Change of hand sensation and function in patients with malignant lymphoma during early-stage vincristine chemotherapy: A single-center observational study.

This study aimed to investigate changes in hand sensation (finger tactile threshold and two-point discrimination) and function in patients with malignant lymphoma, particularly during the early stages of chemotherapy with vincristine. Eighteen patients with malignant lymphoma were enrolled in this study. Data on the Common Terminology Criteria for Adverse Events Version 4.0, the visual analog scale for hand numbness, the Semmes Weinstein monofilament test, static and moving two-point discrimination (2PD), grip strength, pinch strength, and the Purdue Pegboard test were collected at 3 time points: before the start of chemotherapy (T0), after the first cycle of chemotherapy (T1), and after the second cycle of chemotherapy (T2). No significant changes were observed in Semmes Weinstein monofilament test at T0, T1, or T2 in either hand. However, the static 2PD was significantly worse for the right ring, little, and left middle fingers, whereas the moving 2PD was significantly worse for the right ring, left index, middle, and ring fingers. Furthermore, the visual analog scale scores for hand numbness and left-hand grip strength worsened significantly. Right-hand grip strength, pinch strength of both hands, and Purdue Pegboard test showed no significant deterioration. Chemotherapy with vincristine may affect hand sensation and function in patients with malignant lymphoma by exacerbating finger 2PD and hand numbness. Additionally, during the early stages of vincristine chemotherapy, it is important to monitor for a decrease in grip strength specifically in the left hand.

Analgesic Effects and Adverse Reactions of Lidocaine for Patient-Controlled Intravenous Analgesia on Patients Undergoing Open Hepatectomy: A Retrospective Analysis.

PURPOSE: The aim of this study was to investigate the effect of lidocaine for patient controlled intravenous analgesia (PCIA) in patients who underwent open hepatectomy. DESIGN: A retrospective analysis. METHODS: A total of 281 patients who underwent open hepatectomy from July 2018 to December 2018 were included. All patients were assigned into two groups: the lidocaine group (PCIA consisted of lidocaine, sufentanil, tramadol and granisetron) and the control group (PCIA consisted of sufentanil, tramadol and granisetron). The postoperative visual analogue scale (VAS) and complications (including respiratory depression, hypotension, nausea and vomiting, pruritus, numbness of the corners of the mouth, dizziness) between the groups were compared. FINDINGS: There were no significant differences between the characteristics, duration of surgery and anesthesia, and recovery of postoperative activity between the two groups. In the first 3 days after the operation, the postoperative VAS score of the lidocaine group was lower than that of the control group at resting state, while after activity, the postoperative VAS contrast results were completely opposite. In particularly, the resting state at 48 hours (h) (1.05 ± 1.25 vs 1.57 ± 1.54) after surgery and the activity state at 72 h (3.02 ± 1.51 vs 2.2 ± 1.66) after surgery (P < 0.05). The incidence of mouth numbness and dizziness were significantly increased in the lidocaine group (P < 0.05). CONCLUSION: The addition of lidocaine in PCIA was not beneficial to improve the pain during activities and increased the incidence of perioral numbness and dizziness.

Impact of acupuncture and integrative therapies on chemotherapy-induced peripheral neuropathy: A multicentered, randomized controlled trial.

