Antidepressants: update on new agents and indications

A number of antidepressants have emerged in the U.S. market in the past two decades. Selective serotonin reuptake inhibitors have become the drugs of choice in the treatment of depression, and they are also effective in the treatment of obsessive-compulsive disorder, panic disorder, and social phobia. New indications for selective serotonin reuptake inhibitors include post-traumatic stress disorder, premenstrual dysphoric disorder, and generalized anxiety disorder. Extended-release venlafaxine has recently been approved by the U.S. Food and Drug Administration for the treatment of generalized anxiety disorder. Mirtazapine, which is unrelated to the selective serotonin reuptake inhibitors, is unique in its action--stimulating the release of norepinephrine and serotonin. The choice of antidepressant drug depends on the agent's pharmacologic profile, secondary actions, and tolerability. Sexual dysfunction related to the use of antidepressants may be addressed by reducing the dosage, switching to another agent, or adding another drug to overcome the sexual side effects. Augmentation with lithium or triiodothyronine may be useful in patients who are partially or totally resistant to antidepressant treatment. Finally, tapering antidepressant medication may help to avoid discontinuation syndrome or antidepressant withdrawal.     

Metabolic acidosis and generalized seizures secondary to citalopram overdose: a case report

Selective serotonin re‐uptake inhibitors (SSRIs) are widely used in the community for treating many forms of mental illnesses. Citalopram, a newer generation SSRI, is commonly prescribed, but despite its low toxicity profile has a potential to cause seizures and dysarrythmias in overdose. Data on citalopram overdose‐induced metabolic acidosis are scarce. There have been only three cases of metabolic acidosis reported in the literature due to citalopram overdose in humans and we are reporting the fourth one. We report a case of citalopram overdose with metabolic acidosis and generalized seizure. To our best knowledge, this is the first case reported in Saudi Arabia.     

Anticonvulsant and neuroprotective effects of apelin-13 on pentylenetetrazole-induced seizures in male rats

Epilepsy is a common neurological disorder with no effective treatment or cure. Neuropeptide apelin is an endogenous ligand of angiotensin receptor-like 1 (APJ). It has been shown that apelin has protective and anti-neurodegenerative properties. This study was designed to evaluate the effect of apelin-13 on pentylenetetrazole (PTZ)-induced rat model of seizure. Adult male Wistar rats were divided into the experimental groups as follows: control group receiving PTZ; apelin-treated group which received apelin-13 before PTZ; apelin + F13A-treated group which received apelin-13 plus the apelin receptor antagonist (F13A) before PTZ; apelin + naloxone group which received apelin-13 + naloxone before PTZ. Behavioral scoring was used to access seizure. The expression level of APJ was measured by western blotting. Neuronal degeneration, apoptosis and astrocyte activation were evaluated by vanadium acid fuchsin (VAF) staining and immunohistochemistry. Our data demonstrated that apelin-13 pretreatment significantly inhibited seizure threshold (p < 0.001) and tonic-clonic latency (p < 0.001) compared with the control group. In addition, PTZ-induced up-regulation of APJ was attenuated by apelin-13 treatment. Histological and immunohistochemical findings also showed that apelin-13 could protect cortical neurons against PTZ-induced neuroinflammation and apoptosis. In conclusion, apelin-13 has anticonvulsive and neuroprotective properties against PTZ-induced seizure in rats and provided a new pharmacological aspect of the neuropeptide apelin.     

Acute lamotrigine overdose: a systematic review of published adult and pediatric cases

Context: Lamotrigine is a broad-spectrum anticonvulsant commonly used to treat seizure and bipolar mood disorders. Evidence from case series and retrospective studies indicate that lamotrigine overdose is usually benign. However, there are reported cases of cardiac arrest and mortality following lamotrigine overdose. We undertook a systematic review of the literature on lamotrigine overdoses to better understand the clinical severity, the relevance of serum concentrations, and therapeutic interventions for overdose.

