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Background: Increasing Emergency Department (ED) stretcher occupancy with admitted patients at our tertiary care hospital has contributed to long Physician Initial Assessment (PIA) times. As of Oct 2019, median PIA was 2.3 hours and 90th percentile PIA was 5.3 hours, with a consequent 71/74 PIA ranking compared to all Ontario EDs. Ambulatory zone (AZ) models are more commonly used in community EDs compared to tertiary level EDs. An interdisciplinary team trialled an AZ model for five days in our ED to improve PIA times. Aim Statement: We sought to decrease the median PIA for patients in our ED during the AZ trial period as compared to days with similar occupancy and volume. Measures & Design: The AZ was reserved for patients who could walk from a chair to stretcher. In this zone, ED rooms with stretchers were for patient assessment only; when waiting for results or receiving treatment, patients were moved into chairs. We removed nursing assignment ratios to increase patient flow. Our outcome measure was the median PIA for all patients in our ED. Our balancing measure was the 90th percentile PIA, which could increase if we negatively impacted patients who require stretchers. The median and 90th percentile PIA during the AZ trial were compared to similar occupancy and volume days without the AZ. Additional measures included ED Length of Stay (LOS) for non-admitted patients, and patients who leave without being seen (LWBS). Clinicians and patients provided qualitative feedback through surveys. Evaluation/Results: The median PIA during the AZ trial was 1.5 hours, compared to 2.1 hours during control days. Our balancing measure, the 90th percentile PIA was 3.7 hours, compared to 5.0 during control days. A run chart revealed both median and 90th percentile PIA during the trial were at their lowest points over the past 18 months. The number of LWBS patients decreased during the trial; EDLOS did not change. The majority of patients, nurses, and physicians felt the trial could be implemented permanently. Discussion/Impact: Although our highly specialized tertiary care hospital faces unique challenges and high occupancy pressures, a community-hospital style AZ model was successful in improving PIA. Shorter PIA times can improve other quality metrics, such as timeliness of analgesia and antibiotics. We are working to optimize the model based on feedback before we cycle another trial. Our findings suggest that other tertiary care EDs should consider similar AZ models.
Background: Liberal prescribing of opioids is a major contributing factor to the opioid crisis. Patients who take opioids for >5 consecutive days are at greater risk of long-term use. Evidence shows that significantly more opioids are prescribed for emergency department (ED) patients with acute pain compared to amounts consumed. Guidelines recommend prescribing a 3-day supply or 10-15 tablets of opioids for patients with acute pain Aim Statement: By January 2020, >70% of opioid prescriptions from our ED will be for <15 tablets of morphine 5 mg equivalents. Measures & Design: Emergency physicians were educated on best practice of prescribing opioids for discharged patients. An electronic prescription writer was built for discharged ED patients with a pop-up reminder for quantities >15 tablets (indicating a recommended quantity of 10-15 tablets) and a pop-up reminder for quantities >30 tablets (indicating a maximum quantity of 30 tablets and recommended quantity). A feature was built to auto-populate a prescription for morphine 5 mg po q4h prn x 10 tablets to facilitate adherence to guidelines. Outcome Measure % opioid prescriptions for <15 tablets of morphine 5 mg equivalents Process Measure Amount of opioids prescribed for discharged ED patients, measured as morphine 5 mg equivalents Number of opioid prescriptions for >30 tablets of morphine 5 mg equivalents Balancing Measure Number of patients that return to ED within 7 days and receive a repeat opioid prescription. Evaluation/Results: Prior to implementation of the electronic prescription writer a sample audit revealed that 50% of opioid prescriptions were written for <15 tablets of morphine 5 mg equivalents. For the first three quarters of 2019, 62%, 61% and 69% of opioid prescriptions were written for <15 tablets of morphine 5 mg equivalents. Only two prescriptions during the study period were for >30 tablets of morphine 5 mg equivalents. An average number of 7 patients per quarter were given a repeat opioid prescription during a return ED visit. Discussion/Impact: We were successful in influencing emergency physicians to prescribe fewer opioids to discharged patients. This has the potential to avoid converting ED patients with acute pain into long-term opioid users and to avoid the diversion of unused opioid tablets.
