抗精神病药恶性症状群的临床分析

目的：了解抗精神病药致恶性症状群（NMS）的发生原因、临床特征、治疗及预后,并提出预防措施。方法：从住院病历中抽取使用抗精神病药物治疗的25678例患者,按Levenson等提出的NMS诊断标准诊断为NMS的患者24例并进行分析。结果：25678例患者中发生NMS率为0.93‰,发生年龄平均（32.6±7.8）岁,男女比例为1.7∶1,单一用药7例（29.2%）,其中使用氟哌啶醇4例（57.1%）;合并用药17例（70.8%）,其中使用长效制药11例（78.6%）。诱发NMS因素为脱水14例（58.3%）。共死亡1例（4.2%）。结论：NMS大多发生于青壮年,男比女约多1倍,有逐年下降趋势。单一使用氟哌啶醇或合并用药（尤其合并长效制剂）较易发生NMS。脱水是个体因素中诱发NMS的最危险因素。合理使用抗精神病药物,防治个体诱发因素可减少NMS的发生。早期发现和治疗有利于NMS的预后。     

Neuroleptic malignant syndrome during haloperidol treatment in a cancer patient

A case of neuroleptic malignant syndrome (NMS) in a 64-year-old man with cancer of the soft palate is reported. During haloperidol treatment for delirium, the patient showed consciousness disturbance with extrapyramidal signs. With discontinuation of haloperidol and replacement by dantrolene and bromocriptine, the patient recovered completely. Although major tranquilizers are widely used in clinical oncology to manage symptoms, NMS has been rarely reported in cancer patients, presumably because of lack of awareness. Early recognition of NMS and prompt treatment may improve the potentially fatal outcome.     

Neuroleptic malignant syndrome in a patient with head injury

Neuroleptic malignant syndrome is an idiosyncratic reaction associated with the use of neuroleptic drugs. We report a case of this rare syndrome in a head injury patient associated with some unusual features: rhabdomyolysis with a high level of creatine kinase, the development of acute renal failure, the early use of continuous venovenous haemofiltration in treatment and rigidity that was refractory to conventional treatment with dantrolene and bromocriptine. The diagnosis in patients with multiple injuries must be based on a high index of suspicion.     

Health Care Cost in Patients With Schizophrenia Treated With Brexpiprazole Versus Other Oral Atypical Antipsychotic Therapy

PurposeBrexpiprazole is an oral atypical antipsychotic (OAA) for the treatment of schizophrenia (SCZ). This study compared all-cause and psychiatric inpatient hospitalization and medical costs in adult patients with SCZ newly treated with brexpiprazole versus other US Food and Drug Administration–approved OAAs in a real-world setting.MethodsThis retrospective cohort study analyzed data from: (1) the IBM MarketScan Commercial and Medicare Supplemental databases, and the MarketScan Multi-State Medicaid database; and (2) the de-identified Optum Clinformatics Datamart. Adult patients were identified if they had SCZ and initiated either brexpiprazole or another OAA during the study identification period (July 1, 2015, to September 30, 2016, for MarketScan Commercial and Medicare Supplemental and for Optum; July 1, 2015, to June 30, 2016, for MarketScan Multi-State Medicaid) and had ≥12 months of continuous enrollment before (baseline) and after (follow-up) the first treatment date. Linear regression analyses were performed to test associations between treatment groups (brexpiprazole vs another OAA) and costs (total and medical); negative binomial regression models were used to estimate number of hospitalizations per year, adjusting for baseline characteristics and medication adherence to index treatment during the 12-month follow-up.FindingsThe final study sample consisted of 6254 patients with SCZ: 176 initiated brexpiprazole; 391, ziprasidone; 453, paliperidone; 523, lurasidone; 786, aripiprazole; 1234, quetiapine; 1264, olanzapine; and 1427, risperidone. Controlling for baseline characteristics and medication adherence, the adjusted number of hospitalizations (both all-cause and psychiatric), all-cause total costs, and all-cause medical costs did not differ across groups. Brexpiprazole users had the lowest mean psychiatric costs among all OAA users ($12,013; 95% bootstrap CI, 7488–16,538). Compared with brexpiprazole users, paliperidone (incidence rate ratio [95% CI], 1.52 [1.05–2.19]; P = 0.027) and quetiapine (incidence rate ratio [95% CI], 1.47 [1.04–2.07]; P = 0.029) users had more psychiatric hospitalizations per year. Paliperidone had higher psychiatric costs than brexpiprazole (total, $32,066 [95% bootstrap CI, 28,779–35,353] vs $23,851 [18,907–28,795]; medical, $19,343 [16,294–22,392] vs $12,013 [7488–16,538]). Psychiatric medical costs were also $6744 higher in olanzapine users (95% bootstrap CI, 1694–11,795; P = 0.009) than in brexpiprazole users.ImplicationsPatients with SCZ treated with brexpiprazole had fewer psychiatric hospitalizations and lower psychiatric costs than those treated with paliperidone. Differences in the number of all-cause hospitalizations and medical costs among treatments were not statistically significant. Although treatment decisions are driven by a number of factors (eg, clinical circumstances and drug costs), choice of OAA may affect health care costs.     