Objectives: To characterize manifestations of acute lamotrigine overdose, determine if serum concentrations predict poisoning severity, and evaluate the effectiveness of overdose management interventions.

Methods: We performed a literature search across eight databases, including Medline, EMBASE, and the Cochrane Library, from database inception to April 2014. Major bibliographic databases were updated on 31 May 2017. Articles were eligible if they described acute or acute on chronic lamotrigine overdose. At least one serum lamotrigine concentration had to be reported for inclusion. Reports on chronic poisoning, studies describing adverse effects of therapeutic use, and animal studies were excluded.

Results: We retrieved 6238 records; 48 (51 cases) met the inclusion criteria. Cases primarily involved adults (70.6%). Potentially life-threatening symptoms of overdose included seizures (55%), Glasgow Coma Scale ≤8 (20%), hypotension (12%), and wide complex tachycardia (WCT) and cardiac arrest (6%). Among the 25 cases exposed to lamotrigine alone (13 adult; 12 pediatric), 2 adult fatalities occurred (4?g and 7.5?g ingested) and 8 pediatric cases experienced seizures (all children ≤3.5-years-old, 75% without an underlying seizure disorder,?≥?525?mg ingested). The lowest seizure-associated serum concentration was 3.8?mg/L and 25.6?mg/L for pediatric and adult patients, respectively, suggesting children may be more susceptible to CNS toxicity. Cardiovascular toxicities occurred primarily in adult patients (threshold >25?mg/L). Overdose interventions included benzodiazepines (53%), propofol or barbiturates (14%), NaHCO₃ (20%), lipid therapy (12%), and extracorporeal elimination (10%). NaHCO₃ yielded no response in four of nine cases with conduction delays; however, two of the four cases subsequently responded with lipid therapy.

Conclusions: Most cases reporting lamotrigine exposures observed mild or no toxicity; however, large exposures were associated with severe CNS depression, seizures, cardiac conduction delays, wide complex tachycardia, and death. In adults with a serum concentration >25?mg/L, severe toxicity may occur. In patients ≤3.5 years of age, ingestions of ≥525?mg may produce severe CNS depression and seizures.     

Antidepressants and anticonvulsants for diabetic neuropathy and postherpetic neuralgia: a quantitative systematic review

To determine the relative efficacy and adverse effects of antidepressants and anticonvulsants in the treatment of diabetic neuropathy and postherpetic neuralgia, published reports were identified from a variety of electronic databases, including Medline, EMBASE, the Cochrane Library and the Oxford Pain Relief Database, and from two previously published reviews. Additional studies were identified from the reference lists of retrieved reports. The relative benefit (RB) and number-needed-to-treat (NNT) for one patient to achieve at least 50% pain relief was calculated from available dichotomous data, as was the relative risk (RR) and number-needed-to-harm (NNH) for minor adverse effects and drug related study withdrawal. In diabetic neuropathy, 16 reports compared antidepressants with placebo (491 patient episodes) and three compared anticonvulsants with placebo (321). The NNT for at least 50% pain relief with antidepressants was 3.4 (95% confidence interval 2.6–4.7) and with anticonvulsants 2.7 (2.2–3.8). In postherpetic neuralgia, three reports compared antidepressants with placebo (145 patient episodes) and one compared anticonvulsants with placebo (225), giving an NNT with antidepressants of 2.1 (1.7–3) and with anticonvulsants 3.2 (2.4–5). There was little difference in the incidence of minor adverse effects with either antidepressants or anticonvulsants compared with placebo, with NNH (minor) values of about 3. For drug-related study withdrawal, antidepressants had an NNH (major) of 17 (11–43) compared with placebo, whereas with anticonvulsants there was no significant difference from placebo. Antidepressants and anticonvulsants had the same efficacy and incidence of minor adverse effects in these two neuropathic pain conditions. There was no evidence that selective serotonin reuptake inhibitors (SSRIs) were better than older antidepressants, and no evidence that gabapentin was better than older anticonvulsants. In these trials patients were more likely to stop taking antidepressants than anticonvulsants because of adverse effects.     

