One-year outcomes of repeated adjunctive photodynamic therapy during periodontal maintenance: a proof-of-principle randomized-controlled clinical trial

BACKGROUND: Single photodynamic therapy (PDT) has been effective in initial periodontal therapy, but only improved bleeding on probing (BoP) in maintenance patients after a single use. Repeated PDT has not been addressed. OBJECTIVES: To study the possible added benefits of repeated adjunctive PDT to conventional treatment of residual pockets in patients enrolled in periodontal maintenance. MATERIAL AND METHODS: Ten maintenance patients with 70 residual pockets [probing pocket depth (PPD)>or=5 mm] were randomly assigned for treatment five times in 2 weeks (Days 0, 1, 2, 7, 14) with PDT (test) or non-activated laser (control) following debridement. The primary outcome variable was PPD, and the secondary variables were clinical attachment level (CAL) and BoP. These were assessed at 3, 6 and 12 months following the interventions. RESULTS: Greater PPD reductions were observed in the test (-0.67 +/- 0.34; p=0.01) compared with the control patients (-0.04 +/- 0.33; NS) after 6 months. Significant CAL gain (+0.52 +/- 0.31; p=0.01) was noted for the test, but not in the control (-0.27 +/- 0.52; NS) patients after 6 months. BoP percentages decreased significantly in test (97-64%, 67%, 77%), but not control patients after 3, 6 and 12 months. CONCLUSIONS: Repeated (five times) PDT adjunctive to debridement yielded improved clinical outcomes in residual pockets in maintenance patients. The effects were best documented after 6 months.

Periodontal and general health in long-term periodontal maintenance patients treated in a Norwegian private practice: a descriptive report from a compliant and partially compliant survivor population

BACKGROUND There is weak evidence to support the benefit of periodontal maintenance therapy in preventing tooth loss. In addition, the effects of long-term periodontal treatment on general health are unclear. METHODS Patients who were compliant and partially compliant (15 to 25 years' follow-up) in private practice were observed for oral and systemic health changes. RESULTS A total of 219 patients who were compliant (91 males and 128 females) were observed for 19.1 (range 15 to 25; SD ± 2.8) years. Age at reassessment was 64.6 (range: 39 to 84; SD ± 9.0) years. A total of 145 patients were stable (0 to 3 teeth lost), 54 were downhill (4 to 6 teeth lost), and 21 patients extreme downhill (>6 teeth lost); 16 patients developed hypertension, 13 developed type 2 diabetes, and 15 suffered myocardial infarcts (MIs). A minority developed other systemic diseases. Risk factors for MI included overweight (odds ratio [OR]: 9.04; 95% confidence interval [CI]: 2.9 to 27.8; P = 0.000), family history with cardiovascular disease (OR: 3.10; 95% CI: 1.07 to 8.94; P = 0.029), type 1 diabetes at baseline (P = 0.02), and developing type 2 diabetes (OR: 7.9; 95% CI: 2.09 to 29.65; P = 0.000). A total of 25 patients who were partially compliant (17 males and eight females) were observed for 19 years. This group had a higher proportion of downhill and extreme downhill cases and MI. CONCLUSIONS Patients who left the maintenance program in a periodontal specialist practice in Norway had a higher rate of tooth loss than patients who were compliant. Patients who were compliant with maintenance in a specialist practice in Norway have a similar risk of developing type 2 diabetes as the general population. A rate of 0.0037 MIs per patient per year was recorded for this group. Due to the lack of external data, it is difficult to assess how this compares with patients who have periodontal disease and are untreated.

Opioid dependence treatment: options in pharmacotherapy.

The development of effective treatments for opioid dependence is of great importance given the devastating consequences of the disease. Pharmacotherapies for opioid addiction include opioid agonists, partial agonists, opioid antagonists, and alpha-2-adrenergic agonists, which are targeted toward either detoxification or long-term agonist maintenance. Agonist maintenance therapy is currently the recommended treatment for opioid dependence due to its superior outcomes relative to detoxification. Detoxification protocols have limited long-term efficacy, and patient discomfort remains a significant therapy challenge. Buprenorphine's effectiveness relative to methadone remains a controversy and may be most appropriate for patients in need of low doses of agonist treatment. Buprenorphine appears superior to alpha-2 agonists, however, and office-based treatment with buprenorphine in the USA is gaining support. Studies of sustained-release formulations of naltrexone suggest improved effectiveness for retention and sustained abstinence; however, randomized clinical trials are needed.

Using Acceptance and Commitment Therapy during Methadone Dose Reduction: Rationale, Treatment Description, and a Case Report.

