Guideline-based programs in the treatment of complex PTSD

The term “post-traumatic stress disorder” (PTSD) is a relatively new diagnostic label, being formally recognized in 1980 in the Diagnostic Statistical Manual for Psychiatric Illness – Third Edition (DSM-III) of the American Psychiatric Association (APA, 1980). Complex Post-Traumatic Stress Disorder (CP) is a more recently discussed, and newly-classified, phenomenon, initially discussed in the early 1990s (Herman, 1992a). Thus, as research into effective treatments for CP is sparse, the treatment of CP is the topic of this study, in which a guideline-based treatment program developed by the researcher for the treatment of CP is implemented and evaluated. Ten individuals participated in this study, undertaking individualized, guideline-based treatment programs spanning a period of six months. In providing background information relevant to this study, an explanation is provided regarding the nature of CP, and the reasons for its consideration as a separate phenomenon to PTSD. The adequacy of the PTSD formulation in enabling effective assessment and treatment of CP is also explored, with endorsement of previous researchers’ conclusions that the CP construct is more useful than the PTSD construct for assessing and treating survivors of long-term and multiple forms of abuse. The PTSD classification is restrictive, and not necessarily appropriate for certain forms of trauma (such as prolonged trauma, or multiple forms of trauma), as such trauma experiences may lead to specific effects that lay outside those formerly associated with PTSD. Such effects include alterations in affect regulation, consciousness, self-perception, interpersonal relationships, and in systems of meaning. Following discussion regarding the PTSD/CP classification, an examination of treatment methods currently used in the treatment of PTSD, and a review of treatment outcome studies, takes place. The adequacy of primary treatment methods in treating CP symptoms is then examined, with the conclusion that a range of treatment methods could potentially be useful in the treatment of CP symptoms. Individuals with a diagnosis of CP may benefit from the adoption of an eclectic approach, drawing on different treatment options for different symptoms, and constantly evaluating client progress and re-evaluating interventions. This review of treatment approaches is followed by details of an initial study undertaken to obtain feedback from individuals who had suffered long-term/multiple trauma and who had received treatment. Participants in this initial study were asked open-ended questions regarding the treatment approach they had experienced, the most useful aspect of the treatment, the least useful aspect, and other strategies/treatment approaches that may have been useful – but which were not used. The feedback obtained from these individuals was used to inform the development of treatment guidelines for use in the main study, as were recommendations made by Chu (1998). The predominant focus of the treatment guidelines was “ego strengthening”, a term coined by Chu (1998) to describe the “initial (sometimes lengthy) period of developing fundamental skills in maintaining supportive relationships, developing self-care strategies, coping with symptomatology, improving functioning, and establishing a positive self identity” (p.75). Using a case study approach, data are then presented relating to each of the ten individuals involved in the treatment program: details of his/her trauma experience(s)and the impact of the trauma (as perceived by each individual); details of each individual’s treatment program (as planned, and as implemented); post-treatment evaluation of the positive and negative aspects of the treatment program (from the therapist’s perspective); and details of the symptoms reported by the individual post-treatment, via psychometric assessment and also during interview. Analysis and discussion of the data relating to the ten participants in the study are the focal point of this study. The evaluation of the effectiveness of each individual’s treatment has been based predominantly on qualitative data, obtained from an analysis of language (discourse analysis) used by participants to describe their symptoms pre- and post-treatment. Both blatant and subtle changes in the language used by participants to describe themselves, their behaviour, and their relationships pre- and post-treatment have provided an insight into the possible changes that occurred as a result of the treatment program. The language used by participants has been a rich source of data, one that has enabled the researcher to obtain information that could not be obtained using psychometric assessment methods. Most of the participants in this study portrayed notable changes in many of the CP symptoms, including being more stable and having improved capacity to explore their early abuse. Although no direct cause-effect relationship between the participants’ treatment program and the improvements described can be established from this study, the participants’ perception that the program assisted them with their symptoms, and reported many aspects of “ego strengthening”, is of major importance. Such self-perception of strength and empowerment is important if an individual is going to be able to deal with past trauma experiences. In fact, abreactive work may have a greater chance of succeeding if those who have experienced long-term or multiple trauma are feeling more empowered, and more stable, as were the participants in this study (post-intervention). In concluding this study, recommendations have been made in regard to the use of guideline-based treatment programs in the responsible treatment of CP. Strengths and limitations of this study have also been highlighted, and recommendations have been made regarding possibilities for future research related to CP treatment. On the whole, this study has supported strongly other research that highlights the importance of focusing on “ego strengthening” in assisting those who have suffered long-term/multiple trauma experiences. Thus, a guideline-based program focusing on assisting sufferers of long-term trauma with some, or all, of the symptoms of CP, is recommended as an important first stage of any treatment of individuals who have experienced long-term/multiple trauma, allowing them to develop the emotional and psychological strength required to deal with past traumatic events. Clinicians who are treating patients whose history depicts long-term or multiple trauma experiences (either from their childhood, or at some stage in their adult life) need, therefore, to be mindful of assessing individuals for symptoms of CP – so that they can treat these symptoms prior to engaging in any work associated directly with the past traumatic experiences.

