Efficacy and acceptability of noninvasive brain stimulation for treating posttraumatic stress disorder symptoms: A network meta-analysis of randomized controlled trials.

INTRODUCTION: Despite its high lifetime prevalence rate and the elevated disability caused by posttraumatic stress disorder (PTSD), treatments exhibit modest efficacy. In consideration of the abnormal connectivity between the dorsolateral prefrontal cortex (DLPFC) and amygdala in PTSD, several randomized controlled trials (RCTs) addressing the efficacy of different noninvasive brain stimulation (NIBS) modalities for PTSD management have been undertaken. However, previous RCTs have reported inconsistent results. The current network meta-analysis (NMA) aimed to compare the efficacy and acceptability of various NIBS protocols in PTSD management. METHODS: We systematically searched ClinicalKey, Cochrane Central Register of Controlled Trials, Embase, ProQuest, PubMed, ScienceDirect, Web of Science, and ClinicalTrials.gov to identify relevant RCTs. The targeted RCTs was those comparing the efficacy of NIBS interventions, such as transcranial direct current stimulation (tDCS), repetitive transcranial magnetic stimulation (rTMS), and transcutaneous cervical vagal nerve stimulation, in patients with PTSD. The NMA was conducted using a frequentist model. The primary outcomes were changes in the overall severity of PTSD and acceptability (to be specific, rates of dropouts for any reason). RESULTS: We identified 14 RCTs that enrolled 686 participants. The NMA demonstrated that among the investigated NIBS types, high-frequency rTMS over bilateral DLPFCs was associated with the greatest reduction in overall PTSD severity. Further, in comparison with the sham controls, excitatory stimulation over the right DLPFC with/without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms, including depression and anxiety symptoms, and overall PTSD severity. CONCLUSIONS: This NMA demonstrated that excitatory stimulation over the right DLPFC with or without excitatory stimulation over left DLPFC were associated with significant reductions in PTSD-related symptoms. TRIAL REGISTRATION: PROSPERO CRD42023391562.

A systematic review and meta-analysis of the relationship between heavy smoking and probability discounting.

BACKGROUND AND OBJECTIVES: Probability discounting (PD), which refers to the process of adjusting the value of future probabilities when making decisions, is a method of measuring impulsive decision-making; however, the relationship between PD and nicotine remains unclear. The current study aimed at investigating the significance of PD in individuals who smoke. METHODS: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we searched the PubMed, Embase, PsycINFO, and Web of Science databases for articles comparing individuals who smoke and their tobacco-naïve controls using PD task as outcome measure from inception to May 2023. The main outcome was an overall difference in PD function, while subgroup analysis and meta-regression were conducted to examine the analysis methods and the moderators of PD. RESULTS: Fourteen studies in total involving 384 individuals who smoke and 493 controls (mean age = 24.32 years, range = 15.1-38.05 years) were analyzed. The effect of smoking on PD was significant (g = 0.51, p = .02). The discounting parameter from the equation, compared to the area under the curve, was more sensitive to estimating PD function (p = .01). Regression analysis showed positive correlations of PD with female percentage, age, and the number of probability options (all p < .04), but not with the number of choices at each probability and maximum reward magnitude (all p > .07). There was no significant publication bias across the eligible studies (p = .09). CONCLUSION AND SCIENTIFIC SIGNIFICANCE: Our findings, which are the first to demonstrate a smaller PD (i.e., prone to risk-taking) in individuals who smoke, shed light on the appropriate analysis method, gender effect, age, and probability options on the PD function.

Prophylaxis for paediatric emergence delirium in desflurane-based anaesthesia: a network meta-analysis.