Many clients who undergo methadone maintenance (MM) treatment for heroin and other opiate dependence prefer abstinence from methadone. Attempts at methadone detoxification are often unsuccessful, however, due to distressing physical as well as psychological symptoms. Outcomes from a MM client who voluntarily participated in an Acceptance and Commitment Therapy (ACT) - based methadone detoxification program are presented. The program consisted of a 1-month stabilization and 5-month gradual methadone dose reduction period, combined with weekly individual ACT sessions. Urine samples were collected twice weekly to assess for use of illicit drugs. The participant successfully completed the program and had favorable drug use outcomes during the course of treatment, and at the one-month and one-year follow-ups. Innovative behavior therapies, such as ACT, that focus on acceptance of the inevitable distress associated with opiate withdrawal may improve methadone detoxification outcomes.

The role of substance abuse treatment in preventing human immunodeficiency virus transmission among injecting drug users

This exploratory study assesses the utility of substance abuse treatment as a strategy for preventing human immunodeficiency virus (HIV) transmission among injecting drug users (IDUs). Data analyzed in this study were collected in San Antonio, TX, 1989 through 1995 using both qualitative and quantitative methods. Qualitative data included ethnographic interviews with 234 active IDUs; quantitative data included baseline risk assessments and HIV screening plus interviews follow-up interviews administered approximately six months later to 823 IDUs participating in a Federally-funded AIDS community outreach demonstration project.^ Findings that have particularly important implications for substance abuse treatment as an HIV prevention strategy for IDUs are listed below. (1) IDUs who wanted treatment were significantly more likely to be daily heroin users. (2) IDUs who want treatment were significantly more likely to have been to treatment previously. (3) IDUs who wanted treatment at baseline reported significantly higher levels of HIV risk than IDUs who did not want treatment. (4) IDUs who went to treatment between their baseline and follow-up interviews reported significantly higher levels of HIV risk at baseline than IDUs who did not go to treatment. (5) IDUs who went to treatment between their baseline and follow-up interviews reported significantly greater decreases in injection-related HIV risk behaviors. (6) IDUs who went to treatment reported significantly greater decreases in sexual HIV risk behaviors than IDUs who did not go to treatment.^ This study also noted a number of factors that may limit the effectiveness of substance abuse treatment in reducing HIV risk among IDUs. Findings suggest that the impact of methadone maintenance on HIV risk behaviors among opioid dependent IDUs may be limited by the negative manner in which it is perceived by IDUs as well as other elements of society. One consequence of the negative perception of methadone maintenance held by many elements of society may be an unwillingness to provide public funding for an adequate number of methadone maintenance slots. Thus many IDUs who would be willing to enter methadone maintenance are unable to enter it and many IDUs who do enter it are forced to drop out prematurely. ^

Toward individualized cholesterol-lowering treatment in end-stage renal disease.

There is broad evidence that lowering low-density lipoprotein (LDL) cholesterol will reduce cardiovascular risk. However, in patients on maintenance hemodialysis treatment, lowering LDL cholesterol is not as effective in preventing cardiovascular complications as in the general population. Cholesterol is either endogenously synthesized or absorbed from the intestine. It has been suggested that the benefit of using statins to prevent atherosclerotic complications is less pronounced in people with high absorption of cholesterol. Recent data indicate that patients on hemodialysis have high absorption of cholesterol. Therefore, these patients may benefit from dietary counseling to reduce cholesterol intake, from functional foods containing plant sterols and stanols, and from drugs that interfere with intestinal absorption of sterols (i.e., ezetimibe, bile acid resins, and sevelamer). This review discusses cholesterol homeostasis and the perspective of personalized treatment of hypercholesterolemia in hemodialysis.

Comparative effectiveness of long term drug treatment strategies to prevent asthma exacerbations: network meta-analysis

Objective To determine the comparative effectiveness and safety of current maintenance strategies in preventing exacerbations of asthma. Design Systematic review and network meta-analysis using Bayesian statistics. Data sources Cochrane systematic reviews on chronic asthma, complemented by an updated search when appropriate. Eligibility criteria Trials of adults with asthma randomised to maintenance treatments of at least 24 weeks duration and that reported on asthma exacerbations in full text. Low dose inhaled corticosteroid treatment was the comparator strategy. The primary effectiveness outcome was the rate of severe exacerbations. The secondary outcome was the composite of moderate or severe exacerbations. The rate of withdrawal was analysed as a safety outcome. Results 64 trials with 59 622 patient years of follow-up comparing 15 strategies and placebo were included. For prevention of severe exacerbations, combined inhaled corticosteroids and long acting β agonists as maintenance and reliever treatment and combined inhaled corticosteroids and long acting β agonists in a fixed daily dose performed equally well and were ranked first for effectiveness. The rate ratios compared with low dose inhaled corticosteroids were 0.44 (95% credible interval 0.29 to 0.66) and 0.51 (0.35 to 0.77), respectively. Other combined strategies were not superior to inhaled corticosteroids and all single drug treatments were inferior to single low dose inhaled corticosteroids. Safety was best for conventional best (guideline based) practice and combined maintenance and reliever therapy. Conclusions Strategies with combined inhaled corticosteroids and long acting β agonists are most effective and safe in preventing severe exacerbations of asthma, although some heterogeneity was observed in this network meta-analysis of full text reports.

