appears to be a valid model for use in economic evaluations in osteoporosis.

Relationship between airborne pollen count and treatment outcome in Japanese cedar pollinosis patients.

PubMed

Takasaki, Kenji; Enatsu, Kaori; Kumagami, Hidetaka; Takahashi, Haruo

2009-05-01

In Japan, information on daily Japanese cedar pollen counts is made public during pollen season. If symptom severity and treatment outcome are predictable according to these pollen counts, management of seasonal allergic rhinitis may become more precise. The aims of the study were to evaluate the relationship between airborne pollen counts, symptom severity and treatment outcome in Japanese cedar pollinosis patients. In the randomized study, patients with moderate to most severe Japanese pollinosis were treated with fexofenadine (60 mg BD) or fexofenadine and nasal corticosteroids for 2 weeks. During the same period daily airborne pollen counts were measured. A total of 105 adult patients were enrolled. No difference of treatment efficacy was seen among groups. Detailed results of efficacy and safety were previously described elsewhere. In univariate analysis, the mean cumulative amount of airborne pollen exposure for 4 days prior to the study tended to affect symptom severity (P = 0.053) and the mean cumulative amount of airborne pollen during the treatment period tended to show difference among five treatment outcome categories (P = 0.066). In multivariate analysis, the mean cumulative amount of airborne pollen exposure for 4 days prior to the study was identified as the only significant factor of symptom severity (P = 0.0327) and cumulative amount of airborne pollen during the treatment period (P = 0.027) and allergic history (P = 0.027) were significant factors of treatment outcomes. No serious adverse effect was reported during the study. The amount of airborne pollen may be predictive of both symptom severity and treatment outcome.

Neurophysiological model of tinnitus: dependence of the minimal masking level on treatment outcome.

PubMed

Jastreboff, P J; Hazell, J W; Graham, R L

1994-11-01

Validity of the neurophysiological model of tinnitus (Jastreboff, 1990), outlined in this paper, was tested on data from multicenter trial of tinnitus masking (Hazell et al., 1985). Minimal masking level, intensity match of tinnitus, and the threshold of hearing have been evaluated on a total of 382 patients before and after 6 months of treatment with maskers, hearing aids, or combination devices. The data has been divided into categories depending on treatment outcome and type of approach used. Results of analysis revealed that: i) the psychoacoustical description of tinnitus does not possess a predictive value for the outcome of the treatment; ii) minimal masking level changed significantly depending on the treatment outcome, decreasing on average by 5.3 dB in patients reporting improvement, and increasing by 4.9 dB in those whose tinnitus remained the same or worsened; iii) 73.9% of patients reporting improvement had their minimal masking level decreased as compared with 50.5% for patients not showing improvement, which is at the level of random change; iv) the type of device used has no significant impact on the treatment outcome and minimal masking level change; v) intensity match and threshold of hearing did not exhibit any significant changes which can be related to treatment outcome. These results are fully consistent with the neurophysiological interpretation of mechanisms involved in the phenomenon of tinnitus and its alleviation.

Standardized Treatment of Neonatal Status Epilepticus Improves Outcome.

PubMed

Harris, Mandy L; Malloy, Katherine M; Lawson, Sheena N; Rose, Rebecca S; Buss, William F; Mietzsch, Ulrike

2016-12-01

We aimed to decrease practice variation in treatment of neonatal status epilepticus by implementing a standardized protocol. Our primary goal was to achieve 80% adherence to the algorithm within 12 months. Secondary outcome measures included serum phenobarbital concentrations, number of patients progressing from seizures to status epilepticus, and length of hospital stay. Data collection occurred for 6 months prior and 12 months following protocol implementation. Adherence of 80% within 12 months was partially achieved in patients diagnosed in our hospital; in pretreated patients, adherence was not achieved. Maximum phenobarbital concentrations were decreased (56.8 vs 41.0 µg/mL), fewer patients progressed from seizures to status epilepticus (46% vs 36%), and hospital length of stay decreased by 9.7 days in survivors. In conclusion, standardized, protocol-driven treatment of neonatal status epilepticus improves consistency and short-term outcome. © The Author(s) 2016.

Eating disorders in individuals with type 1 diabetes: case series and day hospital treatment outcome.

PubMed

Colton, Patricia Anne; Olmsted, Marion Patricia; Wong, Harmonie; Rodin, Gary Michael

2015-07-01

Women with type 1 diabetes are at high risk for eating disorders (ED), a combination that can increase medical complications and mortality. As little is known about treatment response in this population, clinical presentation and treatment outcome in an extended case series were assessed. A chart review at the Eating Disorders Day Hospital Program at Toronto General Hospital identified a total of 100 individuals with type 1 diabetes assessed 1990-2012. Of 37 who attended day hospital, most experienced improvement in ED symptoms, but only 18.8% had a good immediate treatment outcome, while 43.8% had an intermediate outcome and 37.5% had a poor outcome (meeting diagnostic criteria at discharge). This is poorer than program outcomes in individuals without diabetes (χ(2)  = 12.2, df = 2; p = 0.002). Factors influencing treatment engagement and outcome must be further studied and used to improve treatment results in this high-risk group. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

Treatment adherence and health outcomes in patients with bronchiectasis

PubMed Central

2014-01-01

Background We aimed to determine adherence to inhaled antibiotics, other respiratory medicines and airway clearance and to determine the association between adherence to these treatments and health outcomes (pulmonary exacerbations, lung function and Quality of Life Questionnaire-Bronchiectasis [QOL-B]) in bronchiectasis after 12 months. Methods Patients with bronchiectasis prescribed inhaled antibiotics for Pseudomonas aeruginosa infection were recruited into a one-year study. Participants were categorised as “adherent” to medication (medication possession ratio ≥80% using prescription data) or airway clearance (score ≥80% in the Modified Self-Reported Medication-Taking Scale). Pulmonary exacerbations were defined as treatment with a new course of oral or intravenous antibiotics over the one-year study. Spirometry and QOL-B were completed at baseline and 12 months. Associations between adherence to treatment and pulmonary exacerbations, lung function and QOL-B were determined by regression analyses. Results Seventy-five participants were recruited. Thirty-five (53%), 39 (53%) and 31 (41%) participants were adherent to inhaled antibiotics, other respiratory medicines, and airway clearance, respectively. Twelve (16%) participants were adherent to all treatments. Participants who were adherent to inhaled antibiotics had significantly fewer exacerbations compared to non-adherent participants (2.6 vs 4, p = 0.00) and adherence to inhaled antibiotics was independently associated with having fewer pulmonary exacerbations (regression co-efficient = -0.51, 95% CI [-0.81,-0.21], p < 0.001). Adherence to airway clearance was associated with lower QOL-B Treatment Burden (regression co-efficient = -15.46, 95% CI [-26.54, -4.37], p < 0.01) and Respiratory Symptoms domain scores (regression co-efficient = -10.77, 95% CI [-21.45; -0.09], p < 0.05). There were no associations between adherence to other respiratory medicines and any of the

Treatment adherence and health outcomes in patients with bronchiectasis.

PubMed

McCullough, Amanda R; Tunney, Michael M; Quittner, Alexandra L; Elborn, J Stuart; Bradley, Judy M; Hughes, Carmel M

2014-07-01

We aimed to determine adherence to inhaled antibiotics, other respiratory medicines and airway clearance and to determine the association between adherence to these treatments and health outcomes (pulmonary exacerbations, lung function and Quality of Life Questionnaire-Bronchiectasis [QOL-B]) in bronchiectasis after 12 months. Patients with bronchiectasis prescribed inhaled antibiotics for Pseudomonas aeruginosa infection were recruited into a one-year study. Participants were categorised as "adherent" to medication (medication possession ratio ≥80% using prescription data) or airway clearance (score ≥80% in the Modified Self-Reported Medication-Taking Scale). Pulmonary exacerbations were defined as treatment with a new course of oral or intravenous antibiotics over the one-year study. Spirometry and QOL-B were completed at baseline and 12 months. Associations between adherence to treatment and pulmonary exacerbations, lung function and QOL-B were determined by regression analyses. Seventy-five participants were recruited. Thirty-five (53%), 39 (53%) and 31 (41%) participants were adherent to inhaled antibiotics, other respiratory medicines, and airway clearance, respectively. Twelve (16%) participants were adherent to all treatments. Participants who were adherent to inhaled antibiotics had significantly fewer exacerbations compared to non-adherent participants (2.6 vs 4, p = 0.00) and adherence to inhaled antibiotics was independently associated with having fewer pulmonary exacerbations (regression co-efficient = -0.51, 95% CI [-0.81,-0.21], p < 0.001). Adherence to airway clearance was associated with lower QOL-B Treatment Burden (regression co-efficient = -15.46, 95% CI [-26.54, -4.37], p < 0.01) and Respiratory Symptoms domain scores (regression co-efficient = -10.77, 95% CI [-21.45; -0.09], p < 0.05). There were no associations between adherence to other respiratory medicines and any of the outcomes tested. Adherence to treatment was not associated with

Outcomes of Buccinator Treatment With Botulinum Toxin in Facial Synkinesis.

