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1.  Comparative Efficacy of Seven Psychotherapeutic Interventions for Patients with Depression: A Network Meta-Analysis 
PLoS Medicine  2013;10(5):e1001454.
Jürgen Barth and colleagues use network meta-analysis - a novel methodological approach - to reexamine the comparative efficacy of seven psychotherapeutic interventions for adults with depression.
Please see later in the article for the Editors' Summary
Previous meta-analyses comparing the efficacy of psychotherapeutic interventions for depression were clouded by a limited number of within-study treatment comparisons. This study used network meta-analysis, a novel methodological approach that integrates direct and indirect evidence from randomised controlled studies, to re-examine the comparative efficacy of seven psychotherapeutic interventions for adult depression.
Methods and Findings
We conducted systematic literature searches in PubMed, PsycINFO, and Embase up to November 2012, and identified additional studies through earlier meta-analyses and the references of included studies. We identified 198 studies, including 15,118 adult patients with depression, and coded moderator variables. Each of the seven psychotherapeutic interventions was superior to a waitlist control condition with moderate to large effects (range d = −0.62 to d = −0.92). Relative effects of different psychotherapeutic interventions on depressive symptoms were absent to small (range d = 0.01 to d = −0.30). Interpersonal therapy was significantly more effective than supportive therapy (d = −0.30, 95% credibility interval [CrI] [−0.54 to −0.05]). Moderator analysis showed that patient characteristics had no influence on treatment effects, but identified aspects of study quality and sample size as effect modifiers. Smaller effects were found in studies of at least moderate (Δd = 0.29 [−0.01 to 0.58]; p = 0.063) and large size (Δd = 0.33 [0.08 to 0.61]; p = 0.012) and those that had adequate outcome assessment (Δd = 0.38 [−0.06 to 0.87]; p = 0.100). Stepwise restriction of analyses by sample size showed robust effects for cognitive-behavioural therapy, interpersonal therapy, and problem-solving therapy (all d>0.46) compared to waitlist. Empirical evidence from large studies was unavailable or limited for other psychotherapeutic interventions.
Overall our results are consistent with the notion that different psychotherapeutic interventions for depression have comparable benefits. However, the robustness of the evidence varies considerably between different psychotherapeutic treatments.
Please see later in the article for the Editors' Summary
Editors' Summary
Depression is a very common condition. One in six people will experience depression at some time during their life. People who are depressed have recurrent feelings of sadness and hopelessness and might feel that life is no longer worth living. The condition can last for months and often includes physical symptoms such as headaches, sleeping problems, and weight gain or loss. Treatment of depression can include non-drug treatments (psychotherapy), antidepressant drugs, or a combination of the two. Especially for people with mild or intermediate depression, psychotherapy is often considered the preferred first option. Psychotherapy describes a range of different psychotherapies, and a number of established types of psychotherapies have all shown to work for at least some patients.
Why Was This Study Done?
While it is broadly accepted that psychotherapy can help people with depression, the question of which type of psychotherapy works best for most patients remains controversial. While many scientific studies have compared one psychotherapy with control conditions, there have been few studies that directly compared multiple treatments. Without such direct comparisons, it has been difficult to establish the respective merits of the different types of psychotherapy. Taking advantage of a recently developed method called “network meta-analysis,” the authors re-examine the evidence on seven different types of psychotherapy to see how well they have been shown to work and whether some work better than others.
What Did the Researchers Do and Find?
The researchers looked at seven different types of psychotherapy, which they defined as follows. “Interpersonal psychotherapy” is short and highly structured, using a manual to focus on interpersonal issues in depression. “Behavioral activation” raises the awareness of pleasant activities and seeks to increase positive interactions between the patient and his or her environment. “Cognitive behavioral therapy” focuses on a patient's current negative beliefs, evaluates how they affect current and future behavior, and attempts to restructure the beliefs and change the outlook. “Problem solving therapy” aims to define a patient's problems, propose multiple solutions for each problem, and then select, implement, and evaluate the best solution. “Psychodynamic therapy” focuses on past unresolved conflicts and relationships and the impact they have on a patient's current situation. In “social skills therapy,” patients are taught skills that help to build and maintain healthy relationships based on honesty and respect. “Supportive counseling” is a more general therapy that aims to get patients to talk about their experiences and emotions and to offer empathy without suggesting solutions or teaching new skills.
The researchers started with a systematic search of the medical literature for relevant studies. The search identified 198 articles that reported on such clinical trials. The trials included a total of 15,118 patients and compared one of the seven psychotherapies either with another one or with a common “control intervention”. In most cases, the control (no psychotherapy) was deferral of treatment by “wait-listing” patients or continuing “usual care.” With network meta-analysis they were able to summarize the results of all these trials in a meaningful way. They did this by integrating direct comparisons of several psychotherapies within the same trial (where those were available) with indirect comparisons across all trials (using no psychotherapy as a control intervention).
Based on the combined trial results, all seven psychotherapies tested were better than wait-listing or usual care, and the differences were moderate to large, meaning that the average person in the group that received therapy was better off than about half of the patients in the control group. When comparing the therapies with each other, the researchers saw small or no differences, meaning that none of them really stood out as much better or much worse than the others. They also found that the treatments worked equally well for different patient groups with depression (younger or older patients, or mothers who had depression after having given birth). Similarly, they saw no big differences when comparing individual with group therapy, or person-to-person with internet-based interactions between therapist and patient.
However, they did find that smaller and less rigorous studies generally found larger benefits of psychotherapies, and most of the studies included in the analysis were small. Only 36 of the studies had at least 50 patients who received the same treatment. When they restricted their analysis to those studies, the researchers still saw clear benefits of cognitive-behavioral therapy, interpersonal therapy, and problem-solving therapy, but not for the other four therapies.
What Do these Findings Mean?
Similar to earlier attempts to summarize and make sense of the many study results, this one finds benefits for all of the seven psychotherapies examined, and none of them stood as being much better than some or all others. The scientific support for being beneficial was stronger for some therapies, mostly because they had been tested more often and in larger studies.
Treatments with proven benefits still do not necessarily work for all patients, and which type of psychotherapy might work best for a particular patient likely depends on that individual. So overall this analysis suggests that patients with depression and their doctors should consider psychotherapies and explore which of the different types might be best suited for a particular patient.
The study also points to the need for further research. Whereas depression affects large numbers of people around the world, all of the trials identified were conducted in rich countries and Western societies. Trials in different settings are essential to inform treatment of patients worldwide. In addition, large high-quality studies should further explore the potential benefits of some of therapies for which less support currently exists. Where possible, future studies should compare psychotherapies with one another, because all of them have benefits, and it would not be ethical to withhold such beneficial treatment from patients.
Additional Information
Please access these Web sites via the online version of this summary at
The US National Institute of Mental Health provides information on all aspects of depression (in English and Spanish); information on psychotherapy includes information on its most common forms
The UK National Health Service Choices website also provides detailed information about depression and includes personal stories about depression
The UK nonprofit Mind provides information on depression, including an explanation of the most common psychotherapies in the UK
MedlinePlus provides links to other resources about depression (in English and Spanish)
The UK nonprofit has a unique database of personal and patient experiences on depression
PMCID: PMC3665892  PMID: 23723742
2.  Crisis intervention for people with severe mental illnesses 
A particularly difficult challenge for community treatment of people with serious mental illnesses is the delivery of an acceptable level of care during the acute phases of severe mental illness. Crisis intervention models of care were developed as a possible solution.
To review the effects of crisis intervention models for anyone with serious mental illness experiencing an acute episode, compared with ‘standard care’.
Search methods
We updated the 1998, 2003 and 2006 searches with a search of the Cochrane Schizophrenia Group’s Register of trials (2010) which is based on regular searches of CINAHL, EMBASE, MEDLINE, and PsycINFO.
Selection criteria
We included all randomised controlled trials of crisis intervention models versus standard care for people with severe mental illnesses.
Data collection and analysis
We independently extracted data from these trials and we estimated risk ratios (RR) or mean differences (MD), with 95% confidence intervals (CI). We assumed that people who left early from a trial had no improvement.
Main results
Three new studies have been found since the last review in 2006 to add to the five studies already included in this review. None of the previously included studies investigated crisis intervention alone; all used a form of home care for acutely ill people, which included elements of crisis intervention. However, one of the new studies focuses purely on crisis intervention as provided by Crisis Resolution Home Teams within the UK; the two other new studies investigated crisis houses i.e. residential alternatives to hospitalisation providing home-like environments.
Crisis intervention appears to reduce repeat admissions to hospital after the initial ‘index’ crises investigated in the included studies, this was particularly so for mobile crisis teams supporting patients in their own homes.
Crisis intervention reduces the number of people leaving the study early, reduces family burden, is a more satisfactory form of care for both patients and families and at three months after crisis, mental state is superior to standard care. We found no differences in death outcomes. Some studies found crisis interventions to be more cost effective than hospital care but all numerical data were either skewed or unusable. No data on staff satisfaction, carer input, complications with medication or number of relapses were available.
Authors’ conclusions
Care based on crisis intervention principles, with or without an ongoing home care package, appears to be a viable and acceptable way of treating people with serious mental illnesses. If this approach is to be widely implemented it would seem that more evaluative studies are still needed.
PMCID: PMC4204394  PMID: 22592673
Caregivers [psychology]; Crisis Intervention [*methods]; Mental Disorders [psychology; *therapy]; Randomized Controlled Trials as Topic; Humans
3.  A Multirater Instrument for the Assessment of Simulated Pediatric Crises 
Few validated instruments exist to measure pediatric code team skills. The goal of this study was to develop an instrument for the assessment of resuscitation competency and self-appraisal using multirater and gap analysis methodologies.
Multirater assessment with gap analysis is a robust methodology that enables the measurement of self-appraisal as well as competency, offering faculty the ability to provide enhanced feedback. The Team Performance during Simulated Crises Instrument (TPDSCI) was grounded in the Accreditation Council for Graduate Medical Education competencies. The instrument contains 5 competencies, each assessed by a series of descriptive rubrics. It was piloted during a series of simulation-based interdisciplinary pediatric crisis resource management education sessions. Course faculty assessed participants, who also did self-assessments. Internal consistency and interrater reliability were analyzed using Cronbach α and intraclass correlation (ICC) statistics. Gap analysis results were examined descriptively.