Experimental study of abattoir wastewater treatment from an economic perspective

The most cost effective treatment scheme for effluent from Midfield Meats, an abattoir in Warrnambool, Australia, was evaluated via a series of laboratory and commercial scale experiments. Effectiveness was measured in terms of suspended solids (SS) and biological oxygen demand (BOD) reduction. Economic assessment was based on predicted reduction in trade waste charges versus infrastructure and running costs. From the range of potential treatment technologies, those deemed most appropriate for trialling included pre-screening, sedimentation, coagulation and flocculation treatment and dissolved air floatation (DAF). Prior to evaluation of treatment types, flow, loads and contaminant characterisation of the waste streams was conducted to aid in selection of treatment type and capacity. Prescreening was found to be the most cost effective, followed by sedimentation, coagulation and flocculation treatment and finally DAF. The most economical treatment scheme that satisfied the requirements of Midfield Meats included a combination of prescreening and sedimentation. DAF and coagulation and flocculation treatment satisfactorily treated the wastewater, however were not cost effective under the current trade waste agreement.

The identification of sexual and violent motivations in men who assault women : implication for treatment

A qualitative analysis of interview data with 41 rapists determined that five implicit theories (ITs) underlie rapists’ offense supportive beliefs/feelings/motives: (a) dangerous world (DW)—where men have feelings of generalized anger and/or resentment toward others; (b) women are dangerous—where men hold a set of attitudes that are hostile toward women; (c) women as sexual objects (WSO)—where women are seen as primarily sexual objects; (d) male sex drive is uncontrollable—where sexual urges are seen all consuming; (e) entitlement—where men feel that they can do exactly what they want. Consideration of whether DW or WSO ITs were present or absent indicated that three main groups could be identified: Group 1: violently motivated—presence of DW and/or absence of WSO; Group 2: sexually motivated—presence of WSO and/or absence of DW; Group 3: sadistically motivated—presence of DW and WSO. These results are discussed in terms of treatment needs of rapists.

The Renal Treatment Satisfaction Questionnaire (RTSQ): a measure of satisfaction with treatment for chronic kidney failure.

BACKGROUND: Quality and effectiveness of care can be enhanced through the use of condition-specific measures of satisfaction with treatment. The aim of the present study was to design and develop a measure of satisfaction with treatment for patients with chronic kidney failure (CKF) for use in routine clinical care and clinical trials. The Renal Treatment Satisfaction Questionnaire (RTSQ) was designed to be suitable for people using any of the various treatment modalities for CKF. Items measure satisfaction with aspects of treatment, including convenience, flexibility, freedom, and satisfaction to continue with present form of treatment.

METHODS: A 12-item RTSQ was investigated at a UK hospital-based renal unit, using data from 140 outpatients undergoing renal replacement therapy (hemodialysis, n = 35; continuous ambulatory peritoneal dialysis, n = 57; transplantation, n = 46).

RESULTS: An 11-item scale was developed from the original 12-item version, with a single factor accounting for 59% of the variance and item loadings greater than 0.58. Scale reliability was excellent (alpha = 0.93) in the full sample and proved robust to analysis in separate treatment subgroups. As expected, RTSQ scores differed significantly ( P < 0.0001) between the transplantation and other treatment groups. Those who had received a transplant expressed greater overall satisfaction, with specific advantages of transplantation shown by all individual items, including convenience, time, lifestyle, freedom, and satisfaction to continue current treatment.

