Duloxetine: pharmacoeconomic implications of an antidepressant that alleviates painful physical symptoms

Major depressive disorder (MDD) is a prevalent, chronic, medical disorder that encompasses a broad constellation of symptoms. The salience of painful physical symptoms in depressive presentations is increasingly appreciated. Duloxetine is a novel, potent, balanced, dual monoamine reuptake-inhibitor antidepressant indicated for the symptomatic relief of MDD. Duloxetine is marketed as an antidepressant that has inherent analgesic properties for depressed patients who present with prominent painful physical symptoms. Taken together, available evidence indicates that duloxetine provides a higher probability of, and shorter time to, remission than some antidepressants (e.g., fluoxetine). Duloxetine also offers symptom relief for painful physical symptoms in depressed patients. Pharmacoeconomic and cost-impact modelling analyses should be reformulated to consider duloxetine's symptom-alleviating effect on the somatic dimension of depressive illness.     

Epidemiology and impact of rotavirus diarrhoea in Poland

Hospital and laboratory data were analysed in three hospitals to estimate rotavirus disease burden in 1994-96. Community acquired gastroenteritis was diagnosed in 757 children of whom 41% tested positive for rotavirus. A total of 196 children had rotavirus nosocomial infections (39% of all rotavirus community-acquired and nosocomial cases) Infants less than 24 months old and children less than 3 months old comprised 74% and 11.9% of admissions for rotavirus, respectively. Almost 94% of children with rotavirus infection had severe gastroenteritis (score 11). The annual rate of rotavirus associated hospitalization in Poland in 1996 was 3.1/1000 children under the age of 60 months and 5.2/1000 infants under 24 months of age. The mean hospital stay was 9.5 d (±9.8 d). We estimated that 8918 children under 60 months of age were hospitalized for rotavirus gastroenteritis in 1996; they accounted for 84899 inpatient days. We conclude that rotavirus is a leading aetiological agent of severe gastroenteritis in young children in Poland and that the Burden of this infection is significant. Rotavirus vaccine could significantly decrease the hospitalization rate and the financial impact of rotavirus Gastroenteritis in Poland. □ Acute diarrhoea, disease burden, epidemiology, gastroenteritis, rotavirus     

Predictors of nonresponse to cognitive behavioural therapy or venlafaxine using glucose metabolism in major depressive disorder

Background

Longitudinal neuroimaging investigations of antidepressant treatment offer the opportunity to identify potential baseline biomarkers associated with poor outcome.

Methods

To explore the neural correlates of nonresponse to cognitive behavioural therapy (CBT) or venlafaxine (VEN), we compared pretreatment (18)F-fluoro-2-deoxy-d-glucose positron emission tomography scans of participants with major depressive disorder responding to either 16 weeks of CBT (n = 7) or VEN treatment (n = 9) with treatment nonresponders (n = 8).

Results

Nonresponders to CBT or VEN, in contrast to responders, exhibited pretreatment hypermetabolism at the interface of the pregenual and subgenual cingulate cortices.

Limitations

Limitations of our study include the small sample sizes and the absence of both arterial sampling to determine absolute glucose metabolism and high-resolution structural magnetic resonance imaging coregistration for region-of-interest analyses.

Conclusion

Our current findings are consistent with those reported in previous studies of relative hyperactivity in the ventral anterior cingulate cortex in treatment-resistant populations.     

The prevalence and impact of migraine headache in bipolar disorder: results from the Canadian Community Health Survey