Background: Most emergency departments (ED) utilize medical directives to initiate lab investigations for patients prior to physician assessment. This practice facilitates expedited patient care in the ED, resulting in safer and efficient care. However, some patients choose to leave the ED prior to seeing a physician due to prolonged waiting. Previously, at our hospital there was no defined process for identifying and following up on abnormal test results on patients that leave without being seen (LWBS), resulting in lab results often not being reviewed by a nurse or physician. Aim Statement: By April 2020, we aim to have 90% of ED LWBS patients with abnormal results identified and followed up. Measures & Design: A series of consultations and information gathering occurred that included an environmental scan of other EDs and discussions with emergency nurses, emergency physicians, Risk Management, Legal Department, College of Nurses of Ontario and Canadian Medical Protective Association. A process map was developed collaboratively to standardize the process to identify and follow up on abnormal investigations of LWBS patients and a new hospital policy was developed to officially outline this process. The following are the family of measures: Outcome measure – % LWBS patients with abnormal tests that had follow-up documented in chart Process measure – Number LWBS patients with investigations initiated by medical directive, Number LWBS patients, % LWBS patients Balancing measure – Satisfaction of nurses with new process for LWBS patients Evaluation/Results: At baseline, 29% of LWBS patients with abnormal lab results had follow up documented in the chart. After implementation of the new standardized process and policy, the follow up rate of LWBS patients with abnormal results in August, September and October 2019 was 47%, 28% and 29% respectively. Discussion/Impact: These results indicate that standardization and new policy implementation is insufficient to change practice, even one that aims to provide safer patient care. Nevertheless, these interventions are important first steps to improving the safety for ED LWBS patients. We plan to implement an audit and feedback approach to encourage nursing staff to routinely check lab results on LWBS patients.
Two randomized, controlled trials of L-methylfolate augmentation of SSRIs for major depressive disorder (MDD) were conducted using a novel study design (sequential parallel comparison design- SPCD).
To evaluate the efficacy of L-methylfolate augmentation using the Hamilton Depression Rating Scale.
In study one (TRD-1), 148 outpatients with SSRI-resistant MDD were enrolled in a 60-day, SPCD study, divided into two 30-day periods (phases 1 and 2). Patients were randomized 2:3:3 to receive L-methylfolate (7.5mg/d in phase 1, 15mg/d in phase 2), placebo in phase 1 followed by L-methylfolate 7.5mg/d in phase 2, or placebo for both phases. Study two (TRD-2) involved 75 patients and was identical in design to TRD-1 except for the dose of L-methylfolate (15mg only).
In the TRD-1 Study, L-methylfolate 7.5 mg/d was not found to be more effective than placebo. In phase 1 of the TRD-2 Study, 37% of patients on L-methylfolate 15mg/d responded and 18% of placebo patients responded, while in phase 2 among placebo non-responders, the response rates were 28% on L-methylfolate 15mg/d and 9.5% on placebo. When phases 1 and 2 were pooled according to the SPCD model, the difference in response rates was statistically significant in favor of L-methylfolate (p = 0.0399). The rates of spontaneously reported AEs and rates of study discontinuation appear r comparable between L-methylfolate and placebo in both studies. Rates of study discontinuation were also comparable
These studies suggest that L-methylfolate 15 mg/d may be a safe and effective augmentation strategy for inadequate response to SSRIs.