PubMed

Patel, Priyesh N; Owen, Scott R; Norton, Cathey P; Emerson, Brandon T; Bronaugh, Andrea B; Ries, William R; Stephan, Scott J

2018-05-01

The buccinator, despite being a prominent midface muscle, has been previously overlooked as a target in the treatment of facial synkinesis with botulinum toxin. To evaluate outcomes of patients treated with botulinum toxin to the buccinator muscle in the setting of facial synkinesis. Prospective cohort study of patients who underwent treatment for facial synkinesis with botulinum toxin over multiple treatment cycles during a 1-year period was carried out in a tertiary referral center. Botulinum toxin treatment of facial musculature, including treatment cycles with and without buccinator injections. Subjective outcomes were evaluated using the Synkinesis Assessment Questionnaire (SAQ) prior to injection of botulinum toxin and 2 weeks after treatment. Outcomes of SAQ preinjection and postinjection scores were compared in patients who had at least 1 treatment cycle with and without buccinator injections. Subanalysis was performed on SAQ questions specific to buccinator function (facial tightness and lip movement). Of 84 patients who received botulinum toxin injections for facial synkinesis, 33 received injections into the buccinator muscle. Of the 33, 23 met inclusion criteria (19 [82.6%] women; mean [SD] age, 46 [10] years). These patients presented for 82 treatment visits, of which 44 (53.6%) involved buccinator injections and 38 (46.4%) were without buccinator injections. The most common etiology of facial paralysis included vestibular schwannoma (10 [43.5%] participants) and Bell Palsy (9 [39.1%] participants). All patients had improved posttreatment SAQ scores compared with prebotulinum scores regardless of buccinator treatment. Compared with treatment cycles in which the buccinator was not addressed, buccinator injections resulted in lower total postinjection SAQ scores (45.9; 95% CI, 38.8-46.8; vs 42.8; 95% CI, 41.3-50.4; P = .43) and greater differences in prebotox and postbotox injection outcomes (18; 95% CI, 16.2-21.8; vs 19; 95% CI, 14.2-21.8; P�

Contralateral Vocal Fold Reactive Lesions: Nomenclature, Treatment Choice, and Outcome.

PubMed

Koss, Shira L; Kidwai, Sarah M; Pitman, Michael J

2016-06-01

Contralateral reactive lesions (RLs) represent a distinct entity among benign bilateral vocal fold (VF) lesions. Lack of uniform nomenclature and a myriad of surgical options have hampered attempts to develop treatment guidelines. The objective of this study is to better define RLs and their prognosis, through the development of a standard nomenclature, with an aim to guide treatment and delineate the role of phonosurgery. Case series with chart review. Tertiary care center. Analysis was performed on patients with Current Procedural Terminology code 31545. Operative reports with a primary lesion and contralateral RL were included. Outcomes included the Voice Handicap Index-10 (VHI-10) and GRBAS (grade, roughness, breathiness, asthenia, and strain) scale, lesion persistence/recurrence, mucosal wave, and edge character based on blinded videostroboscopy review. A nomenclature was developed based on intraoperative RLs (n = 30), defined by lesion consistency (fibrous or polypoid) and relationship to normal VF edge (gradual or steep). Reactive lesion treatment included no intervention, excision, potassium titanyl phosphate laser, steroid injection, or a combination thereof. Observations included the following: inconsistent treatment modalities were employed, excision of RLs did not yield better outcomes, fibrous RLs were more likely to persist and polypoid lesions more likely to recur, gradual lesions were more likely to remain disease free, and most treatments showed improved mucosal wave, VHI-10, and GRBAS. Reactive lesions have not been well classified, and treatments are based on subjective intraoperative decision making with unpredictable outcomes. The nomenclature proposed will allow for a better definition of the RL and provide a framework for future research to identify optimal treatment. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.

Causal analysis of ordinal treatments and binary outcomes under truncation by death.

PubMed

Wang, Linbo; Richardson, Thomas S; Zhou, Xiao-Hua

2017-06-01

It is common that in multi-arm randomized trials, the outcome of interest is "truncated by death," meaning that it is only observed or well-defined conditioning on an intermediate outcome. In this case, in addition to pairwise contrasts, the joint inference for all treatment arms is also of interest. Under a monotonicity assumption we present methods for both pairwise and joint causal analyses of ordinal treatments and binary outcomes in presence of truncation by death. We illustrate via examples the appropriateness of our assumptions in different scientific contexts.

Preparation and characterisation of alendronate-loaded chitosan microparticles obtained through the spray drying technique.

PubMed

Ochiuz, Lacramioara; Peris, José-Esteban

2009-03-01

Microparticles of chitosan (CHT) containing alendronate sodium (AL) were prepared in four drug:polymer ratios (1:1, 1:2, 1:4, 1:6) using the spray drying technique. The efficiency of the method was evaluated by determining production yield (about 70 %) and microencapsulation efficiency, which was almost 100 % in the case of all four of the formulations studied. Particles had a mean size of between 3.6 and 4.6 microm, and a near-spherical shape. The formulations with the highest content of AL (drug:polymer ratio 1:1 and 1:2) showed an asymmetrical distribution of particles, which were larger in size, and had a higher proportion of irregular particles than the other formulations. FT-IR analysis revealed an ionic interaction between AL and CHT. Differential scanning calorimetry and thermogravimetric analysis confirmed the microencapsulation of AL and the increased thermal stability of encapsulated AL. The dissolution profiles of AL from CHT microspheres, at pH values of 1.2 and 6.8, showed a delayed release of AL from microspheres, and the dissolution rate was dependent on the pH and the drug:polymer ratio. It can be concluded that spray drying is a suitable technique for preparing AL-loaded CHT microspheres, and that the drug:polymer ratio can be used to control the rate of AL release from microspheres.

Homework Adherence and Cognitive Behaviour Treatment Outcome for Children and Adolescents with Anxiety Disorders.

PubMed

Arendt, Kristian; Thastum, Mikael; Hougaard, Esben

2016-03-01

Homework assignments are considered an essential component for a successful outcome of cognitive behavioural therapy for youths with anxiety disorders. However, only two studies have examined the association between homework adherence and outcome of cognitive behavioural therapy for youths with anxiety disorders. The study examined the association between homework adherence and treatment outcome following a generic group cognitive behaviour treatment program (Cool Kids) for anxiety disordered youths and their parents. The treatment program was completed by 98 children and adolescents (ages 7-16). Homework adherence was measured as time spent doing homework assignments between each session, reported by youths as well as parents. Outcome criteria consisted of youth-reported anxiety symptoms and clinician rated severity of primary anxiety diagnosis at posttreatment and 3-month follow-up. Results did not support an association between homework adherence and treatment outcome when controlling for pretreatment severity. The study found no convincing evidence that homework adherence predicted outcome of cognitive behavioural therapy for youths with anxiety disorders. Reasons for divergent findings on homework adherence in cognitive behavioural therapy for youths compared to adults are discussed.

Predictors of Positive Treatment Outcome in People With Anorexia Nervosa Treated in a Specialized Inpatient Unit: The Role of Early Response to Treatment.