OBJECTIVE: To report on the prevalence of comorbid migraine in bipolar disorder and the implications for bipolar age of onset, psychiatric comorbidity, illness course, functional outcome, and medical service utilization. BACKGROUND: Migraine comorbidity is differentially reported in bipolar versus unipolar depressed clinical samples. The bipolar disorder-migraine association and its consequences have been infrequently reported in epidemiological studies. METHODS: Data for this analysis were derived from respondents (n = 36 984) to the Canadian Community Health Survey - Mental Health and Well-Being (CCHS). Respondents reporting a lifetime WHO-CIDI-defined manic episode and physician-diagnosed migraine (lifetime) were compared to respondents without migraine on sociodemography, course of illness, and medical service utilization indices. RESULTS: An estimated 2.4% of the sample met criteria for bipolar disorder. Persons with bipolar disorder had a relatively higher prevalence of migraine versus the general population (24.8% vs. 10.3%; P < .05). The sex-specific prevalence of comorbid migraine in bipolar disorder was 14.9% for males and 34.7% for females. Bipolar males with comorbid migraine were more likely to live in a low income household (P < .05); receive welfare and social assistance (P < .05); report an earlier age of onset of bipolar disorder (P < .05); and have a higher lifetime prevalence of comorbid anxiety disorders (P < .05). Bipolar males with comorbid migraine were also more likely to utilize primary (P < .05) and mental health care services (P < .05) . Bipolar females with comorbid migraine had more comorbid medical disorders (P < .05) and were more likely to require help with personal or instrumental activities of daily living when compared to bipolar females without migraine. CONCLUSION: Bipolar disorder with comorbid migraine is prevalent and associated with greater dysfunction and medical service utilization, notable in males. Opportunistic screening and surveillance for bipolar and comorbid migraine is warranted.     

Improving outcomes in depression: a focus on somatic symptoms

BACKGROUND: It is hypothesized that somatic symptom alleviation is a significant predictor of overall outcome in depressed primary care patients. METHODS: Depressed primary care patients (N=205) meeting DSM-IV-TR criteria received open-label antidepressant therapy. The primary symptom measurement tool used was the 17-item Hamilton Depression Rating Scale (HAMD-17), with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression Improvement/Severity (CGI-I/S) used as secondary measures. As proxies for somatic symptoms, 8 items from the HAMD-17 (HAMD-S) and 3 items from the MADRS (MADRS-S) that measure somatic symptoms were identified and extracted. RESULTS: There was a significant correlation between improvement on the HAMD-S score and overall reduction on the MADRS total score (r=.766, P<.001), response (r=.594, P<.001), and remission (r=.552, P<.001). Improvement on the MADRS-S also correlated with overall HAMD-17 improvement (r=.782, P<.001), along with response (r=.649, P<.001) and remission (r=.539, P<.001) rates. Both the HAMD-S and the MADRS-S correlated with global improvement as measured by the CGI-I/S (P<.001). CONCLUSIONS: A reciprocal interaction between somatic symptoms and other depressive-symptom domains is implied by this analysis. Clinicians are encouraged to identify, track, and target the somatic symptoms of depressive illnesses.     

Neural response to emotional stimuli associated with successful antidepressant treatment and behavioral activation

Background

Major Depressive Disorder (MDD) is a leading cause of disability globally. Currently available treatments have limited efficacy and combination strategies are frequently used. Several lines of research have demonstrated that MDD patients experience impairments in various components of affective processing, including regulation of affective states.

Aim

To identify baseline and 1-week neuroimaging predictors of response to a 6-week trial of fluoxetine/olanzapine combination treatment during an affective processing task.

Methods

Twenty-one MDD patients and 18 healthy controls were enrolled in the study. MDD patients were treated for 6 weeks with fluoxetine (40–60 mg/day) and olanzapine (5–12.5 mg/day). All participants viewed images from the International Affective Picture Rating System during a functional magnetic resonance (fMRI) scan at baseline and 1 week.

Results

There was a 57% response rate (defined as a 50% decrease in Hamilton Rating Scale for Depression-17 item) at 6 weeks. At baseline, responders had increased premotor activity while viewing negative images compared to non-responders and healthy controls. Higher baseline premotor activity was also predictive of greater percent change on the HAMD-17 and improvement in negative disposition and behavioral drive. Non-responders exhibited increased insular activity at baseline compared to responders. Higher activity in the posterior cingulate cortex was also predictive of greater percent change on the HAMD-17. Change from baseline to 1 week did not produce any significant predictive findings.

Conclusions

Treatment with fluoxetine/olanzapine demonstrated similar biomarkers of response to monotherapeutic strategies. In particular, posterior cingulate cortex, anterior insula, and premotor cortex may show predictive differences in their response to affective images prior to treatment. Further research needs to be conducted to determine the utility of early changes in emotion circuitry in predicting antidepressant response.     

