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By C. Marik. North Georgia College and State University, the Military College of Georgia.

For observational studies discount 2mg coumadin with amex, additional elements such as methods for selection of participants cheap coumadin 2 mg on line, measurement of interventions/exposures 5 mg coumadin visa, addressing any design-specific issues order 1mg coumadin otc, and controlling for confounding were considered buy cheap coumadin 2mg line. To indicate the summary judgment of the quality of individual studies, we used the summary ratings of good, fair, or poor based on the classification scheme presented in Table 2. Definitions of overall quality ratings Quality Rating Description Good A study with the least bias; results are considered valid. A good study has a clear description of the population, setting, interventions, and comparison groups; uses a valid approach to allocate patients to alternative treatments; has a low dropout rate; and uses appropriate means to prevent bias, measure outcomes, and analyze and report results. Fair A study that is susceptible to some bias but probably not enough to invalidate the results. The study may be missing information, making it difficult to assess limitations and potential problems. As the fair-quality category is broad, studies with this rating vary in their strengths and weaknesses. The results of some fair-quality studies are possibly valid, while others are probably valid. Poor A study with significant bias that may invalidate the results. These studies have serious errors in design, analysis, or reporting; have large amounts of missing information; or have discrepancies in reporting. The results of a poor-quality study are at least as likely to reflect flaws in the study design as to indicate true differences between the compared interventions. Studies of different designs were graded within the context of their respective designs. Thus, RCTs were graded good, fair, or poor, and observational studies were separately graded good, fair, or poor. Data Synthesis We began our data synthesis by summarizing key features of the included studies for each KQ: patient characteristics; clinical settings; interventions; and intermediate, final, and adverse event outcomes. We grouped interventions by drug class; in this context, we considered all nondihydropyridine calcium channel blocker drugs to be similar enough to be grouped together and all beta blocker drugs to be similar enough to be grouped together. Similarly, we categorized procedures into electrical cardioversion, atrioventricular node (AVN) ablation, AF ablation by pulmonary vein isolation (either open surgical, minimally invasive, or transcatheter procedures), and surgical Maze procedures, and explored comparisons among these categories. For the KQs focusing on pharmacological agents versus procedures (KQ 3 and KQ 5), we also explored grouping all pharmacological agents together and comparing them to all procedures. Finally for 12 our evaluation of rate- versus rhythm-control strategies (KQ 6), we grouped all rate-control strategies together and all rhythm-control strategies together regardless of the specific agent or procedure. We determined the appropriateness of a quantitative synthesis (i. Where at least three comparable studies reported the same outcome, we used random-effects models to synthesize the available evidence quantitatively using Comprehensive Meta-Analysis software (Version 2; Biostat, Englewood, NJ). We tested for heterogeneity using graphical displays and test statistics 2 (Q and I statistics), while recognizing that the ability of statistical methods to detect heterogeneity may be limited. For comparison, we also performed fixed-effect meta-analyses. We present summary estimates, standard errors, and confidence intervals in our data synthesis. Unless noted otherwise, when we were able to calculate odds ratios (ORs), we assumed that an OR between 0. We anticipated that intervention effects might be heterogeneous. Where there were sufficient studies, we performed subgroup analyses and/or meta-regression analyses to examine these hypotheses. Strength of the Body of Evidence We rated the strength of evidence for each KQ and outcome using the approach described in 22,136 the Methods Guide. In brief, the approach requires assessment of four domains: risk of bias, consistency, directness, and precision (Table 3). Strength of evidence—required domains Domain Rating How Assessed Risk of bias Low Assessed primarily through study design (RCT versus Medium observational study) and aggregate study quality High Consistency Consistent Assessed primarily through whether effect sizes are generally on Inconsistent the same side of “no effect” and the overall range of effect sizes Unknown/not applicable Directness Direct Assessed by whether the evidence involves direct comparisons or Indirect indirect comparisons through use of surrogate outcomes or use of separate bodies of evidence Precision Precise Based primarily on the size of the confidence intervals of effect Imprecise estimates Abbreviation: RCT=randomized controlled trial Additional domains were used when appropriate: strength of association (magnitude of effect) and publication bias (as assessed through a search of ClinicalTrials. These domains were considered qualitatively, and a summary rating of “high,” “moderate,” or “low” strength of 13 evidence was assigned after discussion by two reviewers.