PURPOSE: The prevalence of postoperative emergence delirium in paediatric patients (pedED) following desflurane anaesthesia is considerably high at 50-80%. Although several pharmacological prophylactic strategies have been introduced to reduce the risk of pedED, conclusive evidence about the superiority of these individual regimens is lacking. The aim of the current study was to assess the potential prophylactic effect and safety of individual pharmacotherapies in the prevention of pedED following desflurane anaesthesia. METHODS: This frequentist model network meta-analysis (NMA) of randomized controlled trials (RCTs) included peer-reviewed RCTs of either placebo-controlled or active-controlled design in paediatric patients under desflurane anaesthesia. RESULTS: Seven studies comprising 573 participants were included. Overall, the ketamine + propofol administration [odds ratio (OR) = 0.05, 95% confidence intervals (95%CIs) 0.01-0.33], dexmedetomidine alone (OR = 0.13, 95%CIs 0.05-0.31), and propofol administration (OR = 0.30, 95%CIs 0.10-0.91) were associated with a significantly lower incidence of pedED than the placebo/control groups. In addition, only gabapentin and dexmedetomidine were associated with a significantly higher improvement in the severity of emergence delirium than the placebo/control groups. Finally, the ketamine + propofol administration was associated with the lowest incidence of pedED, whereas gabapentin was associated with the lowest severity of pedED among all of the pharmacologic interventions studied. CONCLUSIONS: The current NMA showed that ketamine + propofol administration was associated with the lowest incidence of pedED among all of the pharmacologic interventions studied. Future large-scale trials to more fully elucidate the comparative benefits of different combination regimens are warranted. TRIAL REGISTRATION: PROSPERO CRD42021285200.

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.

Association of pharmacological prophylaxis with the risk of pediatric emergence delirium after sevoflurane anesthesia: An updated network meta-analysis.

STUDY OBJECTIVE: This updated network meta-analysis aims at exploring whether the concurrent use of midazolam or antiemetics may enhance the efficacy of other pharmacological regimens for delirium prophylaxis in pediatric population after general anesthesia (GA). DESIGN: Network meta-analysis (PROSPERO registration: CRD42020179483). SETTING: Postoperative recovery area. PATIENTS: Pediatric patients undergoing GA with sevoflurane. INTERVENTIONS: Pharmacological interventions applied during GA with sevoflurane. MEASUREMENTS: This network meta-analysis of randomized controlled trials (RCTs) was conducted with a frequentist model. PubMed, Embase, ProQuest, ScienceDirect, Cochrane CENTRAL, ClinicalKey, Web of Science, and ClinicalTrials.gov were searched from their inception dates to April 12, 2020, for RCTs of either placebo-controlled or active-controlled design containing information on the incidence of emergence delirium in pediatric patients undergoing sevoflurane anesthesia. MAIN RESULTS: Seventy studies comprising 6904 participants were included for the analysis of 30 pharmacological interventions. Based on surface under the cumulative ranking curve (SUCRA) analysis, midazolam was ranked the lowest in therapeutic effect (SUCRA: 20%), while antiemetics as a monotherapy had no effect on delirium prophylaxis. However, there was a trend that most combination therapies with midazolam or antiemetics were superior to monotherapies for delirium prophylaxis. Subgroup analyses based on age (i.e., ≤7 years) and a validated scoring system (i.e., the Pediatric Anesthesia Emergence Delirium scale) for delirium also suggested a better efficacy of combination therapies than monotherapies. Overall, combination therapies with midazolam or antiemetics did not have a negative impact on the incidence of postoperative nausea and vomiting, length of stay in the postanesthesia care unit, or time to extubation. The dexmedetomidine-midazolam-antiemetic combination was the most effective strategy for the prevention of emergence delirium. CONCLUSIONS: This network meta-analysis suggested that the incorporation of midazolam or antiemetics as adjuncts for combination therapies may have synergistic effects against pediatric postoperative emergence delirium. Future large-scale placebo-controlled RCTs are warranted to validate our findings.

Feedback inhibition of AMT1 NH4+-transporters mediated by CIPK15 kinase.

