[The ulm emergency algorithm for the acute treatment of drug-induced, bradykinin-mediated angioedema]. / Ulmer Notfallalgorithmus: die Akuttherapie von medikamenteninduzierten bradykininvermittelten Angioödemen.

BACKGROUND: Bradykinin-mediated, drug-induced edema like ACE-inhibitor-induced angioedema (ACEi AE) is almost exclusively located in the head and neck region and is potentially life threatening. To date, there are no guidelines or officially-approved treatments available for this pathology. OBJECTIVES: We sought to provide a structured therapeutic algorithm for the acute treatment of drug-induced bradykinin-mediated angioedema. MATERIALS AND METHODS: We analyzed data (especially the course of disease and therapy) of all patients with acute angioedema, who presented to the Department of Otorhinolaryngology, Head and Neck Surgery at the University of Ulm (2010-2015). We also conducted a literature review on PubMed with the terms "acute angioedema", "angioedema emergency", "ACE angioedema", "bradykinin angioedema" and "angioedema therapy". Other fundamental references were the recent German guidelines "hereditary angioedema", "anaphylaxis" and "airway management". RESULTS: An emergency algorithm was generated as a flowchart for the acute therapy of bradykinin-mediated drug-induced angioedema was generated. We focused on the decision criteria for intubation/airway management and pharmacological therapy: antihistamines and glucocorticoids versus anti-bradykinin treatment. Furthermore, recommendations for inpatient monitoring have been derived. CONCLUSION/DISCUSSION: To date, therapy of drug-induced bradykinin-mediated angioedema is performed according to an "off-label" use and without officially-approved guidelines. The presented emergency algorithm provides a first approach for a structured therapeutic concept for a potentially life-threatening pathology.

Evidence supporting the best clinical management of patients with multimorbidity and polypharmacy: a systematic guideline review and expert consensus.

The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease-oriented guidelines often inadequate and complicates clinical decision making. To address this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow-up: strategies in care planning, self-management and medication-related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self-management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines.

[Pharmacotherapy of Vestibular Disorders, Nystagmus and Cerebellar Disorders]. / Medikamentöse Therapiemöglichkeiten bei vestibulären Störungen, Nystagmus und zerebellären Ataxien.

There are currently different groups of drugs for the pharmacotherapy of vertigo, nystagmus and cerebellar disorders: antiemetics; anti-inflammatories, antimenieres, and antimigraineous medications and antidepressants, anticonvulsants, aminopyridines as well as acetyl-DL-leucine. In acute unilateral vestibulopathy, corticosteroids improve the recovery of peripheral vestibular function, but currently there is not sufficient evidence for a general recommendation. There is insufficient evidence to support the view that 16 mg t. i. d. or 48 mg t. i. d. betahistine has an effect in Menière's disease. Therefore, higher dosages are recommended. In animal studies, it was shown that betahistine increases cochlear blood flow. In vestibular paroxysmia, oxcarbazepine was effective (one randomized controlled trial (RCT)). Aminopyridines are recommended for the treatment of downbeat nystagmus (two RCTs) and episodic ataxia type 2 (EA2, one RCT). There has been no RCT on the efficacy of beta-blockers or topiramate but one RCT on flunarizine in vestibular migraine. Based on clinical experience, a treatment analogous to that for migraine without aura can be recommended. Acetyl-DL-leucine improved cerebellar ataxia (two observational studies); it also accelerated central compensation in an animal model of acute unilateral lesion, but RCTs were negative. There are ongoing RCTs on treatment of vestibular paroxysmia with carbamazepine (VESPA), acute unilateral vestibulopathy with betahistine (BETAVEST), vestibular migraine with metoprolol (PROVEMIG), benign paroxysmal positional vertigo with vitamin D (VitD@BPPV), EA2 with 4-aminopyridine versus acetazolamide (EAT-2-TREAT), and cerebellar ataxias with acetyl-DL-leucine (ALCAT).

Anticholinergic medicines in an older primary care population: a cross-sectional analysis of medicines' levels of anticholinergic activity and clinical indications.