Focus on biological agents in rheumatoid arthritis: newer treatments and therapeutic strategies

Tumour necrosis factor (TNF)-alpha and interleukin (IL)-1 are major regulators of inflammation. TNFalpha inhibitors have been shown to be effective in treating some inflammatory diseases such as rheumatoid arthritis. TNFalpha inhibitors include soluble receptor antagonists (etanercept) and monoclonal antibodies (infliximab, adalimumab). IL-1 inhibitors (anakinra) were also developed, used in therapeutics and licensed in France. TNFalpha inhibitors can be added to background regimens of methotrexate in second-line treatments. Etanercept and adalimumab can be administered alone, especially to patients who have experienced methotrexate toxicity or who do not show clinical and/or radiological improvement. The use of these new agents may optimise rheumatoid arthritis treatment and delay disease progression, particularly when first-line treatments are disappointing. This paper reviews recent data on biological therapies for rheumatoid arthritis: tolerance and their ability to modify the course of disease and prevent radiological damage.     

新生大鼠反复惊厥对海马区肾上腺皮质激素受体表达的影响

目的 研究新生期大鼠反复惊厥对海马区肾上腺皮质激素受体MR和GR表达的影响,以及对成年期大鼠记忆功能的影响,探讨发育期脑损伤和脑内相关受体之间的相互关系.方法 生后7 d的SD大鼠随机分成两组,每组40只,惊厥组每日吸入三氟乙醚诱导惊厥发作1次,每次持续30 min,连续6 d;于反复惊厥后1、3、7、30、60 d处死大鼠取脑,分别采用免疫组织化学方法观察大鼠海马肾上腺皮质激素受体MR和GR表达的变化.最后一组大鼠处死前于第61～65天行Morris水迷宫实验,检测大鼠的学习记忆功能.对照组同样操作但不吸入三氟乙醚.结果 61～64 d,两组大鼠寻找平台时间均逐渐缩短,惊厥组大鼠在第64天的平均寻找平台时间[(82 424.3±35 622.0)ms]与对照组[(40 712.4±29 467.6)ms]比较明显延长(P=0.001).在第65天,惊厥组大鼠120 s内穿越原平台位置次数[(1.2±0.9)次]较对照组[(3.1±1.3)次]明显减少(P<0.001).免疫组化结果显示新生大鼠反复惊厥后的1、3、7、30、60 d海马CA1～4区GR、MR的表达较埘照组明显降低(P<0.05).结论 海马区GR及MR随脑发育成熟表达不断增高,呈现一定规律及分布特点,参与了脑发育过程.新生大鼠反复惊厥造成海马GR、MR表达的持续异常,参与发育期脑损伤.     

Cost and resource implications of clinical supervision in nursing: an Australian perspective

AIM: The aim of this article was to explore the resource and management issues in introducing and maintaining a clinical supervision programme for nurses. BACKGROUND: A number of federal, state and non-governmental agency reports have recently indicted the quality of present-day mental health service provision in Australia. Clinical supervision in nursing has been widely embraced in many parts of the developed world, as a positive contribution to the clinical governance agenda, but remains largely underdeveloped in Australia. METHOD: Using data derived from several empirical clinical supervision research studies conducted in mental health nursing settings, preliminary financial modelling has provided new information for Nurse Managers, about the material implications of implementing clinical supervision. FINDINGS AND CONCLUSIONS: It is suggested that, on average, the cost of giving peer group one-to-one supervision to any nurse represented about 1% of an annual salary. When interpreted as a vanishingly small cap on clinical nursing practice necessary to reap demonstrable benefits, it behoves Nurse Managers to comprehend clinical supervision as bona fide nursing work, not an activity which is separate from nursing work.     