BACKGROUND: Ammonium (NH4+), a key nitrogen form, becomes toxic when it accumulates to high levels. Ammonium transporters (AMTs) are the key transporters responsible for NH4+ uptake. AMT activity is under allosteric feedback control, mediated by phosphorylation of a threonine in the cytosolic C-terminus (CCT). However, the kinases responsible for the NH4+-triggered phosphorylation remain unknown. RESULTS: In this study, a functional screen identified protein kinase CBL-Interacting Protein Kinase15 (CIPK15) as a negative regulator of AMT1;1 activity. CIPK15 was able to interact with several AMT1 paralogs at the plasma membrane. Analysis of AmTryoshka, an NH4+ transporter activity sensor for AMT1;3 in yeast, and a two-electrode-voltage-clamp (TEVC) of AMT1;1 in Xenopus oocytes showed that CIPK15 inhibits AMT activity. CIPK15 transcript levels increased when seedlings were exposed to elevated NH4+ levels. Notably, cipk15 knockout mutants showed higher 15NH4+ uptake and accumulated higher amounts of NH4+ compared to the wild-type. Consistently, cipk15 was hypersensitive to both NH4+ and methylammonium but not nitrate (NO3-). CONCLUSION: Taken together, our data indicate that feedback inhibition of AMT1 activity is mediated by the protein kinase CIPK15 via phosphorylation of residues in the CCT to reduce NH4+-accumulation.

From folk therapy to evidence-based psychiatry practice: The benefit of evidence-based psychiatry in treatment-naive psychotic patients.

BACKGROUND: As Taiwan's Mental Health Act (MHA) clearly states that the human rights and legal rights of psychotic patients should be respected and guaranteed; however, a temple asylum violates the law in the 21st century. Hundreds of patients were constrained in the asylum for years without consent. Because of outbreak of infectious diseases, patients were evacuated from the asylum by the official intervention. AIMS: To evaluate the outcomes of these patients from folk therapy to conventional treatment. METHOD: The study recruited the drug-naive psychotic patients constrained in an asylum for decades. Before and after the formal treatment, 253 patients were diagnosed with schizophrenia and other psychotic disorders with assessment of using the Mini Positive and Negative Syndrome Scale (Mini-PANSS) and Comprehensive Occupational Therapy Evaluation (COTE) scale. In addition, family function, self-care ability and nutritional status were also evaluated. RESULTS: The initial data show the improvement in psychotic symptoms and occupational function in these patients. Furthermore, the ratio of patients who were classified as being at risk for malnutrition was decreased by 21.7% after treatment. There was no statistically significant difference in self-care ability before and after treatment. CONCLUSION: The psychotic symptoms and occupational function of these patients were improved after the formal treatment compared to the folk therapy. The care model for the psychotic patients in the temple asylum should be more thoroughly discussed in consideration of the medical ethics principles.

The risk of glaucoma and serotonergic antidepressants: A systematic review and meta-analysis.

BACKGROUND: The aim of current study was to conduct a systematic review and meta-analysis to explore the relationship between antidepressant use and glaucoma. METHODS: Eight major electronic databases were searched from inception until March 19th, 2018 to obtain relevant studies that evaluated associations of antidepressants [including selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs)] treatment and the risk of primary open-angle glaucoma (POAG) or primary angle-closure glaucoma (PACG) as well as intraocular pressure (IOP), and related anterior chamber parameters compared to participants not exposed to antidepressant treatment. A random-effects meta-analysis was conducted. RESULTS: Six case-control studies and one cohort study were eligible (N = 801,754). The use of SSRIs was not associated with a higher risk of glaucoma (k = 7, pooled adjusted odds ratio (pAOR) = 0.956, 95% confidence interval (CI) = 0.807 to 1.133, p = 0.604). In addition, IOP was lower in participants exposed to antidepressants (SSRIs and SNRIs) (k = 4, Hedges' g = -0.519, 95% CI = -0.743 to -0.296, p < 0.001). Finally, pupillary diameter was higher in participants exposed to antidepressant treatment (k = 4, Hedges' g = 0.681, 95% CI = 0.462 to 0.900, p < 0.001). LIMITATIONS: High heterogeneity of included studies limit the establishment of causal inferences. CONCLUSIONS: This meta-analysis indicates that a putative association between the use of SSRIs and a higher risk of glaucoma remains to be proven. However, antidepressant drug treatment may be associated with significantly lower IOP and higher pupillary diameter. The mechanisms underpinning these associations deserve further investigation.