Background: The Choosing Wisely campaign aims to reduce unnecessary testing. Over testing for urinary tract infections and concomitant overtreatment of asymptomatic bacteriuria is a target of this campaign, aiming to decrease healthcare costs and the risks of side effects such as Clostridium difficile infection, adverse reactions, and antimicrobial resistance. During the study baseline (2017), 95 urine cultures (UC) were sent for every 1000 ED visits (9.5%). Of these, fewer than 20% were positive. Aim Statement: The aim of this improvement initiative was to reduce UC testing in the ED, by 50%, from a baseline average of nearly 100 cultures per 1000 ED patients visits, to 50 cultures per 1000 visits, by May 31st, 2018. Measures & Design: This was an interrupted time series study, analyzed using Statistical Process Control (SPC) methodology. Root cause analysis was performed using an Ishikawa diagram. A Pareto chart was completed via multi-voting. A Driver Diagram was developed using the highest ranked items from the Pareto chart to identify locally relevant and feasible interventions. Interventions 1) Medical directives were modified; Routine paired sending of UC with urinalysis by nurses was removed. 2) Physician Education and implementation of a clinical decision aid (CDA); A CDA was created using PDSA methodology, using an iterative approach from development through implementation. Outcome measure: rate of Urine Cultures sent per 1000 ED patient visits Process measure: percent of positive cultures Balancing measures: rate of 14-day ED return visits and hospital admission for patients diagnosed with UTI/Urosepsis/Pyelonephritis. Evalution/Results: At the study's conclusion, there was a decrease in UC rate, from 95 per 1000 ED visits, to 59 per 1000 ED visits (RR 38%, AR 3.6%) There was evidence of special cause variation on the SPC chart. Positive cultures increased from 19% to 34%. There was no increase in the rate of ED 14-day return visits or hospital admission for patients with a diagnosis of UTI, urosepsis or pyelonephritis. Discussion/Impact: The study interventions of uncoupling routine sending of UA and UC, and physician education and use of a clinical decision aid, effectively decreased the rate of UC testing during the study period. A reduction in inappropriate UC testing is important to limit avoidable patient morbidity and reduce unnecessary health care spending. Further studies are indicated to target interventions on patient subgroups and to reduce unnecessary antibiotic prescriptions.
Background: Choosing Wisely (CW) recommends patients under age 50 with uncomplicated, recurrent renal colic do not require CT scans. Despite this, CT use has risen dramatically in the past two decades, resulting in unnecessary radiation, cost and prolonged length of stay (LOS). Additionally, a common alternative – formal ultrasound (US) – is not always available. Returning for US can add 10 hours to LOS. We introduced a clinical management pathway (CMP) for low-risk patients with renal colic utilizing point-of-care ultrasound (POCUS) and evaluated its impact on emergency department (ED) CT rates and LOS. Aim Statement: By April 2019, we aim to reduce CT utilization by 50% and time from physician initial assessment (PIA) to discharge by 1 hour for patients under age 50 presenting to Sunnybrook ED with uncomplicated, recurrent renal colic. Measures & Design: The primary intervention was a CMP developed collaboratively with local urologists. The CMP uses POCUS to assess for hydronephrosis (HN) as a marker of nephrolithiasis. Patients with HN receive follow-up in urology clinic without confirmatory imaging. Patients without HN proceed to usual care. An Ishikawa diagram helped identify barriers to success. Subsequent PDSA cycles included the introduction of reference cards, POCUS workshops and online modules. Outcome measures were ED CT utilization and PIA to discharge times. Process measures were referrals to urology clinic and proportion of patients receiving XR, US and no imaging. Balancing measures were urology CT utilization, alternate diagnoses and return ED visits. Data was plotted on a run chart. Evaluation/Results: Data collection is ongoing and will conclude by April 2019. Interim data shows patients enrolled in the CMP have a reduction in mean PIA-to-discharge time of 173 minutes. Fidelity – specifically, the willingness of ED physicians to use POCUS compared to the ease of ordering CTs – is the biggest challenge to success. Discussion/Impact: This study addresses the feasibility of CW recommendations and utilizes POCUS as a tool for recurrent renal colic. Collaboration with Urology will provide insight into the CMP's sustainability and downstream impact. Reduction of unnecessary CTs will lead to improved patient safety and reduced costs. Decreased PIA-to-discharge times will reduce overcrowding, shorten wait times and improve access to imaging for other patients. Finally, this project may encourage use of POCUS for low-risk patients with renal colic.
