Early Weeks Of Treatment Research Articles

Prediction of Healing Trajectory of Chronic Wounds Using a Machine Learning Approach.

Objective: New treatment options are emerging for chronic wounds, which represent a growing problem because of population ageing and increasing burden of chronic disease. While promising, the existing evidence for advanced modalities is commonly derived from small and/or poorly controlled studies and clear criteria for selecting patients, who are likely to benefit from these expensive options are lacking. In this study, we develop and validate a machine learning model to predict if a chronic wound, independent of etiology, is expected to heal within 12 weeks to identify cases in potential need of advanced treatment options. Approach: Retrospective analysis of electronic health record data from 2014 to 2018 covering 532 wound care clinics in the United States and 261,398 patients with 620,356 unique wounds. Prediction of 12-week healing trajectories with a machine learning model. Results: The best-performing model in a training dataset of a randomly drawn 75% subset of wounds contained variables for patient demographics, comorbidities, wound characteristics at initial presentation, and changes in wound dimensions over time, with the latter group being the most influential predictors. The final machine learning model had a high predictive accuracy with area under the receiver operating characteristic curves of 0.9 and 0.92 after 4 and 5 weeks of treatment, respectively. Innovation: A machine learning model can identify chronic wounds at risk of not healing by week 12 with high accuracy in the early weeks of treatment. Conclusions: If embedded in real-world care, the generated information could be able to guide effective and efficient treatment decisions.

Linezolid Tolerability in Drug Resistant TB Patients and Its Future use in all Oral Shorter Regimens

Linezolid (Lzd) belongs to group of Oxazolidinones a repurposed drug to treat Drug resistant TB (DR TB). WHO in 2019 placed Lzd in Group A Drugs along with Levofloxacin/Moxifloxacin and Bedaquiline as most effective drugs to treat RR/MDR TB. The RR/MDR TB regimen should be constructed with a combination of at least 4 likely effective drugs. The toxicity profile of Lzd may feature from 22% to 80% and among most common toxicities are myelosuppression and neuropathy and such frequent toxicities lead from temporary interruption to permanent discontinuation of Lzd during RR/MDR TB treatment. The median time to development of toxicity is around 5-6 months of treatment but toxicity may occur even during early weeks of treatment. The Linezolid (Lzd) usual dose of 600 mg OD is also used for <28 days to treat various gram-positive infections. Linezolid toxicity is frequent but relatively easy to detect and manage and is reversible other than complete nerve damage if not detected early and drug interrupted timely. Linezolid (600 mg daily) is also part of WHO recommended BPaLM and BPaL regimens which are safe, shorter, low cost and highly effective as future RR/MDR TB treatment. To ensure safety of patients all TB programs must ensure appropriate adverse drug safety, monitoring and management (DSM) mechanism as essential component of Drug resistance TB treatment.

Non-Prescribed Substance Use during the First Month of Treatment by People Receiving Depot Buprenorphine for Opioid Use Disorder

Background: Non-prescribed substance use (NPSU) during the treatment of opioid use disorder (OUD) is a recognized phenomenon. The use of non-prescribed substances is associated with discontinuing treatment and drop-out can occur within the early weeks of treatment, before benefit from treatment occurs. Recent developments in treatment include long-acting, slow-release depot buprenorphine injections. This article focuses on NPSU during the first month of treatment with depot buprenorphine, addressing the frequency with which it occurs, the substances used, and reasons for use. Methods: 70 semi-structured interviews (held at three time-points) were conducted with 26 patients initiating depot buprenorphine as part of a longitudinal qualitative study. Analysis prioritized content and framework analyses. Findings: 17/26 participants self-reported NPSU at various times during the first month of treatment. NPSU typically involved heroin, crack-cocaine and some use of benzodiazepines and/or cannabis. Participants’ reasons for heroin use were connected to their subjective accounts of opioid withdrawal symptoms, the management of pain, and experimentation (to test the blockade effect of buprenorphine). Frequency of heroin use was typically episodic rather than sustained. Participants associated crack-cocaine use with stimulant-craving and social connections, and considered their use of this substance to be difficult to manage. Conclusions: Patients’ initial engagement with treatment for OUD is rarely examined in qualitative research. This study highlights how NPSU amongst patients receiving new forms of such treatment continues to be a challenge. As such, shared decision-making (between providers and patients) regarding treatment goals and NPSU should be central to the delivery of depot buprenorphine treatment programmes.

