A Multicenter Analysis of Clinical Features and Long-Term Outcomes of POEMS Syndrome in Korea

Background@#POEMS syndrome is a rare form of plasma cell dyscrasia characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal proteins, and skin changes.Owing to its low incidence, there are few reports regarding this syndrome. This multicenter study included 84 patients diagnosed with POEMS syndrome in South Korea. @*Methods@#We retrospectively evaluated 84 patients diagnosed with POEMS syndrome at 8 hospitals in South Korea between January 2000 and October 2022. The clinical characteristics and treatment outcomes were analyzed. @*Results@#The median patient age was 53 years (range, 26–77 years), and 63.1% of the patients were male. All patients had peripheral neuropathy, and 81 (96.4%) had monoclonal plasma cell proliferation. Plasma vascular endothelial growth factor levels were available for 32 patients with a median of 821 pg/mL (range, 26–12,900 pg/mL). Other common features included skin changes (54.2%), volume overload (71.4%), and organomegaly (72.6%). Of the 84 patients, 75 received initial treatment (local radiotherapy, 6 [8.0%]; chemotherapy, 17 [22.7%]; both chemotherapy and local radiotherapy, 9 [12.0%]), upfront autologous stem cell transplantation (ASCT), 43 (57.3%; with induction chemotherapy, n = 12, 16.0%; without induction chemotherapy, n = 31, 41.3%). The median follow-up duration was 40.7 months. The 5-year overall survival (OS) was 78%, and the 5-year progression-free survival (PFS) was 55%. Patients who underwent upfront ASCT and were diagnosed after 2014 had a longer OS and PFS. @*Conclusion@#The demographics of Korean patients with POEMS syndrome were similar to those reported previously. Because of the introduction of new treatment agents and the reduced rate of transplant-related mortality related to ASCT, the treatment outcomes of Korean patients with POEMS syndrome have improved in recent years.

Is an Anatomical Suprapectineal Quadrilateral Surface Plate Superior to Previous Fixation Methods for Anterior Column-Posterior Hemitransverse Acetabular Fractures Typical in the Elderly?: A Biomechanical Study

Background@#This study aimed to compare the mechanical characteristics of four fixation methods including an anatomical suprapectineal quadrilateral surface (QLS) plate in hemipelvic models of anterior column–posterior hemitransverse acetabular fractures typical in elderly patients. @*Methods@#In total, 24 composite hemipelvic models were used and allocated to four groups: group 1, pre-contoured anatomical suprapectineal QLS plate; group 2, suprapectineal reconstruction plate with two periarticular long screws; group 3, suprapectineal reconstruction plate with a buttress reconstruction plate; group 4, suprapectineal reconstruction plate with a buttress T-plate. Axial structural stiffness and displacement of each column fragment in four different fixation constructs were compared. @*Results@#Multiple group comparisons of axial structural stiffness demonstrated significant difference (p = 0.001). Although there was no significant difference between groups 1 and 2 (p = 0.699), group 1 showed greater stiffness than groups 3 and 4 (p = 0.002 and 0.002, respectively). Group 1 showed less displacement in the anterior region of the anterior fragment than group 4 (p = 0.009) and in the posterior region than groups 3 and 4 (p = 0.015 and p = 0.015, respectively). However, group 1 demonstrated greater displacement than group 2 in the posterior region of the posterior fragment (p = 0.004), while showing similar displacement to groups 3 and 4. @*Conclusions@#The anatomical suprapectineal QLS plate provided the mechanical stability comparable or superior to other existing fixations in osteoporotic models of anterior column–posterior hemitransverse acetabular fractures typical in the elderly. However, additional plate modification would be needed for better stability and outcomes.