BACKGROUND: To explore the impact of acupuncture with other complementary and integrative medicine (CIM) modalities on chemotherapy-induced peripheral neuropathy (CIPN) and quality of life (QoL) in oncology patients. METHODS: In this prospective, pragmatic, and patient-preference study, patients with CIPN were treated with acupuncture and CIM therapies (intervention group) or standard care alone (controls) for 6 weeks. Patients in the intervention arm were randomized to twice-weekly acupuncture-only (group A) or acupuncture with additional manual-movement or mind-body CIM therapies (group B). Severity of CIPN was assessed at baseline and at 6 weeks using the Functional Assessment of Cancer Therapy-Taxane (FACT-Tax) tool. Other QoL-related outcomes were assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC); and the Measure Yourself Concerns and Well-being questionnaire. Von Frey measurements examined perception thresholds. RESULTS: Of 168 participants, 136 underwent the study intervention (group A, 69; group B, 67), with 32 controls. Baseline-to-6-week assessment scores improved significantly in the intervention arm (vs controls) on FACT-Tax (p = .038) and emotional well-being (p = .04) scores; FACT-TAX scores for hand numbness/tingling (p = .007) and discomfort (p < .0001); and EORTC physical functioning (p = .045). Intervention groups A and B showed improved FACT-Tax physical well-being (p < .001), FACT-TAX total score (p < .001), FACT-TAX feet discomfort (p = .003), and EORTC pain (p = .017) scores. CONCLUSIONS: Acupuncture, with or without CIM modalities, can relieve CIPN-related symptoms during oncology treatment. This is most pronounced for hand numbness, tingling, pain, discomfort, and for physical functioning.

Analysis of clinical characteristics and prognostic factors in 110 patients with nitrous oxide abuse.

PURPOSE: To review the clinical symptoms, auxiliary examination findings, and outcomes of patients with nitrous oxide (N2 O) abuse, and analyze the factors that affect outcomes. METHODS: Patients with N2 O abuse treated in the Department of Neurology between January 2018 and December 2020 were included. The clinical data of these patients were collected, and follow-up was conducted to determine the outcomes. RESULTS: The average age of the 110 patients with N2 O abuse was 21.4 ± 4.2 years (range: 14-33 years). Clinical presentation primarily included neurological symptoms, such as limb numbness and/or weakness (97%), psychiatric symptoms, changes in appetite, and skin hyperpigmentation. Laboratory test results were characterized by vitamin B12 deficiency (60%, 34 out of 57 cases) and high homocysteine level (69%, 31 out of 45 cases). Electromyography indicated mixed axonal and demyelination injury (92%, 80 out of 87 cases). Motor and sensory nerves were simultaneously involved, and injury primarily involved the lower limbs. One hundred and seven (97%) patients were clinically diagnosed with peripheral neuropathy, of whom 26 (24%) exhibited spinal abnormalities on magnetic resonance imaging, supporting a diagnosis of subacute combined degeneration. Treatment included N2 O withdrawal and vitamin B12 supplementation. Reexamination of six patients indicated that treatment was effective. Follow-up was completed for 51 patients. Thirty-four patients (67%) recovered completely, 17 patients (33%) had residual limb numbness, and only one patient experienced relapse. Sex was an independent prognostic factor; the outcomes of female patients were better than that of male patients. CONCLUSION: The recreational use of N2 O has largely expanded among youth in recent decades, which has become a growing public health concern in China. It highlights the importance of the recognition of various clinical symptoms, particularly limb numbness and/or weakness related to the cases of N2 O abuse. The therapeutic administration of vitamin B12 supplementation and N2 O withdrawal can make the overall prognosis good, especially for female patients.

Self-Reported Severity, Characteristics, and Functional Limitations of Chemotherapy-Induced Peripheral Neuropathy.

