Detecting anxiety and depression in general medical settings.

To aid general practitioners and other non-psychiatrists in the better recognition of mental illness short scales measuring anxiety and depression were derived by latent trait analysis from a standardised psychiatric research interview. Designed to be used by non-psychiatrists, they provide dimensional measures of the severity of each disorder. The full set of nine questions need to be administered only if there are positive answers to the first four. When assessed against the full set of 60 questions contained in the psychiatric assessment schedule they had a specificity of 91% and a sensitivity of 86%. The scales would be used by non-psychiatrists in clinical investigations and possibly also by medical students to familiarise them with the common forms of psychiatric illness, which are often unrecognised in general medical settings.     

Treatment of acute agitation in psychotic disorders

Several psychotic disorders, including schizophrenia, may be associated with symptoms of acute agitation and aggression. While drug treatment of agitation is often essential, non-pharmacological interventions, both environmental and behavioral, also play important roles in the complex management of agitated patients. The most extensively used psychotropic drugs are parenteral formulas of conventional antipsychotics and benzodiazepines. Recently, injection forms of two second generation antipsychotics, olanzapine and ziprasidone, have become available. Both drugs have shown adequate efficacy and tolerability in several double-blind trials of intramuscular administration in acutely agitated psychotic patients. Compared to conventional medication, injection forms of the new antipsychotics may have a faster onset of action and more favorable profile of adverse events. Alternative approaches to injection administration include liquid drug formula, orally disintegrating tablets and wafers, treatment initiation with high doses, or rapid dose escalation. Evidence suggests that second-generation antipsychotics should be among the first-line choices in the treatment of agitation in acute psychosis.     

Acute psychiatric care: approaches to increasing the range of services and improving access and quality of care

Acute services for mental health crises are very important to service users and their supporters, and consume a substantial share of mental health resources in many countries. However, acute care is often unpopular and sometimes coercive, and the evidence on which models are best for patient experience and outcomes remains surprisingly limited, in part reflecting challenges in conducting studies with people in crisis. Evidence on best ap­proaches to initial assessment and immediate management is particularly lacking, but some innovative models involving extended assessment, brief interventions, and diversifying settings and strategies for providing support are potentially helpful. Acute wards continue to be central in the intensive treatment phase following a crisis, but new approaches need to be developed, evaluated and implemented to reducing coercion, addressing trauma, diversifying treatments and the inpatient workforce, and making decision‐making and care collaborative. Intensive home treatment services, acute day units, and community crisis services have supporting evidence in diverting some service users from hospital admission: a greater understanding of how best to implement them in a wide range of contexts and what works best for which service users would be valuable. Approaches to crisis management in the voluntary sector are more flexible and informal: such services have potential to complement and provide valuable learning for statutory sector services, especially for groups who tend to be underserved or disengaged. Such approaches often involve staff with personal experience of mental health crises, who have important potential roles in improving quality of acute care across sectors. Large gaps exist in many low‐ and middle‐income countries, fuelled by poor access to quality mental health care. Responses need to build on a foundation of existing community responses and contextually relevant evidence. The necessity of moving outside formal systems in low‐resource settings may lead to wider learning from locally embedded strategies.     

Treatment of bipolar depression

Antidepressants have insufficient effect in 20-40% of patients treated for depressive disorders. This is particularly true for psychotic and agitated depression. When administered on a long-term basis, antidepressants cause a switch into mania in 25-40% of patients and induce rapid cycling. Classical antipsychotics have exhibited good therapeutic efficacy in the treatment of various forms of depression, especially psychotic and agitated forms, albeit burdened with many, above all extrapyramidal, side effects. When administered over long periods of time, classical antipsychotics may have a depressogenic effect. Second-generation antipsychotics have started to be increasingly used in this indication for a variety of reasons including: their antidepressant effect attributable to raised concentrations of catecholamines in the prefrontal cortex, their impact on serotonin transmission, their antipsychotic effect due to their mode of action including the mesolimbic blockade of dopamine D2 receptors, and the low incidence of extrapyramidal and other side effects. The following text encompasses the results of controlled trials using second-generation antipsychotics in the treatment of acute depressive disorders.     