CONCLUSION: The RTSQ provides a brief reliable measure of satisfaction with treatment for patients with CKF that is suitable for use in routine clinical care and clinical trials.

Advances in the treatment of malignant gliomas

Local control with surgery, radiation, and temozolomide chemotherapy remain the pillars of treatment for high-grade gliomas. Novel therapeutic strategies, including a variety of antiangiogenic agents, are under investigation. One of these agents, bevacizumab, was recently given accelerated approval by the US Food and Drug Administration as a single agent for recurrent glioblastoma. Recent trial results are generating important clinical questions regarding which patients to treat and when, and how best to monitor response. Encouraging results of recent studies are driving willingness to undertake aggressive treatment and to improve outcomes in this population. In this era, better understanding of biology, molecular aspects of cancer, and clinical trial methodology are crucial for clinicians. This review focuses on recent advances in the treatment malignant gliomas, especially antiangiogenic therapy.

Primary hemiarthroplasty for treatment of proximal humeral fractures

Background: Primary hemiarthroplasty of the shoulder is used to treat complex proximal humeral fractures, although the reported functional results following this method of treatment have varied widely. The aim of this study was to prospectively assess the prosthetic survival and functional outcomes in a large series of patients treated with shoulder hemiarthroplasty for a proximal humeral fracture. By determining the factors that affected the outcome, we also aimed to produce models that could be used clinically to estimate the functional outcome at one year following surgery.

Methods: A thirteen-year observational cohort study of 163 consecutive patients treated with hemiarthroplasty for a proximal humeral fracture was performed. Twenty-five patients died or were lost to follow-up in the first year after treatment, leaving 138 patients who had assessment of shoulder function with use of the modified Constant score at one year postinjury.

Results: The overall rate of prosthetic survival was 96.9% at one year, 95.3% at five years, and 93.9% at ten years. The overall median modified Constant score was 64 points at one year, with a typically good score for pain relief (median, 15 points) and poorer scores, with a greater scatter of values, for function (median, 12 points), range of motion (median, 24 points), and muscle power (median, 14 points). Of the factors that were assessed immediately after the injury, only patient age, the presence of a neurological deficit, tobacco usage, and alcohol consumption were significantly predictive of the one-year Constant score (p < 0.05). Of the factors that were assessed at six weeks postinjury, those that predicted the one-year Constant score included the age of the patient, the presence of a persistent neurological deficit, the need for an early reoperation, the degree of displacement of the prosthetic head from the central axis of the glenoid seen radiographically, and the degree of displacement of the tuberosities seen radiographically.

Conclusions: Primary shoulder hemiarthroplasty performed for the treatment of a proximal humeral fracture in medically fit and cooperative adults is associated with satisfactory prosthetic survival at an average of 6.3 years. Although the shoulder is usually free of pain following this procedure, the overall functional result, in terms of range of motion, function, and power, at one year varies. A good functional outcome can be anticipated for a younger individual who has no preoperative neurological deficit, no postoperative complications, and a satisfactory radiographic appearance of the shoulder at six weeks. The results are poorer in the larger group of elderly patients who undergo this procedure, especially if they have a neurological deficit, a postoperative complication requiring a reoperation, or an eccentrically located prosthesis with retracted tuberosities.

Analysis of the stages of change model of drug and alcohol treatment readiness among prisoners

A classification and regression tree (CART) analysis was applied to data for 237 male participants (M = 31.93 years, SD = 7.64) in a prison-based substance abuse treatment program to study the integrity of the Stages of Change model of treatment readiness. Using the Stages of Change Questionnaire (STOCQ), participants were assigned to Contemplation (102), Action (118), or Maintenance (17) groups. A CART analysis then examined differences in the overall group profiles on the basis of scores on the Psychological Inventory of Criminal Thinking, the Situational Confidence Questionnaire, and the Carlson Psychological Survey. The assumption of discrete stages of change was not supported. Alternative models are suggested: one based on states of change and one on personality characteristics. A focus on equal attention to both cognitive and behavioral aspects of substance abuse treatment readiness is suggested.