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Plucking may be con- dysfunction in association cortex order coumadin 5mg visa. Clearly purchase 5 mg coumadin mastercard, much remains to fined to a single patch generic 5 mg coumadin with mastercard, may involve different areas buy 5 mg coumadin with mastercard, or may be done to understand the neuroanatomy of SIB generic coumadin 2mg line, and in- cover the entire scalp. Some patients also report pulling hair deed to integrate behavioral and biological findings in this from a child, significant other, or pet. Patients with hair pulling may demonstrate a range of other stereotypic and self-injurious behaviors (70,71). Indeed, both the personal and the economic costs of this disorder may Compulsive self-injurious behavior is only rarely seen in be significant. Awide range of behaviors may be seen, particularly head banging and self-punching or slapping, but also including lip biting and tongue biting, Neurochemistry eye poking, skin picking, and self-punching or -slapping. Research on the neurobiology of hair pulling was boosted Medical complications have included subdural hematoma by a seminal trial comparing clomipramine and desipramine and vision impairment. As in OCD, trichotillomania re- In a large study, SIB in TS was not correlated with intel- sponded selectively to the SSRI. Nevertheless, although the lectual function, but was significantly associated with sever- SSRIs have seemed effective for trichotillomania in a num- ity of motor tics and with scores of hostility and obsession- ber of open trials, these agents have proved disappointing ality (68). Furthermore, SIB has been described as one of in placebo-controlled trials (72). Thus, although the neurobiology of SIB trichotillomania response to clomipramine may be sustained per se in TS has not been well studied, it is possible that over time, there are also reports that initial response to SSRIs this overlaps with that underlying tics and compulsions. Taken together, this work indicates that it may be premature to overly emphasize the specific role of Neurochemistry serotonin in trichotillomania. Several neurochemical systems have been implicated in TS, Indeed, few studies of trichotillomania patients have di- most notably the dopamine system, but including also the rectly assessed monoamine concentrations. Ninan and col- serotoninergic, noradrenergic, opiatergic, hormonal, and leagues (73) obtained CSF from a small group of patients immunologic systems (see Chapter 117). However, to our with trichotillomania and found that CSF 5-HIAA levels knowledge little of this work has focused specifically on the did not differ from normal controls. This finding is redolent of some work on OCD and suggests that in both disorders response to SSRIs may Neuroanatomy be accompanied by a fall in CSF 5-HIAA levels. From a neuroanatomic perspective, there is strong evidence There are also few studies of serotoninergic pharmaco- that prefrontal–basal ganglia–thalamic circuits are involved logic challenges in trichotillomania. There is also increasing evidence that these circuits (74) found that the 5-HT agonist m-chlorophenylpipera- are among those that mediate TS (see Chapter 117). Of zine (mCPP), which has exacerbated OCD symptoms in note, increased metabolism in the orbitofrontal cortex and some studies, did not lead to an increase in hair pulling in putamen correlated with complex behavioral and cognitive women with trichotillomania (74). The interpretation of features such as self-injurious behavior (69). As in OCD, these data is not straightforward; for example, whereas further work is needed to determine whether this reflects a OCD symptoms may be present throughout the day, hair primary deficit or functional compensation. Of in- 1750 Neuropsychopharmacology: The Fifth Generation of Progress terest, however, trichotillomania subjects described an in- also been partly consistent with involvement of the CSTC crease in feeling 'high,' a phenomenon previously docu- system in trichotillomania (74). Furthermore, a few studies mented in patients with borderline personality disorder. It of brain imaging in trichotillomania have now been under- might be speculated that hair pulling in trichotillomania taken. There is some prelimi- umes in trichotillomania and controls on MRI, but did nary data that dopamine also plays a role in hair pulling. This finding is of particular interest given phenidate in a series of children (75). Asimilar phenome- work demonstrating reduced left putamen volumes in non can be seen in adults with trichotillomania. The atypical neuroleptics, illomania patients compared with normal controls. This which have dopamine and serotonin antagonist effects, may finding does not seem to support the hypothesis that orbito- also be effective augmenting agents in OCD and trichotillo- frontal–basal ganglia circuits are key to this disorder, and mania (78). Christenson and colleagues found no significant differ- However, patients were scanned at rest, rather than during ences in either pain detection or pain tolerance thresholds hair pulling or during the performance of a neuropsycho- between trichotillomania patients and controls. On the logical test that might have activated these structures.