State of the art of integrated therapy approaches in the treatment of schizophrenia: empirical evidence and clinical relevance

Objective: Integrated behavior therapy approaches are defined by the combination of behavioral and or cognitive interventions targeting neurocognition combined with other goal-oriented treatment targets such as social cognition, social skills, or educational issues. The Integrated Psychological Therapy Program (IPT) represents one of the very first behavior therapy approaches combining interventions of neurocognition, social cognition, and social competence. This comprehensive group-based bottom-up and top-down approach consists of five subprograms, each with incremental steps. IPT has been successfully implemented in several countries in Europe, America, Australia and in Asia. IPT worked as a model for some other approaches designed in the USA. IPT was undergone two further developments: based on the social competence part of IPT, the three specific therapy programs focusing residential, occupational or recreational topics were developed. Recently, the cognitive part of INT was rigorously expanded into the Integrated Neurocognitive Therapy (INT) designed exclusively for outpatient treatment: INT includes interventions targeting all neurocognitive and social cognitive domains defined by the NIMH-MATRICS initiative. These group and partially PC-based exercises are structured into four therapy modules, each starting with exercises on neurocognitive domains followed by social cognitive targets. Efficacy: The evidence of integrated therapy approaches and its advantage compared to of one-track interventions was becoming a discussion tool in therapy research as well as in mental health systems. Results of meta-analyses support superiority of integrated approaches compared to one-track interventions in more distal outcome areas such as social functioning. These results are in line with the large body of 37 independent IPT studies in 12 countries. Moreover, IPT research indicates the maintenance of therapy effects after the end of therapy and some evidence generalization effects. Additionally, the international randomized multi-center study on INT with 169 outpatients strongly supports the successful therapy of integrated therapy in proximal and distal outcome such as significant effects in cognition, functioning and negative symptoms. Clinical implication: therapy research as well as expert’s clinical experience recommends integrated therapy approaches such as IPT to be successful agents within multimodal psychiatric treatment concepts. Finally, integrated group therapy based on cognitive remediation seems to motivate and stimulate schizophrenia inpatients and outpatients to more successful and independent life also demanded by the recovery movement.

Opioid maintenance therapy in Switzerland: an overview of the Swiss IMPROVE study

BACKGROUND/AIMS: Switzerland’s drug policy model has always been unique and progressive, but there is a Need to reassess this system in a rapidly changing world. The IMPROVE study was conducted to gain understanding of the attitudes and beliefs towards opioid maintenance therapy (OMT) in Switzerland with regards to quality and Access to treatment. To obtain a “real-world” view on OMT, the study approached its goals from two different angles: from the perspectives of the OMT patients and of the physicians who treat patients with maintenance therapy. The IMPROVE study collected a large body of data on OMT in Switzerland. This paper presents a small subset of the dataset, focusing on the research design and methodology, the profile of the participants and the responses to several key questions addressed by the questionnaires. METHODS: IMPROVE was an observational, questionnaire-based cross-sectional study on OMT conducted in Switzerland. Respondents consisted of OMT patients and treating physicians from various regions of the country. Data were collected using questionnaires in German and French. Physicians were interviewed by phone with a computer-based questionnaire. Patients self-completed a paper-based questionnaire at the physicians’ Offices or OMT treatment centres. RESULTS: A total of 200 physicians and 207 patients participated in the study. Liquid methadone and methadone tablets or capsules were the medications most commonly prescribed by physicians (60% and 20% of patient load, respectively) whereas buprenorphine use was less frequent. Patients (88%) and physicians (83%) were generally satisfied with the OMT currently offered. The current political framework and lack of training or information were cited as determining factors that deter physicians from engaging in OMT. About 31% of OMT physicians interviewed were ≥60 years old, indicating an ageing population. Diversion and misuse were considered a significant problem in Switzerland by 45% of the physicians. CONCLUSION: The subset of IMPROVE data presented gives a present-day, real-life overview of the OMT landscape in Switzerland. It represents a valuable resource for policy makers, key opinion leaders and drug addiction researchers and will be a useful basis for improving the current Swiss OMT model.