RENAL VASCULAR HYPERTENSION

The use of corticosteroids systemically in dermatology has benefited patients with pemphigus and systemic lupus erythematosus in that they now have a better chance to carry on a productive life. These hormones, used cautiously, can alleviate some of the tremendous suffering during the explosive exacerbations and acute crises of atopic and neurodermatitis. Corticosteroids are useful in the widespread and acute contact dermatitis and drug eruptions; they are contraindicated in the treatment of ordinary psoriasis.Every attempt should be made by history-taking, clinical examination and necessary laboratory studies to reach an accurate diagnosis before corticosteroids are used. If use of them is indicated, then total patient care is required to avoid complications, and a very careful follow-up is mandatory.     

Drugs That Cause Weight Gain

Among drugs which cause weight gain, the tricyclic antidepressant medications are a drug class producing persistent and problematic body weight gain in many treated patients. Major depressive illness is often associated with reductions in appetite and body weight, and treatment with antidepressants effectively restores mood, appetite and weight. However, a frequent complaint of patients treated with tricyclic drugs is of excessive and unwanted weight gain, oftentimes resulting in medication noncompliance. The incidence of weight gain during acute and chronic treatment with different, frequently prescribed antidepressant drugs will be reviewed, as will the possible mechanisms by which such drugs alter caloric intake and expenditure, contributing to drug-induced weight gain.     

Rapid pulsed whole genome sequencing for comprehensive acute diagnostics of inborn errors of metabolism

Background

Massively parallel DNA sequencing (MPS) has the potential to revolutionize diagnostics, in particular for monogenic disorders. Inborn errors of metabolism (IEM) constitute a large group of monogenic disorders with highly variable clinical presentation, often with acute, nonspecific initial symptoms. In many cases irreversible damage can be reduced by initiation of specific treatment, provided that a correct molecular diagnosis can be rapidly obtained. MPS thus has the potential to significantly improve both diagnostics and outcome for affected patients in this highly specialized area of medicine.

Results

We have developed a conceptually novel approach for acute MPS, by analysing pulsed whole genome sequence data in real time, using automated analysis combined with data reduction and parallelization. We applied this novel methodology to an in-house developed customized work flow enabling clinical-grade analysis of all IEM with a known genetic basis, represented by a database containing 474 disease genes which is continuously updated. As proof-of-concept, two patients were retrospectively analysed in whom diagnostics had previously been performed by conventional methods. The correct disease-causing mutations were identified and presented to the clinical team after 15 and 18 hours from start of sequencing, respectively. With this information available, correct treatment would have been possible significantly sooner, likely improving outcome.

Conclusions

We have adapted MPS to fit into the dynamic, multidisciplinary work-flow of acute metabolic medicine. As the extent of irreversible damage in patients with IEM often correlates with timing and accuracy of management in early, critical disease stages, our novel methodology is predicted to improve patient outcome. All procedures have been designed such that they can be implemented in any technical setting and to any genetic disease area. The strategy conforms to international guidelines for clinical MPS, as only validated disease genes are investigated and as clinical specialists take responsibility for translation of results. As follow-up in patients without any known IEM, filters can be lifted and the full genome investigated, after genetic counselling and informed consent.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-1090) contains supplementary material, which is available to authorized users.     