PubMed

Wales, Jackie; Brewin, Nicola; Cashmore, Rebecca; Haycraft, Emma; Baggott, Jonathan; Cooper, Amy; Arcelus, Jon

2016-09-01

To investigate factors which predict positive treatment outcome in inpatients with anorexia nervosa (AN), particularly the role of early treatment response. 102 patients entering specialist inpatient treatment were assessed for eating disorder history, psychopathology, and motivation to change. Predictive factors assessed were: early treatment response defined as weight increase of at least 0.5-1 kg/week during the first 6 weeks of treatment (n=87), admission body mass index (BMI), onset age, chronicity, motivation to change, diagnosis, and previous hospitalization for AN. Positive treatment outcome was defined as achieving a BMI of 17.5 kg/m(2) within an individual time frame. Logistic regression indicated that patients were 18 times more likely to reach positive treatment outcome if they met the National Institute for Health and Care Excellence weight guidelines within the first 6 weeks of hospitalization. Higher admission BMI was also found to predict positive treatment outcome. Higher entry BMI and early weight gain predict positive treatment outcome in individuals receiving specialist AN inpatient treatment. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

The anti-osteoporotic and anti-atherogenic effects of alendronate and simvastatin in ovariectomized rats fed high fat diet: A comparative study of combination therapy versus monotherapy.

PubMed

Mohamed, Maha Tarek; Abuelezz, Sally A; Atalla, Suzi Sobhy; El Aziz, Lobna Fouad Abd; Gorge, Sonia Salib

2017-05-01

Epidemiological studies suggest a possible link between osteoporosis and cardiovascular diseases. Mevalonate pathway was pointed to as a part of this link. This study was done to investigate the effects of Alendronate (Al) and Simvastatin (Sim), both act on the mevalonate pathway, on osteoporosis, dyslipidemia and atherosclerotic changes in ovariectomized (OVX) rats fed high fat diet (HFD). 60 female albino rats were equally divided into 5 groups: control sham, OVX-HFD untreated, OVX -HFD treated with Al (3mg/kg/d) or/and Sim (6mg/kg/d). Treatments were taken for 4 weeks by oral gavage and were started 8 weeks after ovariectomy. OVX-HFD untreated group exhibited a significant negative alteration in lipid profile and on different bone markers e.g. alkaline phosphatase, hydroxyproline and osteocalcin. A significant increase in body weights and on serum levels of TNFα, iNOS and leptin were also found compared to control sham group. Vascular reactivity studies revealed a significant decrease in effective concentration 50 of phenylephrine and in acetylcholine% of relaxation and a significant increase in maximum contractile response of phenylephrine. The atherosclerotic and osteoporotic changes were further confirmed histopathologically. Treatment of OVX-HFD with Al or/and Sim significantly improved these deleterious effects compared to OVX-HFD untreated group. Comparing the combination therapy versus the mono-therapy exhibited a significant improvement in different tested parameters which came in favor of the combination therapy. Al and Sim have anti-osteoporotic, anti-dyslipidemic and anti-atherosclerotic beneficial effects. Their combination has more promising effects in treatment of osteoporosis, dyslipidemia and atherosclerosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effect of Intensive Blood-Pressure Treatment on Patient-Reported Outcomes.

PubMed

Berlowitz, Dan R; Foy, Capri G; Kazis, Lewis E; Bolin, Linda P; Conroy, Molly B; Fitzpatrick, Peter; Gure, Tanya R; Kimmel, Paul L; Kirchner, Kent; Morisky, Donald E; Newman, Jill; Olney, Christine; Oparil, Suzanne; Pajewski, Nicholas M; Powell, James; Ramsey, Thomas; Simmons, Debra L; Snyder, Joni; Supiano, Mark A; Weiner, Daniel E; Whittle, Jeff

2017-08-24

The previously published results of the Systolic Blood Pressure Intervention Trial showed that among participants with hypertension and an increased cardiovascular risk, but without diabetes, the rates of cardiovascular events were lower among those who were assigned to a target systolic blood pressure of less than 120 mm Hg (intensive treatment) than among those who were assigned to a target of less than 140 mm Hg (standard treatment). Whether such intensive treatment affected patient-reported outcomes was uncertain; those results from the trial are reported here. We randomly assigned 9361 participants with hypertension to a systolic blood-pressure target of less than 120 mm Hg or a target of less than 140 mm Hg. Patient-reported outcome measures included the scores on the Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Veterans RAND 12-Item Health Survey, the Patient Health Questionnaire 9-item depression scale (PHQ-9), patient-reported satisfaction with their blood-pressure care and blood-pressure medications, and adherence to blood-pressure medications. We compared the scores in the intensive-treatment group with those in the standard-treatment group among all participants and among participants stratified according to physical and cognitive function. Participants who received intensive treatment received an average of one additional antihypertensive medication, and the systolic blood pressure was 14.8 mm Hg (95% confidence interval, 14.3 to 15.4) lower in the group that received intensive treatment than in the group that received standard treatment. Mean PCS, MCS, and PHQ-9 scores were relatively stable over a median of 3 years of follow-up, with no significant differences between the two treatment groups. No significant differences between the treatment groups were noted when participants were stratified according to baseline measures of physical or cognitive function. Satisfaction with blood-pressure care was high in both treatment

Does semiology of status epilepticus have an impact on treatment response and outcome?

PubMed

Baysal-Kirac, Leyla; Feddersen, Berend; Einhellig, Marion; Rémi, Jan; Noachtar, Soheyl

2018-06-01

This study investigated whether there is an association between semiology of status epilepticus (SE) and response to treatment and outcome. Two hundred ninety-eight consecutive adult patients (160 females, 138 males) with SE at the University of Munich Hospital were prospectively enrolled. Mean age was 63.2±17.5 (18-97) years. Patient demographics, SE semiology and electroencephalography (EEG) findings, etiology, duration of SE, treatment, and outcome measures were investigated. Status epilepticus semiology was classified according to a semiological status classification. Patient's short-term outcome was determined by Glasgow Outcome Scale (GOS). The most frequent SE type was nonconvulsive SE (NCSE) (39.2%), mostly associated with cerebrovascular etiology (46.6%). A potentially fatal etiology was found in 34.8% of the patients. More than half (60.7%) of the patients had poor short-term outcome (GOS≤3) with an overall mortality of 12.4%. SE was refractory to treatment in 21.5% of the patients. Older age, potentially fatal etiology, systemic infections, NCSE in coma, refractory SE, treatment with anesthetics, long SE duration (>24h), low Glasgow Coma Scale (GCS) (≤8) at onset, and high Status Epilepticus Severity Score (STESS-3) (≥3) were associated with poor short-term outcome and death (p<0.05). Potentially fatal etiology and low GCS were the strongest predictors of poor outcome (Exp [b]: 4.74 and 4.10 respectively, p<0.05). Status epilepticus semiology has no independent association with outcome, but potentially fatal etiology and low GCS were strong predictive factors for poor short-term outcome of SE. Copyright © 2018 Elsevier Inc. All rights reserved.

Patient Characteristics and Treatment Outcomes for African American, Hispanic, and White Adolescents in DATOS-A.

ERIC Educational Resources Information Center

Rounds-Bryant, Jennifer L.; Staab, Jennifer

2001-01-01

Compared background, pre-treatment characteristics, and post-treatment outcomes of African American, Hispanic, and white adolescent substance abusers participating in the Drug Abuse Treatment Outcome Studies for Adolescents (DATOS-A). Found that patients were similar with respect to basic pre-treatment demographics. Compared to white adolescents,…

Traumatized refugees: morbidity, treatment and predictors of outcome.

PubMed

Buhmann, Caecilie Böck

2014-08-01

Despite large numbers of traumatized refugees, little is known about effective treatment of war trauma in refugees and immigrants. Few studies evaluating treatment have been published and most studies are follow-up studies with methodological limitations and little comparability across studies. The purpose of the PhD is to characterize transcultural trauma patients in Denmark needing psychiatric treatment with regards to psychopathology and predictors of mental health and to evaluate the effects of the treatment. Two studies reported in 4 papers form the basis of the thesis. FORLOB (Paper 1-3) was a follow-up study that included all patients receiving treatment at the Competence Center for Transcultural Psychiatry in Copenhagen from April 2008 to February 2010. Patients completed self-ratings of symptoms of PTSD, depression and anxiety as well as level of functioning and quality of life (HTQ, HSCL-25, SDS & WHO-5) before treatment and after treatment. Associations of co-morbid diagnoses and predictors of the patients' health condition were examined with linear and logistic regression and Pearson's correlation coefficients. Treatment in FORLOB consisted of a combination of Sertraline, Mianserin, psycho-education and Trauma-Focused Cognitive Behavioral Therapy (TFCBT). The treatment administered to each patient was monitored in detail and changes in outcome and predictors of change were analyzed. PTF1 (Paper 4) was a randomized controlled clinical trial with 2x2 factorial design (antidepressants, TFCBT, antidepressants & TFCBT, waiting list). Potential participants were screened amongst adult patients referred to the Competence Center for Transcultural Psychiatry in the period June 2009-2011. Patients with PTSD, war trauma and without a psychotic disorder were included. The manualized treatment consisted of weekly sessions with a physician and/or psychologist over a period of 6 months. The treatment effect was evaluated with a combination of self-ratings and blinded

Patient Preferences for Treatment of Basal Cell Carcinoma: Importance of Cure and Cosmetic Outcome.