Evaluate Dynamics of IL-6 Release during Step-up Dosing of Subcutaneous Administration of Odronextamab Via a Quantitative Systems Pharmacology Modeling Approach

Background Odronextamab is a hinge-stabilized, human CD20×CD3 IgG4-based bispecific antibody that binds CD20-expressing cells and CD3 on T cells, eliciting T-cell-mediated cytotoxicity independent of T-cell receptor-mediated recognition. T-cell activation following odronextamab administration can result in a transient but clinically significant increase in circulating cytokine concentrations. This may lead to cytokine release syndrome (CRS), one of the most important safety concerns with T-cell engaging therapies. As most cytokine release occurs during the early weeks of treatment, a step-up dosing strategy prior to administration of a full treatment dose appears to be a successful strategy to mitigate the level of cytokine release and attenuate the occurrence of CRS. This study was performed to evaluate interleukin (IL)-6 profiles following odronextamab subcutaneous (SC) injection during Cycle 1 step-up dosing (Weeks 1-3) in patients with B-cell non-Hodgkin lymphoma (B-NHL). A quantitative systems pharmacology (QSP) model, which is an emerging mathematical modeling approach that can help improve our understanding of drug-disease interactions and can be used to evaluate hypothetical scenarios in preclinical and clinical settings, was developed and applied to identify SC step-up doses of odronextamab suitable for investigating in clinical studies. Methods A QSP model that can describe IL-6 profiles (a surrogate cytokine associated with CRS) following intravenous (IV) odronextamab was previously developed and calibrated using pharmacodynamic data from the Phase I ELM-1 study (NCT02290951; Toroghi MK. ACoP11 2020. Poster TUE-054). The IV QSP model was updated by adding relevant components (e.g. drug absorption compartment, lymph node compartment) to enable the description of IL-6 profiles following SC administration of odronextamab. Model parameters were calibrated using IL-6 concentration data of other CD20×CD3 bispecific antibodies under SC administration reported in the literature (Matasar M. ASH 2020. Poster 2096). Odronextamab SC step-up doses of interest were proposed and IL-6 profiles of these regimens were simulated with the SC QSP model. In each dosing scenario, IL-6 profiles were simulated in 300 virtual patients. The cytokine release criterion for regimen selection was that the peak IL-6 concentrations of a SC step-up regimen should be lower than peak IL-6 concentrations observed with the previously tested IV regimens. Results Simulation results indicated that the predicted IL-6 profiles were similar with or without split dosing; the former was effectively used in the IV regimen for management of CRS. The predicted highest peak IL-6 value in Week 1 with SC dose of 2 mg was considerably lower than that of IV dosing of 0.7 mg (split 0.2 mg and 0.5 mg over 2 days in Week 1). The predicted highest IL-6 concentration with 2 mg SC was 150 pg/mL and that for 0.7 mg IV was 2,100 pg/mL, indicating a reduction of more than 90%. The predicted IL-6 profiles in Week 4 were similar with 160 mg IV or 400 mg SC doses. Based on the comparison of IL-6 profiles of multiple SC dosing scenarios, SC step-up doses of 2 mg in Week 1, 26 mg in Week 2, and 100 mg in Week 3 were selected, followed by a full dose of 400 mg. The proposed SC regimen is being tested in the clinical study ELM-1 for safety and efficacy evaluations. Conclusion The QSP modeling supported the selection of the odronextamab SC step-up dosing regimen to be evaluated in a clinical study in patients with B-NHL. The selected step-up regimen for SC odronextamab allows adequate step-up to effective therapeutic doses while simplifying and improving overall convenience. The simulations suggest that no split dosing is necessary for SC administration, which may further reduce overall hospital resource burden and requirements for in-patient monitoring.