Development of a Next-generation Sequencing-based Gene Panel Test to Detect Measurable Residual Disease in Acute Myeloid Leukemia

Background@#AML is a heterogeneous disease, and despite intensive therapy, recurrence is still high in AML patients who achieve the criterion for cytomorphologic remission (residual tumor burden [measurable residual disease, MRD]0.99). The test reproducibly detected MRD in three dilution series samples, with a sensitivity of 0.25% for single-nucleotide variants. More than half of samples from patients with morphologic remission after one month of chemotherapy had detectable mutations. NGS-MRD positivity for samples collected after one month of chemotherapy tended to be associated with poor overall survival and progression-free survival. @*Conclusions@#Our highly sensitive and accurate NGS-MRD panel can be readily used to monitor most AML patients in clinical practice, including patients without gene rearrangement. In addition, this NGS-MRD panel may allow the detection of newly emerging clones during clinical relapse, leading to more reliable prognoses of AML.

Predictive Factors of Event-Free Survival at 24 Months in Patients with Peripheral T-Cell Lymphoma: A Retrospective Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Event-free survival at 24 months (EFS24) is known to be a surrogate marker for overall survival (OS) for patients with peripheral T-cell lymphoma (PTCL). We examined the role of EFS24 in PTCL compared to diffuse large B-cell lymphoma (DLBCL), and then assessed the clinical predictive factors of achieving EFS24. @*Materials and Methods@#Patients with newly diagnosed PTCL treated with anthracycline-based chemotherapy were included. Subsequent OS was defined as the time elapsed from 24 months after diagnosis until death from any cause in those who achieved EFS24. @*Results@#Overall, 153 patients were evaluated, and 51 patients (33.3%) achieved EFS24. Patients who achieved EFS24 showed superior OS compared to patients who did not (p < 0.001). EFS24 could stratify the subsequent OS although it did not reach to that of the general population. After matching the PTCL group to the DLBCL group based on the international prognostic index, the subsequent OS in patients who achieved EFS24 was similar between the two groups (p=0.094). Advanced stage was a significant factor to predict the failing EFS24 by multivariable analysis (p < 0.001). @*Conclusion@#Patients with PTCL who achieve EFS24 could have a favorable subsequent OS. Since advanced disease stage is a predictor of EFS24 failure, future efforts should focus on developing novel therapeutic strategies for PTCL patients presenting with advanced disease.

Lenalidomide for anemia correction in lower-risk del(5q) myelodysplastic syndrome patients of Asian ethnicity

Background@#To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. @*Methods@#Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. @*Results@#A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). @*Conclusion@#Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.

Lenalidomide for anemia correction in lower-risk del(5q) myelodysplastic syndrome patients of Asian ethnicity

Background@#To estimate real-world outcomes in East Asian populations, we conducted a nationwide retrospective analysis of the efficacy and safety of lenalidomide for del(5q) myelodysplastic syndrome (MDS) patients with transfusion-dependent anemia in Korea. @*Methods@#Patients aged ≥19 years who had received lenalidomide for the treatment of lower-risk, red blood cell (RBC) transfusion-dependent del(5q) MDS were selected. A filled case report form (CRF) with information from electronic medical records was requested from members of the acute myeloid leukemia (AML)/MDS Working Party of the Korean Society of Hematology. All the CRFs were gathered and analyzed. @*Results@#A total of 31 patients were included in this study. Of 28 evaluable patients, 19 (67.9%) achieved RBC transfusion independence (RBC-TI). Female sex and the development of thrombocytopenia during treatment were associated with achieving RBC-TI. The most common non-hematologic toxicities were pruritus, fatigue, and rashes. All non-hematologic toxicities of grades ≥3 were limited to rash (12.9%) and pruritus (6.5%). Dose reduction was required in 15 of the 19 responders (78.9%). The most common final stable dosing schedule for the responders was 5 mg once every other day (31.6%). @*Conclusion@#Lenalidomide efficacy and tolerability were similar in the Asian del(5q) MDS patients and western patients. Dose reduction during treatment was common, but it was not associated with inferior outcomes.