Introduction: At Sunnybrook Health Sciences Centres Emergency Department (ED), delays occurred in reporting positive microbiology culture results of patients discharged from the ED. Follow-up of culture results was driven by a manual paper based process that was inefficient and resulted in a one to three day delay in reporting results. The previous system was time consuming, labour intensive and prone to human error. Timely reporting of microbiology culture results is important to ensuring that patients receive optimal care. The aim is that >80% of positive microbiology culture results of patients discharged from Sunnybrook Health Sciences Centre ED will be followed-up within 24 hours of results being available from the lab. Methods: Outcome Measure Percentage of positive culture results followed up within 24 hours Process Measure Time from availability of culture results from lab to completion of patient follow-up Balancing Measure Number of positive culture results not displayed in ED server Change Idea Electronically push positive culture results to an ED server that is periodically checked daily and acted upon. An electronic interface was created to capture positive results from the microbiology lab in real time. Results: There was a 45 hour reduction in the mean time to complete a patients follow-up of culture results (59 hours pre vs. 14 hours post, p=0.03). We surpassed our aim of >80% follow-up within 24 hours. Conclusion: A significant reduction to completing a patients follow-up of microbiology culture results was achieved by automating the availability of results and eliminating the manual process previously used in relaying results from the microbiology lab to ED. This new process has the following benefits: 1) Improves timely reporting of culture results to patients, that may require initiation or change in antibiotics 2) Enhanced patient safety due to elimination of human error 3) Decreased workload due to elimination of batching of results and data entry 4) Entire process is streamlined, since only positive culture results are transmitted for follow-up.
Introduction: The 2015 CanMEDS framework requires all residency programs to increase their focus on Quality Improvement and Patient Safety (QIPS). We created a longitudinal (4-year), modular QIPS curriculum for FRCP emergency medicine residents at the University of Toronto (UT) using multiple educational methods. The curriculum addresses three levels of QIPS training: knowledge, practical skills at the microsystem level, and practical skills at the organization level. Aim Statement: To increase the UT FRCP emergency medicine residents absolute score on the QIKAT-R (Quality Improvement Knowledge Application Tool Revised) by 10% after the completion of the QIPS curriculum. Methods: Physicians and other healthcare professionals with QI expertise collaboratively designed and taught the curriculum. We used the QIKAT-R as the outcome measure to evaluate QI knowledge and its applicability. The QIKAT-R is a validated measure that assesses an individuals ability to decipher a QI issue within the healthcare context, and propose a change initiative to address it. The first cohort of residents completed the QIKAT-R prior to the first session in 2014 (pre) and at the completion of the curriculum in 2017 (post). Each response was anonymized and scored by physicians with QI expertise. The QIKAT-R scores and comments from course evaluations are used to make yearly iterative curriculum changes. Results: The QIPS curriculum was implemented in September 2014. All nine residents in the first cohort completed the curriculum; they demonstrated an absolute increase of 19.6% (5.3/27) in the mean QIKAT-R score (13.0 +/− 3.3 pre vs. 18.3 +/− 3.8 post, p=0.001). Of the pre-test responses, 26% were categorized as poor, 70% as good, and 4% as excellent, whereas of the post-test 11% of responses were categorized as poor, 37% as good, and 52% as excellent (p<0.001). Two iterative curriculum changes were made at the end of each academic year since 2014: (1) The time between sessions were decreased to promote knowledge retention, and (2) different PGY3 QI practical project options were provided to suit residents individual QI interests. QIKAT-R scores and resident feedback were used to evaluate the impact of the curriculum changes. Conclusion: A collaborative, modular, longitudinal QIPS curriculum for UT FRCP emergency medicine residents that met CanMEDS requirements was created using multiple educational methods. The first resident cohort that completed the curriculum demonstrated an absolute increase in QI knowledge and its applicability (as measured by the QIKAT-R) by 19.6%. Two PDSA cycles were completed to improve the curriculum with the change ideas generated from resident feedback. Ongoing challenges include limited staff availability to teach and supervise resident QI projects. Future directions include incentivising staff participation and providing mentorship for residents with a career interest in QI beyond what is offered by the curriculum.