1例儿童无症状预激综合征的循证治疗

目的为1例无症状预激综合征儿童患者循证制定治疗方案。方法针对无症状预激综合征患儿是否需要进行预防性射频消融的问题，以“asymptomatic WPW syndrome”为检索词，全面检索Cochrane图书馆（2007年第3期）、MEDLINE（1981—2007）、OVID ACP Journal Club（1991—2007）、BM JClinical Evidence（1999～2007）以及美国国家指南交换中心（1998～2007），获取并评价相关的系统评价、随机对照试验、临床对照试验证据及治疗指南，并将最佳证据用于临床治疗。结果从MEDLINE检索到2篇随机对照试验，结果表明：高危对照组与消融组相比，心律失常事件发生显著增加，高危对照组中多旁道患者比单旁道患者心律失常事件发生显著增加。据此，我们结合医生经验和家长意愿，针对该例患者电生理检查示右侧显性旁道和左侧隐匿性旁道，进行预防性射频消融治疗。出院至今已12个月，未再出现心血管方面的并发症。结论对高危无症状预激综合征患儿进行预防性射频消融安全、有效。     

严重急性呼吸综合症与非典型肺炎X线对比研究

目的 对比严重急性呼吸综合症与非典型肺炎X线诊断价值。方法 回顾分析严重急性呼吸综合症59例与非典型肺炎39例，进行对比研究。结果 全部病例肺部病变分布可单叶或单叶，可单侧或双侧。根据病变发展的不同时期，肺内可见斑片模糊影，条索及粗网状影，肺实变影，细网状或局灶细网状影。结论 严重急性呼吸综合症与非典型肺炎x线表现相似，无特异性。X线检查是严重急性呼吸综合症确诊重要的客观指标之一。     

Decreased Pain and Improved Quality of Life in Fibromyalgia Patients Treated with Olanzapine, an Atypical Neuroleptic

Abstract:   Fibromyalgia is a significant clinical problem associated with generalized pain and significant interference with daily activities. Although a variety of treatment modalities have been utilized, clinicians have struggled to find an effective means of treatment. Therefore, this study assessed the efficacy of the atypical neuroleptic olanzapine for the treatment of fibromyalgia symptoms. To examine the efficacy of olanzapine for the treatment of fibromyalgia symptoms, the charts of 51 patients treated with olanzapine were evaluated for improvements in pain and daily life functioning. At the time of initial assessment, patients had been diagnosed with a variety of medical and psychiatric disorders and a history of neuroleptic treatment. Pain was widespread and characteristic of pain associated with fibromyalgia. Pretreatment ratings on pain and the interference scales averaged 6.54–8.69 on a 0–10 scale. Post-treatment ratings on the same scales revealed significant improvement on virtually all scales. The benefits of olanzapine to improve fibromyalgia symptoms must, however, be carefully considered because there were a variety of side effects (i.e., weight gain, somnolence/sedation) that were of sufficient strength to cause a number of patients to discontinue treatment. In general, the data provide strong support that olanzapine can, in certain patients, improve symptoms associated with fibromyalgia in patients who have had limited success with other treatment modalities.     