下颌种植覆盖义齿的生物力学研究进展

口腔生物力学是用生物力学的概念和方法,研究口腔医学中的有关基础性科学问题、解决口腔医学中的临床实际问题、发展口腔临床技术的一门学科。在口腔正畸学、修复学、种植学及口腔颌面外科学等领域存在着大量的生物力学问题,生物力学已成为口腔医学的基础科学之一。传统全口义齿修复常常会出现固位稳定差、咀嚼效率低、患者有疼痛感、适应时间长等情况,很大程度上不能满足患者的修复要求。种植覆盖义齿对于下颌牙槽嵴严重吸收的患者,效果尤为明显。种植覆盖义齿是义齿与种植体之间以不同的附着体作为连接,形成患者可以自行摘戴的种植体支持的覆盖义齿修复。下颌种植覆盖义齿因其能有效地提高下半口义齿的固位性和稳定性、显著提高了患者的咀嚼效率,目前已成为修复下颌牙槽骨严重吸收的无牙颌患者的有效修复方法。本文针对下颌种植覆盖义齿的生物力学研究进展作一综述。     

Assessing Social Networks in Patients with Psychotic Disorders: A Systematic Review of Instruments

Background

Evidence suggests that social networks of patients with psychotic disorders influence symptoms, quality of life and treatment outcomes. It is therefore important to assess social networks for which appropriate and preferably established instruments should be used.

Aims

To identify instruments assessing social networks in studies of patients with psychotic disorders and explore their properties.

Method

A systematic search of electronic databases was conducted to identify studies that used a measure of social networks in patients with psychotic disorders.

Results

Eight instruments were identified, all of which had been developed before 1991. They have been used in 65 studies (total N of patients = 8,522). They assess one or more aspects of social networks such as their size, structure, dimensionality and quality. Most instruments have various shortcomings, including questionable inter-rater and test-retest reliability.

Conclusions

The assessment of social networks in patients with psychotic disorders is characterized by a variety of approaches which may reflect the complexity of the construct. Further research on social networks in patients with psychotic disorders would benefit from advanced and more precise instruments using comparable definitions of and timescales for social networks across studies.     

Traitement pharmacologique du premier épisode psychotique

Pharmacological treatment has a central role in the treatment of a first episode psychosis. However, drug therapy must be viewed as within a framework of a global approach, whose aim is to facilitate the participation of the patient in the treatment regime. As the initial symptoms of psychotic disorders may often be atypical and complicated by co-morbidity, this can make both the early diagnosis and the choice of an appropriate treatment difficult. In a more dimensional approach to diagnosis rather than a categorical approach, it is important to identify the presence of affective symptoms (depressive or manic) which may necessitate the addition of either an antidepressant or a mood stabilizer. The indication for using atypical antipsychotic drugs as first choice in treatment has been firmly established in the current literature. These novel antipsychotic drugs are less prone to inducing undesirable side-effects, such as cognitive impairment and dysphoria, and appear to have a more favourable effect than conventional neuroleptics on the course of both depressive symptoms as well as hostile and aggressive behaviours. Furthermore, they seem to have a mood stabilizing effect, and are more easily accepted by the patients. Even though there is a reduced risk of acute extrapyramidal side-effects and late onset dyskinesia, the risk of weight gain as well as cardiovascular and endocrinological complications is considerable. This review article focuses on problems related to pharmacological treatment of first episode psychosis. It is the result of an extensive review of the current literature available on this field. The results have been discussed and organised in the form of clinical guidelines for the treatment of both non-affective and affective first episode psychoses.     

The arthropathy of maintenance intermittent peritoneal dialysis.

Among 61 patients undergoing maintenance peritoneal dialysis for an average of 20 months, 13 (21%) had a history of attacks of acute arthritis and 19 (31%) were found to have tender and often swollen joints. Deposits of calcium pyrophosphate dihydrate crystals in articular cartilage were identified in four patients and inflammation probably induced by hydroxyapatite crystals was noted in one. Periarticular calcification was observed in 12 patients and subperiosteal resorption of the phalanges in 20. The average calcium X phosphorus product was significantly higher (P < 0.025) in patients with a history of attacks of acute arthritis or with inflamed joints (58 +/- 12) than in those without (50 +/- 12). In the 19 patients whose treatment was changed to continuous ambulatory peritoneal dialysis there was a significant decrease (P < 0.025) in the calcium X phosphorus product but not in the proportion of patients with attacks of acute arthritis or with inflamed joints. The results indicate that articular complications are frequent among patients undergoing maintenance peritoneal dialysis and may be more common than with long-term hemodialysis.     