PubMed

Martin, Isabelle; Schaarschmidt, Marthe-Lisa; Glocker, Anne; Herr, Raphael; Schmieder, Astrid; Goerdt, Sergij; Peitsch, Wiebke K

2016-03-01

Treatment options for localized resectable basal cell carcinoma (BCC) include micrographically controlled surgery, simple excision, curettage, laser ablation, cryosurgery, imiquimod, 5-fluorouracil, photodynamic therapy and radiotherapy. The aim of this study was to assess the preferences of patients with BCC for outcome (cure and recurrence rate, cosmetic outcome, risk of temporary and permanent complications) and process attributes (type of therapy, treatment location, anaesthesia, method of wound closure, duration of wound healing, out-of-pocket costs) of these treatments with conjoint analysis. Participants (n = 124) attached greatest importance to recurrence rate (relative importance score (RIS) = 17.28), followed by cosmetic outcome (RIS = 16.90) and cure rate (RIS = 15.02). Participants with BCC on the head or neck were particularly interested in cosmetic outcome. Those with a recurrence were willing to trade risk of recurrence, treatment location and duration of wound healing for a better cosmetic result. In summary, participants particularly valued cure and cosmetic outcome, although preferences varied with individual and tumour-associated characteristics.

Effect of glycemic control and type of diabetes treatment on unsuccessful TB treatment outcomes among people with TB-Diabetes: A systematic review

PubMed Central

Jeyashree, Kathiresan; Mahajan, Preetam; Shah, Amar N.; Kirubakaran, Richard; Rao, Raghuram; Kumar, Ajay M. V.

2017-01-01

Background Stringent glycemic control by using insulin as a replacement or in addition to oral hypoglycemic agents (OHAs) has been recommended for people with tuberculosis and diabetes mellitus (TB-DM). This systematic review (PROSPERO 2016:CRD42016039101) analyses whether this improves TB treatment outcomes. Objectives Among people with drug-susceptible TB and DM on anti-TB treatment, to determine the effect of i) glycemic control (stringent or less stringent) compared to poor glycemic control and ii) insulin (only or with OHAs) compared to ‘OHAs only’ on unsuccessful TB treatment outcome(s). We looked for unfavourable TB treatment outcomes at the end of intensive phase and/or end of TB treatment (minimum six months and maximum 12 months follow up). Secondary outcomes were development of MDR-TB during the course of treatment, recurrence after 6 months and/or after 1 year post successful treatment completion and development of adverse events related to glucose lowering treatment (including hypoglycemic episodes). Methods All interventional studies (with comparison arm) and cohort studies on people with TB-DM on anti-TB treatment reporting glycemic control, DM treatment details and TB treatment outcomes were eligible. We searched electronic databases (EMBASE, PubMed, Google Scholar) and grey literature between 1996 and April 2017. Screening, data extraction and risk of bias assessment were done independently by two investigators and recourse to a third investigator, for resolution of differences. Results After removal of duplicates from 2326 identified articles, 2054 underwent title and abstract screening. Following full text screening of 56 articles, nine cohort studies were included. Considering high methodological and clinical heterogeneity, we decided to report the results qualitatively and not perform a meta-analysis. Eight studies dealt with glycemic control, of which only two were free of the risk of bias (with confounder-adjusted measures of effect). An

Effect of glycemic control and type of diabetes treatment on unsuccessful TB treatment outcomes among people with TB-Diabetes: A systematic review.

PubMed

Shewade, Hemant Deepak; Jeyashree, Kathiresan; Mahajan, Preetam; Shah, Amar N; Kirubakaran, Richard; Rao, Raghuram; Kumar, Ajay M V

2017-01-01

Stringent glycemic control by using insulin as a replacement or in addition to oral hypoglycemic agents (OHAs) has been recommended for people with tuberculosis and diabetes mellitus (TB-DM). This systematic review (PROSPERO 2016:CRD42016039101) analyses whether this improves TB treatment outcomes. Among people with drug-susceptible TB and DM on anti-TB treatment, to determine the effect of i) glycemic control (stringent or less stringent) compared to poor glycemic control and ii) insulin (only or with OHAs) compared to 'OHAs only' on unsuccessful TB treatment outcome(s). We looked for unfavourable TB treatment outcomes at the end of intensive phase and/or end of TB treatment (minimum six months and maximum 12 months follow up). Secondary outcomes were development of MDR-TB during the course of treatment, recurrence after 6 months and/or after 1 year post successful treatment completion and development of adverse events related to glucose lowering treatment (including hypoglycemic episodes). All interventional studies (with comparison arm) and cohort studies on people with TB-DM on anti-TB treatment reporting glycemic control, DM treatment details and TB treatment outcomes were eligible. We searched electronic databases (EMBASE, PubMed, Google Scholar) and grey literature between 1996 and April 2017. Screening, data extraction and risk of bias assessment were done independently by two investigators and recourse to a third investigator, for resolution of differences. After removal of duplicates from 2326 identified articles, 2054 underwent title and abstract screening. Following full text screening of 56 articles, nine cohort studies were included. Considering high methodological and clinical heterogeneity, we decided to report the results qualitatively and not perform a meta-analysis. Eight studies dealt with glycemic control, of which only two were free of the risk of bias (with confounder-adjusted measures of effect). An Indian study reported 30% fewer

Treatment outcomes in 4 modes of orthodontic practice.

PubMed

Poulton, Donald; Vlaskalic, Vicki; Baumrind, Sheldon

2005-03-01

This study is a continuation of a previously published report on the outcome of orthodontic treatment provided in offices representing different modes of practice. The sample consisted of duplicate pretreatment (T1) and posttreatment (T2) dental casts of 348 patients from traditional private orthodontic practices (5 offices, 134 patients), company-owned practices (5 offices, 107 patients), offices associated with practice-management organizations (2 offices, 60 patients), and general dental practices (2 offices, 47 patients). Methods were used to obtain random, representative samples from each office, starting with lists of patients who were treated consecutively with full fixed orthodontic appliances. The dental casts were measured by 2 independent judges who used the unweighted PAR score. Good interjudge agreement was shown on the initial casts, but the agreement was not as strong on the final casts. The measurements showed that treatment outcomes were generally satisfactory, although some significant differences between offices and management modes were shown.

Acceptance and relationship context: a model of substance use disorder treatment outcome.

PubMed

Gifford, Elizabeth V; Ritsher, Jennifer B; McKellar, John D; Moos, Rudolf H

2006-08-01

This study presented and tested a model of behavior change in long-term substance use disorder recovery, the acceptance and relationship context (ARC) model. The model specifies that acceptance-based behavior and constructive social relationships lead to recovery, and that treatment programs with supportive, involved relationships facilitate the development of these factors. This study used a prospective longitudinal naturalistic design and controlled for baseline levels of study variables. The model was tested on a sample of 2549 patients in 15 residential substance use disorder treatment programs. Acceptance-based responding (ABR), social relationship quality (SRQ), treatment program alliance (TPA) and substance use-related impairment were assessed using interviews and self-report questionnaires. TPA predicted ABR and SRQ and, in turn, ABR predicted better 2-year and 5-year treatment outcomes. The baseline-controlled model accounted for 41% of the variance in outcome at 2-year follow-up and 28% of the variance in outcome at 5-year follow-up. CONCLUSIONS Patients from treatment programs with an affiliative relationship network are more likely to respond adaptively to internal states associated previously with substance use, develop constructive social relationships and achieve long-term treatment benefits.