Different roles of surveillance positron emission tomography according to the histologic subtype of non-Hodgkin’s lymphoma

Background/Aims@#Although the use of surveillance 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is discouraged in patients with diffuse large B-cell lymphoma, its usefulness in different subtypes has not been thoroughly investigated. @*Methods@#We retrospectively evaluated 157 patients who showed positive results on surveillance FDG-PET/CT every 6 months following complete response for up to 5 years. All of the patients also underwent biopsies. @*Results@#Seventy-eight (49.6%) of 157 patients had true positive results; the remaining 79 (50.3%), including eight (5.1%) with secondary malignancies, were confirmed to yield false positive results. Among the 78 patients with true positive results, the disease in seven (8.9%) had transformed to a different subtype. The positive predictive value (PPV) of FDG-PET/CT for aggressive B-cell non-Hodgkin’s lymphoma (NHL) was lower than that for indolent B-cell or aggressive T-cell NHL (p = 0.003 and p = 0.018, respectively), especially in patients with a low/low-intermediate international prognostic index (IPI) upon a positive PET/CT finding. On the other hand, indolent B-cell and aggressive T-cell NHL patients showed PPVs of > 60%, including those with low/low-intermediate secondary IPIs. @*Conclusions@#The role of FDG-PET/CT surveillance is limited, and differs according to the lymphoma subtype. FDG-PET/CT may be useful in detecting early relapse in patients with aggressive T-cell NHL, including those with low/low-intermediate risk secondary IPI; as already known, FDG-PET/CT has no role in aggressive B-cell NHL. Repeat biopsy should be performed to discriminate relapse or transformation from false positive findings in patients with positive surveillance FDG-PET/CT results.

Effectiveness of Exercise Intervention in Reducing Body Weight and Glycosylated Hemoglobin Levels in Patients with Type 2 Diabetes Mellitus in Korea: A Systematic Review and Meta-Analysis

BACKGROUND: This study aimed to assess the effectiveness of exercise intervention in reducing body weight and glycosylated hemoglobin (HbA1c) level in patients with type 2 diabetes mellitus (T2DM) in Korea. METHODS: Cochrane, PubMed, Embase, KoreaMed, KMbase, NDSL, KCI, RISS, and DBpia databases were used to search randomized controlled trials and controlled clinical trials that compared exercise with non-exercise intervention among patients with non-insulin-treated T2DM in Korea. The effectiveness of exercise intervention was estimated by the mean difference in body weight changes and HbA1c level. Weighted mean difference (WMD) with its corresponding 95% confidence interval (CI) was used as the effect size. The pooled mean differences of outcomes were calculated using a random-effects model. RESULTS: We identified 7,692 studies through literature search and selected 23 articles (723 participants). Compared with the control group, exercise intervention (17 studies) was associated with a significant decline in HbA1c level (WMD, −0.58%; 95% CI, −0.89 to −0.27; I 2=73%). Although no significant effectiveness on body weight was observed, eight aerobic training studies showed a significant reduction in body weight (WMD, −2.25 kg; 95% CI, −4.36 to −0.13; I 2=17%) in the subgroup analysis. CONCLUSION: Exercise significantly improves glycemic control; however, it does not significantly reduce body weight. Aerobic training can be beneficial for patients with non-insulin-treated T2DM in Korea.

Validation of the Korean version of the 16-Item Prodromal Questionnaire in a Non-Help-Seeking College Population

OBJECTIVE: To examine the reliability and validity of the Korean version of the 16-item Prodromal Questionnaire (KPQ-16) in non-help-seeking university students. METHODS: Among 2,246 university students participated in the initial screening, 257 subjects with KPQ-16 scores ≥4 were interviewed. The criteria for ultra-high risk (UHR) of psychosis of the Comprehensive Assessment of At-Risk Mental States (CAARMS) were the gold standard for diagnosis. An exploratory modified version of the questionnaire (mKPQ-16), to which three items from the Eppendorf Schizophrenia Inventory were added, was also used to compensate for items on thought and cognitive problems. RESULTS: Seventeen subjects met the CAARMS criteria for UHR of psychosis. The area under the receiver operating characteristic curve (AUROC) was highest for the mKPQ-16 total score (AUROC=0.831, p < 0.001). The use of cutoff total scores of 7 for the mKPQ-16 and 6 for the KPQ-16 resulted in the best balance of sensitivity (76.5% and 64.7%, respectively) and specificity (75.4% and 71.2%, respectively). CONCLUSION: The Korean versions of the PQ-16 are good instruments for screening for psychosis risk in university students. This validation of a questionnaire version with a small number of items may make it feasible to screen large numbers of young adults in the community.