老年抑郁症患者临床特征及治疗状况对照研究

目的：探讨老年抑郁症患者的临床特征及治疗状况,为临床干预提供依据。方法对66例老年抑郁症患者（老年组）和70例中青年抑郁症患者（对照组）的临床资料进行回顾性分析。结果老年组以焦虑、激越、自杀意念及行为、躯体化等症状为主要表现,伴发躯体疾病发生率显著高于对照组（P＜0．01）;治疗前汉密顿抑郁量表焦虑躯体化、认识障碍、日夜变化、睡眠障碍及绝望感因子分均显著高于对照组（P＜0．05或0．01）,阻滞因子分显著低于对照组（P＜0．01）;两组均以新型抗抑郁剂治疗为主,但老年组联合情绪稳定剂、无抽搐电休克治疗频率显著低于对照组（P＜0．01）。结论老年抑郁症患者多伴有躯体疾病,以焦虑、激越、自杀意念及行为、躯体化等症状为主要表现。临床治疗以单用新型抗抑郁剂治疗为主。     

Some clinical implications of recombinant DNA technology with emphasis on prenatal diagnosis of hemoglobinopathies

Recombinant DNA technology has made possible remarkable advances in understanding the molecular genetics of human and other eucaryotic cells. This technology also has clinical applications, some of which may soon involve clinical laboratories. Restriction endonucleases and cloned DNA probes permit the direct analysis of cellular DNA to detect sequence abnormalities associated with particular genetic disorders. Use of this approach in the antenatal diagnosis of hemoglobinopathies is now possible on a routine basis. The principles behind the methods are quite general and may be applied to other hereditary diseases once suitable DNA probes become available. The same approach may be used to detect carriers of recessive gene defects and so improve genetic counselling. Other clinically related applications of recombinant DNA technology include the production of antigens for vaccine preparation and of specific human proteins (e.g. interferon and human growth hormone) for therapeutic use, as well as the use of nucleic acid hybridization for identification of microbial pathogens. It seems likely that recombinant DNA technology will, in the future, play an increasingly important role in the diagnosis, prevention and treatment of human disease.     

A novel approach for selective brain cooling: implications for hypercapnia and seizure activity

Objective During selective brain cooling (SBC) the brain temperature (T_B) is reduced while the core temperature (T_C) remains unchanged. This animal study investigated changes in brain temperature induced by a novel approach of cooling the brain from the pharynx (pSBC) and whether these temperature changes are related to commonly encountered clinical situations (i.e., seizure activity and hypercapnia).Design Experimental animal study.Subjects Male Sprague-Dawley rats.Interventions pSBC was achieved by a heat exchanger placed in the pharynx; hypercapnia and seizure activity were induced by adding CO₂ to the respiratory gases and by intravenous injection of bicuculline, respectively.Measurements and results T_B, T_C, and pharynx (T_P) were measured continuously with thermocouples. During pSBC T_B declined significantly from 36.9±0.67°C to 33.1±1.23°C. There was a trend towards lower T_C during pSBC (from 36.9±0.70 to 36.4±1.2°C). T_P during pSBC was 29.1±2.19°C. From the lowest achieved pSBC temperature T_B rose during CO₂ challenge by 1.22±0.67°C (vs. 0.85±0.34°C in non-SBC controls). From the lowest pSBC temperature during seizure activity T_B rose by 2.08±0.35°C (vs. 1.15±0.55°C in non-SBC controls).Conclusions Significant cooling of the cortex can be achieved by pSBC in a rat rodent model. Marked increases in T_B with hypercapnia and with seizure activity were observed. These results may have implications for cooling methods in clinical settings. For example, pSBC may offer distinct advantages over alternative methods such as whole-body cooling and externally implemented SBC.     