Randomized controlled trial of the immediate and long-term effect of massage on adult postburn scar

BackgroundOne objective of massage therapy applied to hypertrophic scar (HSc), is to improve the structural properties so skin possesses the strength and elasticity required for normal mobility. However, research supporting this effect is lacking. The objective of this study was to characterize the changes in scar elasticity, erythema, melanin, and thickness immediately after a massage therapy session and after a 12-week course of treatment compared to intra-individual matched control scars. MethodsWe conducted a prospective, randomized, single-blinded, pragmatic, controlled, clinical trial evaluating the impact of a 12-week course of massage therapy. Seventy burn survivors consented to participate and 60 completed the study. Two homogeneous, intra-individual scars were randomized to usual care control or massage therapy plus usual care. Massage, occupational or physical therapists provided massage treatment 3x/week for 12 weeks. Scar site characteristics were evaluated weekly immediately before and after massage treatment including elasticity (Cutometer), erythema and melanin (Mexameter), and thickness (high-frequency ultrasound). Analysis of covariance (ANCOVAs) were performed to test for immediate and long-term treatment effects. A mixed-model approach was used to account for the intra-individual scars. ResultsScar evaluation immediately before and after massage therapy at each time point revealed changes for all scar characteristics, but the group differences were predominantly present during the early weeks of treatment. The within group long-term analysis revealed a significant increase in elasticity, and a reduction in thickness, during the 12-week treatment period for both the control scar (CS) and massage scar (MS). The increase in elasticity reached significance at week 8 for the MS and week 10 for the CS and the reduction in thickness at week 5 for the CS and week 7 for the MS. There was no significant within group long-term differences for either erythema or melanin. There were group differences in erythema at week 8 and 11 where the CS was less erythematous than the MS. ConclusionsThe immediate impact of forces applied during massage therapy may lead patients and therapists to believe that there are long-term changes in elasticity, erythema, and pigmentation, however, once baseline measures, the control scar, and time were incorporated in the analysis there was no evidence of long-term benefit. Massage therapy applied with the objective of increasing scar elasticity or reducing erythema or thickness over the long-term should be reconsidered.

Predicting Responses to Pregabalin for Painful Diabetic Peripheral Neuropathy Based on Trajectory-Focused Patient Profiles Derived from the First 4Weeks of Treatment.

IntroductionPrediction of final clinical outcomes based on early weeks of treatment can enable more effective patient care for chronic pain. Our goal was to predict, with at least 90% accuracy, 12- to 13-week outcomes for pregabalin-treated painful diabetic peripheral neuropathy (pDPN) patients based on 4 weeks of pain and pain-related sleep interference data.MethodsWe utilized active treatment data from six placebo-controlled randomized controlled trials (n = 939) designed to evaluate efficacy of pregabalin for reducing pain in patients with pDPN. We implemented a three-step, trajectory-focused analytics approach based upon patient responses collected during the first 4 weeks using monotonicity, path length, frequency domain (FD), and k-nearest neighbor (kNN) methods. The first two steps were based on combinations of baseline pain, pain at 4 weeks, weekly monotonicity and path length during the first 4 weeks, and assignment of patients to one of four responder groups (based on presence/absence of 50% or 30% reduction from baseline pain at 4 and at 12/13 weeks). The third step included agreement between prediction of logistic regression of daily FD amplitudes and assignment made from kNN analyses.ResultsStep 1 correctly assigned 520/939 patients from the six studies to a responder group using a 3-metric combination approach based on unique assignment to a 50% responder group. Step 2 (applied to the remaining 419 patients) predicted an additional 121 patients, using a blend of 50% and 30% responder thresholds. Step 3 (using a combination of FD and kNN analyses) predicted 204 of the remaining 298 patients using the 50% responder threshold. Our approach correctly predicted 90.0% of all patients.ConclusionBy correctly predicting 12- to 13-week responder outcomes with 90% accuracy based on responses from the first month of treatment, we demonstrated the value of trajectory measures in predicting pDPN patient response to pregabalin.Trial Registrationwww.clinicaltrials.gov identifiers, NCT00156078/NCT00159679/NCT00143156/NCT00553475.FundingPfizer.Plain Language SummaryPlain language summary available for this article.Electronic supplementary materialThe online version of this article (10.1007/s12325-018-0780-3) contains supplementary material, which is available to authorized users.