Determinants Used to Justify the Strength of Recommendations among Korean Clinical Practice Guidelines

BACKGROUND: A standardized systematic approach to grade evidence and the strength of recommendations is important for guideline users to minimize bias and help interpret the most suitable decisions at the point of care. The study aims to identify and classify determinants used to make judgement for the strength of recommendations among 56 Korean clinical practice guidelines (CPGs), and explore strong recommendations based on low quality of evidence. METHODS: Determinants used in the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach among 34 CPGs which have reported both strength of recommendations and level of evidence were reviewed. RESULTS: Five of 34 CPGs (14.7%) considered quality of evidence, benefits and harms, patients' values and preferences, and costs. And 24 of 34 CPGs (70.6%) considered both magnitude of effect and feasibility as additional determinants. Judgement table was not widely provided for use to translate evidence into recommendations. Eighty-two of 121 recommendations (67.8%, ranged 20.0% to 100.0%) among 11 CPGs using the same judgement scheme showed ‘strong’ strength of recommendations based on low or very low quality of evidence. Among 5 paradigmatic situations that justify strong recommendations based on low or very low evidence, situation classified as ‘potential equivalence, one option clearly less risky or costly’ was 87.8% for 82 strong recommendations. Situation classified as ‘uncertain benefit, certain harm’ was 4.9%. CONCLUSION: There is a need to introduce and systematize an evidence-based grading system. Using judgement table to justify the strength of recommendations and applying the 5 paradigmatic situations mentioned above is also recommended in the near future.

HBsAg-Negative, Anti-HBc–Negative Patients Still Have a Risk of Hepatitis B Virus–Related Hepatitis after Autologous Stem Cell Transplantation for Multiple Myeloma or Malignant Lymphoma / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Although hepatitis B surface antigen (HBsAg)–negative, hepatitis B core antibody (anti-HBc)–negative patients are not considered to be at risk for hepatitis B virus (HBV)–related hepatitis, the actual risk remains to be elucidated. This study aimed to evaluate the risk of HBV-related hepatitis in HBsAg-negative, anti-HBc–negative patients receiving autologous stem cell transplantation (ASCT) for multiple myeloma (MM) or malignant lymphoma. MATERIALS AND METHODS: We retrospectively reviewed data from 271 HBsAg-negative patients (161 anti-HBc–negative and 110 anti-HBc–positive at the time of ASCT) who received ASCT for MM or lymphoma. The risk of HBV-related hepatitis was analyzed according to the presence of anti-HBc. HBV serology results at the time of ASCT were compared with those at the time of diagnosis of MM or lymphoma. RESULTS: Three patients (two anti-HBc–negative MMs and one anti-HBc–positive MM) developed HBV-related hepatitis after ASCT. The rate of HBV-related hepatitis did not differ among patients with or without anti-HBc status (p=0.843). HBV-related hepatitis more frequently occurred in MM patients than in lymphoma patients (p=0.041). Overall, 9.1% of patients (16.7% with MM and 5.4% with lymphoma) who were HBsAg–negative and anti-HBc–positive at the time of diagnosis had lost anti-HBc positivity during chemotherapy prior to ASCT. CONCLUSION: Our data suggest that HBsAg-negative, anti-HBc–negative patients at the time of ASCT for MM or lymphoma still might be at a risk for HBV-related hepatitis.