The Effect of 6 versus 9 Years of Zoledronic Acid Treatment in Osteoporosis: A Randomized Second Extension to the HORIZON-Pivotal Fracture Trial (PFT).

While bisphosphonates reduce fracture risk over 3 to 5 years, the optimal duration of treatment is uncertain. In a randomized extension study (E1) of the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly - Pivotal Fracture Trial (HORIZON-PFT), zoledronic acid (ZOL) 5 mg annually for 6 years showed maintenance of bone mineral density (BMD), decrease in morphometric vertebral fractures, and a modest reduction in bone turnover markers (BTMs) compared with discontinuation after 3 years. To investigate the longer-term efficacy and safety of ZOL, a second extension (E2) was conducted to 9 years in which women on ZOL for 6 years in E1 were randomized to either ZOL (Z9) or placebo (Z6P3) for 3 additional years. In this multicenter, randomized, double-blind study, 190 women were randomized to Z9 (n=95) and Z6P3 (n=95). The primary endpoint was change in total hip BMD at year 9 vs. year 6 in Z9 compared with Z6P3. Other secondary endpoints included fractures, BTMs, and safety. From year 6 to 9, the mean change in total hip BMD was -0.54% in Z9 vs. -1.31% in Z6P3 (difference 0.78%; 95% confidence interval [CI]: -0.37%, 1.93%; p=0.183). BTMs showed small, non-significant increases in those who discontinued after 6 years compared with those who continued for 9 years. The number of fractures was low and did not significantly differ by treatment. While generally safe, there was a small increase in cardiac arrhythmias (combined serious and non-serious) in the Z9 group but no significant imbalance in other safety parameters. The results suggest almost all patients who have received six annual ZOL infusions can stop medication for up to 3 years with apparent maintenance of benefits. This article is protected by copyright. All rights reserved.

CD4 T cells are required for both development and maintenance of disease in a new mouse model of reversible colitis

Current therapies to treat inflammatory bowel diseases have limited efficacy, significant side effects, and often wane over time. Little is known about the cellular and molecular mechanisms operative in the process of mucosal healing from colitis. To study such events, we developed a new model of reversible colitis in which adoptive transfer of CD4(+)CD45RB(hi) T cells into Helicobacter typhlonius-colonized lymphopenic mice resulted in a rapid onset of colonic inflammation that was reversible through depletion of colitogenic T cells. Remission was associated with an improved clinical and histopathological score, reduced immune cell infiltration to the intestinal mucosa, altered intestinal gene expression profiles, regeneration of the colonic mucus layer, and the restoration of epithelial barrier integrity. Notably, colitogenic T cells were not only critical for induction of colitis but also for maintenance of disease. Depletion of colitogenic T cells resulted in a rapid drop in tumor necrosis factor α (TNFα) levels associated with reduced infiltration of inflammatory immune cells to sites of inflammation. Although neutralization of TNFα prevented the onset of colitis, anti-TNFα treatment of mice with established disease failed to resolve colonic inflammation. Collectively, this new model of reversible colitis provides an important research tool to study the dynamics of mucosal healing in chronic intestinal remitting-relapsing disorders.Mucosal Immunology advance online publication 16 September 2015; doi:10.1038/mi.2015.93.

Advantages and controversies of depot antipsychotics in the treatment of patients with schizophrenia

BACKGROUND The objective of this article is to give an overview of the advantages and disadvantages of the use of depot antipsychotics in the treatment of schizophrenia. The focus is on efficacy, tolerability, relapse prevention, patient compliance and satisfaction compared to oral administration forms. MATERIAL AND METHODS A literature search was conducted in medical databases. The results of meta-analyses, randomized controlled trials and systematic reviews from the years 1999-2014 were included. RESULTS AND DISCUSSION Depot antipsychotics ensure maintenance of constant blood levels and a continuous medication delivery. The efficacy and tolerability of depot antipsychotics are comparable to oral administration forms. Due to an improved medication compliance a reduction of relapse and hospitalization rates can be achieved. This is a key focus for improving outcomes and reducing costs in the treatment of schizophrenia.