Cronbach α for the instrument was between 0.72 and 0.69. The overall ICC was 0.82. ICC values for the medical knowledge, clinical skills, communication skills, and systems-based practice were between 0.87 and 0.72. The ICC for the professionalism domain was 0.22. Further examination of the professionalism competency revealed a positive skew, 43 simulated sessions (98%) had significant gaps for at least one of the competencies, 38 sessions (86%) had gaps indicating self-overappraisal, and 15 sessions (34%) had gaps indicating self-underappraisal.
The TPDSCI possesses good measures of internal consistency and interrater reliability with respect to medical knowledge, clinical skills, communication skills, systems-based practice, and overall competence in the context of simulated interdisciplinary pediatric medical crises. Professionalism remains difficult to assess. These results provide an encouraging first step toward instrument validation. Gap analysis reveals disparities between faculty and self-assessments that indicate inadequate participant self-reflection. Identifying self-overappraisal can facilitate focused interventions.
PMCID: PMC3186273  PMID: 22379528
4.  Repetitive Transcranial Magnetic Stimulation for the Treatment of Major Depressive Disorder 
Executive Summary
This review was conducted to assess the effectiveness of repetitive transcranial magnetic stimulation (rTMS) in the treatment of major depressive disorder (MDD).
The Technology
rTMS is a noninvasive way to stimulate nerve cells in areas of the brain. During rTMS, an electrical current passes through a wire coil placed over the scalp. The current induces a magnetic field that produces an electrical field in the brain that then causes nerve cells to depolarize, resulting in the stimulation or disruption of brain activity.
Researchers have investigated rTMS as an option to treat MDD, as an add-on to drug therapy, and, in particular, as an alternative to electroconvulsive therapy (ECT) for patients with treatment-resistant depression.
The advantages of rTMS over ECT for patients with severe refractory depression are that general anesthesia is not needed, it is an outpatient procedure, it requires less energy, the simulation is specific and targeted, and convulsion is not required. The advantages of rTMS as an add-on treatment to drug therapy may include hastening of the clinical response when used with antidepressant drugs.
Review Strategy
The Medical Advisory Secretariat used its standard search strategy to locate international health technology assessments and English-language journal articles published from January 1996 to March 2004.
Summary of Findings
Some early meta-analyses suggested rTMS might be effective for the treatment of MDD (for treatment-resistant MDD and as an add-on treatment to drug therapy for patients not specifically defined as treatment resistant). There were, however, several crucial methodological limitations in the included studies that were not critically assessed. These are discussed below.
Recent meta-analyses (including 2 international health technology assessments) have done evidence-based critical analyses of studies that have assessed rTMS for MDD. The 2 most recent health technology assessments (from the Oxford Cochrane Collaboration and the Norwegian Centre for Health Technology Assessment) concluded that there is no evidence that rTMS is effective for the treatment of MDD, either as compared with a placebo for patients with treatment-resistant or nontreatment-resistant MDD, or as an alternative to ECT for patients with treatment-resistant MDD. This mainly due to the poor quality of the studies.
The major methodological limitations were identified in older meta-analyses, recent health technology assessments, and the most recently published trials (Level 2–4 evidence) on the effectiveness of rTMS for MDD are discussed below.
Small sample size was a limitation acknowledged by many of the authors. There was also a lack of a priori sample size calculation or justification.
Biased randomization may have been a problem. Generally, the published reports lacked detailed information on the method of allocation concealment used. This is important because it is impossible to determine if there was a possible influence (direct or indirect) in the allocation of the patients to different treatment groups.
The trials were single blind, evaluated by external blinded assessors, rather than double blind. Double blinding is more robust, because neither the participants nor the investigators know which participants are receiving the active treatment and which are getting a placebo. Those administering rTMS, however, cannot be blinded to whether they are administering the active treatment or a placebo.
There was patient variability among the studies. In some studies, the authors said that patients were “medication resistant,” but the definitions of resistant, if provided, were inconsistent or unclear. For example, some described “medication resistant” as failing at least one trial of drugs during the current depressive episode. Furthermore, it was unclear if the term “medication resistant” referred to antidepressants only or to combinations of antidepressants and other drug augmentation strategies (such as neuroleptics, benzodiazepine, carbamazepine, and lithium). Also variable was the type of depression (i.e., unipolar and/or bipolar), if patients were inpatients or outpatients, if they had psychotic symptoms or no psychotic symptoms, and the chronicity of depression.
Dropouts or withdrawals were a concern. Some studies reported that patients dropped out, but provided no further details. Intent-to-treat analysis was not done in any of the trials. This is important, because ignoring patients who drop out of a trial can bias the results, usually in favour of the treatment. This is because patients who withdraw from trials are less likely to have had the treatment, more likely to have missed their interim checkups, and more likely to have experienced adverse effects when taking the treatment, compared with patients who do not withdraw. (1)
Measurement of treatment outcomes using scales or inventories makes interpreting results and drawing conclusions difficult. The most common scale, the Hamilton Depression Rating Scale (HDRS) is based on a semistructured interview. Some authors (2) reported that rating scales based on semistructured interviews are more susceptible to observation bias than are self-administered questionnaires such as the Beck Depression Inventory (BDI). Martin et al. (3) argued that the lack of consistency in effect as determined by the 2 scales (a positive result after 2 weeks of treatment as measured by the HDRS and a negative result for the BDI) makes definitive conclusions about the nature of the change in mood of patients impossible. It was suggested that because of difficulties interpreting results from psychometric scales, (4) and the subjective or unstable character of MDD, other, more objective, outcome measures such as readmission to hospital, time to hospital discharge, time to adjunctive treatment, and time off work should be used to assess rTMS for the treatment of depression.
A placebo effect could have influenced the results. Many studies reported response rates for patients who received placebo treatment. For example, Klein et al. (5) reported a control group response rate as high as 25%. Patients receiving placebo rTMS may receive a small dose of magnetic energy that may alter their depression.
Short-term studies were the most common. Patients received rTMS treatment for 1 to 2 weeks. Most studies followed-up patients for 2 to 4 weeks post-treatment. Dannon et al. (6) followed-up patients who responded to a course of ECT or rTMS for up to 6 months; however, the assessment procedure was not blinded, the medication regimen during follow-up was not controlled, and initial baseline data for the patient groups were not reported. The long-term effectiveness of rTMS for the treatment of depression is unknown, as is the long-term use, if any, of maintenance therapy. The cost-effectiveness of rTMS for the treatment of depression is also unknown. A lack of long-term studies makes cost-effectiveness analysis difficult.
The complexity of possible combinations for administering rTMS makes comparing like with like difficult. Wasserman and Lisanby (7) have said that the method for precisely targeting the stimulation in this area is unreliable. It is unknown if the left dorsolateral prefrontal cortex is the optimal location for treatment. Further, differences in rTMS administration include number of trains per session, duration of each train, and motor threshold.
Clinical versus statistical significance. Several meta-analyses and studies have found that the degree of therapeutic change associated with rTMS across studies is relatively modest; that is, results may be statistically, but not necessarily clinically, significant. (8-11). Conventionally, a 50% reduction in the HDRS scores is commonly accepted as a clinically important reduction in depression. Although some studies have observed a statistically significant reduction in the depression rating, many have not shows the clinically significant reduction of 50% on the HDRS. (11-13) Therefore, few patients in these studies would meet the standard criteria for response. (9)
Clinical/methodological diversity and statistical heterogeneity. In the Norwegian health technology assessment, Aarre et al. (14) said that a formal meta-analysis was not feasible because the designs of the studies varied too much, particularly in how rTMS was administered and in the characteristics of the patients. They noted that the quality of the study designs was poor. The 12 studies that comprised the assessment had small samples, and highly variable inclusion criteria and study designs. The patients’ previous histories, diagnoses, treatment histories, and treatment settings were often insufficiently characterized. Furthermore, many studies reported that patients had treatment-resistant MDD, yet did not listclear criteria for the designation. Without this information, Aarre and colleagues suggested that the interpretation of the results is difficult and the generalizability of results is questionable. They concluded that rTMS cannot be recommended as a standard treatment for depression: “More, larger and more carefully designed studies are needed to demonstrate convincingly a clinically relevant effect of rTMS.”
In the Cochrane Collaboration systematic review, Martin et al. (3;15) said that the complexity of possible combinations for administering rTMS makes comparison of like versus like difficult. A statistical test for heterogeneity (chi-square test) examines if the observed treatment effects are more different from each other than one would expect due to random error (or chance) alone. (16) However, this statistical test must be interpreted with caution because it has low power in the (common) situation of a meta-analysis when the trials have small sample sizes or are few. This means that while a statistically significant result may indicate a problem with heterogeneity, a nonsignificant result must not be taken as evidence of no heterogeneity.
Despite not finding statistically significant heterogeneity, Martin et al. reported that the overall mean baseline depression values for the severity of depression were higher in the treatment group than in the placebo group. (3;15) Although these differences were not significant at the level of each study, they may have introduced potential bias into the meta-analysis of pooled data by accentuating the tendency for regression to the mean of the more extreme values. Individual patient data from all the studies were not available; therefore, an appropriate adjustment according to baseline severity was not possible. Martin et al. concluded that the findings from the systematic review and meta-analysis provided insufficient evidence to suggest that rTMS is effective in the treatment of depression. Moreover, there were several confounding factors (e.g., definition of treatment resistance) in the studies, thus the authors concluded, “The rTMS technique needs more high quality trials to show its effectiveness for therapeutic use.”
Due to several serious methodological limitations in the studies that have examined the effectiveness of rTMS in patients with MDD, it is not possible to conclude that rTMS either is or is not effective as a treatment for MDD (in treatment-resistant depression or in nontreatment-resistant depression).
PMCID: PMC3387754  PMID: 23074457
5.  Twitter in the Cross Fire—The Use of Social Media in the Westgate Mall Terror Attack in Kenya 
PLoS ONE  2014;9(8):e104136.