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Journal Behavioural Therapy and Experimental Psychiatry 2011; 22:414-421 2mg coumadin free shipping. Using ECT in schizophrenia: a review from a clinical perspective order coumadin 1mg otc. World Journal of Biological Psychiatry 2012; 13: 96-105 order 2 mg coumadin overnight delivery. Hallucinations are false sensory perceptions – that is discount coumadin 1mg with visa, perceptions in the absence of external stimuli – i buy generic coumadin 5 mg on line. Hallucinations may result in secondary delusions – that is, they may lead in inaccurate “explanations” of what is happening. Such experiences have been recorded over hundreds of years. Not to offend anyone – but the religious traditions describe similar phenomena. Sigmund Freud, the father of psychoanalysis wrote, “During the days when I was living alone in a foreign city…. I quite often heard my name suddenly called by an unmistakable and beloved voice…. Mahatma Gandhi relied on an “inner voice” for guidance. Toward the end of his life the voice said, “You are on the right track, move neither to your left, nor right, but keep to the straight and narrow. Professor Henry Sidgewick conducted the “International Census of Waking Hallucinations in the Sane”, in the 1890s. Seventeen thousand people from England, Russia and Brazil were surveyed. Nearly 10% reported they had experienced an unexplained perception; 2. A recent review of publications about “voice-hearing” by healthy individuals was frustrated by the different definitions employed and the very wide ranges reported, but found a median of 13. A recent study of healthy 12-19 year olds, in Ireland, found auditory hallucinations in 13. Thus, healthy people may, from time to time, hear voices. Care has been taken in these paragraphs to avoid calling these experiences, hallucinations - but these experiences do satisfy the technical definition. Briefly, there are usually differences between the voices heard by healthy individuals and the hallucinations of those with mental disorders. In healthy individuals, the voice is usually as if from one person, speaking comprehensibly, in a helpful and comforting manner. Auditory hallucinations in mental disorders, in contrast, may involve more than one voice, sometimes arguing, sometimes commenting about the patient, frequently making little sense, often in a threatening or frightening manner. Hallucinations associated with non-mental disorder conditions Epilepsy may feature hallucinations. Frederic Chopin experienced hallucinatory episodes throughout his life – possibly the result of epilepsy (Vazqez & Branas, 2011). Charles Bonnet syndrome is the experience of nonthreatening visual hallucinations experienced by patients who free of neurological and psychiatric disorder, but who have significant visual impairment secondary to ocular disease (Jackson & Madge, 2011). Other forms of sensory deprivation and fatigue may also lead to hallucinations. Hallucinations may occur with many other brain disorders including tumour, multiple sclerosis, and the very recently described Autoimmune Encephalitis (see Chap 36) – in these organic conditions, visual hallucinations are the most common. Three models of psychosis (Dopamine, Glutamate and Serotonin) have been proposed, based on the triggering substance (Rolland et al, 2014). Hallucinations – three models Pharmacological trigger Molecular effects 1. Dopamine Psychostimulants: cocaine, amphetamine Increased dopamine Model transmission, and hyperactivation of dopamine D2 receptor. Serotonin Psychedelics: lysergic diethylamid (LSD), Stimulation of the serotoninergic Model psilocybin 5HT2A receptor Table. Hallucinations – three potential neurobiological mechanisms, based on the production of hallucinations by pharmacological triggers. Hallucinations in mental disorders Pathological hallucinations take many forms.

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To the contrary generic coumadin 5mg visa, the for data that might better inform the use of prescription choice of patient subject is almost always based on the spon- drug products in children discount coumadin 1 mg otc. This sampling strategy is not of investigational drugs in children a premarket obligation cheap 5mg coumadin with visa. In some patients with the condition for which the treatment 1998 discount coumadin 2mg with mastercard, however 5 mg coumadin fast delivery, the agency issued new regulations (21 CFR will be marketed. For example, prior to the of the patient samples that had been employed in them promulgation of DSM-III in 1980, sedatives, as they were and whether or not long-term maintenance trials had been then known, were granted broad and nonspecific claims for conducted. The strategy employed was intended to reserve anxiety, anxiety neurosis, etc. In recent years, claims have been chotic conditions other than schizophrenia. In dealing with these drugs shown to be effective in studies enrolling schizo- issues, the agency has to consider whether or not already phrenic patients will get claims for use in schizophrenia, approved older claims subsume the new entities. Incidentally, the newly announced approach claim simply a re-expression of a previous one, a claim for to product labeling is perfectly reasonable and certainly con- a subset of the patients covered by the previously approved sistent with the requirements of law, although it is obviously claimed use, or an entirely new claim for a previously nonex- not the one that the author prefers. Drugs are administered to individ- of related claims may be. For example, sponsors often seek uals, not diagnoses. There is advantage in knowing, there- to define a claimed use in a way that will allow the unique fore, whether, and if so how and to what extent, various promotion of their drug product (i. Claims advanced by sponsors for the use of sponse rates among samples of patients assigned identical marketed antipsychotic drug products in the management psychiatric diagnoses documents that our current psychiat- of psychotic demented patients are a case in point. As a consequence, to dem- regularly deemed to be pseudospecific, in the absence of onstrate that their products are effective in use, sponsors evidence to prove the contrary. As discussed, from a far as the author can determine, came about because the strictly regulatory perspective such criticisms are