Psychotic mania in glucose-6-phosphate-dehydrogenase-deficient subjects

BACKGROUND: Glucose-6-phosphate dehydrogenase (G6PD) deficiency has been associated with acute psychosis, catatonic schizophrenia, and bipolar disorders by previous inconclusive reports. A particularly disproportionate rate of enzyme deficiency was found in manic schizoaffective patients from 662 lithium patients surveyed in Sardinia. The purpose of this study was to describe clinical characteristics which may be potentially associated with G6PD deficiency. METHODS: Characteristics of episodes, course of illness, family pattern of illness, laboratory tests, and treatment response of 29 G6PD-deficient subjects with a Research Diagnostic Criteria diagnosis of manic schizoaffective disorder were abstracted from available records. RESULTS: The most peculiar pattern was that of acute recurrent psychotic manic episodes, mostly characterized by loosening of associations, agitation, catatonic symptoms, and/or transient confusion, concurrent hyperbilirubinemia, positive psychiatric family history, and partial response to long-term lithium treatment. CONCLUSIONS: A relationship between psychiatric disorder and G6PD deficiency is to be searched in the bipolar spectrum, particularly among patients with a history of acute episodes with psychotic and/or catatonic symptoms or with transient confusion.     

A Generalized Estimator of the Attributable Benefit of an Optimal Treatment Regime

Summary For many diseases where there are several treatment options often there is no consensus on the best treatment to give individual patients. In such cases, it may be necessary to define a strategy for treatment assignment; that is, an algorithm that dictates the treatment an individual should receive based on their measured characteristics. Such a strategy or algorithm is also referred to as a treatment regime. The optimal treatment regime is the strategy that would provide the most public health benefit by minimizing as many poor outcomes as possible. Using a measure that is a generalization of attributable risk (AR) and notions of potential outcomes, we derive an estimator for the proportion of events that could have been prevented had the optimal treatment regime been implemented. Traditional AR studies look at the added risk that can be attributed to exposure of some contaminant; here we will instead study the benefit that can be attributed to using the optimal treatment strategy. We will show how regression models can be used to estimate the optimal treatment strategy and the attributable benefit of that strategy. We also derive the large sample properties of this estimator. As a motivating example, we will apply our methods to an observational study of 3856 patients treated at the Duke University Medical Center with prior coronary artery bypass graft surgery and further heart‐related problems requiring a catheterization. The patients may be treated with either medical therapy alone or a combination of medical therapy and percutaneous coronary intervention without a general consensus on which is the best treatment for individual patients.     

Treatment of mental illness; the use and misuse of sedation and the seclusion room

Nine hundred and thirty-nine patients admitted to the locked receiving ward in the psychiatric service of the U. S. Naval Hospital, Oakland, over a ten-month period, many of them psychotic and in an acute initial episode, were treated with an intensive group therapy program, which more appropriately should be called a therapeutic community. During this time, the ward medical officer did not put any patients in a seclusion room. Patients who did not require a locked ward were quickly transferred to the open receiving ward which was established five months after this program began. It was possible to greatly diminish the quantity of sleeping medicine prescribed and practically to eliminate the use of barbiturates given parenterally. Restraints were never used. To be dealt with in this atmosphere of candor and relative freedom seemed to evoke a responsive attitude in the patients and many of them benefited from it.     

