Concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer: A multicenter, retrospective, observational study.

OBJECTIVES: There is concern that hydroxyzine exacerbates delirium, but a recent preliminary study suggested that the combination of haloperidol and hydroxyzine was effective against delirium. This study examined whether the concomitant use of hydroxyzine and haloperidol worsened delirium in patients with cancer. METHODS: This retrospective, observational study was conducted at 2 general hospitals in Japan. The medical records of patients with cancer who received haloperidol for delirium from July to December 2020 were reviewed. The treatments for delirium included haloperidol alone or haloperidol combined with hydroxyzine. The primary outcome was the duration from the first day of haloperidol administration to the resolution of delirium, defined as its absence for 2 consecutive days. The time to delirium resolution was analyzed to compare the haloperidol group and hydroxyzine combination group using the log-rank test with the Kaplan-Meier method. Secondary outcomes were (1) the total dose of antipsychotic medications, including those other than haloperidol (measured in chlorpromazine-equivalent doses), and (2) the frequencies of detrimental incidents during delirium, specifically falls and self-removal of drip infusion lines. The unpaired t-test and Fisher's exact test were used to analyze secondary outcomes. RESULTS: Of 497 patients who received haloperidol, 118 (23.7%) also received hydroxyzine. No significant difference in time to delirium resolution was found between the haloperidol group and the hydroxyzine combination group (log-rank test, P = 0.631). No significant difference between groups was found in either chlorpromazine-equivalent doses or the frequency of detrimental incidents. SIGNIFICANCE OF RESULTS: This study showed that the concomitant use of hydroxyzine and haloperidol did not worsen delirium in patients with cancer.

A revision of JPOS/JASCC clinical guidelines for delirium in adult cancer patients: a summary of recommendation statements.

OBJECTIVE: The Japanese Psycho-Oncology Society and the Japanese Association of Supportive Care in Cancer have recently revised the clinical practice guidelines for delirium in adult cancer patients. This article reports the process of developing the revised guidelines and summarizes the recommendations made. METHODS: The guidelines were developed in accordance with the Medical Information Network Distribution Service creation procedures. The guideline development group, consisting of multi-disciplinary members, created three new clinical questions: non-pharmacological intervention and antipsychotics for the prevention of delirium and trazodone for the management of delirium. In addition, systematic reviews of nine existing clinical questions have been updated. Two independent reviewers reviewed the proposed articles. The certainty of evidence and the strength of the recommendations were graded using the grading system developed by the Medical Information Network Distribution Service, following the concept of The Grading of Recommendations Assessment, Development, and Evaluation system. The modified Delphi method was used to validate the recommended statements. RESULTS: This article provides a compendium of the recommendations along with their rationales, as well as a short summary. CONCLUSIONS: These revised guidelines will be useful for the prevention, assessment and management of delirium in adult cancer patients in Japan.

A multi-centre, double-blind, randomized, placebo-controlled trial to evaluate the effectiveness and safety of ramelteon for the prevention of postoperative delirium in elderly cancer patients: a study protocol for JORTC-PON2/J-SUPPORT2103/NCCH2103.

Postoperative delirium is an important issue in cancer patients, affecting surgical outcomes and the quality of life. Ramelteon is a melatonin receptor agonist with high affinity for MT1 and MT2 receptors. Clinical trials and observational studies in Japan, including in surgical cancer patients, have shown efficacy of ramelteon in delirium prevention, with no serious safety concerns. However, clinical trials from the USA have reported conflicting results. A Japanese phase II study investigated the efficacy and safety of ramelteon for delirium prevention following gastrectomy in patients aged ≥75 years, with findings suggesting the feasibility of a phase III trial. The aim of this multi-centre, double-blind, randomized placebo-controlled phase III trial is to evaluate the effectiveness and safety of oral ramelteon for postoperative delirium prevention in cancer patients aged ≥65 years as advanced medical care. The trial protocol is described here.

Prevention of delirium with agitation by yokukansan in older adults after cancer surgery.