BACKGROUND: The early identification of chemotherapy-induced peripheral neuropathy (CIPN) (e.g., numbness or tingling in the fingers or toes) is important due to its frequency and the few effective treatment options available. The identification of common patient-reported CIPN characteristics and associated functional limitations may help to facilitate patient-clinician discussions of CIPN in practice. AIMS: To quantify the severity, duration, location, characteristics, and associated functional limitations of chemotherapy-induced peripheral neuropathy (CIPN) in patients receiving neurotoxic chemotherapy. DESIGN: Exploratory secondary analysis of a prospective, two-phase study SETTING: Breast, gastrointestinal, and multiple myeloma clinics at Dana-Farber Cancer Institute. PARTICIPANTS: 142 individuals who planned to receive at least three more cycles of neurotoxic chemotherapy after consent. METHODS: Participants self-reported CIPN using standardized measures (i.e., PRO-CTCAE™ Numbness and Tingling Items or 0-10 numerical rating scale of worst CIPN pain intensity) and/or study team generated follow up questions about CIPN location, duration, characteristics, and functional limitations prior to three consecutive clinic visits (T1, T2, T3). Participants' responses to the CIPN self-report questionnaires were described by chemotherapy type and age. RESULTS: Over approximately 36.5 days (T1-T3), the percentage of participants reporting at least mild CIPN increased from 59.3% to 71%. At T3, patients with non-painful (n = 98) or painful neuropathy (n = 34) frequently reported symptoms in the fingers (non-painful = 83.5%, painful = 76.5%) or toes (non-painful = 49.5%, painful = 41.2%) and characterized symptoms as numbness (non-painful = 54.1%, painful = 50%) or tingling (non-painful = 68.4%, painful = 82.4%). Self-reported CIPN functional limitations (n = 55) included difficulties with buttoning a shirt (38.2%) or walking (25.5%). Paclitaxel-related CIPN (n = 33) was frequently characterized as "continuous" (30.3%), whereas oxaliplatin-related CIPN (n = 51) was frequently characterized as "intermittent" (41.2%). Young adults (15-39 years old, n = 15) frequently reported moderate-severe non-painful CIPN (46.7%), painful CIPN (40%), and CIPN interference (33.3%). CONCLUSIONS: Consistent with qualitative research, participants frequently described CIPN as numbness and/or tingling in the fingers and/or toes.

Real-world safety data for the Pfizer BNT162b2 SARS-CoV-2 vaccine: historical cohort study.

OBJECTIVE: The Pfizer BNT162b2 vaccine showed a reassuring safety profile in clinical trials, but real-world data are scarce. Bell's palsy, herpes zoster, Guillain-Barré syndrome (GBS) and other neurological complaints in proximity to vaccination have received special public attention. We compared their rates among vaccinated and unvaccinated individuals. METHODS: Individuals ≥16 years vaccinated with at least one dose of BNT162b2 were eligible for this historical cohort study in a health maintenance organization insuring 1.2 million citizens. Each vaccinee was matched to a non-vaccinated control by sex, age, population sector (general Jewish, Arab, ultra-orthodox Jewish) and comorbidities. Diagnosis of Covid-19 before or after vaccination was an exclusion criterion. The outcome was a diagnosis of Bell's palsy, GBS, herpes zoster or symptoms of numbness or tingling, coded in the visit diagnosis field using ICD-9 codes. Diagnoses of Bell's palsy and GBS were verified by individual file review. RESULTS: Of 406 148 individuals vaccinated during the study period, 394 609 (97.2%) were eligible (11 539 excluded). A total of 233 159 (59.1%) were matched with unvaccinated controls. Mean follow was 43 ± 15.14 days. In vaccinated and unvaccinated individuals there were 23 versus 24 cases of Bell's palsy (RR 0.96, CI 0.54-1.70), one versus zero cases of GBS, 151 versus 141 cases of herpes zoster (RR 1.07, CI 0.85-1.35) and 605 versus 497 cases of numbness or tingling (RR 1.22, CI 1.08-1.37), respectively. DISCUSSION: No association was found between vaccination, Bell's palsy, herpes zoster or GBS. Symptoms of numbness or tingling were more common among vaccinees. This study adds reassuring data regarding the safety of the BNT162b2 vaccine.

Ixekizumab exposure associated with myelitis: A case report and a literature review.

We describe a case of a 28-year-old man who developed a cervical myelitis while exposed to ixekizumab (IL-17 inhibitor) for psoriatic arthritis. Spinal MRI showed a T2 hyperintense lesion at the C4-C5 level while brain MRI was unspecific. Oligoclonal bands were absent and extensive screening for autoimmunity was negative. Rechallenge with ixekizumab was positive corroborating a relation between drug exposure and the neurological event. To the best of our knowledge, this is the first case of CNS inflammatory adverse event associated with ixekizumab. We also provide a review of case reports of demyelinating disorders associated with the use of biologic drugs for the treatment of psoriasis and psoriatic arthritis.