Introduction: CT scan is the most common imaging modality for suspected renal colic and is used for about 80% of presentations. Cumulative ionizing radiation exposure from repeat CT scans increases long-term cancer risk. Despite a 10-fold increase in CT use to detect kidney stones in the ED in just over a decade, there has been no increase in the proportion of kidney stones diagnosed, number of significant alternate diagnoses or admissions to hospital. Choosing Wisely recommends to avoid ordering CT of the abdomen/pelvis in otherwise healthy patients<age 50 presenting to the ED with known history of kidney stones and with symptoms consistent with uncomplicated renal colic. The aim is that >90% of patients < age 50 with a history of renal stones arriving in Sunnybrook ED with symptoms consistent with renal colic will be managed without a CT abdomen/pelvis. Methods: Emergency physicians were engaged in the process at various stages, including a brainstorming session to perform a root cause analysis. A Driver diagram was created to generate change ideas. Outcome Measure Number of CT scans ordered for target population (Results: Results to date indicate that there is a non-sustained decrease in the number of CT scans performed on ED patients < age 50 with recurrent renal colic. The STONE score was infrequently used, thus making it difficult to standardize CT ordering for presumed renal colic. Conclusion: As a result of this QI initiative, there is awareness amongst emergency physicians of a patient population that is over imaged with CT scan, often with no change in management. Introduction of a low dose CT scan order was the greatest gain from this QI initiative. In order to decrease CT utilization, physicians need to be shown the lack of benefit of CT use and a safe alternative diagnostic approach.
Introduction: Computed tomography (CT) has increasingly been used as a standard initial investigation for patients presenting to the Emergency Department (ED) with suspected nephrolithiasis. Compared to ultrasound, CT has increased system-level costs, ionizing radiation exposure and frequently does not alter management. For these reasons, Choosing Wisely (CW) recommends avoiding CT imaging of otherwise healthy patients younger than age 50 years presenting with symptoms of uncomplicated renal colic that have a known history of nephrolithiasis or ureterolithiasis. We aimed to evaluate the degree of utilization of CT imaging for this subgroup of patients in a tertiary care centre ED. Methods: A retrospective chart review was performed for all patients younger than 50 years who visited Sunnybrook Health Sciences Centre ED for six months between December 2015 and May 2016 with renal colic symptoms and a history of nephrolithiasis. Demographic data, relevant past medical history, clinical presentation, lab values, urology consultation, ED treatments administered, diagnostic imaging orders and dispositions were recorded for each eligible patient. Results: Out of 130 reviewed patient charts, 73 patients were identified with a previous history of nephrolithiasis and a presentation consistent with uncomplicated renal colic. 54 patients received ultrasound, KUB x-ray, or no imaging. The other 19 (26.0%) of these patients received an abdominal/pelvic CT with an indication of looking for renal or ureteral stones. Of the patients that received CT, none demonstrated significant findings warranting hospital admission or leading to identifiable changes in ED management. Five (26.3%) of these 19 patients had received a total of three to four CTs for renal colic during past Sunnybrook ED visits, while one had previously received 13 CTs. Conclusion: CT scans are often used as an initial diagnostic modality for suspected renal colic despite a Choosing Wisely recommendation to restrict the use of CT scans in a target population and infrequent changes in management after obtaining a CT. These findings highlight the need for quality improvement strategies to decrease CT utilization in this patient population with suspected renal colic.
We argue that a multimodal approach to defining a depictive class of words called ‘ideophones’ by linguists is essential for grasping their meanings. Our argument for this approach is based on the formal properties of Pastaza Quichua ideophones, which set them apart from the non-ideophonic lexicon, and on the cultural assumptions brought by speakers to their use. We analyze deficiencies in past attempts to define this language's ideophones, which have used only audio data. We offer, instead, an audiovisual corpus which we call an ‘antidictionary’, because it defines words not with other words, but with clips featuring actual contexts of use. The major discovery revealed by studying these clips is that ideophones’ meanings can be clarified by means of a distinction found in modality and American Sign Language studies. This distinction between speaker-internal and speaker-external perspective is evident in the intonational and gestural details of ideophones’ use.
Introduction: Tobacco use is a chronic, relapsing condition. While there are proven cessation medications and counselling treatments, uptake of available aids is poor and smokers often do not have access to evidence-based services.