Application of Certain π-Acceptors for the Spectrophotometric Determination of Alendronate Sodium in Pharmaceutical Bulk and Dosage Forms

PubMed Central

Raza, Asad; Zia-ul-Haq, Muhammad

2011-01-01

Two simple, fast, and accurate spectrophotometric methods for the determination of alendronate sodium are described. The methods are based on charge-transfer complex formation of the drug with two π-electron acceptors 7,7,7,8-tetracyanoquinodimethane (TCNQ) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in acetonitrile and methanol medium. The methods are followed spectrophotometrically by measuring the maximum absorbance at 840 nm and 465 nm, respectively. Under the optimized experimental conditions, the calibration curves showed a linear relationship over the concentration ranges of 2–10 μg mL−1 and 2–12 μg mL−1, respectively. The optimal reactions conditions values such as the reagent concentration, heating time, and stability of reaction product were determined. No significant difference was obtained between the results of newly proposed methods and the B.P. Titrimetric procedures. The charge transfer approach using TCNQ and DDQ procedures described in this paper is simple, fast, accurate, precise, and extraction-free. PMID:21760789

The association between social capital and HIV treatment outcomes in South Africa.

PubMed

Mukoswa, Grace Musanse; Charalambous, Salome; Nelson, Gill

2017-01-01

HIV treatment has reduced morbidity and mortality. By 2012, it was estimated that 60.4% of eligible South Africans accessed antiretroviral treatment; however, treatment adherence and retention remain the greatest challenges. There is a growing belief that social capital, seen as "the features of social organization that facilitate cooperation for mutual benefit", is important in promoting HIV treatment retention. The aim of this study was to establish whether social capital is associated with HIV treatment outcomes. This was a cross-sectional analysis of data from a cohort study that investigated how patient outcomes were linked to clinical characteristics, and included exploratory factor and logistic regression analysis. Data from 943 patients were analyzed. Outcomes for the analysis were visit non-adherence, unsuppressed viral load, and treatment failure. Sixteen percent of patients (n = 118) had unsuppressed viral loads; 19% (n = 179) were non-adherent; and 32% (n = 302) experienced treatment failure. Social capital had two dimensions that were described by two factors. There was no association between either factor and visit non-adherence. Social capital factor 1 was marginally associated with lower risks of unsuppressed viral load and treatment failure at 12 months (OR = 0.78; 95% CI = 0.58-1.03 and OR = 0.76; 95% CI = 0.62-0.93, respectively); but not with visit non-adherence (OR = 0.93; 95% CI = 0.71-1.22). After controlling for confounders, the odds of both unsuppressed viral load and treatment failure decreased with an increase in social capital factor 1. This study suggests that social capital, in terms of the number of groups to which an HIV-infected person belongs, the diversity of the groups, availability of child support, and time available for community projects, is protective against poor HIV treatment outcomes. Implementers and policy makers in the areas of HIV treatment and prevention need to consider the inclusion of social capital in the design

Outcome of renal replacement treatment in patients with diabetes mellitus.

PubMed Central

McMillan, M A; Briggs, J D; Junor, B J

1990-01-01

OBJECTIVE--To compare the outcome of renal replacement treatment in patients with diabetes mellitus and in non-diabetic patients with end stage renal failure. DESIGN--Retrospective comparison of cases and matched controls. SETTING--Renal unit, Western Infirmary, Glasgow, providing both dialysis and renal transplantation. PATIENTS--82 Diabetic patients starting renal replacement treatment between 1979 and 1988, compared with 82 matched non-diabetic controls with renal failure and 39 different matched controls undergoing renal transplantation. MAIN OUTCOME MEASURES--Patient characteristics, history of smoking, prevalence of left ventricular hypertrophy and myocardial ischaemia at start of renal replacement treatment; survival of patients with renal replacement treatment and of patients and allografts with renal transplantation. RESULTS--The overall survival of the diabetic patients during the treatment was 83%, 59%, and 50% at one, three, and five years. Survival was significantly poorer in the diabetic patients than the controls (p less than 0.001). Particularly adverse features for outcome at the start of treatment were increasing age (p less than 0.01) and current cigarette smoking (relative risk (95% confidence interval) 2.28 (0.93 to 4.84), p less than 0.05). Deaths were mainly from cardiac and vascular causes. The incidence of peritonitis in patients on continuous ambulatory peritoneal dialysis was the same in diabetic patients and controls (49% in each group remained free of peritonitis after one year), and the survival of renal allografts was not significantly worse in diabetic patients (p less than 0.5). CONCLUSIONS--Renal replacement treatment may give good results in diabetic patients, although the outlook remains less favourable than for non-diabetic patients because of coexistent, progressive vascular disease, which is more severe in older patients. PMID:2207427

Predictors of Short-Term Treatment Outcomes among California's Proposition 36 Participants

ERIC Educational Resources Information Center

Hser, Yih-Ing; Evans, Elizabeth; Teruya, Cheryl; Huang, David; Anglin, M. Douglas

2007-01-01

California's voter-initiated Proposition 36 offers non-violent drug offenders community-based treatment as an alternative to incarceration or probation without treatment. This article reports short-term treatment outcomes subsequent to this major shift in drug policy. Data are from 1104 individuals randomly selected from all Proposition 36…

How home care is essential to ensuring successful orthodontic treatment outcomes.

PubMed

Levin, Roger

2004-09-01

Patients can significantly affect the outcome of their orthodontic treatment. A practice committed to developing the right systems, scripts, and educational materials will experience a more satisfied patient, increased efficiencies, and higher profits. Educating and motivating patients to maintain their oral health and providing recommendations or dispensing of home care tools such as a power toothbrush increases patient compliance, positively impacts treatment outcomes, enhances customer service, and generates a new revenue stream for the practice. In a tight economy and a highly competitive orthodontic market, a power toothbrush can positively impact your marketing and case close rate. Treatment and fees being relatively equal, patients will tend to accept treatment from a practice that can demonstrate concern for the patients' overall oral health and greater value-added components to the orthodontic case. Power toothbrushes as part of a comprehensive orthodontic treatment provide a great differentiating marketing strategy.

Prediction of methylphenidate treatment outcome in adults with attention-deficit/hyperactivity disorder (ADHD).

PubMed

Retz, Wolfgang; Retz-Junginger, Petra

2014-11-01

Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent mental disorder of childhood, which often persists in adulthood. Methylphenidate (MPH) is one of the most effective medications to treat ADHD, but also few adult patients show no sufficient response to this drug. In this paper, we give an overview regarding genetic, neuroimaging, clinical and other studies which have tried to reveal the reasons for non-response in adults with ADHD, based on a systematic literature search. Although MPH is a well-established treatment for adults with ADHD, research regarding the prediction of treatment outcome is still limited and has resulted in inconsistent findings. No reliable neurobiological markers of treatment response have been identified so far. Some findings from clinical studies suggest that comorbidity with substance use disorders and personality disorders has an impact on treatment course and outcome. As MPH is widely used in the treatment of adults with ADHD, much more work is needed regarding positive and negative predictors of long-term treatment outcome in order to optimize the pharmacological treatment of adult ADHD patients.

Child, parent and family dysfunction as predictors of outcome in cognitive-behavioral treatment of antisocial children.

PubMed

Kazdin, A E

1995-03-01

The present study examined factors that predicted favorable treatment outcomes among clinically referred conduct problem children (N = 105, ages 7-13) who received cognitive-behavioral treatment. Three domains (severity and breadth of child impairment, parent stress and psychopathology and family dysfunction) assessed at pretreatment were predicted to affect treatment outcome. The results only partially supported the prediction. Less dysfunction in each of the domains predicted who responded favorably to treatment on parent ratings of deviance and prosocial functioning but not on teacher ratings of these outcomes. The findings have implications for identifying youths who respond to available treatments. The results also underscore fundamental questions about the assessment of treatment effects and the criteria for evaluating outcome.

Associations between nutritional status, weight loss, radiotherapy treatment toxicity and treatment outcomes in gastrointestinal cancer patients.