Open-label, Multicenter, Phase II Study of RC48-ADC, a HER2-Targeting Antibody-Drug Conjugate, in Patients with Locally Advanced or Metastatic Urothelial Carcinoma.

PURPOSE: To evaluate the efficacy and safety of RC48-ADC, a novel humanized anti-HER2 antibody conjugated with monomethyl auristatin E, in patients with HER2+ locally advanced or metastatic urothelial carcinoma (mUC) refractory to standard therapies. PATIENTS AND METHODS: This was a phase II, open-label, multicenter, single-arm study of patients with HER2+ (IHC status 3+ or 2+) locally advanced or mUC who previously failed at least one line of systemic chemotherapy. The primary endpoint was the objective response rate (ORR) assessed by a blinded independent review committee (BIRC). The secondary endpoint included progression-free survival (PFS), disease control rate, duration of response, overall survival (OS), and safety. RESULTS: Forty-three patients were enrolled. The median follow-up was 20.3 months. The overall confirmed ORR as assessed by the BIRC was 51.2% [95% confidence interval (CI), 35.5%-66.7%]. Similar responses were observed in prespecified subgroups, such as those with liver metastasis and those previously treated with anti-programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) therapies. The median PFS and OS were 6.9 months (95% CI, 5.6-8.9) and 13.9 months (95% CI, 9.1-NE), respectively. The most common treatment-related adverse events (TRAE) were hypoesthesia (60.5%), alopecia (55.8%), and leukopenia (55.8%). Twenty-five (58%) patients experienced grade 3 TRAEs, including hypoesthesia (23.3%) and neutropenia (14.0%). No grade 4 or grade 5 TRAEs occurred. CONCLUSIONS: RC48-ADC demonstrated a promising efficacy with a manageable safety profile in patients with HER2+ locally advanced or mUC who had failed at least one line of systemic chemotherapy.

Unintentional Epidural Anesthesia Mimicking Cauda Equina Syndrome from Suprafascial Injection of Liposomal Bupivacaine After Lumbar Foraminotomy: A Case Report.

CASE: This case report describes a 46-year-old woman undergoing right-sided L5 to S1 decompression who received liposomal bupivacaine (LB) for postoperative analgesia and developed unintentional epidural anesthesia with symptoms mimicking cauda equina syndrome. The patient's symptoms resolved 72 hours postoperatively, approximately the length that LB typically lasts. At the 16-month follow-up, the patient demonstrated complete neurological function with no lower extremity strength or sensation deficits. CONCLUSIONS: Tracking of LB into the epidural space after lumbar surgery may cause transient epidural anesthesia with symptoms that mimic cauda equina syndrome.

Painful and non-painful chemotherapy-induced peripheral neuropathy and quality of life in colorectal cancer survivors: results from the population-based PROFILES registry.

PURPOSE: This study aims to (1) examine the prevalence of painful versus non-painful chemotherapy-induced peripheral neuropathy (CIPN) among long-term colorectal cancer (CRC) survivors, (2) identify sociodemographic, clinical, and psychological factors associated with painful and non-painful CIPN, and (3) examine the associations of painful CIPN with health-related quality of life (HRQoL) in comparison with non-painful CIPN, i.e., numbness/tingling. METHODS: All CRC survivors diagnosed between 2000 and 2009 as registered by the population-based Netherlands Cancer Registry (Eindhoven region) were eligible for participation. Chemotherapy-treated survivors (n = 477) completed questions on CIPN (EORTC QLQ-CIPN20) and HRQoL (EORTC QLQ-C30). RESULTS: Painful CIPN was reported by 9% (n = 45) of survivors and non-painful CIPN was reported by 22% (n = 103). Time since diagnosis was related to painful CIPN, and time since diagnosis, a higher disease stage, osteoarthritis, and more anxiety symptoms were related to non-painful CIPN. Finally, survivors with painful CIPN reported a worse global quality of life and worse physical, role, cognitive, and social functioning compared to survivors with non-painful CIPN and those without any sensory CIPN. No differences were found between survivors with non-painful CIPN and those without sensory CIPN. CONCLUSIONS: It seems that painful CIPN must be distinguished from non-painful CIPN, as only painful CIPN was related to a worse HRQoL. Future research is needed to examine whether painful CIPN must be distinguished from non-painful CIPN regarding predictors, mechanisms, and treatment.

Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period.

OBJECTIVE: Tanezumab, a nerve growth factor inhibitor, was investigated for osteoarthritis (OA) of the hip or knee in a study with 24-week treatment and 24-week safety follow-up. METHODS: This double-blind, randomised, phase III study enrolled adults in Europe and Japan with moderate-to-severe OA who had not responded to or could not tolerate standard-of-care analgesics. Patients were randomised to tanezumab 2.5 mg or 5 mg subcutaneously or matching placebo every 8 weeks (three doses). Co-primary end points were change from baseline to week 24 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function, and Patient's Global Assessment of OA (PGA-OA). Joint safety and neurological assessments continued throughout the 48-week study. RESULTS: From March 2016 to December 2017, 849 patients were randomised and evaluated (placebo n=282, tanezumab 2.5 mg n=283, tanezumab 5 mg n=284). At week 24, there was a statistically significant improvement from baseline for tanezumab 5 mg compared with placebo for WOMAC Pain (least squares mean difference±SE -0.62±0.18, p=0.0006), WOMAC Physical Function (-0.71±0.17, p<0.0001) and PGA-OA (-0.19±0.07, p=0.0051). For tanezumab 2.5 mg, there was a statistically significant improvement in WOMAC Pain and Physical Function, but not PGA-OA. Rapidly progressive osteoarthritis (RPOA) was observed in 1.4% (4/283) and 2.8% (8/284) of patients in the tanezumab 2.5 mg and tanezumab 5 mg groups, respectively and none receiving placebo. Total joint replacements (TJRs) were similarly distributed across all three treatment groups (6.7%-7.8%). Tanezumab-treated patients experienced more paraesthesia (5 mg) and hypoaesthesia (both doses) than placebo. CONCLUSION: Tanezumab 5 mg statistically significantly improved pain, physical function and PGA-OA, but tanezumab 2.5 mg only achieved two co-primary end points. RPOA occurred more frequently with tanezumab 5 mg than tanezumab 2.5 mg. TJRs were similarly distributed across all three groups. TRIAL REGISTRATION NUMBER: NCT02709486.

Methotrexate-induced Acute Myelopathy in a Teenager With High-risk Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is one of the most frequent malignancies in childhood whose long-term survival has increased up to 80% thanks to modern therapy enhancements. Nevertheless, methotrexate (MTX) remains a mainstay of ALL therapy, but also represents one of the major causes of neurotoxicity in patients with ALL. MTX-induced toxicity occurs in about 9% of patients treated for ALL. It usually affects deep white matter region leading to leukoencephalopathy, which has varying clinical manifestations ranging from acute neurologic disturbances to seizures or chronic permanent encephalopathy. Here we describe a 13-year-old girl affected with ALL who developed lower limbs hypesthesia and static ataxia due to transverse myelopathy after intrathec administration of MTX therapy. A high-dose corticotherapy combined to vitamin supplementation and rehabilitation was tested. Neurological evolution was characterized by slow and partial recovery.

Real-World Experience With 100 Consecutive Patients Undergoing Neck Contouring With ATX-101 (Deoxycholic Acid): An Updated Report With A 2-Year Analysis.