Marginal donor liver versus standard donor liver: A single-center observational study

Background: The effectiveness and safety of marginal donor livers remain controversial. This study aimed to investigate the clinical efficacy of marginal donor livers in patients with liver transplantation (LT). Methods: This study included 199 liver donors (including 16 split donors) and 206 liver recipients from January 1, 2018 to January 27, 2020, with case follow-up until July 31, 2021. Clinical data of donors and recipients were retrospectively analyzed and were divided into the marginal donor and standard donor groups according to the criteria of marginal donor livers. Indices of liver and kidney functions, complications, and survival curves of the two groups were compared. Results: Compared with the standard donor group, the blood creatinine levels were significantly higher in the marginal donor group in the first week after operation ( P < 0.05); there were no significant differences in alanine aminotransferase, aspartate aminotransferase, and total bilirubin levels after LT (all P > 0.05); there was no significant difference in the incidence of complications after LT ( P > 0.05); there was also no significant difference in the survival curve ( P = 0.335). Conclusions: There were no significant differences in liver and kidney function and survival curve between the standard donor and marginal donor groups. The marginal donor liver appears safe and reliable for LT and may be an important strategy to expand the donor pool and solve the shortage of organs.     

三氧化二β－锗丙酸对硝基苯酯的合成和结构性质

三氧化二β－锗丙酸对硝基苯酯的合成和结构性质上官国强，张树功，倪嘉缵（山东济宁医学院化学教研室，济宁２７２１１３；中国科学院长春应用化学研究所，长春１３００２２）羧基乙基锗倍半氧化物［（ＨＯＯＣＣＨ２ＣＨ２Ｇｅ）２Ｏ３，１３２Ｇｅ］的广谱抗癌活性引起...     

大鼠单侧后牙缺失后颞颌关节内P物质、降钙素基因相关肽的表达变化

目的 :观察单侧后牙缺失造成偏侧咀嚼的大鼠颞颌关节内P物质 (substanceP ,SP)和降钙素基因相关肽 (calcitoningene relatedpeptide ,CGRP)的表达情况 ,进一步探讨颞颌关节病的发病机制。方法 :Wistar雄性大鼠 12只 ,随机分为 4组 ,包括 2个实验组及相应的对照组 ,每组 3只。拔除实验组动物右侧上、下颌磨牙 ,人为造成偏侧咀嚼。同一部位的切片分 2组 ,分别行SP ,CGRP免疫组织化学反应 (SABC法 )。光镜观察 ,并用LUZEX F型显微图像分析仪分别进行测定。结果 :每一实验组咀嚼侧和非咀嚼侧颞颌关节内单位面积内SP ,CGRP阳性纤维面积与各自对照组比较显著增加 (P <0 .0 1) ,但 3个月组较 1个月组有较低的增长趋势。在每一实验组内 ,非咀嚼侧单位面积内SP ,CGRP阳性纤维面积明显高于咀嚼侧 (P <0 .0 1)。结论 :SP ,CGRP均参与了偏侧咀嚼引起的颞颌关节病的病理变化过程 ,且在偏侧咀嚼条件下 ,两侧颞颌关节病理变化程度不同     

肝靶向抗病毒药NGA－ACV的制备及其趋肝性

以无唾液酸糖蛋白受体（ａｓｉａｌｏｇｌｙｃｏｐｒｏｔｅｉｎｒｅｃｅｐｔｏｒ，ＡＳＧＰＲ）的特异性配体半乳糖基拟糖白蛋白（ｎｅｏｇｌｙｃｏａｌｂｕｍｉｎ，ＮＧＡ）为载体，通过丁二酰基桥将抗病毒药无环鸟苷（ａｃｙｃｌｏｖｉｒ，ＡＣＶ）与ＮＧＡ偶联，得到肝靶向抗病毒药ＮＧＡＡＣＶ。差热分析和高效液相色谱分析结果表明，ＮＧＡＡＣＶ是共价键偶联物，且在血液中稳定性很好。将偶联物用１３１Ｉ标记后进行家兔放射性显像比较研究。结果，高、低药密度ＮＧＡＡＣＶ的肝脏放射性分别是全身放射性的８１．６％和８６．６％，其趋肝性无明显差别。研究小鼠体内高药密度１３１ＩＮＧＡＡＣＶ的分布，在５ｍｉｎ时肝脏放射性达到峰值，为注入量的８１．７±１０．４％。受体竞争抑制实验表明ＮＧＡＡＣＶ的肝靶向机理为受体介导的主动靶向过程。初步体外抗乙肝病毒比较研究表明，ＮＧＡＡＣＶ较ＡＣＶ的抗病毒剂量有明显降低。