PubMed

Hill, Amanda; Kiss, Nicole; Hodgson, Belinda; Crowe, Timothy C; Walsh, Adam D

2011-02-01

Patients with gastrointestinal cancers are susceptible to nutritional deterioration which may be compounded by radiotherapy treatment toxicities. This study aimed to determine whether nutritional status at radiotherapy commencement or changes in nutritional status throughout radiotherapy were associated with treatment toxicity and outcomes in gastrointestinal cancer patients. Seventy-three gastrointestinal cancer patients receiving curative radiotherapy underwent medical record audits assessing body weight, radiotherapy toxicity, unplanned treatment breaks or hospital admissions and completion of prescribed treatment/s. Nutritional status was assessed in a subset of patients (n = 11) using the Patient-Generated Subjective Global Assessment tool. Seventy-five percent of patients lost weight throughout radiotherapy. Weight loss was significantly greater in patients experiencing unplanned radiotherapy breaks (-3.1% vs -1.6%, p < 0.05) and in patients not completing prescribed chemotherapy (-3.3% vs -1.6%, p < 0.05). Toxicity severity was strongly correlated with Patient-Generated Subjective Global Assessment score (rho = 0.839, p < 0.001) and was increased in patients experiencing unplanned admissions compared to those without admission (42.1% vs 9.3% with grade 3 toxicity respectively, p < 0.001). Deterioration in nutritional status during radiotherapy (as measured by weight loss) may be associated with poorer short-term treatment outcomes in gastrointestinal cancer patients. Patient numbers were too small to definitively determine the effect of nutritional status at radiotherapy commencement or changes in nutritional status throughout radiotherapy (defined by PG-SGA) on treatment outcomes. Further research is required to investigate this in larger, longer-term studies. Copyright © 2010. Published by Elsevier Ltd.

A Review of Educational Outcomes in the Children's Mental Health Treatment Literature

ERIC Educational Resources Information Center

Becker, Kimberly D.; Brandt, Nicole Evangelista; Stephan, Sharon H.; Chorpita, Bruce F.

2014-01-01

We examined the measurement of educational outcomes related to children's mental health treatments. A total of 85 papers describing 88 randomized controlled trials that included at least one educational outcome and one mental health outcome were included in these analyses. Forty-five different measures were identified as the primary educational…

Predictors of short-term treatment outcomes among California's Proposition 36 participants.

PubMed

Hser, Yih-Ing; Evans, Elizabeth; Teruya, Cheryl; Huang, David; Anglin, M Douglas

2007-05-01

California's voter-initiated Proposition 36 offers non-violent drug offenders community-based treatment as an alternative to incarceration or probation without treatment. This article reports short-term treatment outcomes subsequent to this major shift in drug policy. Data are from 1104 individuals randomly selected from all Proposition 36 participants assessed for treatment in five California counties during 2004. The overall study sample was 30% female, 51% white, 18% Black, 24% Hispanic, and 7% other racial/ethnic groups. The mean+/-SD age was 37+/-10 years. Counties varied considerably in participant characteristics, treatment service intensity, treatment duration, urine testing, and employment and recidivism outcomes, but not in drug use at 3-month follow-up. Controlling for county, logistic regression analysis showed that drug abstinence was predicted by gender (female), employment at baseline (full or part-time), residential (vs. outpatient) stay, low psychiatric severity, frequent urine testing by treatment facility, and more days in treatment. Recidivism was predicted only by shorter treatment duration. Employment predictors included age (younger), gender (male), baseline employment, and lower psychiatric severity. The study findings support drug testing to monitor abstinence and highlight the need to address employment and psychiatric problems among Proposition 36 participants.

A systematic review and analysis of long-term outcomes in attention deficit hyperactivity disorder: effects of treatment and non-treatment

PubMed Central

2012-01-01

Background In childhood, attention deficit/hyperactivity disorder (ADHD) is characterized by age-inappropriate levels of inattentiveness/disorganization, hyperactivity/impulsiveness, or a combination thereof. Although the criteria for ADHD are well defined, the long-term consequences in adults and children need to be more comprehensively understood and quantified. We conducted a systematic review evaluating the long-term outcomes (defined as 2 years or more) of ADHD with the goal of identifying long-term outcomes and the impact that any treatment (pharmacological, non-pharmacological, or multimodal) has on ADHD long-term outcomes. Methods Studies were identified using predefined search criteria and 12 databases. Studies included were peer-reviewed, primary studies of ADHD long-term outcomes published between January 1980 to December 2010. Inclusion was agreed on by two independent researchers on review of abstracts or full text. Published statistical comparison of outcome results were summarized as poorer than, similar to, or improved versus comparators, and quantified as percentage comparisons of these categories. Results Outcomes from 351 studies were grouped into 9 major categories: academic, antisocial behavior, driving, non-medicinal drug use/addictive behavior, obesity, occupation, services use, self-esteem, and social function outcomes. The following broad trends emerged: (1) without treatment, people with ADHD had poorer long-term outcomes in all categories compared with people without ADHD, and (2) treatment for ADHD improved long-term outcomes compared with untreated ADHD, although not usually to normal levels. Only English-language papers were searched and databases may have omitted relevant studies. Conclusions This systematic review provides a synthesis of studies of ADHD long-term outcomes. Current treatments may reduce the negative impact that untreated ADHD has on life functioning, but does not usually 'normalize' the recipients. PMID:22947230

The influence of body mass index to in-vitro fertilisation treatment outcome, risk of miscarriage and pregnancy outcome.

PubMed

Thum, M Y; El-Sheikhah, A; Faris, R; Parikh, J; Wren, M; Ogunyemi, T; Gafar, A; Abdalla, H

2007-10-01

The aim of this work was to evaluate the effects of extreme body mass index (BMI) on assisted reproductive treatment outcome and pregnancy outcome. This is a descriptive cohort study that evaluated 8,145 consecutive in-vitro fertilisation/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) cycles in which BMI were known, from July 1997 to June 2005 in an inner London major fertility clinic. The data were collected prospectively and analysed retrospectively on women undergoing IVF/ICSI and ET. Patients' weight and height were established prior to treatment. IVF/ICSI treatment was then started using either a long or an antagonist protocol. Patients were divided into five groups: Group A (BMI < 19); Group B (BMI between 19 and 25.9); Group C (BMI between 26 and 30.9); Group D (BMI between 31 and 35.9); Group E (BMI > 36). The main outcomes measured were number of eggs collected, fertilisation rate, number of embryos available for transfer, pregnancy rate (PR), live-birth rate (LBR) and miscarriage rate (MR). The results showed no significant difference in the average number of days taking follicle stimulating hormone (FSH) for ovarian stimulation, the average amount of gonadotrophin used for stimulation, number of eggs collected and fertilisation rate. The pregnancy rate, miscarriage rate and the live-birth rate were not statistically different between all groups. However, in group E the miscarriage rate was significantly higher and the LBR was statistically lower compared with group B. We concluded that extreme BMI did not affect the super-ovulation outcome fertilisation rate and pregnancy rate. Women with a BMI > 35 had a higher miscarriage rate and hence a lower live-birth rate, but a reasonable pregnancy and live-birth rate can be achieved. For women with a BMI < 20 there was no difference in assisted reproduction treatment (ART) outcome and pregnancy outcome when compared with women with a normal BMI. This information should be used to advise patients

Military sexual assault, gender, and PTSD treatment outcomes of U.S. Veterans.

PubMed

Tiet, Quyen Q; Leyva, Yani E; Blau, Kathy; Turchik, Jessica A; Rosen, Craig S

2015-04-01

This study examined whether gender and military sexual assault (MSA) were associated with psychiatric severity differences at initiation of treatment for posttraumatic stress disorder (PTSD) and whether MSA and gender predicted psychiatric treatment outcomes. Male (n = 726) and female (n = 111) patients were recruited from 7 U.S. Department of Veterans Affairs (VA) PTSD specialty intensive treatment programs and completed an intake survey; 69% (n = 574) of the participants completed a 4-month postdischarge follow-up survey. Measures included current PTSD and depressive symptoms, aggressive/violent behaviors, alcohol and drug use severity, and quality of life. Multilevel multivariate regression analyses were conducted to examine the main and interaction effects of gender and MSA on psychiatric treatment outcomes at 4-month follow-up, including demographics, baseline severity, hostile fire, and treatment length of stay. Baseline PTSD severity did not differ by gender or MSA status, but women had more severe depressive symptoms (d = 0.40) and less aggressive/violent symptoms (d = -0.46) than men. Gender, MSA status, and the interaction between gender and MSA did not predict treatment outcomes as hypothesized. Male and female veterans with and without MSA responded equally well to treatment in VA PTSD intensive treatment programs. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Treatment outcomes for professional voice users.