BACKGROUND: Deoxycholic acid (DCA; ATX-101) injection was approved for the treatment of mild-to-moderate convexity associated with submental fat in 2015. OBJECTIVE: To evaluate the experience with DCA injections in a clinical practice setting. MATERIALS AND METHODS: This ongoing, prospective, single-center, single-arm, observational study evaluated 100 consecutive patients treated with subcutaneous DCA (2 mg/cm) injections (maximum 6 sessions at ≥1-month intervals). Treatment response was assessed using the clinician-reported submental fat rating scale (CR-SMFRS) and confirmed by independent physician review of photographs at 1 and 5 to 7 weeks after treatment. RESULTS: Since the previous published report, 17 patients have undergone additional treatment sessions, with a total of 100 patients having undergone 195 treatment sessions: 41, 36, 14, 6, 2, and 1 patient underwent 1, 2, 3, 4, 5, and 6 sessions, respectively. Overall, 91.7% of patients in the single treatment session group and 100% in the multiple treatment session group had an improvement of ≥1 point on the CR-SMFRS. The mean (SD) duration of local edema, numbness, and tenderness after treatment was 7.1 (5.1), 27.9 (11.3), and 3.5 (3.5) days, respectively. CONCLUSION: Deoxycholic acid injections were generally well tolerated, and ≥2 treatment sessions were required to achieve the desired aesthetic goal in a private practice setting.

The risk factors for oxaliplatin-induced peripheral sensory neuropathy and thrombocytopenia in advanced gastric cancer.

PURPOSE: Peripheral sensory neuropathy (PSN) and thrombocytopenia are the main dose-limiting toxicities of oxaliplatin for the treatment of advanced gastric cancer (AGC). Because the risk factors for those toxicities in practice have not been clarified, we conducted this prospective study. METHODS: AGC patients who received oxaliplatin-based therapy at any of seven institutions participating in the Kyushu Medical Oncology Group were assessed after we obtained written informed consent. RESULTS: A total of 60 patients including 39 males and 21 females were examined. The median age was 66 years. The numbers of patients receiving oxaliplatin as the first, second, or third and later lines of therapy were 39, 16, and 5, respectively. An initial dose of 130, 100, or < 100 mg/m2 oxaliplatin was administered to 12, 39, and 9 patients, respectively. S-1 or capecitabine as a concomitant drug was administered in 54 and 6 patients, respectively. In multivariate analysis, the comorbidity of diabetes mellitus was associated with ≥ grade 2 thrombocytopenia (p = 0.035). No significant risk factor was associated with ≥ grade 2 PSN. However, the accumulated dose of oxaliplatin exhibited a strong correlation with ≥ grade 2 PSN (p = 0.0043), and the predicted accumulated dose of oxaliplatin in which 10% of patients developed ≥ grade 2 PSN was 800 mg/m2. The frequency of PSN in subsequent paclitaxel therapy in patients with ≥ grade 2 or worse PSN in oxaliplatin-based chemotherapy did not increase compared to those with none or grade 1 PSN in oxaliplatin. CONCLUSION: Thrombocytopenia in AGC patients with diabetes mellitus should be carefully monitored during oxaliplatin-based therapy.

Protective effect of alpha-linolenic acid on gentamicin-induced ototoxicity in mice.

Alpha-linolenic acid is one of the fatty acids known as omega 3. Previous studies have shown the antioxidant and anti-inflammatory effects of alpha-linolenic acid, which prevented cell damage by inhibiting apoptotic pathway. Also, it is known that gentamicin activates apoptotic mediators and causes necrosis in the kidney. Due to this reason, we planned a study to evaluate the protective effects of alpha-linolenic acid on gentamicin induced ototoxicity by evaluating inflammation and apoptotic mediators. For this purpose, 100 mg/kg gentamicin (i.p; intraperitoneally) and 200 mg/kg alpha-linolenic acid (gavage) are administered to mice for 9 days. On 9th and 10th days, rotarod performance was assessed to test the effect of gentamicin and alpha-linolenic acid treatment on the motor coordination of mice. Gentamicin treatment decreased fall latency of mice and gentamicin treatment together with alpha-linolenic acid increased fall latency of mice. Gentamicin treatment also increased expression of phospholipase A2(plA2), cyclooxygenase-2(COX-2) and inducible nitric oxide syntheses (iNOS). Furthermore, it increased Bax and caspase-3, which are proapoptotic proteins and decreased bcl-2 that is an antiapoptotic protein. Gentamicin treatment together alpha-linolenic acid recovered the change of expression of these enzymes. In conclusion, this study showed that alpha-linolenic acid will be useful to prevent gentamicin-induced ototoxicity by inhibiting apoptosis and inflammation.