Neuroleptic malignant syndrome associated with olanzapine therapy: a case report

We present the case of a 42-year-old male with a history of schizophrenia who developed signs and symptoms consistent with Neuroleptic Malignant Syndrome (NMS) after 3 weeks of treatment with Olanzapine. The patient presented with hyperpyrexia, tremors, labile blood pressure, and mental status changes that had progressed over the preceding 24 h. Laboratory data revealed a metabolic acidosis and an escalating creatinine phosphokinase. Olanzapine is a relatively new atypical anti-psychotic agent first introduced in November of 1996 under the trade name of zyprexa. Olanzapine differs from typical anti-psychotic agents in that it has a lower affinity for dopaminergic receptors and binds antagonistically to serotonin receptors in the nigrostriatal pathway. These unique properties result in relatively fewer extra-pyramidal symptoms when compared to traditional anti-psychotics. Because of olanzapine’s favorable side-effect profile, it has quickly gained popularity in the psychiatric community. Although NMS is a recognized complication of anti-psychotic use, there has been only one case of olanzapine induced NMS reported in the literature. The POISONINDEX system, used by toxicologists throughout the United States, does not list NMS as a potential reaction to olanzapine. The pharmacists at our institution were also unaware that NMS was a possible complication of olanzapine. We present this case to make clinicians aware of the potential for Olanzapine induced NMS.     

抗精神病药物致恶性症状群的护理

总结6例抗精神病药物所致恶性症状群的临床特征及护理对策。提高对本病的认识水平和护理质量，是早发现、早治疗，预防并发症、降低死亡率的关键。     

Atypical meningococcal meningitis with rashless presentation: A case report

Meningococcal disease is the major health problem in developing world. The clinical presentation is varied, ranging from transient fever and bacteraemia to fulminant disease with death ensuing within hours of the onset of clinical symptoms. The classical clinical manifestations of meningococcal disease have been well described, but atypical presentations if unrecognized, may lead to a delay in treatment and fatal outcome. We here report a case presented with atypical presentation of meningococcal meningitis without classical rash, which was diagnosed and managed successfully.     

Pain Management of Malignant Psoas Syndrome Under Epidural Analgesia During Palliative Radiotherapy

Malignant psoas syndrome is a rare malignant condition presenting as lumbosacral plexopathy and painful fixed flexion of the hip. Metastasis to the psoas muscle is observed, which damages the nerve bundles in the lumbosacral plexuses. The syndrome presents as refractory lower back pain with several other neurological symptoms. The pain is difficult to control because it is a mixture of nociceptive and neuropathic pain, which indicates that treatment requires a versatile approach. The authors report a case of severe back pain caused by metastasis to the psoas muscle of advanced gastric cancer in a patient who underwent palliative radiotherapy under epidural analgesia. Despite conventional analgesics and subcutaneous oxycodone, he had difficulties in maintaining supine position because of the back pain and had a problem to receive radiotherapy, which required him to stay still in the same position during the treatment. By epidural analgesia, he could remain in supine position and complete radiotherapy without increasing opioid administration. His back pain was improved after the radiotherapy. Epidural analgesia is an effective treatment choice for a patient who is unable to keep the position during palliative radiotherapy.     

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis: an etiology worth considering in the differential diagnosis of delirium

Abstract

Background. Medical toxicologists are frequently consulted when young patients present with delirium attributed to suspected poisoning. Medical toxicologists should be aware of non-toxicological mimics of delirium. We describe two patients ultimately diagnosed with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis for which a toxicological consultation was requested to evaluate for neuroleptic malignant syndrome (NMS). Case 1. A 21 year old male was sent from a psychiatric facility for new, worsening psychotic symptoms. He had autonomic instability, confusion, and hyper-reflexia. He was treated for NMS without improvement, and after an extensive workup was unrevealing, he was discharged home with significant cognitive dysfunction. Stored CSF later tested positive for anti-NMDAR antibodies. Case 2. A 27 year old female was sent from a psychiatric facility for a seizure and new psychiatric symptoms. She was agitated and had violent, alternating extremity flexion and extension along with autonomic instability. She was treated for NMS, rhabdomyolysis, and rabies before analysis of CSF demonstrated anti-NMDAR antibodies. Treatment included surgical resection of a suspicious ovarian cyst, steroids and IVIG, with moderate improvement. Discussion. Autoimmune syndromes of the central nervous system result from receptor dysfunction after an antibody response to extracellular or intracellular antigens, such as subunits of the NMDA receptor. The NMDA subunits NR2b and NR2a, in addition to the N-terminal region of the glycine binding NR1 subunit, have been implicated. Typical features such as memory loss, movement disorders, and hallucinations reflect the density and distribution of neuronal NDMA receptors. As young people, particularly young women, are predominantly affected, initial symptoms may be attributed to encephalopathy from drug abuse or schizophrenia. Toxicologists may be consulted as many features mimic NMS. Serum and cerebrospinal fluid can be checked for anti-NMDAR antibodies as part of a paraneoplastic or meningioencephalitis panel. Effective treatments have been described and include surgical resection and immunosuppressive medications.     