WHAT IS KNOWN AND OBJECTIVES: Adverse clinical outcomes have been associated with cumulative anticholinergic burden (to which low-potency as well as high-potency anticholinergic medicines contribute). The clinical indications for which anticholinergic medicines are prescribed (and thus the 'phenotype' of patients with anticholinergic burden) have not been established. We sought to establish the overall prevalence of prescribing of anticholinergic medicines, the prevalence of prescribing of low-, medium- and high-potency anticholinergic medicines, and the clinical indications for which the medicines were prescribed in an older primary care population. METHODS: This was a cross-sectional analysis of a cohort study of Australian early-career general practitioners' (GPs') clinical consultations - the Registrar Clinical Encounters in Training (ReCEnT) study. In ReCEnT, GPs collect detailed data (including medicines prescribed and their clinical indication) for 60 consecutive patients, on up to three occasions 6 months apart. Anticholinergic medicines were categorized as levels 1 (low-potency) to 3 (high-potency) using the Anticholinergic Drug Scale (ADS). RESULTS: During 2010-2014, 879 early-career GPs (across five of Australia's six states) conducted 20 555 consultations with patients aged 65 years or older, representing 35 506 problems/diagnoses. Anticholinergic medicines were prescribed in 10·4% [95% CIs 9·5-10·5] of consultations. Of the total anticholinergic load of prescribed medicines ('community anticholinergic load') 72·7% [95% CIs 71·0-74·3] was contributed by Level 1 medicines, 0·8% [95% CIs 0·5-1·3] by Level 2 medicines and 26·5% [95% CIs 24·8-28·1] by Level 3 medicines. Cardiac (40·0%), Musculoskeletal (16·9%) and Respiratory (10·6%) were the most common indications associated with Level 1 anticholinergic prescription. For Level 2 and 3 medicines (combined data), Psychological (16·1%), Neurological (16·1%), Musculoskeletal (15·7%) and Urological (11·1%) indications were most common. WHAT IS NEW AND CONCLUSION: Anticholinergic medicines are frequently prescribed in Australian general practice, and the majority of the 'community' anticholinergic burden is contributed by 'low'-anticholinergic potency medicines whose anticholinergic effects may be largely 'invisible' to prescribing GPs. Furthermore, the clinical 'phenotype' of the patient with high anticholinergic burden may be very different to common stereotypes (patients with urological, psychological or neurological problems), potentially making recognition of risk of anticholinergic adverse effects additionally problematic for GPs.

[Pharmacotherapy of Vestibular Disorders, Nystagmus and Cerebellar Disorders]. / Medikamentöse Therapiemöglichkeiten bei vestibulären Störungen, Nystagmus und zerebellären Ataxien.

There are currently different groups of drugs for the pharmacotherapy of vertigo, nystagmus and cerebellar disorders: antiemetics; anti-inflammatories, antimenieres, and antimigraineous medications and antidepressants, anticonvulsants, aminopyridines as well as acetyl-DL-leucine. In acute unilateral vestibulopathy, corticosteroids improve the recovery of peripheral vestibular function, but currently there is not sufficient evidence for a general recommendation. There is insufficient evidence to support the view that 16 mg t. i. d. or 48 mg t. i. d. betahistine has an effect in Menière's disease. Therefore, higher dosages are recommended. In animal studies, it was shown that betahistine increases cochlear blood flow. In vestibular paroxysmia, oxcarbazepine was effective (one randomized controlled trial (RCT)). Aminopyridines are recommended for the treatment of downbeat nystagmus (two RCTs) and episodic ataxia type 2 (EA2, one RCT). There has been no RCT on the efficacy of beta-blockers or topiramate but one RCT on flunarizine in vestibular migraine. Based on clinical experience, a treatment analogous to that for migraine without aura can be recommended. Acetyl-DL-leucine improved cerebellar ataxia (two observational studies); it also accelerated central compensation in an animal model of acute unilateral lesion, but RCTs were negative. There are ongoing RCTs on treatment of vestibular paroxysmia with carbamazepine (VESPA), acute unilateral vestibulopathy with betahistine (BETAVEST), vestibular migraine with metoprolol (PROVEMIG), benign paroxysmal positional vertigo with vitamin D (VitD@BPPV), EA2 with 4-aminopyridine versus acetazolamide (EAT-2-TREAT), and cerebellar ataxias with acetyl-DL-leucine (ALCAT).