irrelevant. Support for other and/or more demanding standards for establishing the existence of this entity derived primarily from the testi- drug effectiveness, but it did not. Although there is little doubt that the algo- rather than a true drug effect, accounts for the positive study rithm endorsed by the PDAC does capture demented indi- reports submitted in the application. Reviewers search for evidence that classes of drugs to be something else: nutriceuticals, botani- the randomization process failed, the treatment mask was cals, food supplements, etc. These substances escape the penetrated, subjects failed to comply with protocol require- premarket drug clearance requirements of the FDDCA be- ments, etc. The extent, pattern, and timing of premature cause they are deemed by DSHEA not to be drugs. Subsumed within the ill-described mix of botanicals, equal). The lack of data bearing on the safety and efficacy of THE FUTURE OF DRUG REGULATION these drug substances did not deter the Congressional Lead- ership, however; to the contrary, when Senator Orin Hatch, These are, at once, the best of times and the worst of times a sponsor of DSHEA, introduced the bill he asserted that for medical therapeutics. In my own hold sanguine expectations for the future in regard to the state of Utah, healthy life-styles, coupled with common use discovery and development of effective new treatments. On of dietary supplements have made a real difference. Our the other hand, the armamentarium stands at increasing state is one of the healthiest in the nation and we enjoy one risk of being polluted by worthless, even unsafe drugs. Signs of the lowest incidence rates for cancer and heart disease. In Utah, the use of herbs is a well-accepted practice that The public is gullible and uncritical where therapeutic has passed from generation to generation (18). Even more alarming is the infer- lars on unproved, perhaps unsafe, remedies and nostrums. It is arguable whether such dual demonstrated that it can, with the limited authority it has expectations truly advance the interests of the public health, under the FFDCA, serve as an effective guardian of the however. As the former head of the FAA noted when she drug supply. An egregious and illuminating example of its scientific, and health care communities. Princeton, NJ: Princeton University Press, By what is as close to an Orwellian 1984-like maneuver 1970:151–174. Berkeley: University of psychiatric drugs: an historical context.

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People with factitious disorder are accepted as legitimate patients; it is argued that they have emotional needs (as we all do) generic 5 mg coumadin free shipping, but lack understanding of their own emotional life purchase coumadin 1mg amex, and the ability to satisfy their emotional needs in more appropriate/adaptive ways purchase coumadin 5 mg on line. Last modified: November discount coumadin 1 mg without a prescription, 2017 3 Three types have been described: 1 cheap 5mg coumadin with amex. Women (72%) - frequently (66%) working in health related areas (Krahn et al, 2003). Typically, they do not travel to present at different treatment centres. Often have a history of emotional deprivation and current sexual and/or relationship problems. The term “factitious nurses” has been applied (Kanaan & Wessely, 2010). He frequently travels from one treatment centre to another, often in different cities. There are usually also self-aggrandizing lies (pseudologia fantastica) – which led to the condition being named for Baron Munchausen. This is a distinct problem and will be dealt with under a separate heading. Factitious disorder most commonly presents with physical complaints. The prevalence is difficult to estimate, however, estimates include that 0. The prevalence probably varies with speciality, with up to 15% of presentations to neurologists and dermatologists involving factitious symptoms (McCullumsmith & Ford, 2011). The prevalence of factitious disorder among psychiatric patients is unclear. Catalina et al (2008) to identify factitious behaviour in psychiatric inpatients - developed an 8 criteria suspicion of factitious disorder test - the identification threshold - 3 positive criteria responses. Using this tool they found 8% of psychiatric inpatients demonstrated factitious behaviour. Inconsistent symptoms (with respect to presenting syndrome) 3. Disappearance of symptoms immediately after admission 5. Appearance of symptoms similar to those of other patients 7. Claimed background of non-verified physical or emotional disorders Pridmore S. Last modified: November, 2017 4 While people with factitious disorder want to be patients, they do not (usually) want to be psychiatry patients. This may be because psychiatry is a low status speciality or does not provide the preferred type of care. Other factors may be that being referred to psychiatry suggests that the doctors believe there is no pressing organic problem. When people with factitious disorder are confronted with irrefutable evidence of feigning, they usually angrily refute the irrefutable, or cry and flee the scene (Hamilton et al, 2009), then represent at another hospital, or the same one using a different name. The treatment of people with factitious disorder is difficult and there is little evidence (yet) to guide the clinician. Eastwood and Bisson (2008) reviewed all available case studies and series. They found there was no difference in outcome whether or not 1) patients were confronted with true nature of their behavior, 2) psychotherapy was provided, or 3) psychiatric medication was provided. Occasionally, it is possible to encourage these patients into a therapeutic relationship to address the difficulties of their psychological lives. They have usually suffered emotionally deprived early lives, often coming from homes where illness has been a prominent feature. Often, relatives have also presented with factitious disorder. The aim of treatment is for the patient to gain insight into their emotional lives and learn more adaptive methods of communicating their emotional needs and dealing with their distress. This calls for a long-term commitment by both the patient and the treating clinicians. Psychotherapy of most forms (in spite of the findings of Eastwood and Bisson (2008)) may have something to offer.

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