Practical Strategies for Management of Lenalidomide-Associated Cytopenias in Myelodysplastic Syndromes With del(5q)

CASE STUDY A male patient aged 67 years with a 2-year history of refractory anemia and myelodysplastic syndromes (MDS) with del(5q) started lenalidomide (Revlimid) treatment as a participant in the MDS-001 trial (List et al., 2005). At the time of the study, this patient had been transfusion-dependent since 2001, and at study entry he had received a total of 12 units of red blood cells (RBCs). The patient started lenalidomide at 25 mg daily for 21 days of each 28-day cycle on April 2, 2002. (Please note that as a result of subsequent trials, the approved starting dose for lenalidomide in patients with del[5q] MDS is 10 mg.) The patient developed treatment-related pancytopenia in the first 3 weeks of treatment (see Figure on next page). On day 24, lenalidomide was withheld. Platelet and white blood cell (WBC) counts were recovered during a 21-day period, and treatment was resumed with lenalidomide at 10 mg daily. During this initial dose interruption, the patient's hemoglobin level improved. He achieved RBC-transfusion independence (TI) during week 5 of treatment-his last RBC transfusion was on April 22, 2002. Bone marrow (BM) analysis, including fluorescence in situ hybridization, after 3 months of therapy, did not show the del(5q) abnormality. A repeat BM analysis after 57 months of treatment revealed minimal residual dyspoiesis, normal metaphase cytogenetics, and normal cell morphology. Subsequent BM biopsies showed transient trisomy 8 abnormalities but no del(5q) abnormality. The patient required one additional dose reduction during the first year of treatment. The patient did not require hospitalization during lenalidomide treatment but did have a history of seasonal allergies and a propensity for acute sinusitis. He received a single dose of pegfilgrastim (Neulasta) and a short course of antibiotics for active infections, generally one course of antibiotics per year. This patient continued on lenalidomide at 5 mg daily for 21 days of every 28-day cycle without further dose reduction. The patient achieved durable RBC-TI and continued to receive treatment for more than 11 years. The levels of hemoglobin, platelets, and WBCs for an 11-year period in this patient are shown in the Figure. This patient had one normal platelet count in 11 years of lenalidomide treatment but no bleeding episodes. The average platelet count in the 11-year period was 67 × 1,000/∝L (normal range, 150-425 × 1,000/∝L). Similarly, the WBC count remained below normal, with an average of 3.1 × 1,000/∝L (normal range, 3.4-10.4 × 1,000/∝L). He remained active and continued working as an aerospace engineer until age 75. This case demonstrates how effective management of cytopenias, through dose interruptions and modifications in the early weeks of treatment, helps to enable long-term lenalidomide treatment and a high quality of life. Despite the persistence of moderate, asymptomatic cytopenias, the patient was able to remain on lenalidomide therapy and maintained RBC-TI for more than 11 years. The patient died on October 4, 2014, at age 79.5, due to coronary artery disease and heart failure.