Efficacy and Tolerability of Asenapine Compared with Olanzapine in Borderline Personality Disorder: An Open-Label Randomized Controlled Trial.

BACKGROUND: Asenapine is a new second-generation antipsychotic that is understudied in borderline personality disorder (BPD). Only one study investigating the use of the drug in this indication (an open-label pilot study) has been conducted to date. OBJECTIVE: The present open-label, randomized, controlled trial aimed to evaluate the efficacy and tolerability of asenapine in comparison with olanzapine, the most broadly studied antipsychotic in BPD. METHODS: A total of 51 outpatients aged between 18 and 50 years with a diagnosis of BPD based on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria were assigned for 12 weeks to asenapine (5-10 mg/day) or olanzapine (5-10 mg/day). Participants were assessed at baseline and after 12 weeks with the following instruments: the Clinical Global Impression Scale, Severity item (CGI-S), Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Social Occupational Functioning Assessment Scale (SOFAS), Borderline Personality Disorder Severity Index (BPDSI), Barratt Impulsiveness Scale, version 11 (BIS-11), Modified Overt Aggression Scale (MOAS), Self-Harm Inventory (SHI), and Dosage Record and Treatment Emergent Symptom Scale (DOTES). Analysis of variance repeated measures was performed. Intention-to-treat analysis with last observation carried forward was conducted. RESULTS: There were 11 drop-outs (21.57%): six patients taking asenapine and five patients receiving olanzapine. Two patients who received asenapine stopped the drug, one due to oral hypoesthesia and the other due to moderate anxiety. Two patients receiving olanzapine discontinued the treatment because of significant weight gain (≥3 kg). The remaining seven drop-outs resulted from the lack of compliance with the trial prescription. Forty out of the 51 patients (78%) completed the trial: 19 patients received asenapine, while 21 patients received olanzapine. We found a significant within-subject effect (trial duration) for all rating scales, except from the HAM-D, the MOAS, and two items of the BPDSI, namely, "identity disturbance" and "parasuicidal behaviors." A significant effect between subjects was found for the two items of the BPDSI "affective instability" and "dissociation/paranoid ideation." Asenapine was found superior to olanzapine in reducing the affective instability score (P = 0.001), whereas olanzapine was found superior to asenapine in reducing dissociation/paranoid ideation (P = 0.012). However, the study was found to be underpowered to detect a difference between the drugs on the dissociation/paranoid ideation item of the BPDSI. Two patients receiving asenapine experienced akathisia and another two restlessness/anxiety, while three patients receiving olanzapine reported somnolence and two fatigue. CONCLUSIONS: Asenapine and olanzapine were demonstrated to have a similar efficacy. While asenapine was found to be more efficacious than olanzapine in treating affective instability, olanzapine was superior to asenapine in treating paranoid ideation and dissociation. However, the study was underpowered to detect a difference between groups on the dissociation/paranoid ideation item. Both medications were well tolerated, with asenapine being related to a higher frequency of oral hypoesthesia and akathisia, and olanzapine being prone to induce weight gain. The open-label study design, lack of a placebo group, and small sample size constitute major limitations of this trial. Our findings need to be replicated in further studies. Clinical Trials Registry code: ACTRN12614000551695.

Safety and pharmacodynamics of dalazatide, a Kv1.3 channel inhibitor, in the treatment of plaque psoriasis: A randomized phase 1b trial.