OBJECTIVE: Preventing postoperative delirium with agitation is vital in the older population. We examined the preventive effect of yokukansan on postoperative delirium with agitation in older adult patients undergoing highly invasive cancer resection. METHODS: We performed a secondary per-protocol analysis of 149 patients' data from a previous clinical trial. Patients underwent scheduled yokukansan or placebo intervention 4-8 days presurgery and delirium assessment postoperatively. Delirium with agitation in patients aged ≥75 years was assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, and the Japanese version of the Delirium Rating Scale-Revised-98. We assessed odds ratios for yokukansan (TJ-54) compared with placebo for the manifestation of postoperative delirium with agitation across patients of all ages (n = 149) and those aged ≥65 years (n = 82) and ≥ 75 years (n = 21) using logistic regression. RESULTS: Delirium with agitation manifested in 3/14 and 5/7 patients in the TJ-54 and placebo groups, respectively, among those aged ≥75 years. The odds ratio for yokukansan vs. placebo was 0.11 (95% confidence interval: 0.01-0.87). An age and TJ-54 interaction effect was detected in patients with delirium with agitation. No intergroup differences were observed in patients aged ≥65 years or across all ages for delirium with agitation. CONCLUSIONS: This is the first study investigating the preventive effect of yokukansan on postoperative delirium with agitation in older adults. Yokukansan may alleviate workforce burdens in older adults caused by postoperative delirium with agitation following highly invasive cancer resection.

Preoperative Anxiety as a Predictor of Delirium in Cancer Patients: A Prospective Observational Cohort Study.

BACKGROUND: Postoperative delirium is a common and important complication in cancer patients. We need to identify patients at high risk of postoperative delirium such that it can be prevented preoperatively or in early postoperative phase. The aim of this study was to investigate whether preoperative anxiety predicted onset of postoperative delirium in cancer patients, not only in order to identify high-risk groups but also to help develop new preventive approaches. METHODS: This was a prospective observational cohort study of cancer patients undergoing tumor resections. Postoperative delirium was assessed using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). Preoperative anxiety was evaluated with the Hospital Anxiety and Depression Scale-Anxiety (HADS-A), and we defined HADS-A > 7 as clinical anxiety. We conducted multivariate logistic regression to determine which factors were predictors of delirium. RESULTS: The final analysis included 91 patients, 29 of whom met the criteria for postoperative delirium. In multivariable logistic regression, age (5-year increments; odds ratio (OR) = 1.565, 95% confidence interval (CI) = 1.057-2.317, p = 0.025) and HADS-A > 7 (OR = 4.370, 95% CI = 1.051-18.178, p = 0.043) predicted delirium onset. These variables explained 74.2% of the variance. CONCLUSIONS: Preoperative anxiety strongly predicted postoperative delirium in cancer patients. Our findings suggest that preoperative anxiety may be a new target for prevention of postoperative delirium. Trial registration number This study was registered at UMIN000018980.

Implication of P-glycoprotein in formation of depression-prone personality: association study between the C3435T MDR1 gene polymorphism and interpersonal sensitivity.

BACKGROUND AND AIM: Interpersonal sensitivity is defined as undue and excessive awareness of, and sensitivity to, the behavior and feelings of others. Previous studies suggested that interpersonal sensitivity is one of the vulnerable factors to depression, and that genetic factors and cortisol are involved in the formation of interpersonal sensitivity. On the other hand, P-glycoprotein, which is encoded by the multidrug resistance 1 (MDR1) gene, serves as a barrier to entry and as an active eliminator for xenobiotics and cellular metabolites including cortisol, which is implicated in multiple brain functions. In the present study, we examined the effects of the MDR1 C3435T polymorphism (rs1045642) on interpersonal sensitivity in healthy subjects. METHODS: The subjects were 842 healthy Japanese volunteers (mean age = 26.7 years, male/female ratio = 490/352). The C3435T polymorphism of MDR1 gene was detected by a PCR method, and interpersonal sensitivity was assessed by the Interpersonal Sensitivity Measure (IPSM). RESULTS: The 2-factor analysis of covariance (ANCOVA) showed a significant main effect of the MDR1 genotype on the IPSM scores with a significant interaction between the genotype and gender. The subsequent 1-factor ANCOVA showed that in females the C/C genotype group had higher IPSM scores than the C/T genotype group (p < 0.001) and the T/T genotype group (p < 0.001), and the C/T genotype group had higher IPSM scores than the T/T genotype group (p = 0.014). In males no significant association was found between the MDR1 genotype and the IPSM scores. In allelic analyses using the χ(2) tests, the C allele frequency in females was significantly higher (p < 0.001) in the high IPSM group than in the low IPSM group, while there was no significant difference in the C allele frequency between the high and low IPSM groups in total subjects and males. CONCLUSION: The present study suggests that the C3435T polymorphism of the MDR1 gene affects the formation of a depression-prone personality trait in Japanese females.