One-year outcomes of early-crossover patients in a cohort receiving nonoperative care for lumbar disc herniation

OBJECTIVE The authors comprehensively studied the recovery course and 1-year outcomes of early-crossover patients who were randomized to the nonoperative care arm of the Leiden-The Hague Spine Intervention Prognostic Study. The primary goal was to gain insight into the differences in the recovery patterns of early-crossover patients and those treated nonoperatively; secondary goals were to identify predictors of good 1-year outcomes, and to understand when and why patients were likely to cross over. METHODS Individual EuroQol-5D scores were obtained at baseline and at 2, 4, 8, 12, 26, 38, and 52 weeks for 142 patients. Early-crossover patients were defined as those electing to undergo surgery during the first 12 weeks of treatment. Crossover and noncrossover groups were compared using Kruskal-Wallis, Wilcoxon-Mann-Whitney, and chi-square tests. Linear mixed-effects models were used to examine the growth trajectories of crossover and noncrossover groups. Recursive partitioning trees were used to model crossover events and the timing of crossover decisions. Multivariable logistic regression models were used to identify predictors of good 1-year outcomes. RESULTS Of the 142 patients randomized to receive prolonged nonoperative care, 136 were selected for the study. In this cohort, 43/136 (32%) opted for surgery, and 31/43 (72%) of crossover events occurred before the 12-week time point. Early-crossover patients had significantly greater functional impairment at Week 2 than noncrossover patients (p = 0.031), but experienced greater recovery by 26 weeks and better 1-year outcomes (p = 0.045). Patients who did not experience an improvement in their symptoms between 2 and 8 weeks were more likely to cross over (OR 3.5, 95% CI 1.2-10.1; p = 0.01). Recursive partitioning trees were able to identify crossover patients with 76% accuracy. Regression models suggested that better recovery at 26 weeks (p < 0.01) was predictive of good 1-year outcome; declining health status between Weeks 4 and 8 was negatively predictive of good outcome (p < 0.01). CONCLUSIONS This study is the first to comprehensively analyze the recovery and outcomes of crossover patients, and compare them to nonoperatively treated patients. The results suggest that patients who have a low EuroQol-5D score during the early weeks of treatment and who do not respond to nonoperative care during the first few weeks of treatment are most likely to cross over. Early-crossover patients experience a greater rate of recovery and more frequently have a good 1-year outcome when compared with nonoperatively treated patients. The current results motivate a broader investigation into the timing of surgery and the identification of patient populations that will be most benefited by early surgical treatment for lumbar disc herniation.

Hyperphosphatemia in a patient with spinal cord injury who received etidronate for the treatment of heterotopic ossification.

Heterotopic ossification (HO) is defined as ectopic bone formation around peripheral joints and in soft tissues. HO is a common complication of diseases of the central nervous system, such as spinal cord injury (SCI) and traumatic brain injury. HO is seen in up to 50% of patients with SCI and typically occurs in the first 12 weeks after onset of injury. Although no treatment method is proven to be curative, nonsteroidal anti-inflammatory drugs, irradiation of the involved body part and bisphosphonates are commonly used in the management of HO. Here we present a 27-year-old male patient with a T10 ASIA Impairment Scale (AIS) A SCI, who developed hyperphosphatemia as a complication of bisphosphonate therapy initiated for the treatment of HO during the 6th post-operative week. After cessation of etidronate use, phosphate levels gradually returned to normal over 2 weeks. Hyperphosphatemia is a rare complication of etidronate use. It is speculated to result from increased renal tubular phosphate reabsorption and is usually asymptomatic. Although mostly asymptomatic, this complication must be kept in mind while administering etidronate to SCI patients and blood phosphate levels should be monitored in the early weeks of treatment.

The Effectiveness of the Treatment Readiness and Induction Program (TRIP) for Improving During-Treatment Outcomes

Treatment engagement is a primary pathway to change. Because motivation consistently predicts engagement and sustained recovery following treatment, targeted efforts at improving problem recognition (i.e., a significant ingredient in motivation) during early weeks of treatment are critical. The purpose of this study is to compare the effectiveness of Standard Operating Practice (SOP) versus SOP plus an 8-session Treatment Readiness and Induction Program (TRIP; delivered in the first weeks of treatment) on cognitive indicators and treatment engagement among youth in 5 residential substance use treatment settings. Structural Equation Modeling (SEM) documented higher problem recognition, decision making, and treatment engagement (participation, satisfaction, counselor rapport) among youth receiving TRIP (compared to SOP only), even when controlling for background characteristics such as age, race-ethnicity, gender, baseline drug use severity, etc. Findings suggest that TRIP is an effective induction tool that directly impacts targeted constructs (i.e., problem recognition, decision making), and also directly affects indicators of engagement.