On September 2013 an attack on the Westgate mall in Kenya led to a four day siege, resulting in 67 fatalities and 175 wounded. During the crisis, Twitter became a crucial channel of communication between the government, emergency responders and the public, facilitating the emergency management of the event. The objectives of this paper are to present the main activities, use patterns and lessons learned from the use of the social media in the crisis. Using TwitterMate, a system developed to collect, store and analyze tweets, the main hashtags generated by the crowd and specific Twitter accounts of individuals, emergency responders and NGOs, were followed throughout the four day siege. A total of 67,849 tweets were collected and analyzed. Four main categories of hashtags were identified: geographical locations, terror attack, social support and organizations. The abundance of Twitter accounts providing official information made it difficult to synchronize and follow the flow of information. Many organizations posted simultaneously, by their manager and by the organization itself. Creating situational awareness was facilitated by information tweeted by the public. Threat assessment was updated through the information posted on social media. Security breaches led to the relay of sensitive data. At times, misinformation was only corrected after two days. Social media offer an accessible, widely available means for a bi-directional flow of information between the public and the authorities. In the crisis, all emergency responders used and leveraged social media networks for communicating both with the public and among themselves. A standard operating procedure should be developed to enable multiple responders to monitor, synchronize and integrate their social media feeds during emergencies. This will lead to better utilization and optimization of social media resources during crises, providing clear guidelines for communications and a hierarchy for dispersing information to the public and among responding organizations.
PMCID: PMC4143241  PMID: 25153889
6.  Early intervention for psychosis 
Proponents of early intervention have argued that outcomes might be improved if more therapeutic efforts were focused on the early stages of schizophrenia or on people with prodromal symptoms. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection, and phase-specific treatment (phase-specific treatment is a psychological, social or physical treatment developed, or modified, specifically for use with people at an early stage of the illness).
Early detection and phase-specific treatment may both be offered as supplements to standard care, or may be provided through a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia.
To evaluate the effects of: (a) early detection; (b) phase-specific treatments; and (c) specialised early intervention teams in the treatment of people with prodromal symptoms or first-episode psychosis.
Search methods
We searched the Cochrane Schizophrenia Group Trials Register (March 2009), inspected reference lists of all identified trials and reviews and contacted experts in the field.
Selection criteria
We included all randomised controlled trials (RCTs) designed to prevent progression to psychosis in people showing prodromal symptoms, or to improve outcome for people with first-episode psychosis. Eligible interventions, alone and in combination, included: early detection, phase-specific treatments, and care from specialised early intervention teams. We accepted cluster-randomised trials but excluded non-randomised trials.
Data collection and analysis
We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis (ITT).
Main results
Studies were diverse, mostly small, undertaken by pioneering researchers and with many methodological limitations (18 RCTs, total n=1808). Mostly, meta-analyses were inappropriate. For the six studies addressing prevention of psychosis for people with prodromal symptoms, olanzapine seemed of little benefit (n=60, 1 RCT, RR conversion to psychosis 0.58 CI 0.3 to 1.2), and cognitive behavioural therapy (CBT) equally so (n=60, 1 RCT, RR conversion to psychosis 0.50 CI 0.2 to 1.7). A risperidone plus CBT plus specialised team did have benefit over specialist team alone at six months (n=59, 1 RCT, RR conversion to psychosis 0.27 CI 0.1 to 0.9, NNT 4 CI 2 to 20), but this was not seen by 12 months (n=59, 1 RCT, RR 0.54 CI 0.2 to 1.3). Omega 3 fatty acids (EPA) had advantage over placebo (n=76, 1 RCT, RR transition to psychosis 0.13 CI 0.02 to 1.0, NNT 6 CI 5 to 96). We know of no replications of this finding.
The remaining trials aimed to improve outcome in first-episode psychosis. Phase-specific CBT for suicidality seemed to have little effect, but the single study was small (n=56, 1 RCT, RR suicide 0.81 CI 0.05 to 12.26). Family therapy plus a specialised team in the Netherlands did not clearly affect relapse (n=76, RR 1.05 CI 0.4 to 3.0), but without the specialised team in China it may (n=83, 1 RCT, RR admitted to hospital 0.28 CI 0.1 to 0.6, NNT 3 CI 2 to 6). The largest and highest quality study compared specialised team with standard care. Leaving the study early was reduced (n=547, 1 RCT, RR 0.59 CI 0.4 to 0.8, NNT 9 CI 6 to 18) and compliance with treatment improved (n=507, RR stopped treatment 0.20 CI 0.1 to 0.4, NNT 9 CI 8 to 12). The mean number of days spent in hospital at one year were not significantly different (n=507, WMD, −1.39 CI −2.8 to 0.1), neither were data for ‘Not hospitalised’ by five years (n=547, RR 1.05 CI 0.90 to 1.2). There were no significant differences in numbers ‘not living independently’ by one year (n=507, RR 0.55 CI 0.3 to 1.2). At five years significantly fewer participants in the treatment group were ‘not living independently’ (n=547, RR 0.42 CI 0.21 to 0.8, NNT 19 CI 14 to 62). When phase-specific treatment (CBT) was compared with befriending no significant differences emerged in the number of participants being hospitalised over the 12 months (n=62, 1 RCT, RR 1.08 CI 0.59 to 1.99).
Phase-specific treatment E-EPA oils suggested no benefit (n=80, 1 RCT, RR no response 0.90 CI 0.6 to 1.4) as did phase-specific treatment brief intervention (n=106, 1 RCT, RR admission 0.86 CI 0.4 to 1.7). Phase-specific ACE found no benefit but participants given vocational intervention were more likely to be employed (n=41, 1 RCT, RR 0.39 CI 0.21 to 0.7, NNT 2 CI 2 to 4). Phase-specific cannabis and psychosis therapy did not show benefit (n=47, RR cannabis use 1.30 CI 0.8 to 2.2) and crisis assessment did not reduce hospitalisation (n=98, RR 0.85 CI 0.6 to 1.3). Weight was unaffected by early behavioural intervention.
Authors’ conclusions
There is emerging, but as yet inconclusive evidence, to suggest that people in the prodrome of psychosis can be helped by some interventions. There is some support for specialised early intervention services, but further trials would be desirable, and there is a question of whether gains are maintained. There is some support for phase-specific treatment focused on employment and family therapy, but again, this needs replicating with larger and longer trials.
PMCID: PMC4163966  PMID: 21678345
*Psychotic Disorders [diagnosis; therapy]; *Schizophrenia [diagnosis; therapy]; Cognitive Therapy; Early Diagnosis; Randomized Controlled Trials as Topic; Suicidal Ideation; Time Factors; Humans
7.  Endovascular Repair of Descending Thoracic Aortic Aneurysm 
Executive Summary
To conduct an assessment on endovascular repair of descending thoracic aortic aneurysm (TAA).
Clinical Need
Aneurysm is the most common condition of the thoracic aorta requiring surgery. Aortic aneurysm is defined as a localized dilatation of the aorta. Most aneurysms of the thoracic aorta are asymptomatic and incidentally discovered. However, TAA tends to enlarge progressively and compress surrounding structures causing symptoms such as chest or back pain, dysphagia (difficulty swallowing), dyspnea (shortness of breath), cough, stridor (a harsh, high-pitched breath sound), and hoarseness. Significant aortic regurgitation causes symptoms of congestive heart failure. Embolization of the thrombus to the distal arterial circulation may occur and cause related symptoms. The aneurysm may eventually rupture and create a life-threatening condition.
The overall incidence rate of TAA is about 10 per 100,000 person-years. The descending aorta is involved in about 30% to 40% of these cases.
The prognosis of large untreated TAAs is poor, with a 3-year survival rate as low as 25%. Intervention is strongly recommended for any symptomatic TAA or any TAA that exceeds twice the diameter of a normal aorta or is 6 cm or larger. Open surgical treatment of TAA involves left thoracotomy and aortic graft replacement. Surgical treatment has been found to improve survival when compared with medical therapy. However, despite dramatic advances in surgical techniques for performing such complex operations, operative mortality from centres of excellence are between 8% and 20% for elective cases, and up to 50% in patients requiring emergency operations. In addition, survivors of open surgical repair of TAAs may suffer from severe complications. Postoperative or postprocedural complications of descending TAA repair include paraplegia, myocardial infarction, stroke, respiratory failure, renal failure, and intestinal ischemia.
The Technology
Endovascular aortic aneurysm repair (EVAR) using a stent graft, a procedure called endovascular stent-graft (ESG) placement, is a new alternative to the traditional surgical approach. It is less invasive, and initial results from several studies suggest that it may reduce mortality and morbidity associated with the repair of descending TAAs.
The goal in endovascular repair is to exclude the aneurysm from the systemic circulation and prevent it from rupturing, which is life-threatening. The endovascular placement of a stent graft eliminates the systemic pressure acting on the weakened wall of the aneurysm that may lead to the rupture. However, ESG placement has some specific complications, including endovascular leak (endoleak), graft migration, stent fracture, and mechanical damage to the access artery and aortic wall.
The Talent stent graft (manufactured by Medtronic Inc., Minneapolis, MN) is licensed in Canada for the treatment of patients with TAA (Class 4; licence 36552). The design of this device has evolved since its clinical introduction. The current version has a more flexible delivery catheter than did the original system. The prosthesis is composed of nitinol stents between thin layers of polyester graft material. Each stent is secured with oversewn sutures to prevent migration.
Review Strategy
To compare the effectiveness and cost-effectiveness of ESG placement in the treatment of TAAs with a conventional surgical approach
To summarize the safety profile and effectiveness of ESG placement in the treatment of descending TAAs
Measures of Effectiveness
Primary Outcome
Mortality rates (30-day and longer term)
Secondary Outcomes
Technical success rate of introducing a stent graft and exclusion of the aneurysm sac from systemic circulation
Rate of reintervention (through surgical or endovascular approach)
Measures of Safety
Complications were categorized into 2 classes:
Those specific to the ESG procedure, including rates of aneurysm rupture, endoleak, graft migration, stent fracture, and kinking; and
Those due to the intervention, either surgical or endovascular. These include paraplegia, stroke, cardiovascular events, respiratory failure, real insufficiency, and intestinal ischemia.