Effects of Group Cognitive-Behavioral Therapy in Young Patients in the Early Stage of Psychosis

OBJECTIVE: To develop a model of group cognitive-behavioral therapy (CBT) for Korean patients with early psychosis. METHODS: The group CBT utilized in the present study consisted of metacognitive training, cognitive restructuring, and lifestyle managements. The Subjective Well-being Under Neuroleptics (SWN-K), Ambiguous Intentions Hostility Questionnaire (AIHQ), Drug Attitude Inventory (DAI), Beck Depression Inventory (BDI), Perceived Stress Scale (PSS), and Clinical Global Impression (CGI) were administered prior to and after CBT sessions. The participants were categorized into two groups according to the median duration of untreated psychosis (DUP; 4 months). RESULTS: A total of 34 patients were included in this analysis. From pre- to post-therapy, there were significant increases in the SWN-K and DAI scores and significant decreases in the hostility subscale of the AIHQ, PSS, and CGI scores. Significant time × DUP interaction effects were observed for the SWN-K, DAI, and BDI scores, such that there were significant changes in patients with a short DUP but not in those with a long DUP. CONCLUSION: The group CBT program had a positive effect on subjective wellbeing, attitude toward treatment, perceived stress, and suspiciousness of young Korean patients with early psychosis. These effects were particularly significant in patients with a short DUP.

Clinical characteristics and treatment outcomes of isolated myeloid sarcoma without bone marrow involvement: a single-institution experience

BACKGROUND: Isolated myeloid sarcoma (MS) is a rare extramedullary tumor mass composed of malignant myeloid precursor cells without any evidence of leukemia in the peripheral blood and bone marrow. We describe the clinical characteristics and outcomes of patients diagnosed with isolated MS at our institution. METHODS: We retrospectively reviewed 9 of 497 acute myeloid leukemia (AML) patients (1.8%) with isolated MS. Isolated MS patients were divided into 2 groups according to the first-line treatment strategy: systemic treatment only (S) or local treatment with or without systemic treatment (LS). RESULTS: The most common site of MS occurrence was the head and neck area (N=4, 44.4%), followed by the anterior mediastinum (N=2, 22.2%) and the gastrointestinal tract (N=2, 22.2%). The tumors of 4 patients (44.4%) eventually evolved to AML, in a median time of 13.4 months (range, 2.4–20.1 mo). The number of patients achieving complete remission after first-line treatment was higher in the LS group (N=5, 83.3%) than in the S group (N=1, 33.3%) (P =0.226). All patients in the LS group survived, but those in the S group died (P=0.012). CONCLUSION: Accurate and rapid diagnosis using various modalities and the early initiation of intensive combined treatment may be the optimal strategies to reduce the risk of isolated MS subsequently evolving to AML. To fully understand the characteristics of isolated MS, a larger number of patients from a multinational study is necessary.

Pretreatment Lymphopenia, Poor Performance Status, and Early Courses of Therapy Are Risk Factors for Severe Bacterial Infection in Patients with Multiple Myeloma during Treatment with Bortezomib-based Regimens

The aim of this study was to identify the risk factors associated with severe bacterial infection (SBI) in multiple myeloma (MM) patients during treatment with bortezomib-based regimens. A total of 98 patients with MM were evaluated during 427 treatment courses. SBI occurred in 57.1% (56/98) of the patients and during 19.0% (81/427) of the treatment courses. In the multivariate analysis for the factors associated with the development of SBI in each treatment course, poor performance status (Eastern Cooperative Oncology Group ≥ 2, P < 0.001), early course of therapy (≤ 2 courses, P < 0.001), and pretreatment lymphopenia (absolute lymphocyte count < 1.0 × 10(9)/L, P = 0.043) were confirmed as independent risk factors. The probability of developing SBI were 5.1%, 14.9%, 23.9% and 59.5% in courses with 0, 1, 2, and 3 risk factors, respectively (P < 0.001). In conclusion, we identified three pretreatment risk factors associated with SBI in each course of bortezomib treatment. Therefore, MM patients with these risk factors should be more closely monitored for the development of SBI during bortezomib-based treatment.