IMF®-Therapy (Intention controlled Myo-Feedback) — an innovative method in the treatment of peripheral nerve lesions

Physiotherapy is a well established part of the rehabilitation of peripheral nerve paralysis. The aim of this type of treatment is to re-establish arbitrary functions by improving the patients’ active and passive mobility as well as their strength and stamina. IMF®-Therapy (Intention controlled Myo-Feedback) is an innovative method in the treatment of peripheral nerve lesions that goes beyond the purely neuro-scientific framework and also takes into account methods and concepts of the psychology of learning. The essential assumption is that things learnt in the past are firmly established in the long term motor memory and can be reactivated by the patient. From results achieved in 32 patients treated with this therapy it can be concluded that IMF®-Therapy may be a promising additional rehabilitation tool in peripheral nerve lesion.

Effect of surface treatment and knit structure on comfort properties of wool fabrics

The comfort properties of the pique and single jersey knitted wool fabrics were investigated using the Wool ComfortMeter (WCM). The fabrics were knitted in three cover factors and treated with either plasma or a silicone softening agent and were compared with untreated fabrics. Plasma treatment did not show significant effects on the comfort value. However, silicone polymer significantly reduced WCM values suggesting that the silicone coating reduced the number of protruding fibres on the fabric surface. Regardless of treatment used, pique fabrics showed a lower WCM value, and therefore were perceived to be more comfortable than the single jersey structure. While the effect of cover factor was not significant, in fitted model to predict the WCM value of fabrics, mass/unit area and fabric thickness were significant predictors along with fabric structure and finishing treatment.

DSM-5 mixed specifier for manic episodes: evaluating the effect of depressive features on severity and treatment outcome using asenapine clinical trial data

Background:
To describe the frequency of mixed specifier as proposed in DSM-5 in bipolar I patients with manic episodes, and to evaluate the effect of mixed specifier on symptom severity and treatment outcome.

Methods:
This post-hoc analysis used proxies for DSM-5 mixed features specifier by using MADRS or PANSS items.

Results:
Of the 960 patients analysed, 34%, 18% and 4.3% of patients, respectively, had ≥3 depressive features with mild (score ≥1 for MADRS items and ≥2 for PANSS item), moderate (score ≥2 MADRS, ≥3 PANSS) and severe (score ≥3 MADRS, ≥4 PANSS) symptoms. In patients with ≥3 depressive features and independent of treatment: MADRS remission (score ≤12) rate decreased with increasing severity (61–43%) and YMRS remission (score ≤12) was similar for mild and moderate patients (36–37%), but higher for severe (54%). In asenapine-treated patients, the MADRS remission rate was stable regardless of baseline depressive symptom severity (range 64–67%), whereas remission decreased with increasing severity with olanzapine (63–38%) and placebo (49–25%). Reduction in YMRS was significantly greater for asenapine compared with placebo at day 2 across the 3 severity cut-offs and continued to decrease throughout the treatment period. The difference between olanzapine and placebo was statistically significant in mild and moderate patients.

Limitations:
Results are from post-hoc analyses.

Conclusions:
These analyses support the validity of proposed DSM-5 criteria. They confirm that depressive features are frequent in bipolar patients with manic episodes. With increasing baseline severity of depressive features, treatment outcome was poorer with olanzapine and placebo, but remained stable with asenapine.

Is lower income associated with an increased likelihood of qualification for treatment for osteoporosis in Canadian women?

The authors examined whether low income was associated with an increased likelihood of treatment qualification for osteoporotic fracture probability determined by Canada FRAX in women aged ≥50 years. A significant negative linear association was observed between income and treatment qualification when FRAX included bone mineral density (BMD), which may have implications for clinical practice.

Recombinant human growth hormone for the treatment of growth disorders in children: a systematic review and economic evaluation