Parental care influences leukocyte telomere length with gender specificity in parents and offsprings.

BACKGROUND: There have been several reports suggesting that adverse childhood experiences such as physical maltreatment and long institutionalization influence telomere length. However, there has been no study examining the relationship of telomere length with variations in parental rearing. In the present study, we examined the relationship of leukocyte telomere length with parental rearing in healthy subjects. METHODS: The subjects were 581 unrelated healthy Japanese subjects. Perceived parental rearing was assessed by the Parental Bonding Instrument consisting of the care and protection factors. Leukocyte relative telomere length was determined by a quantitative real-time PCR method for a ratio of telomere/single copy gene. RESULTS: In the multiple regression analyses, shorter telomere length in males was related to lower scores of paternal care (ß = 0.139, p < 0.05), while that in females was related to lower scores of maternal care (ß = 0.195, p < 0.01). CONCLUSION: The present study suggests that there is linear relationship between parental care and telomere length which covers both lower and higher ends of parental care, and that the effects of parental care on telomere length are gender-specific in parents and offsprings.

Affectionless control by the same-sex parents increases dysfunctional attitudes about achievement.

BACKGROUND: The affectionless control parenting has been associated with depression in recipients. The aim of this study was to examine the effect of this parenting style on dysfunctional attitudes predisposing to depression. METHODS: The subjects were 666 Japanese volunteers. Perceived parental rearing was evaluated by the Parental Bonding Instrument, which has the care and protection subscales. Parental rearing was classified into four types, i.e., optimal parenting (high care/low protection), affectionate constraint (high care/high protection), neglectful parenting (low care/low protection), and affectionless control (low care/high protection). Dysfunctional attitudes were evaluated by the 24-item Dysfunctional Attitude Scale, which has the achievement, dependency and self-control subscales. RESULTS: Males with paternal affectionless control had higher achievement scores than those with paternal optimal parenting (P=.016). Similarly, females with maternal affectionless control had higher achievement scores than those with maternal optimal parenting (P=.016). CONCLUSION: The present study suggests that affectionless control by the same-sex parents increases dysfunctional attitudes about achievement.

Relationship of the FKBP5 C/T polymorphism with dysfunctional attitudes predisposing to depression.

FK506-binding protein 51 (FKBP5) is a co-chaperone of the glucocorticoid receptor, and plays an important role in the negative feedback regulation of the hypothalamic-pituitary-adrenal axis. The C/T single nucleotide polymorphism in the intron 2 of the FKBP5 gene affects cortisol secretion, and has been implicated in the pathophysiology of depression. In this study, the relationship of the FKBP5 C/T polymorphism with dysfunctional attitudes predisposing to depression was examined. The subjects were 300 healthy Japanese. The FKBP5 genotypes were determined by a real-time PCR and cycling probe technology for SNP typing. Dysfunctional attitudes were assessed by the 24-item version of the Dysfunctional Attitude Scale (DAS-24), which has the Achievement, Self-control, and Dependency subscales. DAS-24 total scores were significantly higher in the group with the T allele than in that without this allele (p=0.001). Regarding the subscales, scores of the Achievement (p=0.003) and Self-control (p=0.009) subscales, but not those of the Dependency subscale, were significantly higher in the former group than in the latter group. The present study suggests that the FKBP5 C/T polymorphism is implicated in formation of dysfunctional attitudes, especially those about achievement and self-control.

Distinctive correlations of sociotropy and autonomy with working models of the self and other.