Inclusion Criteria
Studies comparing the clinical outcomes of ESG treatment with surgical approaches
Studies reporting on the safety and effectiveness of the ESG procedure for the treatment of descending TAAs
Exclusion Criteria
Studies investigating the clinical effectiveness of ESG placement for other conditions such as aortic dissection, aortic ulcer, and traumatic injuries of the thoracic aorta
Studies investigating the aneurysms of the ascending and the arch of the aorta
Studies using custom-made grafts
Literature Search
The Medical Advisory Secretariat searched The International Network of Agencies for Health Technology Assessment and the Cochrane Database of Systematic Reviews for health technology assessments. It also searched MEDLINE, EMBASE, Medline In-Process & Other Non-Indexed Citations, and Cochrane CENTRAL from January 1, 2000 to July 11, 2005 for studies on ESG procedures. The search was limited to English-language articles and human studies.
One health technology assessment from the United Kingdom was identified. This systematic review included all pathologies of the thoracic aorta; therefore, it did not match the inclusion criteria. The search yielded 435 citations; of these, 9 studies met inclusion criteria.
Summary of Findings
The results of a comparative study found that in-hospital mortality was not significantly different between ESG placement and surgery patients (2 [4.8%] for ESG vs. 6 [11.3%] for surgery).
Pooled data from case series with a mean follow-up ranging from 12 to 38 months showed a 30-day mortality and late mortality rate of 3.9% and 5.5%, respectively. These rates are lower than are those reported in the literature for surgical repair of TAA.
Case series showed that the most common cause of early death in patients undergoing endovascular repair is aortic rupture, and the most common causes of late death are cardiac events and aortoesophageal or aortobronchial fistula.
Technical Success Rate
Technical success rates reported by case series are 55% to 100% (100% and 94.4% in 2 studies with all elective cases, 89% in a study with 5% emergent cases, and 55% in a study with 42% emergent cases).
Surgical Reintervention
In the comparative study, 3 (7.1%) patients in the ESG group and 14 (26.5%) patients in the surgery group required surgical reintervention. In the ESG group, the reasons for surgical intervention were postoperative bleeding at the access site, paraplegia, and type 1 endoleak. In the surgical group, the reasons for surgery were duodenal perforation, persistent thoracic duct leakage, false aneurysm, and 11 cases of postoperative bleeding.
Pooled data from case series show that 9 (2.6%) patients required surgical intervention. The reasons for surgical intervention were endoleak (3 cases), aneurysm enlargement and suspected infection (1 case), aortic dissection (1 case), pseudoaneurysm of common femoral artery (1 case), evacuation of hematoma (1 case), graft migration (1 case), and injury to the access site (1 case).
Endovascular Revision
In the comparative study, 3 (7.1%) patients required endovascular revision due to persistent endoleak.
Pooled data from case series show that 19 (5.3%) patients required endovascular revision due to persistent endoleak.
Graft Migration
Two case series reported graft migration. In one study, 3 proximal and 4 component migrations were noted at 2-year follow-up (total of 5%). Another study reported 1 (3.7%) case of graft migration. Overall, the incidence of graft migration was 2.6%.
Aortic Rupture
In the comparative study, aortic rupture due to bare stent occurred in 1 case (2%). The pooled incidence of aortic rupture or dissection reported by case series was 1.4%.
Postprocedural Complications
In the comparative study, there were no statistically significant differences between the ESG and surgery groups in postprocedural complications, except for pneumonia. The rate of pneumonia was 9% for those who received an ESG and 28% for those who had surgery (P = .02). There were no cases of paraplegia in either group. The rate of other complications for ESG and surgery including stroke, cardiac, respiratory, and intestinal ischemia were all 5.1% for ESG placement and 10% for surgery. The rate for mild renal failure was 16% in the ESG group and 30% in the surgery group. The rate for severe renal failure was 11% for ESG placement and 10% for surgery.
Pooled data from case series show the following postprocedural complication rates in the ESG placement group: paraplegia (2.2%), stroke (3.9%), cardiac (2.9%), respiratory (8.7%), renal failure (2.8%), and intestinal ischemia (1%).
Time-Related Outcomes
The results of the comparative study show statistically significant differences between the ESG and surgery group for mean operative time (ESG, 2.7 hours; surgery, 5 hours), mean duration of intensive care unit stay (ESG, 11 days; surgery, 14 days), and mean length of hospital stay (ESG, 10 days; surgery, 30 days).
The mean duration of intensive care unit stay and hospital stay derived from case series is 1.6 and 7.8 days, respectively.
Ontario-Based Economic Analysis
In Ontario, the annual treatment figures for fiscal year 2004 include 17 cases of descending TAA repair procedures (source: Provincial Health Planning Database). Fourteen of these have been identified as “not ruptured” with a mean hospital length of stay of 9.23 days, and 3 cases have been identified as “ruptured,” with a mean hospital length of stay of 28 days. However, because one Canadian Classification of Health Interventions code was used for both procedures, it is not possible to determine how many were repaired with an EVAR procedure or with an open surgical procedure.
Hospitalization Costs
The current fiscal year forecast of in-hospital direct treatment costs for all in-province procedures of repair of descending TAAs is about $560,000 (Cdn). The forecast in-hospital total cost per year for in-province procedures is about $720,000 (Cdn). These costs include the device cost when the procedure is EVAR (source: Ontario Case Costing Initiative).
Professional (Ontario Health Insurance Plan) Costs
Professional costs per treated patient were calculated and include 2 preoperative thoracic surgery or EVAR consultations.
The professional costs of an EVAR include the fees paid to the surgeons, anesthetist, and surgical assistant (source: fee service codes). The procedure was calculated to take about 150 minutes.
The professional costs of an open surgical repair include the fees of the surgeon, anesthetist, and surgical assistant. Open surgical repair was estimated to take about 300 minutes.
Services provided by professionals in intensive care units were also taken into consideration, as were the costs of 2 postoperative consultations that the patients receive on average once they are discharged from the hospital. Therefore, total Ontario Health Insurance Plan costs per treated patient treated with EVAR are on average $2,956 (ruptured or not ruptured), as opposed to $5,824 for open surgical repair and $6,157 for open surgical repair when the aneurysm is ruptured.
Endovascular stent graft placement is a less invasive procedure for repair of TAA than is open surgical repair.
There is no high-quality evidence with long-term follow-up data to support the use of EVAR as the first choice of treatment for patients with TAA that are suitable candidates for surgical intervention.
However, short- and medium-term outcomes of ESG placement reported by several studies are satisfactory and comparable to surgical intervention; therefore, for patients at high risk of surgery, it is a practical option to consider. Short- and medium-term results show that the benefit of ESG placement over the surgical approach is a lower 30-day mortality and paraplegia rate; and shorter operative time, ICU stay, and hospital stay.
PMCID: PMC3382300  PMID: 23074469
8.  Optimum Methadone Compliance Testing 
Executive Summary
The objective of this analysis was to determine the diagnostic utility of oral fluid testing collected with the Intercept oral fluid collection device.
Clinical Need: Target Population and Condition
Opioids (opiates or narcotics) are a class of drugs derived from the opium poppy plant that typically relieve pain and produce a euphoric feeling. Methadone is a long-acting synthetic opioid used to treat opioid dependence and chronic pain. It prevents symptoms of opioid withdrawal, reduces opioid cravings and blocks the euphoric effects of short-acting opioids such as heroin and morphine. Opioid dependence is associated with harms including an increased risk of exposure to Human Immunodeficiency Virus and Hepatitis C as well as other health, social and psychological crises. The goal of methadone treatment is harm reduction. Treatment with methadone for opioid dependence is often a long-term therapy. The Ontario College of Physicians and Surgeons estimates that there are currently 250 physicians qualified to prescribe methadone, and 15,500 people in methadone maintenance programs across Ontario.
Drug testing is a clinical tool whose purpose is to provide objective meaningful information, which will reinforce positive behavioral changes in patients and guide further treatment needs. Such information includes knowledge of whether the patient is taking their methadone as prescribed and reducing or abstaining from using opioid and other drugs of abuse use. The results of drug testing can be used with behavior modification techniques (contingency management techniques) where positive reinforcements such as increased methadone take-home privileges, sustained employment or parole are granted for drug screens negative for opioid use, and negative reinforcement including loss of these privileges for drug screens positive for opioid used.
Body fluids including blood, oral fluid, often referred to as saliva, and urine may contain metabolites and the parent drug of both methadone and drugs of abuse and provide a means for drug testing. Compared with blood which has a widow of detection of several hours, urine has a wider window of detection, approximately 1 to 3 days, and is therefore considered more useful than blood for drug testing. Because of this, and the fact that obtaining a urine specimen is relatively easy, urine drug screening is considered the criterion measure (gold standard) for methadone maintenance monitoring. However, 2 main concerns exist with urine specimens: the possibility of sample tampering by the patient and the necessity for observed urine collection. Urine specimens may be tampered with in 3 ways: dilution, adulteration (contamination) with chemicals, and substitution (patient submits another persons urine specimen). To circumvent sample tampering the supervised collection of urine specimens is a common and recommended practice. However, it has been suggested that this practice may have negative effects including humiliation experienced by patient and staff, and may discourage patients from staying in treatment. Supervised urine specimen collection may also present an operational problem as staff must be available to provide same-sex supervision. Oral fluid testing has been proposed as a replacement for urine because it can be collected easily under direct supervision without infringement of privacy and reduces the likelihood of sample tampering. Generally, the results of oral fluid drug testing are similar to urine drug testing but there are some differences, such as lower concentrations of substances in oral fluid than urine, and some drugs remain detectable for longer periods of time in urine than oral fluid.
The Technology Being Reviewed
The Intercept Oral Specimen Collection Device (Ora-Sure Technologies, Bethlehem, PA) consists of an absorbent pad mounted on a plastic stick. The pad is coated with common salts. The absorbent pad is inserted into the mouth and placed between the cheek and gums for 3 minutes on average. The pad absorbs the oral fluid. After 3 minutes (range 2min-5 min) the collection device is removed from the mouth and the absorbent pad is placed in a small vial which contains 0.8mL of pH-balanced preservative, for transportation to a laboratory for analysis. It is recommended that the person undergoing oral fluid drug testing have nothing to eat or drink for a 10- minute period before the oral fluid specimen is collected. This will remove opportunity for adulteration. Likewise, it is recommended that the person be observed for the duration of the collection period to prevent adulteration of the specimen. An average of 0.4 mL of saliva can be collected. The specimen may be stored at 4C to 37C and tested within 21 days of collection (or within 6 weeks if frozen).