Recombinant human growth hormone (rhGH) is licensed for short stature associated with growth hormone deficiency (GHD), Turner syndrome (TS), Prader-Willi syndrome (PWS), chronic renal insufficiency (CRI), short stature homeobox-containing gene deficiency (SHOX-D) and being born small for gestational age (SGA). To assess the clinical effectiveness and cost-effectiveness of rhGH compared with treatment strategies without rhGH for children with GHD, TS, PWS, CRI, SHOX-D and those born SGA. The systematic review used a priori methods. Key databases were searched (e.g. MEDLINE, EMBASE, NHS Economic Evaluation Database and eight others) for relevant studies from their inception to June 2009. A decision-analytical model was developed to determine cost-effectiveness in the UK. Two reviewers assessed titles and abstracts of studies identified by the search strategy, obtained the full text of relevant papers, and screened them against inclusion criteria. Data from included studies were extracted by one reviewer and checked by a second. Quality of included studies was assessed using standard criteria, applied by one reviewer and checked by a second. Clinical effectiveness studies were synthesised through a narrative review. Twenty-eight randomised controlled trials (RCTs) in 34 publications were included in the systematic review. GHD: Children in the rhGH group grew 2.7 cm/year faster than untreated children and had a statistically significantly higher height standard deviation score (HtSDS) after 1 year: -2.3 ± 0.45 versus -2.8 ± 0.45. TS: In one study, treated girls grew 9.3 cm more than untreated girls. In a study of younger children, the difference was 7.6 cm after 2 years. HtSDS values were statistically significantly higher in treated girls. PWS: Infants receiving rhGH for 1 year grew significantly taller (6.2 cm more) than those untreated. Two studies reported a statistically significant difference in HtSDS in favour of rhGH. CRI: rhGH-treated children in a 1-year study grew an average of 3.6 cm more than untreated children. HtSDS was statistically significantly higher in treated children in two studies. SGA: Criteria were amended to include children of 3+ years with no catch-up growth, with no reference to mid-parental height. Only one of the RCTs used the licensed dose; the others used higher doses. Adult height (AH) was approximately 4 cm higher in rhGH-treated patients in the one study to report this outcome, and AH-gain SDS was also statistically significantly higher in this group. Mean HtSDS was higher in treated than untreated patients in four other studies (significant in two). SHOX-D: After 2 years' treatment, children were approximately 6 cm taller than the control group and HtSDS was statistically significantly higher in treated children. The incremental cost per quality adjusted life-year (QALY) estimates of rhGH compared with no treatment were: 23,196 pounds for GHD, 39,460 pounds for TS, 135,311 pounds for PWS, 39,273 pounds for CRI, 33,079 pounds for SGA and 40,531 pounds for SHOX-D. The probability of treatment of each of the conditions being cost-effective at 30,000 pounds was: 95% for GHD, 19% for TS, 1% for PWS, 16% for CRI, 38% for SGA and 15% for SHOX-D.

Entecavir for the treatment of chronic hepatitis B infection

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of entecavir for the treatment of chronic hepatitis B (CHB) in adults based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from five randomised controlled trials (RCTs), of good methodological quality and measuring a range of clinically relevant outcomes, comparing entecavir with lamivudine. After 1 year of treatment entecavir was statistically superior to lamivudine in terms of the proportion of patients achieving hepatitis B virus (HBV) DNA suppression, alanine aminotransferase (ALT) normalisation and histological improvement, but not in terms of the proportion of patients achieving hepatitis B e antigen (HBeAg) seroconversion. The incidence of adverse or serious adverse events was similar for both treatments. The results of the manufacturer's mixed treatment comparison (MTC) model to compare entecavir with the comparator drugs in nucleoside-naive patients were considered to be uncertain because of concerns over its conduct and reporting. For the economic evaluation the manufacturer constructed two Markov state transition models, one in HBeAg-positive and one in HBeAg-negative patients. The modelling approach was considered reasonable subject to some uncertainties and concerns over some of the structural assumptions. In HBeAg-positive patients the base-case incremental cost-effectiveness ratios (ICER) for entecavir compared with lamivudine and pegylated interferon alpha-2a were 14,329 pounds and 8403 pounds per quality-adjusted life-year (QALY) respectively. Entecavir was dominated by telbivudine. In HBeAg-negative patients the base-case ICERs for entecavir compared with lamivudine, pegylated interferon alpha-2a and telbivudine were 13,208 pounds, 7511 pounds and 6907 pounds per QALY respectively. In HBeAg-positive lamivudine-refractory patients entecavir dominated adefovir added to lamivudine. In one-way deterministic sensitivity analysis on all key input parameters for entecavir compared with lamivudine in nucleoside-naive patients, ICERs generally remained under 30,000 pounds per QALY. In probabilistic sensitivity analysis in nucleoside-naive HBeAg-positive patients the probability of the ICER for entecavir being below 20,000 pounds per QALY was 57%, 82% and 45% compared with lamivudine, pegylated interferon alpha-2a and telbivudine respectively. In nucleoside-naive HBeAg-negative patients the probabilities were 90%, 100% and 96% respectively. The manufacturer's lifetime treatment scenario for HBeAg-negative patients and the ERG's 20-year treatment scenario for HBeAg-positive patients increased the ICERs, particularly in the latter case. Amending the HBeAg-negative model so that patients with compensated cirrhosis would also receive lifetime treatment gave probabilities of entecavir being cost-effective at a willingness to pay of 20,000 pounds and 30,000 pounds of 4% and 40% respectively. The NICE guidance issued in August 2008 as a result of the STA states that entecavir is recommended as an option for the treatment of people with chronic HBeAg-positive or HBeAg-negative hepatitis B in whom antiviral treatment is indicated.