Aims: The Association for the Treatment of Tobacco Use and Dependence (ATTUD) is an organisation of tobacco treatment specialists (TTSs) representing a wide array of disciplines and healthcare settings. This case vignette was intended to provide a clinical example of an interdisciplinary approach to tobacco use treatment.
Methods: ATTUD Interdisciplinary Committee members representing tobacco-cessation experts from five professions were asked to respond to the same composite case vignette detailing key areas of clinical consideration and treatment.
Results/Findings: While there were common treatment themes across professions, each provider also offered a unique treatment perspective addressing different facets of the patient's complex care needs, including attention to other chronic illnesses, mental illnesses, and preventive services. Expert responses highlighted that different treatment approaches across a continuum of healthcare settings are complementary.
Conclusions: Responses to this vignette support the need to address tobacco use from an interdisciplinary approach. Existing chronic care and patient-centred models should be utilised to ensure that tobacco users receive a sufficient range of cessation services.
A scalable approach for synthesis of ultra-thin (<10 nm) transition metal dichalcogenides (TMD) films on stretchable polymeric materials is presented. Specifically, magnetron sputtering from pure TMD targets, such as MoS2 and WS2, was used for growth of amorphous precursor films at room temperature on polydimethylsiloxane substrates. Stacks of different TMD films were grown upon each other and integrated with optically transparent insulating layers such as boron nitride. These precursor films were subsequently laser annealed to form high quality, few-layer crystalline TMDs. This combination of sputtering and laser annealing is commercially scalable and lends itself well to patterning. Analysis by Raman spectroscopy, scanning probe, optical, and transmission electron microscopy, and x-ray photoelectron spectroscopy confirm our assertions and illustrate annealing mechanisms. Electrical properties of simple devices built on flexible substrates are correlated to annealing processes. This new approach is a significant step toward commercial-scale stretchable 2D heterostructured nanoelectronic devices.
Depression can adversely affect employment status.
To examine whether there is a relative advantage of cognitive therapy or
antidepressant medication in improving employment status following
treatment, using data from a previously reported trial.
Random assignment to cognitive therapy (n = 48) or the
selective serotonin reuptake inhibitor paroxetine (n =
93) for 4 months; treatment responders were followed for up to 24 months.
Differential effects of treatment on employment status were examined.
At the end of 28 months, cognitive therapy led to higher rates of
full-time employment (88.9%) than did antidepressant medication among
treatment responders (70.8%), χ21 = 5.78, P = 0.02, odds ratio (OR) = 5.66,
95% CI 1.16–27.69. In the shorter-term, the main effect of treatment on
employment status was not significant following acute treatment
(χ21 = 1.74, P = 0.19, OR = 1.77, 95% CI
0.75–4.17); however, we observed a site×treatment interaction
(χ21 = 6.87, P = 0.009) whereby cognitive
therapy led to a higher rate of full-time employment at one site but not
at the other.
Cognitive therapy may produce greater improvements in employment
v. medication, particularly over the longer term.
Efforts to respond to performance-based accountability mandates for public health emergency preparedness have been hindered by a weak evidence base linking preparedness activities with response outcomes. We describe an approach to measure development that was successfully implemented in the Centers for Disease Control and Prevention Public Health Emergency Preparedness Cooperative Agreement. The approach leverages insights from process mapping and experts to guide measure selection, and provides mechanisms for reducing performance-irrelevant variation in measurement data. Also, issues are identified that need to be addressed to advance the science of measurement in public health emergency preparedness.
The Briar Creek Bonebed (Artinskian, Nocona Formation) in Archer County is one of the richest sources of Dimetrodon bones in the Lower Permian of Texas, USA. Based on size, a small (D. natalis), an intermediate (D. booneorum), and a large species (D. limbatus) have been described from this locality. It has been proposed that these traditionally recognised species represent an ontogenetic series of only one species. However, the ontogenetic series hypothesis is inconsistent with the late ontogenetic state of the small bones, as suggested by their osteology and degree of ossification. Histological analysis of newly excavated material from the Briar Creek Bonebed has resolved some of the discretion between these two competing hypothesis, confirming the coexistence of a small (D. natalis) with at least one larger Dimetrodon species. An external fundamental system is present in the largest sampled long bones identified as D. natalis. The histology of D. natalis postcrania is described as incipient fibro lamellar bone. This tissue is a combination of parallel-fibred and woven-fibred bone that is highly vascularised by incipient primary osteons. The species status of D. booneorum and D. limbatus remain unresolved.