The oral fluid specimen must be analyzed in a laboratory setting. There is no point-of-care (POC) oral fluid test kit for drugs of abuse (other than for alcohol). In the laboratory the oral fluid is extracted from the vial after centrifugation and a screening test is completed to eliminate negative specimens. Similar to urinalysis, oral fluid specimens are analyzed first by enzyme immunoassay with positive specimens sent for confirmatory testing. Comparable cut-off values to urinalysis by enzyme immunoassay have been developed for oral fluids
Review Strategy
Research Question
What is the diagnostic utility of the Intercept oral specimen device?
Inclusion criteria:
Studies evaluating paired urine and oral fluid specimens from the same individual with the Intercept oral fluid collection device.
The population studied includes drug users.
Exclusion criteria:
Studies testing for marijuana (THC) only.
Sensitivity and Specificity of oral fluid testing compared to urinalysis for methadone (methadone metabolite), opiates, cocaine, benzodiazepines, and alcohol.
Quality of the Body of Evidence
The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was used to evaluate the overall quality of the body of evidence (defined as 1 or more studies) supporting the research questions explored in this systematic review. A description of the GRADE system is reported in Appendix 1.
Summary of Findings
A total of 854 potential citations were retrieved. After reviewing titles and abstracts, 2 met the inclusion and exclusion criteria. Two other relevant studies were found after corresponding with the author of the 2 studies retrieved from the literature search. Therefore a total of 4 published studies are included in this analysis. All 4 studies carried out by the same investigator meet the definition of Medical Advisory Secretariat level III (not a-randomized controlled trial with contemporaneous controls) study design. In each of the studies, paired urine and oral fluid specimens where obtained from drug users. Urine collection was not observed in the studies however, laboratory tests for pH and creatinine were used to determine the reliability of the specimen. Urine specimens thought to be diluted and unreliable were removed from the evaluation. Urinalysis was used as the criterion measurement for which to determine the sensitivity and specificity of oral fluid testing by the Intercept oral fluid device for opiates, benzodiazepines, cocaine and marijuana. Alcohol was not tested in any of the 4 studies. From these 4 studies, the following conclusions were drawn:
The evidence indicates that oral fluid testing with the Intercept oral fluid device has better specificity than sensitivity for opiates, benzodiazepines, cocaine and marijuana.
The sensitivity of oral fluids testing with the Intercept oral fluid device seems to be from best to worst: cocaine > benzodiazepines >opiates> marijuana.
The sensitivity and specificity for opiates of the Intercept oral fluid device ranges from 75 to 90% and 97- 100% respectively.
The consequences of opiate false-negatives by oral fluid testing with the Intercept oral fluid device need to be weighed against the disadvantages of urine testing, including invasion of privacy issues and adulteration and substitution of the urine specimen.
The window of detection is narrower for oral fluid drug testing than urinalysis and because of this oral fluid testing may best be applied in situations where there is suspected frequent drug use. When drug use is thought to be less frequent or remote, urinalysis may offer a wider (24-48 hours more than oral fluids) window of detection.
The narrow window of detection for oral fluid testing may mean more frequent testing is needed compared to urinalysis. This may increase the expense for drug testing in general.
POC oral fluid testing is not yet available and may limit the practical utility of this drug testing methodology. POC urinalysis by immunoassay is available.
The possible applications of oral fluid testing may include:
Because of its narrow window of detection compared to urinalysis oral fluid testing may best be used during periods of suspected frequent or recent drug use (within 24 hours of drug testing). This is not to say that oral fluid testing is superior to urinalysis during these time periods.
In situations where an observed urine specimen is difficult to obtain. This may include persons with “shy bladder syndrome” or with other urinary conditions limiting their ability to provide an observed urine specimen.
When the health of the patient would make urine testing unreliable (e,g., renal disease)
As an alternative drug testing method when urine specimen tampering practices are suspected to be affecting the reliability of the urinalysis test.
Possible limiting Factors to Diffusion of Oral Fluid Technology
No oral fluid POC test equivalent to onsite urine dips or POC analyzer reducing immediacy of results for patient care.
Currently, physicians get reimbursed directly for POC urinalysis. Oral fluid must be analyzed in a lab setting removing physician reimbursement, which is a source of program funding for many methadone clinics.
Small amount of oral fluid specimen obtained; repeat testing on same sample will be difficult.
Reliability of positive oral fluid methadone (parent drug) results may decrease because of possible contamination of oral cavity after ingestion of dose. Therefore high methadone levels may not be indicative of compliance with treatment. Oral fluid does not as yet test for methadone metabolite.
There currently is no licensed provincial laboratory that analyses oral fluid specimens.
2-ethylidene- 1,5-dimethyl-3,3-diphenylpyrrolidine
enzyme immunoassay
Enzyme Linked Immunosorbent Assay (ELISA),
Enzyme Multiplied Immunoassay Test (EMIT)
Gas chromatography
gas chromatography/mass spectrometry
High-performance liquid chromatography
Limit of Detection
Mass spectrometry
Methadone Maintenance Treatment
Oral fluid testing
Point of Care Testing
11-nor-delta-9-tetrhydrocannabinol-9-carboxylic acid
urine drug testing
PMCID: PMC3379523  PMID: 23074492
9.  Effect of sickle cell crises on glomerular filtration rate in children with sickle cell disease in Ilorin, Nigeria 
Indian Journal of Nephrology  2013;23(5):354-357.
Children with sickle cell disease (SCD) are plagued with incessant crises. There are few studies on the effect of sickle cell crises on renal function as determined by the glomerular filtration rate (GFR). This study was done to assess the effect of sickle cell crises on GFR during crises and after recovery into the steady state. GFR was assessed using the formula derived by Schwartz et al., for consecutive SCD patients aged between 3 and 18 years who came in crises and after recovery into the steady state. A total of 81 patients with a mean age of 9.95 ± 4.15 years in 81 episodes of crises met the inclusion criteria. Majority of the children (47) had vasooclusive crises, 19 had hyperhaemolytic crises, and 15 had features of both vasooclusive and hyperhaemolytic crises. The means value of GFR in ml/min/1.73 m2 rose from 81.09 ± 22.92 to 116.24 ± 22.11 subsequent to recovery from vasooclusive crises into the steady state, from 77.45 ± 18.48 to 99.54 ± 17.71 following recovery from hyperhaemolytic crises into the steady state and from 90.95 ± 17.53 to 114.01 ± 22.44 following recovery from crises with features of both vasooclusive and hyperhaemolytic crises with corresponding significant P values of 0.000, 0.001, and 0.004 respectively. The reduced GFR observed during vasooclusive and hyperhaemolytic crises improved significantly following recovery into the steady state.
PMCID: PMC3764710  PMID: 24049272
Glomerular filtration rate; schwartz formula; sickle cell crises; sickle cell disease
10.  Costs of treating patients with schizophrenia who have illness-related crisis events 
BMC Psychiatry  2008;8:72.
Relatively little is known about the relationship between psychosocial crises and treatment costs for persons with schizophrenia. This naturalistic prospective study assessed the association of recent crises with mental health treatment costs among persons receiving treatment for schizophrenia.
Data were drawn from a large multi-site, non-interventional study of schizophrenia patients in the United States, conducted between 1997 and 2003. Participants were treated at mental health treatment systems, including the Department of Veterans Affairs (VA) hospitals, community mental health centers, community and state hospitals, and university health care service systems. Total costs over a 1-year period for mental health services and component costs (psychiatric hospitalizations, antipsychotic medications, other psychotropic medications, day treatment, emergency psychiatric services, psychosocial/rehabilitation group therapy, individual therapy, medication management, and case management) were calculated for 1557 patients with complete medical information. Direct mental health treatment costs for patients who had experienced 1 or more of 5 recent crisis events were compared to propensity-matched samples of persons who had not experienced a crisis event. The 5 non-mutually exclusive crisis event subgroups were: suicide attempt in the past 4 weeks (n = 18), psychiatric hospitalization in the past 6 months (n = 240), arrest in the past 6 months (n = 56), violent behaviors in the past 4 weeks (n = 62), and diagnosis of a co-occurring substance use disorder (n = 413).
Across all 5 categories of crisis events, patients who had a recent crisis had higher average annual mental health treatment costs than patients in propensity-score matched comparison samples. Average annual mental health treatment costs were significantly higher for persons who attempted suicide ($46,024), followed by persons with psychiatric hospitalization in the past 6 months ($37,329), persons with prior arrests ($31,081), and persons with violent behaviors ($18,778). Total cost was not significantly higher for those with co-occurring substance use disorder ($19,034).
Recent crises, particularly suicide attempts, psychiatric hospitalizations, and criminal arrests, are predictive of higher mental health treatment costs in schizophrenia patients.
PMCID: PMC2533651  PMID: 18727831
11.  Efficacy of treatment for hyperglycemic crisis in elderly diabetic patients in a day hospital 
The purpose of this prospective cohort study was to compare the costs of day hospital (DH) care for hyperglycemic crisis in elderly diabetic patients with those of conventional hospitalization (CH). Secondary objectives were to compare these two clinical scenarios in terms of glycemic control, number of emergency and outpatient visits, readmissions, hypoglycemic episodes, and nosocomial morbidity.
The study population comprised diabetic patients aged >74 years consecutively admitted to a tertiary teaching hospital in Spain for hyperglycemic crisis (sustained hyperglycemia [>300 mg/dL] for at least 3 days with or without ketosis). The patients were assigned to DH or CH care according to time of admission and were followed for 6 months after discharge. Exclusion criteria were ketoacidosis, hyperosmolar crisis, hemodynamic instability, severe intercurrent illness, social deprivation, or Katz index >D.
Sixty-four diabetic patients on DH care and 36 on CH care were included, with no differences in baseline characteristics. The average cost per patient was 1,345.1±793.6 € in the DH group and 2,212.4±982.5 € in the CH group (P<0.001). There were no differences in number of subjects with mild hypoglycemia during follow-up (45.3% DH versus 33.3% CH, P=0.24), nor in the percentage of patients achieving a glycated hemoglobin (HbA1c) <8% (67.2% DH versus 58.3% CH, P=0.375). Readmissions for hyperglycemic crisis and pressure ulcer rates were significantly higher in the CH group.
DH care for hyperglycemic crises is more cost-effective than CH care, with a net saving of 1,418.4 € per case, lower number of readmissions and pressure ulcer rates, and similar short-term glycemic control and hypoglycemia rates.