Percentage reduction of depression severity versus absolute severity after initial weeks of treatment to predict final response or remission

Percentage reduction of depression severity has been used to predict both response and remission of major depression. We aimed to compare the accuracy to predict response or remission by percentage reduction of depression score or depression score after initial weeks of treatment. The subjects were 126 depressed inpatients who received 20 mg/day fluoxetine for 6 weeks. Symptom severity was assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17). Response was defined as a reduction of 50% or more of the HAMD-17. Remission was defined as a score of ≤7 of the HAMD-17. At weeks 1, 2, 3 and 4, the percentages of HAMD-17 score reduction, the percentages of mood cluster score reduction, HAMD-17 scores, and mood cluster scores were regarded as potential predictors. The receiver operating characteristic curve was applied to determine the cut-off point of predictors at weeks 1, 2, 3, and 4. One-hundred and seven patients completed the 6-week trial. At weeks 1, 2, 3, and 4, percentages of HAMD-17 score reduction or HAMD-17 scores were the best predictors of responder or remitters, respectively. Using the percentage of HAMD-17 score reduction at each assessment as a predictor of response generated a larger area under the curve than other predictors. Conversely, applying the absolute HAMD-17 score at each assessment as a predictor of remission had the largest area under the curve. Applying percentage of reduction in depression severity during the early weeks of treatment can predict response, and it is reasonable to apply depression severity to predict remission.

Examining variation in and barriers to widespread implementation of an innovation

to evaluate change in thinking and processing and (b) using these composites compare changes from intake to 45days in the ratings of TRIP and non-TRIP clients. Preliminary analyses suggest that clients attending at least four TRIP sessions showed significant interactions across time on most composite measures including pre-contemplation and decision making. These results support the initial effects of TRIP on improving judgment and decision making in the early weeks of treatment.

Improving adolescent judgment and decision-making in the early weeks of treatment

Improving adolescent judgment and decision-making in the early weeks of treatment

HIV-1 RNA May Decline More Slowly in Semen than in Blood following Initiation of Efavirenz-Based Antiretroviral Therapy

ObjectivesAntiretroviral therapy (ART) decreases HIV-1 RNA levels in semen and reduces sexual transmission from HIV-1-infected men. Our objective was to study the time course and magnitude of seminal HIV-1 RNA decay after initiation of efavirenz-based ART among 13 antiretroviral-naïve Kenyan men.MethodsHIV-1 RNA was quantified (lower limit of detection, 120 copies/mL) in blood and semen at baseline and over the first month of ART. Median log10 HIV-1 RNA was compared at each time-point using Wilcoxon Signed Rank tests. Perelson’s two-phase viral decay model and nonlinear random effects were used to compare decay rates in blood and semen.ResultsMedian baseline HIV-1 RNA was 4.40 log10 copies/mL in blood (range, 3.20–5.08 log10 copies/mL) and 3.69 log10 copies/mL in semen (range, <2.08–4.90 log10 copies/mL). The median reduction in HIV-1 RNA by day 28 was 1.90 log10 copies/mL in blood (range, 0.56–2.68 log10 copies/mL) and 1.36 log10 copies/mL in semen (range, 0–2.66 log10 copies/mL). ART led to a decrease from baseline by day 7 in blood and day 14 in semen (p = 0.005 and p = 0.006, respectively). The initial modeled decay rate was slower in semen than in blood (p = 0.06). There was no difference in second-phase decay rates between blood and semen.ConclusionsEfavirenz-based ART reduced HIV-1 RNA levels more slowly in semen than in blood. Although this difference was of borderline significance in this small study, our observations suggest that there is suboptimal suppression of seminal HIV-1 RNA for some men in the early weeks of treatment.