BACKGROUND: Dalazatide is a specific inhibitor of the Kv1.3 potassium channel. The expression and function of Kv1.3 channels are required for the function of chronically activated memory T cells, which have been shown to be key mediators of autoimmune diseases, including psoriasis. OBJECTIVE: The primary objective was to evaluate the safety of repeat doses of dalazatide in adult patients with mild-to-moderate plaque psoriasis. Secondary objectives were to evaluate clinical proof of concept and the effects of dalazatide on mediators of inflammation in the blood and on chronically activated memory T cell populations. METHODS: Patients (n = 24) were randomized 5:5:2 to receive dalazatide at 30 mcg/dose, 60 mcg/dose, or placebo twice weekly by subcutaneous injection (9 doses total). Safety was assessed on the basis of physical and neurological examination and laboratory testing. Clinical assessments included body-surface area affected, Psoriasis Area and Severity Index (PASI), and investigator and patient questionnaires. RESULTS: The most common adverse events were temporary mild (Grade 1) hypoesthesia (n = 20; 75% placebo, 85% dalazatide) and paresthesia (n = 15; 25% placebo, 70% dalazatide) involving the hands, feet, or perioral area. Nine of 10 patients in the 60 mcg/dose group had a reduction in their PASI score between baseline and Day 32, and the mean reduction in PASI score was significant in this group (P < 0.01). Dalazatide treatment reduced the plasma levels of multiple inflammation markers and reduced the expression of T cell activation markers on peripheral blood memory T cells. LIMITATIONS: The study was small and drug treatment was for a short duration (4 weeks). CONCLUSION: This study indicates that dalazatide is generally well tolerated and can improve psoriatic skin lesions by modulating T cell surface and activation marker expression and inhibiting mediators of inflammation in the blood. Larger studies of longer duration are warranted.

Ipsilateral and contralateral sensory changes in healthy subjects after experimentally induced concomitant sensitization and hypoesthesia.

BACKGROUND: In unilateral neuropathic pain. e.g. after peripheral nerve injury, both positive and negative sensory signs occur often, accompanied by minor but equally directed contralateral sensory changes. To mimic this feature, we experimentally aimed to induce concomitant c-fibre sensitization and block in healthy subjects and analyzed the bilateral sensory changes by quantitative sensory testing (QST) using the protocol of the German Research Network on Neuropathic Pain. METHODS: Twenty eight healthy subjects were firstly randomized in 2 groups to receive either topical capsaicin (0.6%, 12 cm2, application duration: 15 min.) or a lidocaine/prilocaine patch (25/25 mg, 10 cm2, application duration: 60 min.) on the right volar forearm. Secondly, 7-14 days later in the same area either at first capsaicin (for 15 min.) and immediately afterwards local anesthetics (for 60 min.) was applied (Cap/LA), or in inversed order with the same application duration (LA/Cap). Before, after each application and 7-14 days later a QST was performed bilaterally. STATISTICS: Wilcoxon-test, ANOVA, p < 0.05. RESULTS: Single application of 0,6% capsaicin induced thermal hypoesthesia, cold hypoalgesia, heat hyperalgesia and tactile allodynia. Lidocaine/prilocaine alone induced thermal and tactile hypoesthesia as well as mechanical and cold hypoalgesia, and a heat hyperalgesia (to a smaller extent). Ipsilaterally both co-applications induced a combination of the above mentioned changes. Significant contralateral sensory changes occurred only after the co-application with concomitant sensitization and hypoesthesia and comprised increased cold (Cap/LA, LA/Cap) and mechanical detection as well as cold pain threshold (LA/Cap). CONCLUSION: The present experimental model using combined application of capsaicin and LA imitates partly the complex sensory changes observed in patients with unilateral neuropathic pain and might be used as an additional surrogate model. Only the concomitant use both agents in the same area induces both positive and negative sensory signs ipsilaterally as well as parallel contralateral sensory changes (to a lesser extent). TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT01540877 , registered on 23 February 2012.