Methodological Quality Appraisal of 27 Korean Guidelines Using a Scoring Guide Based on the AGREE II Instrument and a Web-based Evaluation

This study evaluated the methodological quality of CPGs using the Korean AGREE II scoring guide and a web-based appraisal system and was conducted by qualified appraisers. A total of 27 Korean CPGs were assessed under 6 domains and 23 items on the AGREE II instrument using the Korean scoring guide. The domain scores of the 27 guidelines were as following: the mean domain score was 82.7% (median 84.7%, ranging from 55.6% to 97.2%) for domain 1 (scope and purpose); 53.4% (median 56.9%, ranging from 11.1% to 95.8%) for domain 2 (stakeholder involvement); 63.0% (median 71.4%, ranging from 13.5% to 90.6%) for domain 3 (rigor of development); 88.9% (median 91.7%, ranging from 58.3% to 100.0%) for domain 4 (clarity of presentation); 30.1% (median 27.1%, ranging from 3.1% to 67.7%) for domain 5 (applicability); and 50.2% (median 58.3%, ranging from 0.0% to 93.8%) for domain 6 (editorial independence). Three domains including scope and purpose, rigor of development, and clarity of presentation were rated at more than 60% of the scaled domain score. Three domains including stakeholder involvement, applicability, and editorial independence were rated at less than 60% of the scaled domain score. Finally, of the 27 guidelines, 18 (66.7%) were rated at more than 60% of the scaled domain score for rigor of development and were categorized as high-quality guidelines.

Subclinical Ulnar Neuropathy at the Elbow in Diabetic Patients

OBJECTIVE: To demonstrate the prevalence and characteristics of subclinical ulnar neuropathy at the elbow in diabetic patients. METHODS: One hundred and five patients with diabetes mellitus were recruited for the study of ulnar nerve conduction analysis. Clinical and demographic characteristics were assessed. Electrodiagnosis of ulnar neuropathy at the elbow was based on the criteria of the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM1 and AANEM2). The inching test of the ulnar motor nerve was additionally performed to localize the lesion. RESULTS: The duration of diabetes, the existence of diabetic polyneuropathy (DPN) symptoms, the duration of symptoms, and HbA1C showed significantly larger values in the DPN group (p<0.05). Ulnar neuropathy at the elbow was more common in the DPN group. There was a statistically significant difference in the number of cases that met the three diagnostic criteria between the no DPN group and the DPN group. The most common location for ulnar mononeuropathy at the elbow was the retrocondylar groove. CONCLUSION: Ulnar neuropathy at the elbow is more common in patients with DPN. If the conduction velocities of both the elbow and forearm segments are decreased to less than 50 m/s, it may be useful to apply the AANEM2 criteria and inching test to diagnose ulnar neuropathy.

Osteogenic Differentiation of Bone Marrow Stem Cell in Poly(Lactic-co-Glycolic Acid) Scaffold Loaded Various Ratio of Hydroxyapatite

BACKGROUND AND OBJECTIVES: Hydroxyapatite has biocompatibility and bioactivity and similar to bone of in human body. The purpose of this study is to evaluate osteogenic differentiation of bone marrow stem cell (BMSC) in PLGA Scaffold added various ratio of hydroxyapatite (HAp). METHODS AND RESULTS: PLGA and PLGA/HAp scaffold were prepared using solvent casting/salt-leaching method. BMSC was seeded on the PLGA and PLGA/HAp scaffold and the samples were cultured in 37degrees C incubator with 5% CO2 for 28 days. Alkaline phosphatase (ALP) was carried out to evaluate alkaline phosphatase activity at 1, 3, 7, 10 and 14 days. Alizarin Red S stating was performed to identify calcium in scaffold at 1, 7, 14, 21 and 28 days. Compressive strength was measured to evaluate mechanical property of scaffold. To confirm cell viability, MTT was carried out at 1, 3, 7, 14 and 28 days. RT-PCR was performed to verify specific marker expression of osteoblast and stem cell at 7, 14, 21 and 28 days. CONCLUSIONS: Osteogenic differentiation of BMSC was confirmed through ALP, RT-PCR, and alizarin red S staining in this study. These results suggest that HAp helps osteogenic differentiation of BMSC.