Faster Onset of Antidepressant Effects of Citalopram Compared With Sertraline in Drug-Naïve First-Episode Major Depressive Disorder in a Chinese Population

Several previous studies, including a meta-analysis, reported no significant differences between various selective serotonin reuptake inhibitors (SSRIs) in the treatment of major depressive disorder. However, because of the different chemical structure of SSRIs and the difference in the frequency of serotonin transporter polymorphisms between ethnic groups, a head-to-head comparative study between SSRIs in different populations may be enlightening. We compared the efficacy and adverse effect profiles of citalopram and sertraline in a double-blinded randomized clinical trial in a Chinese population of drug-naïve patients with first-episode major depressive disorder. Fifty-one patients were randomly assigned to citalopram or sertraline treatment. The Montgomery-Åsberg Depression Rating Scale (MADRS) was used as the primary outcome. Efficacy and adverse effects were analyzed in an intent-to-treat population. Efficacy was analyzed using a last-observation-carried-forward method for early terminators. There were no significant differences in demographic characteristics at baseline. No significant differences were found in MADRS scores between citalopram and sertraline at baseline (36.6 ± 5.5 vs 38.2 ± 4.9; P = 0.322) or at the end of treatment (week 6; 10.8 ± 10.0 vs 16.7 ± 11.3; P = 0.082). However, MADRS scores in the citalopram group were significantly lower at week 1 (25.2 ± 8.5 vs 30.4 ± 6.1; P = 0.029) and week 3 (15.9 ± 10.0 vs 22.1 ± 8.7; P = 0.037). Overall, treatment-emergent adverse effects were reported by 14.3% and 28.6% of patients in the citalopram and sertraline groups, respectively. In conclusion, citalopram and sertraline were both efficacious and well tolerated. However, citalopram exhibited a significantly faster onset than sertraline during the early weeks of treatment and tended to have a better efficacy in overall treatment, although the statistic was not significant.

Efficacy and tolerability of mirtazapine in treating major depressive disorder with anxiety symptoms: an 8-week open-label randomised paroxetine-controlled trial

Prominent anxiety symptoms are related to poor clinical course and outcome in major depressive disorder (MDD). The aim of this randomised, open-label, controlled study is to compare the efficacy and tolerability of mirtazapine in the form of orally disintegrating tablets against paroxetine in treating MDD patients with anxiety symptoms. A total of 60 MDD patients with a score above 18 on the Hamilton Anxiety Rating Scale (HARS) were randomly assigned to 8 weeks of fixed dosing treatment with mirtazapine (15-30 mg/day) and paroxetine (10-20 mg/day). Efficacy was primarily assessed with the HARS and with the 17-item Hamilton Depression Rating Scale (HDRS) at weeks 1, 2, 4 and 8 after treatment. Tolerability was assessed from adverse events. The generalised estimating equations (GEE) models showed that the rates of improvement in HDRS scores from baseline to week 8 were similar between mirtazapine and paroxetine groups. However, patients with mirtazapine exhibited earlier improvement in HARS scores at weeks 1 and 2. Week-by-week GEE models showed that these significant differences in improvement of HARS scores between the two treatment groups were detectable from the first evaluation after the treatment (week 1) and maintained through week 2. There was no difference in the overall frequency of adverse events experienced between the two treatment groups. The most common adverse event in the mirtazapine group was somnolence (n = 8), whereas that in the paroxetine group was gastrointestinal discomfort (n = 9). Mirtazapine and paroxetine were equally effective and well tolerated for the depressive symptoms in MDD patients with the high level of anxiety symptoms. Mirtazapine was, however, more effective in reducing the anxiety symptoms than paroxetine in the early weeks of treatment, suggesting that mirtazapine may have an earlier-onset action for the anxiety symptoms in MDD patients.