PubMed

Wingate, Judith M; Brown, William S; Shrivastav, Rahul; Davenport, Paul; Sapienza, Christine M

2007-07-01

Professional voice users comprise 25% to 35% of the U.S. working population. Their voice problems may interfere with job performance and impact costs for both employers and employees. The purpose of this study was to examine treatment outcomes of two specific rehabilitation programs for a group of professional voice users. Eighteen professional voice users participated in this study; half had complaints of throat pain or vocal fatigue (Dysphonia Group), and half were found to have benign vocal fold lesions (Lesion Group). One group received 5 weeks of expiratory muscle strength training followed by six sessions of traditional voice therapy. Treatment order was reversed for the second group. The study was designed as a repeated measures study with independent variables of treatment order, laryngeal diagnosis (lesion vs non-lesion), gender, and time. Dependent variables included maximum expiratory pressure (MEP), Voice Handicap Index (VHI) score, Vocal Rating Scale (VRS) score, Voice Effort Scale score, phonetogram measures, subglottal pressures, and acoustic and perceptual measures. Results showed significant improvements in MEP, VHI scores, and VRS scores, subglottal pressure for loud intensity, phonetogram area, and dynamic range. No significant difference was found between laryngeal diagnosis groups. A significant difference was not observed for treatment order. It was concluded that the combined treatment was responsible for the improvements observed. The results indicate that a combined modality treatment may be successful in the remediation of vocal problems for professional voice users.

Long-term outcome of neuroparacoccidioidomycosis treatment.

PubMed

Francesconi, Fabio; da Silva, Marcus Tulius Teixeira; Costa, Regina Lana Braga; Francesconi, Valeska Albuquerque; Carregal, Eleonora; Talhari, Sinésio; Valle, Antonio Carlos Francesconi do

2011-01-01

Neuroparacoccidioidomycosis (NPCM) is a term used to describe the invasion of the central nervous system by the pathogenic fungus Paracoccidioides brasiliensis. NPCM has been described sporadically in some case reports and small case series, with little or no focus on treatment outcome and long-term follow-up. All patients with NPCM from January 1991 to December 2006 were analyzed and were followed until December 2009. Fourteen (3.8%) cases of NPCM were identified out of 367 patients with paracoccidioidomycosis (PCM). A combination of oral fluconazole and sulfamethoxazole/trimethoprim (SMZ/TMP) was the regimen of choice, with no documented death due to Paracoccidioides brasiliensis infection. Residual neurological deficits were observed in 8 patients. Residual calcification was a common finding in neuroimaging follow-up. All the patients in this study responded positively to the association of oral fluconazole and sulfamethoxazole/trimethoprim, a regimen that should be considered a treatment option in cases of NPCM. Neurological sequela was a relatively common finding. For proper management of these patients, anticonvulsant treatment and physical therapy support were also needed.

Mapping clinical outcomes expectations to treatment decisions: an application to vestibular schwannoma management.

PubMed

Cheung, Steven W; Aranda, Derick; Driscoll, Colin L W; Parsa, Andrew T

2010-02-01

Complex medical decision making obligates tradeoff assessments among treatment outcomes expectations, but an accessible tool to perform the necessary analysis is conspicuously absent. We aimed to demonstrate methodology and feasibility of adapting conjoint analysis for mapping clinical outcomes expectations to treatment decisions in vestibular schwannoma (VS) management. Prospective. Tertiary medical center and US-based otologists/neurotologists. Treatment preference profiles among VS stakeholders-61 younger and 74 older prospective patients, 61 observation patients, and 60 surgeons-were assessed for the synthetic VS case scenario of a 10-mm tumor in association with useful hearing and normal facial function. Treatment attribute utility. Conjoint analysis attribute levels were set in accordance to the results of a meta-analysis. Forty-five case series were disaggregated to formulate microsurgery facial nerve and hearing preservation outcomes expectations models. Attribute utilities were computed and mapped to the realistic treatment choices of translabyrinthine craniotomy, middle fossa craniotomy, and gamma knife radiosurgery. Among the treatment attributes of likelihoods of causing deafness, temporary facial weakness for 2 months, and incurable cancer within 20 years, and recovery time, permanent deafness was less important to tumor surgeons, and temporary facial weakness was more important to tumor surgeons and observation patients (Wilcoxon rank-sum, p < 0.001). Inverse mapping of preference profiles to realistic treatment choices showed all study cohorts were inclined to choose gamma knife radiosurgery. Mapping clinical outcomes expectations to treatment decisions for a synthetic clinical scenario revealed inhomogeneous drivers of choice selection among study cohorts. Medical decision engines that analyze personal preferences of outcomes expectations for VS and many other diseases may be developed to promote shared decision making among health care stakeholders

Specific Infectious Organisms Associated With Poor Outcomes in Treatment for Hip Periprosthetic Infection.

PubMed

Cunningham, Daniel J; Kavolus, Joseph J; Bolognesi, Michael P; Wellman, Samuel S; Seyler, Thorsten M

2017-06-01

Periprosthetic hip infection treatment remains a significant challenge for orthopedics. Some studies have suggested that methicillin resistance and gram-negative organism type are associated with increased treatment failure. The aim of this research is to determine if specific organisms were associated with poor outcomes in treatment for hip periprosthetic infection. Records were reviewed of all patients between 2005 and 2015 who underwent treatment for infected partial or total hip arthroplasty. Characteristics of each patient's treatment course were determined including baseline characteristics, infecting organism(s), infection status at final follow-up, surgeries for infection, and time in hospital. Baseline characteristics and organisms that were associated with clinical outcomes in univariate analysis were incorporated into multivariable outcomes models. When compared with patients infected with other organism(s), patients infected with the following organisms had significantly decreased infection-free rates: Pseudomonas, methicillin-resistant Staphylococcus aureus (MRSA), and Proteus. Infection with certain organisms was associated with 1.13-2.58 additional surgeries: methicillin-sensitive S aureus, coagulase-negative Staphylococcus, MRSA, Pseudomonas, Peptostreptococcus, Klebsiella, Candida, diphtheroids, Propionibacterium acnes, and Proteus species. Specific organisms were associated with 8.56-24.54 additional days in hospital for infection: methicillin-sensitive S aureus, coagulase-negative Staphylococcus, Proteus, MRSA, Enterococcus, Pseudomonas, Klebsiella, beta-hemolytic Streptococcus, and diphtheroids. Higher comorbidity score was also associated with greater length of hospitalization. MRSA, Pseudomonas, and Proteus were associated with all 3 outcomes of lower infection-free rate, more surgery, and more time in hospital in treatment for hip periprosthetic infection. Organism-specific outcome information may help individualize patient

Outcomes of mandated treatment for women with histories of abuse and co-occurring disorders.

PubMed

Clark, Colleen; Young, M Scott

2009-12-01

Although there is much momentum for behavioral health policies supporting mandated treatment, there is little evidence supporting its safety and effectiveness for individuals with complex issues. The authors used a national study of women with co-occurring psychiatric, substance use disorders and histories of trauma to compare mandated and voluntary treatment by examining psychiatric, substance use, and trauma-related outcomes following treatment. This quasi-experimental study included 2,726 women, with measures completed at baseline, 6-month, and 12-month follow-up. Two-way analyses of covariance examined the main and interactive effects of coercive status (mandated vs. voluntary) and condition (integrated treatment vs. services as usual) on psychiatric distress, trauma-related symptoms, and substance use outcomes. Women did better with integrated treatment and with mandated treatment regardless of treatment condition for psychiatric, trauma, and substance use outcomes at both follow-ups. Further research clarifying unintended side effects and change mechanisms of mandated treatment is needed to inform policy decisions.

A meta-analysis of the relation between therapeutic alliance and treatment outcome in eating disorders.