Synthesis of vibroarthrographic signals in knee osteoarthritis diagnosis training.

BACKGROUND: Vibroarthrographic (VAG) signals are used as useful indicators of knee osteoarthritis (OA) status. The objective was to build a template database of knee crepitus sounds. Internships can practice in the template database to shorten the time of training for diagnosis of OA. METHODS: A knee sound signal was obtained using an innovative stethoscope device with a goniometer. Each knee sound signal was recorded with a Kellgren-Lawrence (KL) grade. The sound signal was segmented according to the goniometer data. The signal was Fourier transformed on the correlated frequency segment. An inverse Fourier transform was performed to obtain the time-domain signal. Haar wavelet transform was then done. The median and mean of the wavelet coefficients were chosen to inverse transform the synthesized signal in each KL category. The quality of the synthesized signal was assessed by a clinician. RESULTS: The sample signals were evaluated using different algorithms (median and mean). The accuracy rate of the median coefficient algorithm (93 %) was better than the mean coefficient algorithm (88 %) for cross-validation by a clinician using synthesis of VAG. CONCLUSIONS: The artificial signal we synthesized has the potential to build a learning system for medical students, internships and para-medical personnel for the diagnosis of OA. Therefore, our method provides a feasible way to evaluate crepitus sounds that may assist in the diagnosis of knee OA.

State-dependent increase in the levels of neurotrophin-3 and neurotrophin-4/5 in patients with bipolar disorder: A meta-analysis.

Bipolar disorder (BD) is one of the most serious psychiatric disorders in the world, but its pathophysiology is still unclear. Regulation of neurotrophic factors have been thought to play a role in this process. There have been inconsistent findings regarding the differences in blood neurotrophin-3 (NT-3) and neurotrophin-4/5 (NT-4/5) between patients with BD and healthy controls (HCs). The aim of the current meta-analysis is to examine the changes in the levels of NT-3 and NT-4/5 in BD patients at different affective states. Eight articles (including 465 BD patients and 353 HCs) were included in the analysis, and their results were pooled by using a random effects model. We found the levels of both NT-3 (p = 0.0046) and NT-4/5 (p = 0.0003) were significantly increased in BD patients, compared to HCs. Through subgroup analysis, this increase persisted only in patients in depressed state (p = 0.0038 for NT-3 and p = 0.0001 for NT-4/5), but not in manic or euthymic state. In addition, we found the differences in NT-3 and NT-4/5 were significantly associated with the duration of illness, but not by the mean age or female proportion. Our results suggest a state-dependent increase in NT-3 and NT-4/5 levels in patients with BD. Further studies are needed to examine dynamic changes of these neurotrophins in BD patients along the disease course.

Significantly Higher Prevalence Rate of Asthma and Bipolar Disorder Co-Morbidity: A Meta-Analysis and Review Under PRISMA Guidelines.

Asthma and bipolar disorder (BD) are 2 distinct diseases that share similar pathophysiology. This study aimed to determine their relationship thorough a meta-analysis of articles on their comorbidity rate. The aim of the study is to examine the overall prevalence rate of BD in asthmatic patients and of asthma in BD patients compared to healthy controls. Electronic research of PubMed and ClinicalTrials.gov was performed. Articles discussing the prevalence rate of BD in patients with/without asthma and the prevalence rate of asthma in those with/without BD, as well as clinical trials in humans and case-controlled trials or cohort studies, were all included. Case reports or series and nonclinical trials were excluded. Through a random-effects model, a meta-analysis of the results of 4 studies comparing the prevalence rate of BD in patients with/without asthma, and in 6 studies comparing the prevalence rate of asthma in subjects with/without BD were performed. There were significantly higher prevalence rates of BD in asthmatic patients than in healthy controls (P < 0.001) and of asthma in BD patients than in healthy controls (P < 0.001). Only the patient's mean age significantly modulated the odds ratio of the prevalence rate of asthma in BD patients (slope = 0.015, P < 0.001). Only 10 studies were included and most were cross-sectional studies. The possible confounding effect of medication on BD or asthma onset was not investigated. Any possible etiology of the comorbidity was also not determined. This meta-analysis highlights the importance of the significantly high comorbid rate of BD and asthma, and the positive association with age. Special attention must be given to the comorbidity of asthma and BD, especially in older patients.