This study examined therapist–patient interactions during clinical management with antidepressant medication and pill-placebo.
The sample consisted of 80 patients on active medication and 40 patients in a pill-placebo condition from a randomized controlled trial for moderate to severe depression. Pharmacotherapist–patient interactions were characterized using observer ratings of the therapeutic alliance, pharmacotherapist-offered facilitative conditions, pharmacotherapist adherence to clinical management treatment guidelines and pharmacotherapist competence. Patients, therapists and raters were blind to treatment condition and outcome.
Provision of greater non-specific support (facilitative conditions) in early sessions predicted less subsequent improvement in depressive symptoms for patients receiving pill-placebo but not those receiving active medications, for which none of the process ratings predicted subsequent change. Early symptom change predicted later alliance and adherence in both conditions and therapist competence in the active condition.
Higher levels of support in early sessions predict poorer subsequent response among placebo patients. It remains unclear whether patients who are likely to be refractory elicit greater non-specific support or whether the provision of such support has a deleterious effect in unmedicated patients. Differences in treatment process variables between conditions late in treatment are likely to be largely a consequence of symptom relief produced by active medications.
Introduction: Concomitant psychotropic medication (CPM) treatment is common in persons with major depression (MDD). However, relationships with patient characteristics and response to treatment are unclear.
Methods: Participants with nonpsychotic MDD (N=2682) were treated with citalopram, 20–60 mg/day. Sociodemographic, clinical, and treatment outcome characteristics were compared between those using CPMs at study entry or during up to 14 weeks of citalopram treatment, and non-users.
Results: About 35% of participants used a CPM. Insomnia was the predominant indication (70.3%). CPM users were more likely to be seen in primary care settings (69.3% versus 30.7%), be white, of non-Hispanic ethnicity, married, and have a higher income, private insurance, and certain comorbid disorders. CPM users had greater depressive severity, poorer physical and mental functioning, and poorer quality of life than non-users. Response and remission rates were also lower. CPM users were more likely to achieve ≥50 mg/day of citalopram, to report greater side effect intensity, and to have serious adverse events, but less likely to be intolerant of citalopram.
Conclusion: CPMs are associated with greater illness burden, more Axis I comorbidities (especially anxiety disorders), and lower treatment effectiveness. This suggests that CPM use may identify a more difficult to treat population that needs more aggressive treatment.
Major depression (MDD) is a common and potentially life-threatening condition. Widespread neurobiological abnormalities suggest abnormalities in fundamental cellular mechanisms as possible physiological mediators. Cyclic AMP-dependent protein kinase [also known as protein kinase A (PKA)] and protein kinase C (PKC) are important components of intracellular signal transduction cascades that are linked to G-coupled receptors. Previous research using both human peripheral and post-mortem brain tissue specimens suggests that a subset of depressed patients exhibit reduced PKA and PKC activity, which has been associated with reduced levels of specific protein isoforms. Prior research also suggests that specific clinical phenotypes, particularly melancholia and suicide, may be particularly associated with low activity. This study examined PKA and PKC protein levels in human post-mortem brain tissue samples from persons with MDD (n=20) and age- and sex-matched controls (n=20). Specific PKA subunits and PKC isoforms were assessed using Western blot analysis in post-mortem samples from Brodmann area 10, which has been implicated in reinforcement and reward mechanisms. The MDD sample exhibited significantly lower protein expression of PKA regulatory Iα (RIα), PKA catalytic α (Cα) and Cβ, PKCβ1, and PKCε relative to controls. The melancholic subgroup showed low PKA RIα and PKA Cβ, while the portion of the MDD sample who died by suicide had low PKA RIα and PKA Cα. These data continue to support the significance of abnormalities of these two key kinases, and suggest linkages between molecular endophenotypes and specific clinical phenotypes.