PMCID: PMC4027922  PMID: 24868152
day hospital; conventional hospitalization; hyperglycemic crisis
12.  Health Technology Assessment of laparoscopic compared to conventional surgery with and without mesh for incisional hernia repair regarding safety, efficacy and cost-effectiveness 
Incisional hernias are a common complication following abdominal surgery and they represent about 80% of all ventral hernia. In uncomplicated postoperative follow-up they can develop in about eleven percent of cases and up to 23% of cases with wound infections or other forms of wound complications. Localisation and size of the incisional hernia can vary according to the causal abdominal scar. Conservative treatment (e. g. weight reduction) is only available to relieve symptoms while operative treatments are the only therapeutic treatment option for incisional hernia. Traditionally, open suture repair was used for incisional hernia repair but was associated with recurrence rates as high as 46%. To strengthen the abdominal wall and prevent the development of recurrences the additional implantation of an alloplastic mesh is nowadays commonly used. Conventional hernia surgery as well as minimally invasive surgery, introduced in the early 90s, make use of this mesh-technique and thereby showed marked reductions in recurrence rates. However, there are possible side effects associated with mesh-implantation. Therefore recommendations remain uncertain on which technique to apply for incisional hernia repair and which technique might, under specific circumstances, be associated with advantages over others.
The goal of this HTA-Report is to compare laparoscopic incisional hernia repair (LIHR) and conventional incisional hernia repair with and without mesh-implantation in terms of their medical efficacy and safety, their cost-effectiveness as well as their ethical, social und legal implications. In addition, this report aims to compare different techniques of mesh-implantation and mesh-fixation as well as to identify factors, in which certain techniques might be associated with advantages over
Relevant publications were identified by means of a structured search of databases accessed through the German Institute of Medical Documentation and Information (DIMDI) as well as by a manual search. The former included the following electronic resources:
SOMED (SM78), Cochrane Library – Central (CCTR93), MEDLINE Alert (ME0A), MEDLINE (ME95), CATFILEplus (CATLINE) (CA66), ETHMED (ED93), GeroLit (GE79), HECLINET (HN69), AMED (CB85), CAB Abstracts (CV72), GLOBAL Health (AZ72), IPA (IA70), Elsevier BIOBASE (EB94), BIOSIS Previews (BA93), EMBASE (EM95), EMBASE Alert (EA08), SciSearch (IS90), Cochrane Library – CDSR (CDSR93), NHS-CRD-DARE (CDAR94), NHS-CRD-HTA (INAHTA) as well as NHSEED (NHSEED).
The present report includes German and English literature published until 31.08.2005. The search parameters can be found in the appendix. No limits were placed on the target population. The methodological quality of the included clinical studies was assessed using the criteria recommended by the “Scottish Intercollegiate Guidelines Network Grading Review Group“. Economic studies were evaluated by the criteria of the German Scientific Working Group Technology Assessment for Health Care.
The literature search identified 17 relevant medical publications. One of these studies compared laparoscopic and conventional surgery with and without mesh for incisional hernia repair, while 16 studies compared laparoscopic and conventional surgery with mesh for incisional hernia repair. Among these studies were 14 primary studies (one randomised controlled trial (RCT), two systematic reviews and one HTA-Report. The only study comparing laparoscopic and conventional surgery without mesh found substantial differences in terms of baseline characteristics between treatment groups. The outcome parameters showed decreased recurrence rates for the laparoscopic repair and similar safety of the procedures. Studies comparing laparoscopic and conventional surgery with mesh found similar outcome in terms of medical efficacy and safety. However, there was a trend towards lower recurrence rates, length of hospital stay, and postoperative pain as well as decreased complication rates for laparoscopic repair in the majority of studies. The impact of the technique of mesh-implantation and -fixation as well as the impact of certain factors on the choice of technique has not been systematically assessed in any of the studies.
All identified studies suffer from significant methodological weaknesses, such as differences between treatment groups, mainly due to the non-randomised study design, small treatment groups causing low case numbers and lack of statistical power as well as the neglect of important risk factors or adjustment for those. Therefore, no conclusive differences could be identified concerning compared operative techniques, mesh-implantation and -fixation techniques or certain risk factors. Only the comparison of laparoscopic and conventional technique with mesh provides some evidence for a trend towards similar or slightly improved outcome in terms of medical efficacy and safety for the laparoscopic technique. However, there is still a great need for further research to investigate these questions.
Basically, there is no full economic evaluation focussing on the relevant alternatives. Cost compareisons were available, even though only briefly attached to clinical research results. None of the studies primarily aimed to investigate costs or even cost-effectiveness.
When deciding on the choice of operative technique for incisional hernia repair, surgeons take various considerations into account, including patient characteristics, hernia characteristics and their own experience. The studies included in this HTA did not provide conclusive evidence to answer the research questions. Nonetheless, laparoscopic surgery demonstrated a trend towards similar or slightly improved outcome following incisional hernia repair. However, for more conclusive recommendations on the choice of operative technique, high quality trials are required
From the economic perspective, alternative methods are not yet assessed. Only five of the studies involve a cost analysis, though in an insufficient manner. None of the studies identified were laid out as a health economic evaluation. Hence, further research is strongly recommended.
PMCID: PMC3011306  PMID: 21289907
13.  The Impact of Economic Crises on Communicable Disease Transmission and Control: A Systematic Review of the Evidence 
PLoS ONE  2011;6(6):e20724.
There is concern among public health professionals that the current economic downturn, initiated by the financial crisis that started in 2007, could precipitate the transmission of infectious diseases while also limiting capacity for control. Although studies have reviewed the potential effects of economic downturns on overall health, to our knowledge such an analysis has yet to be done focusing on infectious diseases. We performed a systematic literature review of studies examining changes in infectious disease burden subsequent to periods of crisis. The review identified 230 studies of which 37 met our inclusion criteria. Of these, 30 found evidence of worse infectious disease outcomes during recession, often resulting from higher rates of infectious contact under poorer living circumstances, worsened access to therapy, or poorer retention in treatment. The remaining studies found either reductions in infectious disease or no significant effect. Using the paradigm of the “SIR” (susceptible-infected-recovered) model of infectious disease transmission, we examined the implications of these findings for infectious disease transmission and control. Key susceptible groups include infants and the elderly. We identified certain high-risk groups, including migrants, homeless persons, and prison populations, as particularly vulnerable conduits of epidemics during situations of economic duress. We also observed that the long-term impacts of crises on infectious disease are not inevitable: considerable evidence suggests that the magnitude of effect depends critically on budgetary responses by governments. Like other emergencies and natural disasters, preparedness for financial crises should include consideration of consequences for communicable disease control.
PMCID: PMC3112201  PMID: 21695209
14.  The effects of crisis plans for patients with psychotic and bipolar disorders: a randomised controlled trial 
BMC Psychiatry  2009;9:41.
Crises and (involuntary) admissions have a strong impact on patients and their caregivers. In some countries, including the Netherlands, the number of crises and (involuntary) admissions have increased in the last years. There is also a lack of effective interventions to prevent their occurrence. Previous research has shown that a form of psychiatric advance statement – joint crisis plan – may prevent involuntary admissions, but another study showed no significant results for another form. The question remains which form of psychiatric advance statement may help to prevent crisis situations. This study examines the effects of two other psychiatric advance statements. The first is created by the patient with help from a patient's advocate (Patient Advocate Crisis Plan: PACP) and the second with the help of a clinician only (Clinician facilitated Crisis Plan: CCP). We investigate whether patients with a PACP or CCP show fewer emergency visits and (involuntary) admissions as compared to patients without a psychiatric advance statement. Furthermore, this study seeks to identify possible mechanisms responsible for the effects of a PACP or a CCP.
This study is a randomised controlled trial with two intervention groups and one control condition. Both interventions consist of a crisis plan, facilitated through the patient's advocate or the clinician respectively.
Outpatients with psychotic or bipolar disorders, who experienced at least one psychiatric crisis during the previous two years, are randomly allocated to one of the three groups. Primary outcomes are the number of emergency (after hour) visits, (involuntary) admissions and the length of stay in hospital. Secondary outcomes include psychosocial functioning and treatment satisfaction. The possible mediator variables of the effects of the crisis plans are investigated by assessing the patient's involvement in the creation of the crisis plan, working alliance, insight into illness, recovery style, social support, locus of control, service engagement and coping with crises situations. The interviews take place before randomisation, nine month later and finally eighteen months after randomisation.
This study examines the effects of two types of crisis plans. In addition, the results offer an understanding of the way these advance statements work and whether it is more effective to include a patients' advocate in the process of creating a psychiatric advance statement. These statements may be an intervention to prevent crises and the use of compulsion in mental health care. The strength and limitations of this study are discussed.
Trial registration
Current Controlled Trails NTR1166.
PMCID: PMC2716324  PMID: 19589145
To compare the correlation of intracranial pressure (ICP) measurement and time to detection of ICP crises (defined as ICP ≥ 20 mm Hg for ≥ 5 min) between an intraparenchymal (IP) monitor and external ventricular drain (EVD) in children where continuous cerebrospinal fluid (CSF) diversion was used as a therapy for severe traumatic brain injury (TBI).
Academic, pediatric intensive care unit.
Retrospective review of a prospectively-collected Pediatric Neurotrauma database.
Children with severe TBI (GCS ≤ 8) who underwent ICP monitoring with both IP and EVD techniques were studied. In Cohort 1 (n = 58), hourly ICP measurements were extracted from the medical record. In Cohort 2 (n = 4), ICP measurements were collected every minute by an automated data collection system.
Measurements and Main Results
The mean absolute difference in ICP (|ICP|) and intraclass correlation coefficients (ICC) were calculated. Timing to detection of ICP crises was analyzed. Data expressed as mean ± SEM. In cohort 1, 7,387 hours of data were analyzed and 399 hours (23,940 min) were analyzed in Cohort 2. In Cohort 1, |ICP| = 3.10 ± 0.04 mm Hg (ICC = 0.98, p < 0.001). |ICP| in Cohort 2 was 3.30 ± 0.05 mm Hg (ICC = 0.98, p < 0.001). In Cohort 2, a total of 75 ICP crises were observed. Fifty-five (73%) were detected first by the IP monitor, of which 35 were not identified by the EVD monitor. Time between IP and EVD detection of a crisis was 12.60 ± 2.34 min.