Extracellular vesicles and pancreatitis: mechanisms,status and perspectives

Comprehensive reviews and large population-based cohort studies have played an important role in the diagnosis and treatment of pancreatitis and its sequelae. The incidence and mortality of pancreatitis have been reduced significantly due to substantial advancements in the pathophysiological mechanisms and clinically effective treatments. The study of extracellular vesicles (EVs) has the potential to identify cell-to-cell communication in diseases such as pancreatitis. Exosomes are a subset of EVs with an average diameter of 50~150 nm. Their diverse and unique constituents include nucleic acids, proteins, and lipids, which can be transferred to trigger phenotypic changes of recipient cells. In recent years, many reports have indicated the role of EVs in pancreatitis, including acute pancreatitis, chronic pancreatitis and autoimmune pancreatitis, suggesting their potential influence on the development and progression of pancreatitis. Plasma exosomes of acute pancreatitis can effectively reach the alveolar cavity and activate alveolar macrophages to cause acute lung injury. Furthermore, upregulated exosomal miRNAs can be used as biomarkers for acute pancreatitis. Here, we summarized the current understanding of EVs in pancreatitis with an emphasis on their biological roles and their potential use as diagnostic biomarkers and therapeutic agents for this disease.     

Linear demasking techniques are unreliable for estimating the circadian phase of ambulatory temperature data.

Clinical investigators often use ambulatory temperature monitoring to assess the endogenous phase and amplitude of an individual's circadian pacemaker for diagnostic and research purposes. However, an individual's daily schedule includes changes in levels of activity, in posture, and in sleep-wake state, all of which are known to have masking or evoked effects on core body temperature (CBT) data. To compensate for or to correct these masking effects, many investigators have developed "demasking" techniques to extract the underlying circadian phase and amplitude data. However, the validity of these methods is uncertain. Therefore, the authors tested a variety of analytic methods on two different ambulatory data sets from two different studies in which the endogenous circadian pacemaker was not synchronized to the sleep-wake schedule. In both studies, circadian phase estimates calculated from CBT collected when each subject was ambulatory (i.e., free to perform usual daily activities) were compared to those calculated during the same study when the same subject's activities were controlled. In the first study, 24 sighted young and older subjects living on a 28-h scheduled "day" protocol were studied for approximately 21 to 25 cycles of 28-h each. In the second study, a blind man whose endogenous circadian rhythms were not synchronized to the 24-h day despite his maintenance of a regular 24-h sleep-wake schedule was studied for more than 80 consecutive 24-h days. During both studies, the relative phase of the endogenous (circadian) and evoked (scheduled activity-rest) components of the ambulatory temperature data changed progressively and relatively slowly, enabling analysis of the CBT rhythm at nearly all phase relationships between the two components. The analyses of the ambulatory temperature data demonstrate that the masking of the CBT rhythm evoked by changes in activity levels, posture, or sleep-wake state associated with the evoked schedule of activity and rest can significantly obscure the endogenous circadian component of the signal, the object of study. In addition, the masking effect of these evoked responses on temperature depends on the circadian phase at which they occur. These nonlinear interactions between circadian phase and sleep-wake schedule render ambulatory temperature data unreliable for the assessment of endogenous circadian phase. Even when proposed algebraic demasking techniques are used in an attempt to reveal the endogenous temperature rhythm, the phase estimates remain severely compromised.     

How to distinguish healthy from diseased? Classification strategy for mass spectrometry‐based clinical proteomics

SELDI-TOF-MS is rapidly gaining popularity as a screening tool for clinical applications of proteomics. Application of adequate statistical techniques in all the stages from measurement to information is obligatory. One of the statistical methods often used in proteomics is classification: the assignment of subjects to discrete categories, for example healthy or diseased. Lately, many new classification methods have been developed, often specifically for the analysis of X-omics data. For proteomics studies a good strategy for evaluating classification results is of prime importance, because usually the number of objects will be small and it would be wasteful to set aside part of these as a 'mere' test set. The present paper offers such a strategy in the form of a protocol which can be used for choosing among different statistical classification methods and obtaining figures of merit of their performance. This paper also illustrates the usefulness of proteomics in a clinical setting, serum samples from Gaucher disease patients, when used in combination with an appropriate classification method.     