Recognition and management of critical illness by midwives: implications for service provision

AIM: The aim of this study was to explore midwives' recognition and management of critical illness in obstetric women in order to inform service provision. BACKGROUND: Critical illness is not confined to Intensive Care. Limited published work was located examining factors affecting critical care provision by midwives. METHODS: A multi-method design incorporating a paper and pencil simulation (n = 11) and in-depth interviewing (n = 5) was conducted with midwives from a large London National Health Service Trust. This study details and discusses the findings. RESULTS: Findings indicated that frequency and type of critical illness experience impact upon midwives' critical care knowledge and skills. Midwives, especially those who were more junior, expressed anxiety regarding this aspect of practice, and considered the support of senior midwives, medical and nursing staff as crucial to effective client management. CONCLUSION: This study has yielded important insights into midwives' management of critical illness. Possible mechanisms to enhance the quality of service provision, and midwife support in this area are highlighted.     

Clinical practice: an emphasis strategy for promotion and tenure

TOPIC: Emphasizing clinical practice in promotion and tenure materials. PURPOSE: To share a successful strategy centered on clinical practice with members of the tenure track, advanced practice nurse faculty. SOURCE: Published literature, author's experience. CONCLUSION: Creativity and planning can assist tenure track faculty members in emphasizing their clinical practice for promotion and tenure. Recognition and rewards for clinical practice beyond the school of nursing continue to be challenges in the larger univerisity.     

Clinical leadership in contemporary clinical practice: implications for nursing in Australia

BACKGROUND: Leadership in the clinical practice environment is important to ensure both optimal patient outcomes and successive generations of motivated and enthusiastic clinicians. AIM: The present paper seeks to define and describe clinical leadership and identify the facilitators and barriers to clinical leadership. We also describe strategies to develop clinical leaders in Australia. Key drivers to the development of nursing leaders are strategies that recognize and value clinical expertise. These include models of care that highlight the importance of the nursing role; evidence-based practice and measurement of clinical outcomes; strategies to empower clinicians and mechanisms to ensure participation in clinical decision-making. KEY ISSUES: Significant barriers to clinical leadership are organizational structures that preclude nurses from clinical decision making; the national shortage of nurses; fiscal constraints; absence of well evaluated models of care and trends towards less skilled clinicians. CONCLUSIONS: Systematic, strategic initiatives are required to nurture and develop clinical leaders. These strategies need to be collegial collaborations between the academic and health care sectors in order to provide a united voice for advancing the nursing profession.     

The supervision of Project 2000 students in the clinical setting: issues and implications for practitioners

• ? The aim of this 2-year study funded by the English National Board for Nursing, Midwifery and Health Visiting was to examine the relationship between teaching, support, supervision and role modelling in student clinical learning within the context of Project 2000 courses.
• ? The research, using a two-stage case-study design, employing predominantly qualitative methods of data collection, investigated the perceptions of students, tutors and practitioners of their experiences of these processes in the clinical setting.
• ? This paper focuses on the findings obtained from the practitioner data, highlighting not only the significant role played by practitioners in facilitating student learning, but also the implications for practitioners in undertaking this role.
• ? The preparation required for supervising clinical learning, the integration of theory and practice and the organization of patient care have been identified as particularly important to the development of effective clinical learning environments.

     

IgD型多发性骨髓瘤临床特征、新药治疗效果及预后分析

目的 探讨IgD型多发性骨髓瘤（multiple myeloma, MM）患者的临床特征、治疗、生存及预后影响因素。方法 回顾性分析2013年6月至2021年9月复旦大学附属中山医院血液科收治的25例IgD型MM患者的病例资料。分析患者的基线特征、实验室检查及细胞遗传学指标;根据国际骨髓瘤工作组（International Myeloma Working Group,IMWG）诊断标准评估疗效。采用Kaplan-Meier方法进行生存分析,采用log-rank检验进行单因素分析,将P<0.15的变量纳入多因素Cox回归分析。结果 25例IgD型MM患者中男性17例（68%）,21例（84%）年龄低于65岁,λ轻链型24例（96%）;DS分期Ⅲ期21例（84%）,国际分期系统（International Staging System,ISS）分期Ⅲ期12例（48%）;荧光原位杂交(fluorescence in situ hybridization,FISH）结果显示77.3%(17/22)患者存在细胞遗传学异常,以1q21扩增（14例,63.6%）和IgH重排（9例,40.9%）...