EVD and IP measurements of ICP were highly correlated, although intermittent EVD ICP measurements may fail to identify ICP events when continuously draining CSF. In institutions using continuous CSF diversion as a therapy, a two-monitor system may be valuable for accomplishing monitoring and therapeutic goals.
PMCID: PMC3670608  PMID: 20625341
16.  Does Bereavement-Related Major Depression Differ From Major Depression Associated With Other Stressful Life Events? 
The American journal of psychiatry  2008;165(11):1449-1455.
Of the stressful life events influencing risk for major depression, DSM-III and DSM-IV assign a special status to bereavement. A depressive episode that is bereavement-related and has clinical features and course characteristic of normal grief is not diagnosed as major depression. This study evaluates the empirical validity of this exclusion criterion.
To determine the similarities of bereavement-related depression and depression related to other stressful life events, the authors identified and compared cases on a range of validators in a large-population-based sample of twins. The authors evaluated whether cases of bereavement-related depression that also met DSM criteria for “normal grief” were qualitatively distinct from other depressive cases.
Eighty-two individuals with confirmed bereavement-related depression and 224 with confirmed depression related to other stressful life events were identified. The two groups did not differ in age at onset of major depression, number of prior episodes, duration of index episode, number of endorsed “A criteria,” risk for future episodes, pattern of comorbidity, levels of extraversion, risk for major depression in their co-twin, or the proportion meeting criteria for “normal grief.” However, individuals with bereavement-related depression were slightly older, and more likely to be female, and had lower levels of neuroticism, treatment-seeking, and guilt and higher levels of fatigue and loss of interest. Interaction analyses failed to find unique features of people whose illness met criteria for both bereavement-related depression and normal grief compared to those whose illness was related to other life stressors.
The similarities between bereavement-related depression and depression related to other stressful life events substantially outweigh their differences. These results question the validity of the bereavement exclusion for the diagnosis of major depression.
PMCID: PMC2743738  PMID: 18708488
17.  Challenges of the management of mass casualty: lessons learned from the Jos crisis of 2001 
Jos has witnessed a series of civil crises which have generated mass casualties that the Jos University Teaching Hospital has had to respond to from time to time. We review the challenges that we encountered in the management of the victims of the 2001 crisis.
We reviewed the findings of our debriefing sessions following the sectarian crisis of September 2001 and identified the challenges and obstacles experienced during these periods.
Communication was a major challenge, both within and outside the hospital. In the field, there was poor field triage and no prehospital care. Transportation and evacuation was hazardous, for both injured patients and medical personnel. This was worsened by the imposition of a curfew on the city and its environs. In the hospital, supplies such as fluids, emergency drugs, sterile dressings and instruments, splints, and other consumables, blood and food were soon exhausted. Record keeping was erratic. Staff began to show signs of physical and mental exhaustion as well as features of anxiety and stress. Tensions rose between different religious groups in the hospital and an attempt was made by rioters to attack the hospital. Patients suffered poor subsequent care following resuscitation and/or surgery and there was neglect of patients on admission prior to the crisis as well as non trauma medical emergencies.
Mass casualties from disasters that disrupt organized societal mechanisms for days can pose significant challenges to the best of institutional disaster response plans. In the situation that we experienced, our disaster plan was impractical initially because it failed to factor in such a prolongation of both crisis and response. We recommend that institutional disaster response plans should incorporate provisions for the challenges we have enumerated and factor in peculiarities that would emanate from the need for a prolonged response.
PMCID: PMC3819470  PMID: 24164778
Challenges; Crisis; Disaster; Mass casualty; Trauma
18.  A framework for assessing health system resilience in an economic crisis: Ireland as a test case 
The financial crisis that hit the global economy in 2007 was unprecedented in the post war era. In general the crisis has created a difficult environment for health systems globally. The purpose of this paper is to develop a framework for assessing the resilience of health systems in terms of how they have adjusted to economic crisis. Resilience can be understood as the capacity of a system to absorb change but continue to retain essentially the same identity and function. The Irish health system is used as a case study to assess the usefulness of this framework.
The authors identify three forms of resilience: financial, adaptive and transformatory. Indicators of performance are presented to allow for testing of the framework and measurement of system performance. Both quantitative and qualitative methods were used to yield data for the Irish case study. Quantitative data were collected from government documents and sources to understand the depth of the recession and the different dimensions of the response. Semi-structured interviews were conducted with key decision makers to understand the reasons for decisions made.
In the Irish case there is mixed evidence on resilience. Health funding was initially protected but was then followed by deep cuts as the crisis deepened. There is strong evidence for adaptive resilience, with the health system showing efficiency gains from the recession. Nevertheless, easy efficiencies have been made and continued austerity will mean cuts in entitlements and services. The prospects for building and maintaining transformatory resilience are unsure. While the direction of reform is clear, and has been preserved to date, it is not certain whether it will remain manageable given continued austerity, some loss of sovereignty and capacity limitations.
The three aspects of resilience proved a useful categorisation of performance measurement though there is overlap between them. Transformatory resilience may be more difficult to assess precisely. It would be useful to test out the framework against other country experiences and refine the measures and indicators. Further research on both the comparative resilience of different health systems and building resilience in preparation for crises is encouraged.
PMCID: PMC3816300  PMID: 24171814
Resilience; Health systems; Sustainability; Economic crisis; Ireland
19.  A Framework and Methodology for Navigating Disaster and Global Health in Crisis Literature 
PLoS Currents  2013;5:ecurrents.dis.9af6948e381dafdd3e877c441527cba0.
Both ‘disasters’ and ‘global health in crisis’ research has dramatically grown due to the ever-increasing frequency and magnitude of crises around the world. Large volumes of peer-reviewed literature are not only a testament to the field’s value and evolution, but also present an unprecedented outpouring of seemingly unmanageable information across a wide array of crises and disciplines. Disaster medicine, health and humanitarian assistance, global health and public health disaster literature all lie within the disaster and global health in crisis literature spectrum and are increasingly accepted as multidisciplinary and transdisciplinary disciplines. Researchers, policy makers, and practitioners now face a new challenge; that of accessing this expansive literature for decision-making and exploring new areas of research. Individuals are also reaching beyond the peer-reviewed environment to grey literature using search engines like Google Scholar to access policy documents, consensus reports and conference proceedings. What is needed is a method and mechanism with which to search and retrieve relevant articles from this expansive body of literature. This manuscript presents both a framework and workable process for a diverse group of users to navigate the growing peer-reviewed and grey disaster and global health in crises literature. Methods: Disaster terms from textbooks, peer-reviewed and grey literature were used to design a framework of thematic clusters and subject matter ‘nodes’. A set of 84 terms, selected from 143 curated terms was organized within each node reflecting topics within the disaster and global health in crisis literature. Terms were crossed with one another and the term ‘disaster’. The results were formatted into tables and matrices. This process created a roadmap of search terms that could be applied to the PubMed database. Each search in the matrix or table results in a listed number of articles. This process was applied to literature from PubMed from 2005-2011. A complementary process was also applied to Google Scholar using the same framework of clusters, nodes, and terms expanding the search process to include the broader grey literature assets. Results: A framework of four thematic clusters and twelve subject matter nodes were designed to capture diverse disaster and global health in crisis-related content. From 2005-2011 there were 18,660 articles referring to the term [disaster]. Restricting the search to human research, MeSH, and English language there remained 7,736 identified articles representing an unmanageable number to adequately process for research, policy or best practices. However, using the crossed search and matrix process revealed further examples of robust realms of research in disasters, emergency medicine, EMS, public health and global health. Examples of potential gaps in current peer-reviewed disaster and global health in crisis literature were identified as mental health, elderly care, and alternate sites of care. The same framework and process was then applied to Google Scholar, specifically for topics that resulted in few PubMed search returns. When applying the same framework and process to the Google Scholar example searches retrieved unique peer-reviewed articles not identified in PubMed and documents including books, governmental documents and consensus papers. Conclusions: The proposed framework, methodology and process using four clusters, twelve nodes and a matrix and table process applied to PubMed and Google Scholar unlocks otherwise inaccessible opportunities to better navigate the massively growing body of peer-reviewed disaster and global health in crises literature. This approach will assist researchers, policy makers, and practitioners to generate future research questions, report on the overall evolution of the disaster and global health in crisis field and further guide disaster planning, prevention, preparedness, mitigation response and recovery.
PMCID: PMC3625621  PMID: 23591457
20.  Treatment and outcomes of crisis resolution teams: a prospective multicentre study 
BMC Psychiatry  2011;11:183.
Crisis resolution teams (CRTs) aim to help patients in acute mental health crises without admitting them to hospital. The aims of this study were to investigate content of treatment, service practice, and outcomes of crises of CRTs in Norway.
The study had a multicentre prospective design, examining routine data for 680 patients and 62 staff members of eight CRTs. The clinical staff collected data on the demographic, clinical, and content of treatment variables. The service practices of the staff were assessed on the Community Program Practice Scale. Information on each CRT was recorded by the team leaders. The outcomes of crises were measured by the changes in Global Assessment of Functioning scale scores and the total scores on the Health of the Nation Outcome Scales between admission and discharge. Regression analysis was used to predict favourable outcomes.
The mean length of treatment was 19 days for the total sample (N = 680) and 29 days for the 455 patients with more than one consultation; 7.4% of the patients had had more than twice-weekly consultations with any member of the clinical staff of the CRTs. A doctor or psychologist participated in 55.5% of the treatment episodes. The CRTs collaborated with other mental health services in 71.5% of cases and with families/networks in 51.5% of cases. The overall outcomes of the crises were positive, with a small to medium effect size. Patients with depression received the longest treatments and showed most improvement of crisis. Patients with psychotic symptoms and substance abuse problems received the shortest treatments, showed least improvement, and were most often referred to other parts of the mental health services. Length of treatment, being male and single, and a team focus on out-of-office contact were predictors of favourable outcomes of crises in the adjusted model.
Our study indicates that, compared with the UK, the Norwegian CRTs provided less intensive and less out-of-office care. The Norwegian CRTs worked more with depression and suicidal crises than with psychoses. To be an alternative to hospital admission, the Norwegian CRTs need to intensify their treatment and meet more patients outside the office.