PubMed

Graves, Tiffany A; Tabri, Nassim; Thompson-Brenner, Heather; Franko, Debra L; Eddy, Kamryn T; Bourion-Bedes, Stephanie; Brown, Amy; Constantino, Michael J; Flückiger, Christoph; Forsberg, Sarah; Isserlin, Leanna; Couturier, Jennifer; Paulson Karlsson, Gunilla; Mander, Johannes; Teufel, Martin; Mitchell, James E; Crosby, Ross D; Prestano, Claudia; Satir, Dana A; Simpson, Susan; Sly, Richard; Lacey, J Hubert; Stiles-Shields, Colleen; Tasca, Giorgio A; Waller, Glenn; Zaitsoff, Shannon L; Rienecke, Renee; Le Grange, Daniel; Thomas, Jennifer J

2017-04-01

The therapeutic alliance has demonstrated an association with favorable psychotherapeutic outcomes in the treatment of eating disorders (EDs). However, questions remain about the inter-relationships between early alliance, early symptom improvement, and treatment outcome. We conducted a meta-analysis on the relations among these constructs, and possible moderators of these relations, in psychosocial treatments for EDs. Twenty studies met inclusion criteria and supplied sufficient supplementary data. Results revealed small-to-moderate effect sizes, βs = 0.13 to 0.22 (p < .05), indicating that early symptom improvement was related to subsequent alliance quality and that alliance ratings also were related to subsequent symptom reduction. The relationship between early alliance and treatment outcome was partially accounted for by early symptom improvement. With regard to moderators, early alliance showed weaker associations with outcome in therapies with a strong behavioral component relative to nonbehavioral therapies. However, alliance showed stronger relations to outcome for younger (vs. older) patients, over and above the variance shared with early symptom improvement. In sum, early symptom reduction enhances therapeutic alliance and treatment outcome in EDs, but early alliance may require specific attention for younger patients and for those receiving nonbehaviorally oriented treatments. © 2017 Wiley Periodicals, Inc.

One session treatment for specific phobias in children: Comorbid anxiety disorders and treatment outcome.

PubMed

Ryan, Sarah M; Strege, Marlene V; Oar, Ella L; Ollendick, Thomas H

2017-03-01

One-Session Treatment (OST) for specific phobias has been shown to be effective in reducing phobia severity; however, the effect of different types of co-occurring anxiety disorders on OST outcomes is unknown. The present study examined (1) the effects of co-occurring generalized anxiety disorder (GAD), social anxiety disorder (SAD), or another non-targeted specific phobia (OSP) on the efficacy of OST for specific phobias, and (2) the effects of OST on these co-occurring disorders following treatment. Three groups of 18 youth (7-15 years) with a specific phobia and comorbid GAD, SAD, or OSP were matched on age, gender, and phobia type. Outcome measures included diagnostic status and severity, and clinician rated improvement. All groups demonstrated an improvement in their specific phobia following treatment. Treatment was equally effective regardless of co-occurring anxiety disorder. In addition, comorbid anxiety disorders improved following OST; however, this effect was not equal across groups. The SAD group showed poorer improvement in their comorbid disorder than the GAD group post-treatment. However, the SAD group continued to improve and this differential effect was not evident six-months following treatment. The current study sample was small, with insufficient power to detect small and medium effect sizes. Further, the sample only included a portion of individuals with primary GAD or SAD, which may have attenuated the findings. The current study demonstrated that co-occurring anxiety disorders did not interfere with phobia treatment. OST, despite targeting a single specific phobia type, significantly reduced comorbid symptomatology across multiple anxiety disorders. Copyright © 2016 Elsevier Ltd. All rights reserved.

Personality and mental health treatment: Traits as predictors of presentation, usage, and outcome.

PubMed

Thalmayer, Amber Gayle

2018-03-08

Self-report scores on personality inventories predict important life outcomes, including health and longevity, marital outcomes, career success, and mental health problems, but the ways they predict mental health treatment have not been widely explored. Psychotherapy is sought for diverse problems, but about half of those who begin therapy drop out, and only about half who complete therapy experience lasting improvements. Several authors have argued that understanding how personality traits relate to treatment could lead to better targeted, more successful services. Here self-report scores on Big Five and Big Six personality dimensions are explored as predictors of therapy presentation, usage, and outcomes in a sample of community clinic clients (N = 306). Participants received evidence-based treatments in the context of individual-, couples-, or family-therapy sessions. One measure of initial functioning and three indicators of outcome were used. All personality trait scores except Openness associated with initial psychological functioning. Higher Conscientiousness scores predicted more sessions attended for family therapy but fewer for couples-therapy clients. Higher Honesty-Propriety and Extraversion scores predicted fewer sessions attended for family-therapy clients. Better termination outcome was predicted by higher Conscientiousness scores for family- and higher Extraversion scores for individual-therapy clients. Higher Honesty-Propriety and Neuroticism scores predicted more improvement in psychological functioning in terms of successive Outcome Questionnaire-45 administrations. Taken together, the results provide some support for the role of personality traits in predicting treatment usage and outcome and for the utility of a 6-factor model in this context. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Multihospital System Membership and Patient Treatments, Expenditures, and Outcomes

PubMed Central

Madison, Kristin

2004-01-01

Objective To determine the relationship between hospital membership in systems and the treatments, expenditures, and outcomes of patients. Data Sources The Medicare Provider Analysis and Review dataset, for data on Medicare patients admitted to general medical-surgical hospitals between 1985 and 1998 with a diagnosis of acute myocardial infarction (AMI); the American Hospital Association Annual Survey, for data on hospitals. Study Design A multivariate regression analysis. An observation is a fee-for-service Medicare AMI patient admitted to a study hospital. Dependent variables include patient transfers, catheterizations, angioplasties or bypass surgeries, 90-day mortality, and Medicare expenditures. Independent variables include system participation, other admission hospital and patient traits, and hospital and year fixed effects. The five-part system definition incorporates the size and location of the index admission hospital and the size and distance of its partners. Principal Findings While the effects of multihospital system membership on patients are in general limited, patients initially admitted to small rural system hospitals that have big partners within 100 miles experience lower mortality rates than patients initially admitted to independent hospitals. Regression results show that to the extent system hospital patients experience differences in treatments and outcomes relative to patients of independent hospitals, these differences remain even after controlling for the admission hospital's capacity to provide cardiac services. Conclusions Multihospital system participation may affect AMI patient treatment and outcomes through factors other than cardiac service offerings. Additional investigation into the nature of these factors is warranted. PMID:15230926

Evaluation of port-wine stain treatment outcomes using multispectral imaging

NASA Astrophysics Data System (ADS)

Samatham, Ravikant; Choudhury, Niloy; Krol, Alfons L.; Jacques, Steven L.

2012-02-01

Port-wine Stain (PWS) is a vascular malformation characterized by ectasia of superficial dermal capillaries. The flash-lamp pumped pulsed dye laser (PDL) treatment has been the mainstay of PWS for the last decade. Despite the success of the PDL in significantly fading the PWS, the overall cure rate is less than 10%. The precise efficacy of an individual PDL treatment is hard to evaluate and the treatment outcome is measured by visual observation of clinical fading. A hand-held multi-spectral imaging system was developed to image PWS before and after PDL treatment. In an NIH-funded pilot study multi-spectral camera was used to image PWS in children (2- 17 years). Oxygen saturation (S) and blood content (B) of PWS before and after the treatment was determined by analysis of the reflectance spectra. The outcome of the treatment was evaluated during follow up visits of the patients. One of the major causes of failure of laser therapy of port-wine stains (PWS) is reperfusion of the lesion after laser treatment. Oxygen saturation and blood content maps of PWS before and after treatment can predict regions of reperfusion and subsequent failure of the treatment. The ability to measure reperfusion and to predict lesions or areas susceptible to reperfusion, will help in selection of patients/lesions for laser treatment and help to optimize laser dosimetry for maximum effect. The current studies also should provide a basis for monitoring of future alternative therapies or enhancers of laser treatment in resistant cases.

Outcomes assessment following treatment of spasmodic dysphonia with botulinum toxin.

PubMed

Courey, M S; Garrett, C G; Billante, C R; Stone, R E; Portell, M D; Smith, T L; Netterville, J L

2000-09-01

Spasmodic dysphonia (SD), a disabling focal dystonia involving the laryngeal musculature, is most commonly treated by the intramuscular injection of botulinum toxin (BTX). Although the treatment is well tolerated and generally produces clinical voice improvement, it has never been statistically shown to alter the patient's perception of voice quality or general health. Declining resources for medical care mandate that treatment outcomes be documented. A prospective analysis of the effects of BTX on the patient's perception of voice and general health was undertaken. The Voice Handicap Index (VHI) and Short Form 36 (SF-36) surveys were administered to patients before treatment and 1 month after. Pretreatment and posttreatment scores were analyzed with a Student's t-test. On the VHI, improvements in the patients' perception of their functional, physical, and emotional voice handicap reached statistical significance (p < or = .0005). On the SF-36, patients had statistically significant improvements in mental health (p < or = .03) and social functioning (p < or = .04). Treatment of SD with BTX significantly lessened the patients' perception of dysphonia. In addition, it improved their social functioning and their perception of their mental health. These outcome measures justify the continued treatment of SD with BTX.