Central ocular motor disorders, including gaze palsy and nystagmus.

An impairment of eye movements, or nystagmus, is seen in many diseases of the central nervous system, in particular those affecting the brainstem and cerebellum, as well as in those of the vestibular system. The key to diagnosis is a systematic clinical examination of the different types of eye movements, including: eye position, range of eye movements, smooth pursuit, saccades, gaze-holding function and optokinetic nystagmus, as well as testing for the different types of nystagmus (e.g., central fixation nystagmus or peripheral vestibular nystagmus). Depending on the time course of the signs and symptoms, eye movements often indicate a specific underlying cause (e.g., stroke or neurodegenerative or metabolic disorders). A detailed knowledge of the anatomy and physiology of eye movements enables the physician to localize the disturbance to a specific area in the brainstem (midbrain, pons or medulla) or cerebellum (in particular the flocculus). For example, isolated dysfunction of vertical eye movements is due to a midbrain lesion affecting the rostral interstitial nucleus of the medial longitudinal fascicle, with impaired vertical saccades only, the interstitial nucleus of Cajal or the posterior commissure; common causes with an acute onset are an infarction or bleeding in the upper midbrain or in patients with chronic progressive supranuclear palsy (PSP) and Niemann-Pick type C (NP-C). Isolated dysfunction of horizontal saccades is due to a pontine lesion affecting the paramedian pontine reticular formation due, for instance, to brainstem bleeding, glioma or Gaucher disease type 3; an impairment of horizontal and vertical saccades is found in later stages of PSP, NP-C and Gaucher disease type 3. Gaze-evoked nystagmus (GEN) in all directions indicates a cerebellar dysfunction and can have multiple causes such as drugs, in particular antiepileptics, chronic alcohol abuse, neurodegenerative cerebellar disorders or cerebellar ataxias; purely vertical GEN is due to a midbrain lesion, while purely horizontal GEN is due to a pontomedullary lesion. The pathognomonic clinical sign of internuclear ophthalmoplegia is an impaired adduction while testing horizontal saccades on the side of the lesion in the ipsilateral medial longitudinal fascicule. The most common pathological types of central nystagmus are downbeat nystagmus (DBN) and upbeat nystagmus (UBN). DBN is generally due to cerebellar dysfunction affecting the flocculus bilaterally (e.g., due to a neurodegenerative disease). Treatment options exist for a few disorders: miglustat for NP-C and aminopyridines for DBN and UBN. It is therefore particularly important to identify treatable cases with these conditions.

[Cardinal symptom vertigo from the neurologist's perspective]. / Leitsymptom Schwindel aus Sicht des Neurologen.

In most patients with vertigo, the first and clinically most important question posed to neurologists is whether it is a central or a peripheral syndrome. In more than 90 % of cases, this differentiation is made possible by systematically recording the patient history (asking about the type of vertigo, the duration, triggers and accompanying symptoms) and conducting a physical examination. Particularly in the case of acute vertigo disorders, a five-step procedure has proven useful: 1. A cover test to look for vertical divergence (skew deviation) as a central sign and component of the ocular tilt reaction (OTR); 2. Examination with and without Frenzel goggles to differentiate between peripheral vestibular spontaneous nystagmus and central fixation nystagmus; 3. Examination of smooth pursuit; 4. Examination of the gaze-holding function (particularly gaze-evoked nystagmus beating in the opposite direction to spontaneous nystagmus); 5. The head impulse test to look for a deficit in the vestibulo-ocular reflex (VOR). Considerable advances have been made in the pharmacotherapy of vertigo disorders during the last 10 years, including cortisone for the treatment of acute vestibular neuritis, betahistine as a high-dose long-term treatment for Menière's disease, carbamazepine to treat vestibular paroxysmia and aminopyridine for down- and upbeat nystagmus and episodic ataxia type 2.