Light therapy in the treatment of patients with bipolar depression: A meta-analytic study.

Light therapy (LT) has been widely used in the treatment of seasonal affective disorder. Recently some evidence indicated that LT may play a role in bipolar depression, either as monotherapy or in combination with total sleep deprivation (TSD). However, the studies examining the treatment effect of LT in bipolar depression resulted in inconsistent findings. To clarify the role of LT in the disorder, we conducted a meta-analysis to compare the efficacy of LT in the treatment of bipolar depression. The results of individual studies were synthesized by a random effects model. Nine studies including 489 patients with bipolar depression were included in this current meta-analysis. We found that disease severity was significantly decreased after LT, in both with and without TSD, and with concomitant medication (p<0.001). Augmentation treatment with LT significantly decreased disease severity compared to treatment without LT (p=0.024). Our results highlight the significant efficacy of LT, either as monotherapy or in combination with TSD, in the treatment of bipolar depression. However, the detailed mechanism of LT still remains elusive. Further well-designed controlled trials are required to investigate the optimal intensity and frequency of LT in the treatment of bipolar depression.

Significantly Higher Peripheral Insulin-Like Growth Factor-1 Levels in Patients With Major Depressive Disorder or Bipolar Disorder Than in Healthy Controls: A Meta-Analysis and Review Under Guideline of PRISMA.

An increasing amount of research has focused on insulin-like growth factor-1 (IGF-1) because of multiple neurotrophic effects, including neurogenesis, remyelination, and synaptogenesis. In addition, IGF-1 can mediate an antidepressant effect in patients with major affective disorder, and its levels in the cerebrospinal fluid have been found to vary with antidepressant treatment. Furthermore, it has been proven to crossover the blood-brain barrier, with a reciprocal feedback loop being the central effect. However, recent studies have reported inconclusive findings about the role of IGF-1 in major affective disorder. The aim of the current study was to conduct a thorough meta-analysis of changes in peripheral IGF-1 levels in patients with major depressive disorder (MDD) or bipolar disorder (BD). We conducted a thorough literature search and compared peripheral IGF-1 levels in patients with MDD or BD and in healthy controls, and investigated clinical variables through meta-regression. Electronic research was conducted through platform of PubMed. We used inclusion criteria as clinical trials discussing comparisons of peripheral IGF-1 protein levels in patients with MDD or BD and those in healthy controls. We analyzed the cases from 9 studies with the random-effect model. The main finding was that peripheral IGF-1 levels in the patients were significantly higher than in the healthy controls (P < 0.001), with a significant inverse association with duration of illness (P = 0.03). In meta-analysis comparing peripheral IGF-1 levels in patients with BD or MDD before and after treatment, there was no significant change in peripheral IGF-1 levels after treatment (P = 0.092). The small numbers of studies and lack of correlation data with growth hormone in current studies are the main limitations of this meta-analysis. Our results indicated that peripheral IGF-1 levels may not be an indicator of disease severity, but may be a disease trait marker or an indicator of cognition. However, further investigations on the correlation between cognitive function and peripheral IGF-1 levels are needed to explore the role of IGF-1 in the pathophysiology of MDD and BD.

Significant Effect of Valproate Augmentation Therapy in Patients With Schizophrenia: A Meta-analysis Study.