The shorter the better? A follow-up analysis of 10-session psychiatric treatment including the motive-oriented therapeutic relationship for borderline personality disorder

OBJECTIVE: There is little research on short-term treatments for borderline personality disorder (BPD). While the core changes may occur only in long-term treatments, short-term treatments may enable the study of early generic processes of engagement in therapy and thus inform about effective treatment components. It was shown that a 10-session version of a psychiatric treatment was effective in reducing borderline symptoms at the end of this treatment [Kramer, U., Kolly, S., Berthoud, L., Keller, S., Preisig, M., Caspar, F., … Despland, J.-N. (2014). Effects of motive-oriented therapeutic relationship in a ten-session general psychiatric treatment for borderline personality disorder: A randomized controlled trial. Psychotherapy and Psychosomatics, 83, 176-186.]. Also, it was demonstrated in a randomized design that adding the motive-oriented therapeutic relationship (MOTR), following an individualized case formulation based on Plan Analysis, further increased general outcome after session 10 and had a positive effect on the early changes in self-esteem and alliance. METHOD: The present study focuses on the follow-up period after this initial treatment, examining treatment density and outcomes after 6 months and service utilization after 12 months. Outcome was measured using the OQ-45. RESULTS: Results on a sub-sample of N = 40 patients with available OQ-45 data at follow-up (n = 21 for MOTR-treatment, n = 19 for comparison treatment) showed maintenance of gains over the follow-up period, which did not differ between both conditions. It appeared for this sample that MOTR treatments, while using the same number of sessions, lasted more weeks (i.e., lower treatment density, defined as the number of sessions per week), when compared to the treatments without MOTR. Density marginally predicted symptom reduction at follow-up. Patients in MOTR treatments had a greater likelihood of entering structured psychotherapy after the initial sessions than patients in the comparison group. CONCLUSIONS: These results are overall consistent with earlier studies on short-term treatments for BPD and underline the importance of individualizing interventions, by using case formulations that rely on idiographic methods and integrative concepts.

Tocilizumab for induction and maintenance of remission in giant cell arteritis: a phase 2, randomised, double-blind, placebo-controlled trial.

BACKGROUND Giant cell arteritis is an immune-mediated disease of medium and large-sized arteries that affects mostly people older than 50 years of age. Treatment with glucocorticoids is the gold-standard and prevents severe vascular complications but is associated with substantial morbidity and mortality. Tocilizumab, a humanised monoclonal antibody against the interleukin-6 receptor, has been associated with rapid induction and maintenance of remission in patients with giant cell arteritis. We therefore aimed to study the efficacy and safety of tocilizumab in the first randomised clinical trial in patients with newly diagnosed or recurrent giant cell arteritis. METHODS In this single centre, phase 2, randomised, double-blind, placebo-controlled trial, we recruited patients aged 50 years and older from University Hospital Bern, Switzerland, who met the 1990 American College of Rheumatology criteria for giant cell arteritis. Patients with new-onset or relapsing disease were randomly assigned (2:1) to receive either tocilizumab (8 mg/kg) or placebo intravenously. 13 infusions were given in 4 week intervals until week 52. Both groups received oral prednisolone, starting at 1 mg/kg per day and tapered down to 0 mg according to a standard reduction scheme defined in the study protocol. Allocation to treatment groups was done using a central computerised randomisation procedure with a permuted block design and a block size of three, and concealed using central randomisation generated by the clinical trials unit. Patients, investigators, and study personnel were masked to treatment assignment. The primary outcome was the proportion of patients who achieved complete remission of disease at a prednisolone dose of 0·1 mg/kg per day at week 12. All analyses were intention to treat. This trial is registered with ClinicalTrials.gov, number NCT01450137. RESULTS Between March 3, 2012, and Sept 9, 2014, 20 patients were randomly assigned to receive tocilizumab and prednisolone, and ten patients to receive placebo and glucocorticoid; 16 (80%) and seven (70%) patients, respectively, had new-onset giant cell arteritis. 17 (85%) of 20 patients given tocilizumab and four (40%) of ten patients given placebo reached complete remission by week 12 (risk difference 45%, 95% CI 11-79; p=0·0301). Relapse-free survival was achieved in 17 (85%) patients in the tocilizumab group and two (20%) in the placebo group by week 52 (risk difference 65%, 95% CI 36-94; p=0·0010). The mean survival-time difference to stop glucocorticoids was 12 weeks in favour of tocilizumab (95% CI 7-17; p<0·0001), leading to a cumulative prednisolone dose of 43 mg/kg in the tocilizumab group versus 110 mg/kg in the placebo group (p=0·0005) after 52 weeks. Seven (35%) patients in the tocilizumab group and five (50%) in the placebo group had serious adverse events. INTERPRETATION Our findings show, for the first time in a trial setting, the efficacy of tocilizumab in the induction and maintenance of remission in patients with giant cell arteritis. FUNDING Roche and the University of Bern.