N-terminal prohormone of brain natriuretic peptide: a useful tool for the detection of acute pulmonary artery embolism in post-surgical patients.

BACKGROUND: Acute pulmonary embolism (APE) is an important clinical problem in patients after major surgery and often remains a difficult diagnosis because of unspecific clinical symptoms. Therefore, we investigated the role of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) for the detection of APE. METHODS: In 44 patients with suspected APE referred to the intensive care unit after major surgery, serum NT-proBNP, troponin-I, and D-dimers were measured according to the standard hospital protocol. To definitively confirm or exclude APE, all patients underwent an angiographic CT scan of the thorax. RESULTS: APE was confirmed in 28 and excluded in 16 patients by CT scan. NT-proBNP was significantly (P<0.01) higher in patients with APE [4425 (sd 8826; range 63-35 000) pg ml(-1)] compared with those without [283 (sd 327; range 13-1133) pg ml(-1)]. The sensitivity of the NT-proBNP screening was 93%, specificity 63%, positive predictive value 81%, and negative predictive value 83%. There were no significant (P = 0.96) differences in D-dimers between subjects with and without APE [confirmed APE: 511 (sd 207; range 83-750) µg litre(-1); excluded APE: 509 (sd 170; range 230-750) µg litre(-1)]. Troponin-I levels were not elevated in 32% of the patients with APE. CONCLUSIONS: D-dimer levels are frequently elevated in post-surgical patients and not applicable for confirmation or exclusion of APE. In contrast, NT-proBNP appears to be a useful biomarker for APE diagnosis in the postoperative setting. In the case of NT-proBNP levels below the upper reference limit, haemodynamically relevant APE is unlikely. Troponin-I in contrast is not considered to be helpful.

Effects of FLIRT on bubble growth in man.

Recompression during decompression has been suggested to possibly reduce the risk of decompression sickness (DCS). The main objective of the current study was to investigate the effects of FLIRT (First Line Intermittent Recompression Technique) on bubble detection in man. 29 divers underwent 2 simulated dives in a dry recompression chamber to a depth of 40 msw (500 kPa ambient pressure) in random order. A Buehlmann-based decompression profile served as control and was compared to an experimental profile with intermittent recompression during decompression (FLIRT). Circulating bubbles in the right ventricular outflow tract (RVOT) were monitored by Doppler ultrasound and quantified using the Spencer scoring algorithm. Heat shock protein 70 (HSP70), thrombocytes, D-Dimers and serum osmolarity were analyzed before and 120 min after the dive. Both dive profiles elicited bubbles in most subjects (range Spencer 0-4). However, no statistically significant difference was found in bubble scores between the control and the experimental dive procedure. There was no significant change in either HSP70, thrombocytes, and D-Dimers. None of the divers had clinical signs or symptoms suggestive of DCS. We conclude that FLIRT did not significantly alter the number of microbubbles and thus may not be considered superior to classical decompression in regards of preventing DCS.

The Aarhus statement: improving design and reporting of studies on early cancer diagnosis.

Early diagnosis is a key factor in improving the outcomes of cancer patients. A greater understanding of the pre-diagnostic patient pathways is vital yet, at present, research in this field lacks consistent definitions and methods. As a consequence much early diagnosis research is difficult to interpret. A consensus group was formed with the aim of producing guidance and a checklist for early cancer-diagnosis researchers. A consensus conference approach combined with nominal group techniques was used. The work was supported by a systematic review of early diagnosis literature, focussing on existing instruments used to measure time points and intervals in early cancer-diagnosis research. A series of recommendations for definitions and methodological approaches is presented. This is complemented by a checklist that early diagnosis researchers can use when designing and conducting studies in this field. The Aarhus checklist is a resource for early cancer-diagnosis research that should promote greater precision and transparency in both definitions and methods. Further work will examine whether the checklist can be readily adopted by researchers, and feedback on the guidance will be used in future updates.

Pulmonary function in children after open water SCUBA dives.