A Prospective Flexible-Dose Study of Paliperidone Palmitate in Nonacute But Symptomatic Patients With Schizophrenia Previously Unsuccessfully Treated With Oral Antipsychotic Agents

Purpose

The goal of this study was to explore the tolerability, safety, and treatment response of flexible doses of once-monthly paliperidone palmitate (PP) in the subset of nonacute but symptomatic adult patients with schizophrenia previously unsuccessfully treated with oral antipsychotic agents in the PALMFlexS (Paliperidone Palmitate Flexible Dosing in Schizophrenia) study.

Methods

This was an interventional, single-arm, international, multicenter, unblinded, 6-month study performed in patients with schizophrenia. Patients were categorized according to reasons for switching. In patients switching because of lack of efficacy or for other reasons, primary efficacy outcomes were the proportion achieving treatment response (defined as ≥20% improvement in Positive and Negative Syndrome Scale [PANSS] total score from baseline to last-observation-carried-forward end point) and maintained efficacy (defined as noninferiority in the change in PANSS total score at end point versus baseline [Schuirmann’s test]), respectively.

Findings

A total of 593 patients (intention-to-treat population) were enrolled: 63.1% were male; their mean (SD) age was 38.4 (11.8) years; and 78.6% had paranoid schizophrenia. The main reasons for transition to PP were patient’s wish (n = 259 [43.7%]), lack of efficacy (n = 144 [24.3%]), lack of compliance (n = 138 [23.3%]), and lack of tolerability (n = 52 [8.8%]) with the previous oral antipsychotic medication. The recommended PP initiation regimen (150 milligram equivalents [mg eq] day 1 and 100 mg eq day 8) was administered in 93.9% of patients. Mean PANSS total score decreased from 71.5 (14.6) at baseline to 59.7 (18.1) at end point (mean change, –11.7 [15.9]; 95% CI, –13.0 to –10.5; P < 0.0001). Sixty-four percent of patients showed an improvement of ≥20% in PANSS total score, and the percentage of patients rated mildly ill or less in Clinical Global Impression–Severity increased from 31.8% to 63.2%. Mean personal and social performance total score (SD) increased (ie, improved) significantly for all patients from baseline to end point (58.1 [13.4] to 66.1 [15.7]; P < 0.0001).

Implications

The PALMFlexS study is a pragmatic interventional study compared with randomized controlled trials, conducted in a large, more representative sample of patients with schizophrenia, and designed specifically to mimic real-world clinical situations. The findings support the results from randomized controlled studies. They also demonstrate that a clinically relevant treatment response is possible in patients who are considered to be clinically stable by their physician, supporting the use of flexibly dosed PP in such patients. Clinical trials.gov number: NCT01281527.     

Adenosine Induced Torsades de Pointes in a Child with Congenital Long QT Syndrome

Torsades de pointes is a rare arrhythmia characterized by its bradycardia dependence and increased adrenergic discharge, whether it occurs as a congenital anomaly or as an acquired problem resuiting from drug intoxication or other conditions. There are no reliable tests to assess the propensity toward torsades de pointes or evaluate the efficacy of treatment in these patients. Adenosine can result in marked slowing of sinus and ventricular rate and leads to increased sympathic discharge when given intravenously. We induced torsades de pointes in a child with congenital long QT syndrome (Jervell-Lange-Nielsen syndrome) using 200 μg/kg IV adenosine bolus. Higher dosage of adenosine (600 μg/kg) did not lead to torsades de pointes after β blockade. Adenosine may induce torsades de pointes in patients with the long QT syndrome and may be used as a test to reproduce the clinical arrhythmia. Whether adenosine proves to be useful for assessing the efficacy of treatment will require extensive investigation in larger series of patients.     

Malignant glaucoma presenting with uncontrolled intraocular pressure and myopic refractive surprise after cataract surgery

We present a seemingly typical case of bilateral angle closure with elevated intraocular pressures. After cataract surgery, there was axial shallowing, escalating intraocular pressure, anterior displacement of the IOL, and myopic shift in the left eye. Irido‐zonulo‐hyaloido‐vitrectomy resolved the angle closure, normalized intraocular pressure, and corrected the myopic shift.