Placebo Effects and Clinical Trials of Neuropsychiatric Drugs

The placebo effect, a response observed during the placebo arm of a clinical trial, is produced by the psychobiological action of the placebo as well as by other potential contributors to symptom amelioration such as spontaneous improvement, regression to the mean, biases, concurrent treatments, and study design. From a psychological viewpoint, there are many mechanisms that contribute to placebo effects, including expectations, conditioning, learning, and anxiety reduction. Placebo responses are also mediated by opioid and non-opioid mechanisms including dopamine, serotonin, cholecystokinin, and immune mediators. During recent years, a trend towards increased placebo effects in clinical trials of neuropsychiatric drugs has been noted. Indeed, the placebo effects observed in clinical trials constitute an increasing problem and interfere with signal-detection analyses of potential treatments. Several potential factors including protocol/study design and conduct related factors may account for the placebo effect observed in clinical trials. This paper reviews key issues related to this problem and aims to identify potential solutions.

Comparison of Stigma according to the Term Used for Schizophrenia : Split-Mind Disorder vs. Attunement Disorder / 신경정신의학

OBJECTIVES: In Korea, the term for schizophrenia has been changed from 'split-mind disorder' to 'attunement disorder'. This study compared the stigma of, and prejudice against, people with schizophrenia, according to use of the term 'split-mind disorder' or 'attunement disorder'. METHODS: We conducted a survey of 360 college students majoring in nursing science in order to assess their prejudice regarding the danger posed by schizophrenia and discrimination regarding relationships and privileges for patients with schizophrenia using the social stigma scale and the discrimination scale for patients with mental illness, respectively. Study subjects were randomly divided into two groups, and the same scales were assigned to each group using different instructions, beginning with either 'split-mind disorder' or 'attunement disorder'. RESULTS: In multivariate analysis, scores for prejudice with regard to the danger posed by, and discrimination against, patients with schizophrenia were significantly higher in the group assigned the term split-mind disorder, compared with the term attunement disorder. Scores for discrimination with regard to relationships and privileges were significantly lower for subjects with experience to contact the mentally ill, compared to those without such experience. CONCLUSION: Our findings suggest that renaming split-mind disorder as attunement disorder can result in reduced prejudice and discrimination against people with schizophrenia. In addition to renaming schizophrenia, implementation of anti-stigma campaigns, including contact with schizophrenia patients, may help to reduce discrimination against them.

Optimal Stimulation Site for Deep Peroneal Motor Nerve Conduction Study Around the Ankle: Cadaveric Study

OBJECTIVE: To identify the optimal distal stimulation point for conventional deep peroneal motor nerve (DPN) conduction studies by a cadaveric dissection study. METHOD: DPN was examined in 30 ankles from 20 cadavers. The distance from the DPN to the tibialis anterior (TA) tendon was estimated at a point 8 cm proximal to the extensor digitorum brevis (EDB) muscle. Relationships between the DPN and tendons including TA, extensor hallucis longus (EHL), and extensor digitorum longus (EDL) tendons were established. RESULTS: The median distance from the DPN to the TA tendon in all 30 cadaver ankles was 10 mm (range, 1-21 mm) at a point 8 cm proximal to the EDB muscle. The DPN was situated between EHL and EDL tendons in 18 cases (60%), between TA and EHL tendons in nine cases (30%), and lateral to the EDL tendon in three cases (10%). CONCLUSION: The optimal distal stimulation point for the DPN conduction study was approximately 1 cm lateral to the TA tendon at the level of 8 cm proximal to the active electrode. The distal stimulation site for the DPN should be reconsidered in cases with a weaker distal response but without an accessory peroneal nerve.