BACKGROUND: Beck's cognitive theory of depression postulates personality vulnerability factors termed sociotropy and autonomy, which are accompanied by characteristic interpersonal styles. Meanwhile, Bartholomew contends that negative working models of the self and other built through insecure attachment relationships are externalized as distinctive interpersonal styles. The present study examined the relationships of sociotropy and autonomy with the self- and other-models, and attempted to promote understanding of the two personality traits from an attachment perspective. METHODS: The subjects were 510 healthy Japanese medical students or hospital staffs. Sociotropy and autonomy were assessed by the Sociotropy-Autonomy Scale, and working models of the self and other were evaluated by the Relationship Scales Questionnaire. RESULTS: The sociotropy score was correlated negatively with the self-model score (ß=-0.52, p<0.001) and positively with the other-model score (ß=0.11, p<0.01). The autonomy score was correlated positively with the self-model score (ß=0.10, p<0.05) and negatively with the other-model score (ß=-0.33, p<0.001). LIMITATIONS: It may be risky to generalize the present results to general populations or other ethnic groups. CONCLUSIONS: The present study suggests that both sociotropy and autonomy are associated with attachment insecurity, but the marked difference in their correlation patterns with the self- and other-models leads to the distinctive interpersonal styles of the two personality orientations.

Correlations of interpersonal sensitivity with negative working models of the self and other: evidence for link with attachment insecurity.

BACKGROUND: It has been suggested that interpersonal sensitivity, a personality trait associated with depression and anxiety disorders, is linked with attachment insecurity. To confirm this link, we studied the correlations of interpersonal sensitivity with working models of the self and other. METHODS: The subjects were 301 healthy Japanese. Interpersonal sensitivity and working models of the self and other were assessed by the Interpersonal Sensitivity Measure (IPSM) and the Relationship Scales Questionnaire, respectively. The correlations of the IPSM total scores with the self-model or other-model scores were analyzed by the multiple regression analysis. RESULTS: The IPSM total scores were correlated negatively with the self-model scores (ß = -0.48, p < 0.001) and to a lesser extent with the other-model scores (ß = -0.15, p < 0.01). CONCLUSIONS: The present study suggests that interpersonal sensitivity is correlated with negative working models of the self and other, providing evidence for its link with attachment insecurity.

[Conservative treatment improved corrosive esophagitis and pneumomediastinum in a patient who ingested bleaching agent containing sodium hypochlorite and sodium hydroxide].

A 69-year-old man was admitted to the emergency department 3 hours after ingestion of a bleaching agent containing hypochlorous acid and sodium hydroxide in a suicide attempt. Enhanced chest computed tomography scans taken on admission indicated an edematous esophagus and air bubbles in the mediastinum. He underwent endotracheal intubation and mechanical ventilation until day 9 because of laryngeal edema. On day 10, his endoscopy indicated diffuse reddish mucosal hyperemia, erosions, and lacerated mucosal lesions in the esophagus that were indicative of grade 2b corrosive esophagitis. Treatment with a proton pump inhibitor was initiated, with which the condition of the esophagus improved, and on day 44, a slight stricture of the upper part of the esophagus was observed. He was discharged on day 64 without any complaints. The ingestion of sodium hypochlorite induces corrosive esophagitis and acute phase of gastritis. Ingestion of any corrosive agent is known as a risk factor for esophagus cancer in the long-term. In such cases with esophageal stricture, esophagectomy is recommended for preventing esophagus cancer. Considering the age of the patient, however, he did not undergo esophagectomy.

Severe behavioral and psychological symptoms of dementia successfully treated at home with a blonanserin transdermal patch: A case report.

AIM: Behavioral psychological symptoms of dementia (BPSD) are sometimes difficult to treat due to severe psychiatric symptoms such as delusions of poisoning and violent behavior. Moreover, in cases of parental neglect, the management of these psychiatric symptoms becomes more difficult. Therefore, home-visiting doctors sometimes have to manage patients with BPSD and severe psychiatric symptoms, and a new approach is needed. In this case report, the effect of blonanserin transdermal patch on these patients is to be highlighted. METHODS: The patient is a 91-year-old woman diagnosed with Alzheimer's disease. She had severe BPSD such as delusion of robbery and violent behavior, and refused oral medications including memantine and yokukansan. Then she was treated with blonanserin transdermal patch (20 mg/day). The severity of psychiatric symptoms of BPSD was assessed over time using the Neuropsychiatric Inventory (NPI) score. Moreover, the patient's cognitive function was also assessed over time by Mini-Mental State Examination (MMSE). RESULTS: After the introduction of blonanserin patch, the patient's psychiatric symptoms were stabilized markedly, and both NPI and MMSE scores improved. The patient was able to stay at home calmly and was mentally well stabilized to the extent that she did not require hospitalization. No apparent side effects were admitted. CONCLUSIONS: The blonanserin transdermal patch may be able to manage BPSD at home and is effective in patients who refuse oral medications. Home-visiting doctors may consider the use of blonanserin patches at home for patients with severe BPSD, manifesting as delusions of poisoning and refusing oral drugs.