An increasing number of children and adolescents is diving with Self-Contained Underwater Breathing Apparatus (SCUBA). SCUBA diving is associated with health risks such as pulmonary barotrauma, especially in children and in individuals with airflow limitation. As no data has been published on the effects of open-water diving on pulmonary function in children, the objective of this study was to evaluate the effects of SCUBA dives on airflow in children. 16 healthy children aged 10-13 years underwent spirometry and a cycle-exercise challenge while breathing cold air. They subsequently performed dives to 1-m and 8-m depth in random order. Pulmonary function was measured before and after the exercise challenge and the dives. There were statistically significant decreases in FEV1, FVC, FEV1/FVC, MEF25 and MEF50 after the cold-air exercise challenge and the dives. Changes in lung function following the exercise challenge did not predict the responses to SCUBA diving. In 3 children the post-dive decrements in FEV1 exceeded 10%. These children had a lower body weight and BMI percentile. SCUBA diving in healthy children may be associated with relevant airflow limitation. A low body mass might contribute to diving-associated bronchoconstriction. In the majority of subjects, no clinically relevant airway obstruction could be observed.

[Garbage in - garbage out? Validity of coded diagnoses from GP claims records]. / Garbage in - Garbage out? Validität von Abrechnungsdiagnosen in hausärztlichen Praxen.

CONTEXT: ICD-10-coded diagnoses from claims records are frequently used as morbidity indicators for research as well as for risk adjustment purposes in quality management and remuneration. A requirement for this application is the high validity of the diagnoses. In GP practices in particular, it is questionable whether claims-based diagnoses realistically reflect the health problems of patients treated over a one year period. METHODS: In a retrospective cross-sectional study of a random sample of 250 patients from 10 GP practices we examined whether, on the basis of the patients' medical records, health problems treated in the year 2003 matched claims-based diagnoses within the same time period. RESULTS: In spite of a high mean of 6.1 claims-based diagnoses per patient, health problems treated within the study period were under-reported in 30% of the cases, mainly relating to non-severe diagnoses frequently encountered in GP practice, chronic conditions not requiring medication, and diagnoses justifying a screening test. An over-reporting for diseases not treated within the study period was observed in 19% of the cases, most often in the case of permanent chronic conditions. In 11% of cases the ICD-10 codes of claims-based diagnoses and the diagnoses in the medical records did not match ("erroneous codes"). For six of the diagnoses most common in GP practice (hypertension, diabetes, hyperlipoproteinemia, cardiovascular disease, back pain, and acute respiratory tract infections) correctness at 71-93% was higher than completeness (56-86%). CONCLUSION: The low validity of ICD-10-coded diagnoses from GP claims records calls their usefulness as morbidity indicators into question.

Lung hyperinflation: foe or friend?

Breath-hold divers employ glossopharyngeal insufflation (GI) in order to prevent the lungs from compressing at great depth and to increase intrapulmonary oxygen stores, thus increasing breath-hold time. The presented case study shows the physiological data and dynamic magnetic resonance imaging (dMRI) findings of acute hyperinflation, deliberately induced by GI, in a breath-hold diver and discusses the current state of knowledge regarding the associated hazards of this unique competitive sport. Static and dynamic lung volumes and expiratory flows were within the normal range, with vital capacity and peak expiratory flow being higher than the predicted values. Airway resistance and diffusing capacity of the lung for carbon monoxide were normal. Static compliance was normal and increased five-fold with hyperinflation. dMRI revealed a preserved shape of the thorax and diaphragm with hyperinflation. A herniation of the lung beneath the sternum and enlargement of the costodiaphragmatic angle were additional findings during the GI manoeuvre. After expiration, complete resolution to baseline was demonstrated. Hyperinflation can be physiological and even protective under abnormal physical conditions in the sense of acute adaptation to deep breath-hold diving. Dynamic magnetic resonance imaging is adequate for visualisation of the sequence of the glossopharyngeal insufflation manoeuvre and the complete reversibility of deliberate hyperinflation.

[Diving fitness of children and adolescents. Importance for ENT doctors]. / Tauchtauglichkeit von Kindern und Jugendlichen. Bedeutung für den HNO-Arzt.