Valproate is an anticonvulsant, which is also widely used for treating psychiatric disorders. Some clinical trials have demonstrated benefits of valproate augmentation therapy in schizophrenia. Previous meta-analysis showed inconsistent findings because of limited literature at that time. The aim of this study is to update the newer published data by conducting a meta-analysis of clinical efficacy of valproate augmentation therapy in patients with schizophrenia or schizoaffective disorder. Data sources include electronic research through platform of PubMed. Study eligibility criteria, participants, and interventions were as follows: the inclusion criteria included articles discussing comparisons of the treatment effect in schizophrenic patients treated with antipsychotic augmented with valproate and antipsychotics with/without placebo; articles on clinical trials in humans. The exclusion criteria were case reports or series and nonclinical trials. We compared the effect between antipsychotic treatment with valproate augmentation and antipsychotic monotherapy. Data from clinical trials were pooled by random-effects model, and possible confounding variables were examined through meta-regression and subgroup analysis. Data from 11 articles including 889 patients were included into current meta-analysis. We found patients treated with antipsychotics with valproate augmentation showed significantly more improvement in total psychopathology than those treated with antipsychotics only (P = 0.02). Results from open trials, but not from randomized controlled trials (P = 0.20), showed significant improvement (P = 0.01). In addition, the significance only persisted in the studies conducted with a shorter treatment duration (P < 0.001) rather than longer treatment duration (P = 0.23). There is no difference in the dropout rate between valproate augmentation and antipsychotic treatment only (P = 0.14). We could not perform a detailed meta-analysis for every category of antipsychotics, long-term effect, and safety profiles of valproate augmentation therapy in maintenance treatment, safety in pregnant patients, and subtype of schizophrenia. Our meta-analysis highlights the significantly better treatment effect with valproate augmentation therapy in patients with schizophrenia or schizoaffective disorder, and provides important evidence for supporting the practice of valproate augmentation therapy in these patients.

Significant treatment effect of adjunct music therapy to standard treatment on the positive, negative, and mood symptoms of schizophrenic patients: a meta-analysis.

BACKGROUND: Music therapy (MT) has been used as adjunct therapy for schizophrenia for decades. However, its role is still inconclusive. A recent meta-analysis demonstrated that MT for schizophrenic patients only significantly benefits negative symptoms and mood symptoms rather than positive symptoms. In addition, the association between specific characteristics of MT and the treatment effect remains unclear. The aim of this study was to update the published data and to explore the role of music therapy in adjunct treatment in schizophrenia with a thorough meta-analysis. METHODS: We compared the treatment effect in schizophrenic patients with standard treatment who did and did not receive adjunct MT through a meta-analysis, and investigated the clinical characteristics of MT through meta-regression. RESULTS: The main finding was that the treatment effect was significantly better in the patients who received adjunct MT than in those who did not, in negative symptoms, mood symptoms, and also positive symptoms (all p < 0.05). This significance did not change after dividing the patients into subgroups of different total duration of MT, amounts of sessions, or frequency of MT. Besides, the treatment effect on the general symptoms was significantly positively associated with the whole duration of illness, indicating that MT would be beneficial for schizophrenic patients with a chronic course. CONCLUSIONS: Our meta-analysis highlights a significantly better treatment effect in schizophrenic patients who received MT than in those who did not, especially in those with a chronic course, regardless of the duration, frequency, or amounts of sessions of MT. These findings provide evidence that clinicians should apply MT for schizophrenic patients to alleviate disease severity.

Tennis Elbow Diagnosis Using Equivalent Uniform Voltage to Fit the Logistic and the Probit Diseased Probability Models.