Disrupted sleep in breast and prostate cancer patients undergoing radiation therapy: the role of coping processes

Sleep problems are a common complaint in cancer patients that have been understudied. This study examined changes in sleep in 33 breast cancer (BC) patients and 23 prostate cancer (PC) patients during radiation therapy and over a 6-month followup. Coping processes were examined as predictors of sleep. Self-reported sleep was assessed at eight time-points before, during, and after treatment using the Medical Outcomes Study-Sleep Scale. The COPE Scale was used to assess coping processes before treatment onset. Mixed effects linear modeling analyses revealed that both BC and PC patients reported the most sleep problems prior to and during the early weeks of treatment. Coping strategies predicted sleep trajectories in both groups. In particular, approach coping predicted better sleep in PC patients, whereas avoidance coping predicted worst sleep in both PC and BC patients (p's<0.05). These findings highlight the importance of evaluating sleep in patients as they undergo treatment for cancer. Additionally, they suggest that interventions aimed at increasing the use of approach-oriented coping strategies may improve sleep and quality of life in these patients.

Predictors of attrition and weight loss success: Results from a randomized controlled trial

Attrition is a common problem in weight loss trials. The present analysis examined several baseline and early-treatment process variables, as predictors of attrition and outcome in a clinical trial that combined pharmacotherapy and behavior therapy for weight loss. Participants were 224 obese adults who were treated with sibutramine alone, lifestyle modification alone, combined therapy, or sibutramine plus brief lifestyle modification. Predictors included baseline characteristics (e.g., demographic, weight-related, psychological, and consumption-related variables), plus attendance, adherence, and weight loss in the early weeks of treatment. Outcomes were attrition and weight loss success (i.e., ≥5% reduction in body weight) at 1 year. Multivariable models, adjusting for other relevant variables, found that younger age and greater baseline depressive symptoms were related to increased odds of attrition ( ps ≤ 0.003). Greater early weight loss marginally reduced the odds of attrition ( p = 0.06). Predictors of weight loss success at 1 year were Caucasian ethnicity ( p = 0.04), lower baseline depressive symptoms ( p = 0.04), and weight loss during the first 3 weeks of treatment ( p < 0.001). Thus, depressive symptoms at baseline were a significant predictor of both attrition and weight loss success. As a process variable, early weight loss appears to have more predictive value than early attendance at treatment sessions or early adherence.

Comparison of a 3-step acne system containing solubilized benzoyl peroxide versus benzoyl peroxide/clindamycin: A multicenter, investigator-blind, randomized study

CONCLUSIONS The 3-step acne system is an effective antibiotic-free approach to the treatment of acne. Compared with a combination BPO/clindamycin product, the acne system is at least as effective in reducing the noninflammatory lesion count and may enhance the speed at which these lesions are reduced. The acne system also demonstrates comparable efficacy against inflammatory lesions and comparable tolerability. Its potential for a more rapid onset of action against non-inflammatory lesions is likely attributable to the improved solubilization of BPO enhancing the bioavailability and intrafollicular penetration of the BPO. The unique solvent technology employed in the BPO formulation might also play a role in enhancing efficacy in the early weeks of treatment.

Improving access to sterile syringes and safe syringe disposal for injection drug users in methadone maintenance treatment

We evaluated a novel intervention designed to improve access to sterile syringes and safe syringe disposal for injection drug users (IDUs) newly enrolled in methadone maintenance, through interviews with two sequential cohorts of 100 recent entrants into a methadone program in the Bronx, NY. A substantial number of participants had injected in the previous 6 months, and most continued injecting during the early weeks of treatment. The intervention was associated with significant behavior changes among IDUs, including increased use of pharmacies as a primary source of syringes (11% vs. 37%, p < .05) and decreases in both purchasing of syringes on the street (51% vs. 27%, p < .05) and needle sharing (40% vs. 7%, p < .01). The intervention had no impact on the prevalence of injection or on syringe disposal practices. Our findings suggest that drug treatment programs can serve an important role in reducing injection-related risk behavior by facilitating access to sterile syringes.