About 10% of all sport scuba divers are children and adolescents. Little is known about the particular risks and consequences of this sport on a child's health. Due to the peculiarities of childhood anatomy and physiology, certain restrictions apply to the diving fitness of children and adolescents. Before starting scuba training, the presence of particular cognitive abilities must be demonstrated and eustachian tube dysfunction must be ruled out by a specialist. Medical contra-indications to scuba diving for adults apply to children too but must be adapted. Relative risks for adults may translate to absolute contra-indications in children and adolescents. When planning dives, there should be rigorous limitations as to depth and time. Experienced adult divers must always assist with dive planning and accompany children and adolescents when scuba diving.

[Water rescue. A unique area of emergency medicine with many facets]. / Wasserrettung. Ein notfallmedizinisches Spezialgebiet mit vielen Facetten.

Emergencies on or in water are relatively rare in the rescue service. For this reason, water accident treatment and management does not receive much attention in the training of emergency medicine physicians. Consequently doctors working in emergency medicine often have minimal knowledge in this area. On the other hand, the number of fatal accidents on and in water has increased in recent years. In Germany the number of non-swimmers is also increasing, so it can be assumed that the number of water-related accidents will continue to rise. Drowning accidents and near drowning are important in this context and will be discussed in detail in this review as well as hypothermia (a frequent problem), accompanying injuries and diving accidents.

[Oxygen therapy in diving accidents]. / Sauerstofftherapie nach Tauchunfall.

Diving accidents represent a departure from the routine practice of emergency physicians. The incidence of non-fatal diving accidents is reported as 1-2 per 10,000 dives. Apart from adequate intravenous hydration, oxygen is the only medication with a proven effect in the treatment of diving accidents. After a typical diving accident, administration of oxygen at an inspired concentration (F(I)O(2) 1.0) as high as possible is recommended. Many divers bring along their own oxygen administration systems to the diving sites and these are often better suited for the treatment of diving accidents than the oxygen systems of many emergency responders. Pressure regulators supplying low constant flow oxygen, nasal prongs and inhalation masks are inappropriate. When using artificial ventilation bags with face masks, an oxygen flow of at least 15 l/min should be used. Demand regulators are simple to use and able to deliver a F(I)O2 of 1.0. Their ease of use has earned them high marks in the emergency management of diving accidents and their similarity to standard diving equipment has also aided relatively widespread acceptance. Circulation breathing systems are more technologically complex oxygen delivery systems which permit CO2 absorption and re-breathing at low oxygen flow. In contrast to the demand modules, the likelihood of mistakes during their usage is higher. In diving accidents, the administration of normobaric oxygen, already begun in the field, is the most important therapy and should not be interrupted. Presented with an inadequate supplemental oxygen supply, the inspired oxygen concentration should not be decreased, rather the duration of the oxygen administration should be reduced. Hyperbaric oxygen therapy should be the mainstay of further treatment.

Case management to improve major depression in primary health care: a systematic review.

BACKGROUND: Deficits in the care of depression lead to poor medication adherence, which increases the risk of an unfavourable outcome for this care. This review evaluates effects on symptoms and medication adherence of case management in primary health care. METHOD: A systematic literature search was performed. The quality of the studies was rated according to the Cochrane Effective Practice and Organization of Care Group (EPOC) criteria. To conduct a subgroup analysis interventions were classified as either 'standard' or 'complex' case management. RESULTS: Thirteen studies met the inclusion criteria. In a meta-analysis we calculated a standard mean difference/effect size on symptom severity after 6-12 months of -0.40 (95% CI -0.60 to -0.20). Patients in the intervention groups were more likely to achieve remission after 6-12 months [relative risk (RR) 1.39, 95% CI 1.30-1.48]. The relative risk for clinical response was 1.82 (95% CI 1.68-2.05). Patients in intervention groups had better medication adherence than the control group (RR 1.5, 95% CI 1.28-1.86). We found heterogeneous results when assessing effects of different types of intervention. CONCLUSIONS: We conclude that case management improves management of major depression in primary health-care settings.