Neutrophil-to-lymphocyte ratio is a prognostic factor reflecting immune condition of tumor microenvironment in squamous cell lung cancer.

Inflammatory factors in the peripheral blood, such as the C-reactive protein level and neutrophil-to-lymphocyte ratio (NLR), are prognostic markers in multiple types of cancer, including non-small cell lung cancer (NSCLC). However, the association between inflammatory factors and prognosis based on histological types has not been adequately reported. In addition, the relationship between these factors and the immune condition of the tumor microenvironment (TME) is unclear. In this single center, retrospective study, we first investigated the relationship between preoperative inflammatory markers and clinical outcomes in 176 patients with NSCLC who underwent surgery. Lung adenocarcinoma (LUAD) showed no significant prognostic marker, whereas for lung squamous cell carcinoma (LUSC), a multivariate analysis showed that a high NLR was significantly associated with postoperative recurrence. In LUSC patients, the median time of postoperative recurrence-free survival in patients with a low NLR was longer than that in patients with a high NLR. We then compared the tumor-infiltrating lymphocyte (TIL) profile with inflammatory markers in peripheral blood and found that the NLR was negatively correlated with the frequencies of T cells and B cells in LUSC tissues. Thus, the NLR is a useful predictive biomarker for postoperative recurrence and may reflect the immune condition of the TME in LUSC.

Parental overprotection engenders dysfunctional attitudes about achievement and dependency in a gender-specific manner.

BACKGROUND: It has been suggested that dysfunctional attitudes, cognitive vulnerability to depression, have developmental origins. The present study examined the effects of parental rearing on dysfunctional attitudes in three areas of life with special attention to gender specificity. METHODS: The subjects were 665 Japanese healthy volunteers. Dysfunctional attitudes were assessed by the 24-item Dysfunctional Attitude Scale, which has the Achievement, Dependency and Self-control subscales. Perceived parental rearing was assessed by the Parental Bonding Instrument, which has the Care and Protection subscales. RESULTS: Higher scores of the Achievement (ß = 0.293, p < 0.01) and Dependency (ß = 0.224, p < 0.05) subscales were correlated with higher scores of the Protection subscale in the combination of mother and daughter, but not in other combinations of parents and recipients. Scores of the Self-control subscale were not correlated with paternal or maternal rearing scores. CONCLUSIONS: The present study suggests that parental overprotection engenders dysfunctional attitudes about achievement and dependency in a gender-specific manner.

Relationship of the 24-item dysfunctional attitude scale with the temperament and character inventory in healthy subjects.

BACKGROUND: The 24-item Dysfunctional Attitude Scale (DAS-24) has three subscales to evaluate dysfunctional attitudes predisposing to depression in the areas of achievement, dependency and self-control. AIM: The purpose of the present investigation was to characterize the three subscales in relation to broad dimensions of personality. METHODS: The subjects were 528 healthy Japanese volunteers. Personality assessment was conducted by the Temperament and Character Inventory (TCI), which has seven dimensions. The correlations of the DAS-24 subscales with the TCI dimensions were examined by the multiple regression analysis. RESULTS: All DAS-24 subscales had negative correlations with the self-directedness dimension. However, the three subscales had differential patterns of correlations with the reward dependence, persistence, cooperativeness and harm avoidance dimensions. CONCLUSIONS: The present study suggests that dysfunctional attitudes measured by the DAS-24 are closely related to low self-directedness of the TCI. Also, the differential patterns of correlations with some TCI dimensions support the content-specificity of the three subscales.

Delirium due to Trousseau syndrome treated with memantine and perospirone: A case report.