Investigation of consumer satisfaction with cognitive-behaviour therapy and sertraline in the treatment of adolescent depression

Objective: A new instrument, the Adolescent Depression Treatment Satisfaction Questionnaire (ADTSQ) was devised to measure the consumer satisfaction of depressed adolescents and their parents. The objectives of the paper were to present the psychometric proper ties ofthe ADTSQ and to investigate the relative consumer satisfaction with cognitive-behavioural therapy (CBT), sertraline (SRT) and a combined treatment of CBT and SRT (COMBINED) for the treatment of adolescent depression. In addition, participants were asked to rank their most preferred treatment from the following approaches: medication, individual counselling, group program and family therapy.Method: Thirty-eight adolescents with a unipolar depressive disorder and 37 parents who participated in a randomized clinical trial of CBT versus SRT versus COMBINED completed the ADTSQ following the completion of acute treatment.Results: The ADTSQ was found to have high internal consistency and exploratory factor analysis detected three underlying factors. High levels of consumer satisfaction were reported by both adolescents and parents in all three treatments. Those treated with CBT treatments reported higher levels of skill acquisition than those treated with SRT. Of the four treatment approaches, most parents and adolescentsrated individual counsellingas their first preference.Conclusions: The ADTSQ is a useful measure of consumer satisfaction for depressed adolescents and their parents. CBT, SRT and COMBINED were shown to have high consumer satisfaction with CBT's higher skills training content reflected in the participants' reports. Individual counselling was perceived as the most favourable choice of treatment for adolescent depression. Although limitations associated with the measurement of consumer satisfaction and of the study are acknowledged, it is recommended that the inclusion of consumer satisfaction measures be considered in clinical trials that examine treatment efficacy.

Protocol and rationale-the efficacy of minocycline as an adjunctive treatment for major depressive disorder: a double blind, randomised, placebo controlled trial

While current pharmacotherapies are efficacious, there remain a clear shortfall between symptom remission and functional recovery. With the explosion in our understanding of the biology of these disorders, the time is ripe for the investigation of novel therapies. Recently depression is conceptualized as an immune-inflammatory and nitro-oxidative stress related disorder. Minocycline is a tetracycline antibiotic that has anti-inflammatory, pro-oxidant, glutamatergic, neurotrophic and neuroprotective properties that make it a viable target to explore as a new therapy. This double blind, randomised, placebo controlled adjunctive trial will investigate the benefits of 200 mg/day of minocycline treatment, in addition to any usual treatment, as an adjunctive treatment for moderate-severe major depressive disorder. Sixty adults are being randomised to 12 weeks of treatment (with a 4 week follow-up post-discontinuation). The primary outcome measure for the study is mean change on the Montgomery-Asberg Depression Rating Scale (MADRS), with secondary outcomes including the Social and Occupational Functioning Assessment Scale (SOFAS), Clinical Global Impressions (CGI), Hamilton Rating Scale for Anxiety (HAM-A), Patient Global Impression (PGI), Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and Range of Impaired Functioning Tool (LIFE-RIFT). Biomarker analyses will also be conducted at baseline and week 12. The study has the potential to provide new treatment targets, both by showing efficacy with a new class of 'antidepressant' but also through the analysis of biomarkers that may further inform our understanding of the pathophysiology of unipolar depression.