Methods for evaluating response to treatment in adult acute leukemia

The criteria for evaluating response to treatment for patients with adult acute leukemia are objective, quantitative, and effective. The first objective of treatment is to achieve a complete clinical and hematological remission, since in the absence of such response the disease has a rapidly progressive and inevitably fatal outcome. Logistic regression analysis and the generation of models for predicting the probability of response for each patient have proven to be extremely useful techniques for evaluating new candidates for front-line treatment in acute leukemia. In prospective tests, such modeling procedures have proven to predict accurately for response. It is evident that this methodology will be highly effective for selecting treatment for individual patients and for detecting improved treatments for patients who respond poorly to conventional treatment. For patients who achieve complete remission, the duration of that remission can also be evaluated by logistic regression analysis. Variables which predict for duration of remission have proven to be different from those variables which predict for probability of response. In addition, variables which predict for prolonged remission--that is, beyond 2 and 3 years--have proven to be different from variables which predict for relapse in the first year of remission. Therefore, the models which estimate risk of relapse per unit of time at risk should prove most valuable for evaluating not only the choice of treatments to be used during remission, but the duration of treatment and the strategy of treatment, that is, whether intensive treatment or low-dose intermittent treatment should be chosen. Finally, the demonstration that a significant fraction of the patients in complete remission will have long term disease-free and treatment-free survival makes the identification of such patients even more important. Evaluation of innovative higher-risk strategies for treatment of the patient in remission should be offered primarily to patients who have a low probability of having already been cured with conventional treatment. Thus, the rapid evolution of effective treatment for adult acute leukemia over the last 15 years has necessitated the development of more precise and more effective methods for evaluating the effects of those treatments on patients with this disease.     

Comparison of Different Methods for the Evaluation of Treatment Effects from the Sleep EEG of Patients with Major Depression

In healthy subjects, sleep has a typical structure of three to five cyclic transitions between different sleep states. In major depression, this regular pattern is often destroyed but can be reestablished during successful treatment. The differences between healthy and abnormal sleep are generally assessed in a time-consuming process, which consists of determining the nightly variations of the sleep states (the hypnogram) based on visual inspection of the electroencephalogram (EEG), electrooculogram, and electromyogram. In this study, three different methods of sleep EEG analysis (spectrum, outlier, and recurrence analysis) have been examined with regard to their ability to extract information about treatment effects in patients with major depression. Our data suggest that improved sleep patterns during treatment with antidepressant medication can be identified with an appropriate analysis of the EEG. By comparing different methods, we have found that many treatment effects identified by spectrum analysis can be reproduced by the much simpler technique of outlier analysis. Finally, the cyclic structure of sleep and its modification by antidepressant treatment is best illustrated by a non-linear approach, the so-called recurrence method.     

Ten ways to improve the treatment of depression and anxiety in adults

Complaints of depression and anxiety are very common among adult patients seeking treatment in primary care settings, and primary care providers prescribe the majority of medications for these conditions. Psychiatrists are often asked to evaluate and manage patients with major depression or anxiety disorders who have not improved after treatment in primary care.We highlight ten frequently overlooked aspects of the care of patients who present with depression and anxiety in primary care. Chief among these aspects is the consideration of a thorough differential diagnosis, particularly bipolar disorder, psychotic disorders, dementia and substance abuse, each of which requires specific treatment approaches. Additional considerations include avoidance of medications or doses that may aggravate anxiety symptoms and regular follow-ups to assess symptomatic and functional improvement. Finally, it is important to actively manage the treatment through dose escalation, switching medications or employing additional treatment components until remission is achieved.Judicious use of benzodiazepine clonazepam and appropriate referrals to psychotherapy can contribute to optimal treatment outcomes.