Background: Trousseau syndrome is a hypercoagulability syndrome associated with cancer. It is known that delirium occasionally occurs after the onset of Trousseau syndrome. However, there have been no detailed reports about treatment for psychiatric symptoms of delirium associated with Trousseau syndrome. Case Presentation: A 61-year-old man with lung cancer was hospitalized due to Trousseau syndrome. Delirium occurred after hospitalization and psychiatric symptoms worsened. Although haloperidol, risperidone, and chlorpromazine were used, severe insomnia persisted. After memantine (5 mg/day) was used with perospirone, the patient's psychiatric symptoms gradually decreased; he could sleep for 4-5 h at night. Due to psychiatric improvement, he was able to return home and resume immunotherapy for lung cancer as scheduled. Conclusion: We report the first case of Trousseau syndrome delirium treated by memantine used with perospirone. Although further studies are needed, memantine and perospirone might be candidates for the management of psychiatric symptoms associated with Trousseau syndrome.

Data-driven categorization of postoperative delirium symptoms using unsupervised machine learning.

Background: Phenotyping analysis that includes time course is useful for understanding the mechanisms and clinical management of postoperative delirium. However, postoperative delirium has not been fully phenotyped. Hypothesis-free categorization of heterogeneous symptoms may be useful for understanding the mechanisms underlying delirium, although evidence is currently lacking. Therefore, we aimed to explore the phenotypes of postoperative delirium following invasive cancer surgery using a data-driven approach with minimal prior knowledge. Methods: We recruited patients who underwent elective invasive cancer resection. After surgery, participants completed 5 consecutive days of delirium assessments using the Delirium Rating Scale-Revised-98 (DRS-R-98) severity scale. We categorized 65 (13 questionnaire items/day × 5 days) dimensional DRS-R-98 scores using unsupervised machine learning (K-means clustering) to derive a small set of grouped features representing distinct symptoms across all participants. We then reapplied K-means clustering to this set of grouped features to delineate multiple clusters of delirium symptoms. Results: Participants were 286 patients, of whom 91 developed delirium defined according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria. Following the first K-means clustering, we derived four grouped symptom features: (1) mixed motor, (2) cognitive and higher-order thinking domain with perceptual disturbance and thought content abnormalities, (3) acute and temporal response, and (4) sleep-wake cycle disturbance. Subsequent K-means clustering permitted classification of participants into seven subgroups: (i) cognitive and higher-order thinking domain dominant delirium, (ii) prolonged delirium, (iii) acute and brief delirium, (iv) subsyndromal delirium-enriched, (v) subsyndromal delirium-enriched with insomnia, (vi) insomnia, and (vii) fit. Conclusion: We found that patients who have undergone invasive cancer resection can be delineated using unsupervised machine learning into three delirium clusters, two subsyndromal delirium clusters, and an insomnia cluster. Validation of clusters and research into the pathophysiology underlying each cluster will help to elucidate the mechanisms of postoperative delirium after invasive cancer surgery.

Black cohosh extracts in women with menopausal symptoms: an updated pairwise meta-analysis.

OBJECTIVE: Menopausal symptoms are common in midlife women and have broad impacts on their daily functioning and quality of life. Black cohosh extracts have been widely used to relieve menopausal symptoms. However, the comparative benefits of different combined black cohosh regimens remain inconclusive. The aim of the current updated meta-analysis is to address the comparative efficacies of different black cohosh regimens in improving menopausal symptoms. METHODS: Random-effect model pairwise meta-analysis of randomized controlled trials was conducted to investigate the treatment effect on menopausal symptoms by the black cohosh extract both alone or combined with other related active ingredients. The outcomes studied were changes in menopausal symptoms after treatment with black cohosh extracts in menopausal women. RESULTS: Twenty-two articles including information on 2,310 menopausal women were included in the analyses. Black cohosh extracts were associated with significant improvements in overall menopausal symptoms (Hedges' g = 0.575, 95% CI = 0.283 to 0.867, P < 0.001), as well as in hot flashes (Hedges' g = 0.315, 95% CIs = 0.107 to 0.524, P = 0.003), and somatic symptoms (Hedges' g = 0.418, 95% CI = 0.165 to 0.670, P = 0.001), compared with placebo. However, black cohosh did not significantly improve anxiety (Hedges' g = 0.194, 95% CI = -0.296 to 0.684, P = 0.438) or depressive symptoms (Hedges' g = 0.406, 95% CI = -0.121 to 0.932, P = 0.131). The dropout rate for black cohosh products was similar to that for placebo (odds ratio = 0.911, 95% CI = 0.660 to 1.256, P = 0.568). CONCLUSIONS: This study provides updated evidence regarding the potentially beneficial effects of black cohosh extracts for relieving menopausal symptoms in menopausal women.