To develop the logistic and the probit models to analyse electromyographic (EMG) equivalent uniform voltage- (EUV-) response for the tenderness of tennis elbow. In total, 78 hands from 39 subjects were enrolled. In this study, surface EMG (sEMG) signal is obtained by an innovative device with electrodes over forearm region. The analytical endpoint was defined as Visual Analog Score (VAS) 3+ tenderness of tennis elbow. The logistic and the probit diseased probability (DP) models were established for the VAS score and EMG absolute voltage-time histograms (AVTH). TV50 is the threshold equivalent uniform voltage predicting a 50% risk of disease. Twenty-one out of 78 samples (27%) developed VAS 3+ tenderness of tennis elbow reported by the subject and confirmed by the physician. The fitted DP parameters were TV50 = 153.0 mV (CI: 136.3-169.7 mV), γ 50 = 0.84 (CI: 0.78-0.90) and TV50 = 155.6 mV (CI: 138.9-172.4 mV), m = 0.54 (CI: 0.49-0.59) for logistic and probit models, respectively. When the EUV ≥ 153 mV, the DP of the patient is greater than 50% and vice versa. The logistic and the probit models are valuable tools to predict the DP of VAS 3+ tenderness of tennis elbow.

Normal tissue complication probability modeling for cochlea constraints to avoid causing tinnitus after head-and-neck intensity-modulated radiation therapy.

BACKGROUND: Radiation-induced tinnitus is a side effect of radiotherapy in the inner ear for cancers of the head and neck. Effective dose constraints for protecting the cochlea are under-reported. The aim of this study is to determine the cochlea dose limitation to avoid causing tinnitus after head-and-neck cancer (HNC) intensity-modulated radiation therapy (IMRT). METHODS: In total 211 patients with HNC were included; the side effects of radiotherapy were investigated for 422 inner ears in the cohort. Forty-nine of the four hundred and twenty-two samples (11.6%) developed grade 2+ tinnitus symptoms after IMRT, as diagnosed by a clinician. The Late Effects of Normal Tissues-Subjective, Objective, Management, Analytic (LENT-SOMA) criteria were used for tinnitus evaluation. The logistic and Lyman-Kutcher-Burman (LKB) normal tissue complication probability (NTCP) models were used for the analyses. RESULTS: The NTCP-fitted parameters were TD 50 = 46.31 Gy (95% CI, 41.46-52.50), γ 50 = 1.27 (95% CI, 1.02-1.55), and TD 50 = 46.52 Gy (95% CI, 41.91-53.43), m = 0.35 (95% CI, 0.30-0.42) for the logistic and LKB models, respectively. The suggested guideline TD 20 for the tolerance dose to produce a 20% complication rate within a specific period of time was TD 20 = 33.62 Gy (95% CI, 30.15-38.27) (logistic) and TD 20 = 32.82 Gy (95% CI, 29.58-37.69) (LKB). CONCLUSIONS: To maintain the incidence of grade 2+ tinnitus toxicity <20% in IMRT, we suggest that the mean dose to the cochlea should be <32 Gy. However, models should not be extrapolated to other patient populations without further verification and should first be confirmed before clinical implementation.

Atypical neuroleptic malignant syndrome in patients treated with aripiprazole and clozapine: a case-series study and short review.

OBJECTIVES: Neuroleptic malignant syndrome (NMS) requires emergency treatment and can be fatal. Combined aripiprazole and clozapine therapy is rarely used in clinical settings, and NMS related this combination still lacks evaluation. Herein, we present two cases of atypical NMS treated with aripiprazole and clozapine. METHODS: Case 1 was a schizophrenic male with a history of NMS under treatment with aripiprazole 20 mg. He was hospitalized and maintained with aripiprazole 5 mg and clozapine 225 mg. On the 25th day, atypical NMS occurred with rigidity, elevated creatine kinase, and stupor, which subsided with supportive therapy. He was discharged under treatment with aripiprazole 15 mg and fluoxetine 60 mg. Case 2 was a female with schizoaffective disorder without a history of NMS. She was hospitalized and maintained with clozapine 50 mg and aripirazole 30 mg. On the 11th day, atypical NMS occurred with mild fever, delirium, and rigidity, which subsided under supportive therapy. RESULTS AND CONCLUSIONS: Our cases highlight the atypical features of NMS in patients being treated with combined ari-piprazole and clozapine. Consciousness change, modest elevation of creatine kinase, and leukocytosis were the most consistent findings; hyperthermia accounts for only some of the cases. This is a reminder of the importance of earlier detection of the soft signs and atypical features of NMS under this combined treatment.