PMCID: PMC3258194  PMID: 22108030
21.  Defining urine output criterion for acute kidney injury in critically ill patients 
Background. The widespread use of RIFLE and AKIN classification systems for acute kidney injury (AKI) diagnosis and staging has established the association between AKI severity and adverse outcomes. However, as a result of the difficulties in measuring and recording the urine output every hour, a few prospective studies have validated the urine output criterion as stated in these classification systems. We assessed hourly urine output in ICU patients using an automated and accurate device to determine if changes in urine flow and volume could be a sensitive marker of AKI. Additionally, we assessed various definitions of oliguria to determine whether measurement of urine output using a fixed 6-h interval that matches nurses’ shifts would be equivalent to the current standard for AKI diagnosis and staging.
Methods. Hourly urine output was recorded continuously using a digital monitor in a medical ICU. Serum creatinine measurements were done at least once per 24 h. We assessed changes in urine output by four different definitions of oliguria. Patients with no AKI by either criterion were compared with patients diagnosed exclusively by the urine output criterion, exclusively by serum creatinine criterion and by both criteria.
Results. Fifty-five percent of patients had an episode of oliguria during the ICU stay. There was no significant difference assessing urine output every hour or the total urine volume in a 6-h period for the detection of episodes of oliguria. Twenty-one patients (28%) were diagnosed as AKI using the serum creatinine criterion, whereas additional 24 (32%) were identified by the urine output criterion.
Conclusions. Episodes of oliguria occur frequently in ICU patients and identify a higher percentage of AKI patients compared to serum creatinine criterion. Alterations in urine flow may be a sensitive marker of renal dysfunction and need to be validated in larger cohorts.
PMCID: PMC3108356  PMID: 20562094
acute kidney injury; clinical epidemiology; critically ill; oliguria; urine output
22.  Use of task-shifting to rapidly scale-up HIV treatment services: experiences from Lusaka, Zambia 
The World Health Organization advocates task-shifting, the process of delegating clinical care functions from more specialized to less specialized health workers, as a strategy to achieve the United Nations Millennium Development Goals. However, there is a dearth of literature describing task shifting in sub-Saharan Africa, where services for antiretroviral therapy (ART) have scaled up rapidly in the face of generalized human resource crises. As part of ART services expansion in Lusaka, Zambia, we implemented a comprehensive task-shifting program among existing health providers and community-based workers. Training begins with didactic sessions targeting specialized skill sets. This is followed by an intensive period of practical mentorship, where providers are paired with trainers before working independently. We provide on-going quality assessment using key indicators of clinical care quality at each site. Program performance is reviewed with clinic-based staff quarterly. When problems are identified, clinic staff members design and implement specific interventions to address targeted areas. From 2005 to 2007, we trained 516 health providers in adult HIV treatment; 270 in pediatric HIV treatment; 341 in adherence counseling; 91 in a specialty nurse "triage" course, and 93 in an intensive clinical mentorship program. On-going quality assessment demonstrated improvement across clinical care quality indicators, despite rapidly growing patient volumes. Our task-shifting strategy was designed to address current health care worker needs and to sustain ART scale-up activities. While this approach has been successful, long-term solutions to the human resource crisis are also urgently needed to expand the number of providers and to slow staff migration out of the region.
PMCID: PMC2628658  PMID: 19134202
23.  Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study 
Malignant hyperthermia (MH) is a rare pharmacogenetic disorder which is characterized by life-threatening metabolic crises during general anesthesia. Classical triggering substances are volatile anesthetics and succinylcholine (SCh). The molecular basis of MH is excessive release of Ca2+ in skeletal muscle principally by a mutated ryanodine receptor type 1 (RyR1). To identify factors explaining the variable phenotypic presentation and complex pathomechanism, we analyzed proven MH events in terms of clinical course, muscle contracture, genetic factors and pharmocological triggers.
In a multi-centre study including seven European MH units, patients with a history of a clinical MH episode confirmed by susceptible (MHS) or equivocal (MHE) in vitro contracture tests (IVCT) were investigated. A test result is considered to be MHE if the muscle specimens develop pathological contractures in response to only one of the two test substances, halothane or caffeine. Crises were evaluated using a clinical grading scale (CGS), results of IVCT and genetic screening. The effects of SCh and volatile anesthetics on Ca2+ release from sarcoplasmic reticulum (SR) were studied in vitro.
A total of 200 patients met the inclusion criteria. Two MH crises (1%) were triggered by SCh (1 MHS, 1 MHE), 18% by volatile anesthetics and 81% by a combination of both. Patients were 70% male and 50% were younger than 12 years old. Overall, CGS was in accord with IVCT results. Crises triggered by enflurane had a significantly higher CGS compared to halothane, isoflurane and sevoflurane. Of the 200 patients, 103 carried RyR1 variants, of which 14 were novel. CGS varied depending on the location of the mutation within the RyR1 gene. In contrast to volatile anesthetics, SCh did not evoke Ca2+ release from isolated rat SR vesicles.
An MH event could depend on patient-related risk factors such as male gender, young age and causative RyR1 mutations as well as on the use of drugs lowering the threshold of myoplasmic Ca2+ release. SCh might act as an accelerant by promoting unspecific Ca2+ influx via the sarcolemma and indirect RyR1 activation. Most MH crises develop in response to the combined administration of SCh and volatile anesthetics.
PMCID: PMC3896768  PMID: 24433488
Malignant hyperthermia; Succinylcholine; Suxamethonium; Volatile anesthetics; RyR1 mutations; In vitro contracture test
24.  Patients with type 1 Gaucher disease in South Florida, USA: demographics, genotypes, disease severity and treatment outcomes 
Gaucher disease, an autosomal recessive condition due to deficiency of lysosomal glucocerebrosidase, is a multisystemic disease, with variable age of onset, severity and progression. It is classified into subtypes delineated by the absence (type 1) or presence (type 2 and 3) of primary nervous system involvement.
The ethnically diverse, largely immigrant population in South Florida has a spectrum of Gaucher disease phenotypes, creating a challenge for optimization of disease management and an opportunity to explore treatment patterns.
Ninety-three records from patients with Gaucher type I in South Florida were retrieved from the International Collaborative Gaucher Group (ICGG) Registry. Individual genotypes were correlated with severity scores and success at achieving published therapeutic goals for haemoglobin concentration, platelet count, spleen volume, liver volume and amelioration of bone pain and bone crises.
The majority of patients were diagnosed during the fifth decade of life. Almost two-thirds were homozygous for the N370S mutation, reflecting the large Ashkenazi Jewish population in South Florida. The majority received imiglucerase (62.8%) at various intervals. 24.5% of patients underwent splenectomy before starting enzyme replacement therapy. After a median 12 treatment years, South Florida patients matched or exceeded the ICCG 4 year therapeutic goal achievement for platelet count (85.4% vs. 79.6% success), spleen volume (93.3% vs. 78.0% success), liver volume (93.4% vs. 90.6% success), and bone crises (100% vs. 99% success). Nevertheless, fewer patients with intact spleens had sustained achievement of all 6 therapeutic goals (30.4% versus 41.4%) and only 40% of the splenectomy patients sustained achievement of 5/5 possible goals. 54.7% of the intact spleen patients continued to have bone pain vs. 29.8% in ICCG. Significantly, only 37% of the ICGG patient cohort had bone pain prior to initiation of treatment compared to 73.4% of the South Florida patients (moderate or severe pain in 59.6%).
Demographic characteristics are a significant determinant of the differences in response to treatment observed in South Florida Gaucher patients compared to those described in the international population enrolled in the ICGG Gaucher Registry. Individual genotypes and ethnic background are important considerations for optimizing patient care for Gaucher disease.
PMCID: PMC4230272  PMID: 24685312
Gaucher disease; Glucocerebrosidase; Phenotype; Genotype; South Florida; Natural history; Enzyme replacement therapy; Treatment outcomes; Severity score
25.  Cognitive Behavioral Therapy versus Short Psychodynamic Supportive Psychotherapy in the outpatient treatment of depression: a randomized controlled trial 
BMC Psychiatry  2007;7:58.
Previous research has shown that Short Psychodynamic Supportive Psychotherapy (SPSP) is an effective alternative to pharmacotherapy and combined treatment (SPSP and pharmacotherapy) in the treatment of depressed outpatients. The question remains, however, how Short Psychodynamic Supportive Psychotherapy compares with other established psychotherapy methods. The present study compares Short Psychodynamic Supportive Psychotherapy to the evidence-based Cognitive Behavioral Therapy in terms of acceptability, feasibility, and efficacy in the outpatient treatment of depression. Moreover, this study aims to identify clinical predictors that can distinguish patients who may benefit from either of these treatments in particular. This article outlines the study protocol. The results of the study, which is being currently carried out, will be presented as soon as they are available.
Adult outpatients with a main diagnosis of major depressive disorder or depressive disorder not otherwise specified according to DSM-IV criteria and mild to severe depressive symptoms (Hamilton Depression Rating Scale score ≥ 14) are randomly allocated to Short Psychodynamic Supportive Psychotherapy or Cognitive Behavioral Therapy. Both treatments are individual psychotherapies consisting of 16 sessions within 22 weeks. Assessments take place at baseline (week 0), during the treatment period (week 5 and 10) and at treatment termination (week 22). In addition, a follow-up assessment takes place one year after treatment start (week 52). Primary outcome measures are the number of patients refusing treatment (acceptability); the number of patients terminating treatment prematurely (feasibility); and the severity of depressive symptoms (efficacy) according to an independent rater, the clinician and the patient. Secondary outcome measures include general psychopathology, general psychotherapy outcome, pain, health-related quality of life, and cost-effectiveness. Clinical predictors of treatment outcome include demographic variables, psychiatric symptoms, cognitive and psychological patient characteristics and the quality of the therapeutic relationship.
This study evaluates Short Psychodynamic Supportive Psychotherapy as a treatment for depressed outpatients by comparing it to the established evidence-based treatment Cognitive Behavioral Therapy. Specific strengths of this study include its strong external validity and the clinical relevance of its research aims. Limitations of the study are discussed.
Trial registration
Current Controlled Trails ISRCTN31263312
PMCID: PMC2174932  PMID: 17963493

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