Relationship between inflammatory laboratory parameters and severity of adolescent idiopathic scoliosis: A pilot study.

BACKGROUND: Adolescent idiopathic scoliosis is a complex condition whose pathogenesis may include inflammation and signs of joint and bone degeneration. OBJECTIVE: The main objective of this study is to evaluate the relationship between the severity of adolescent idiopathic scoliosis and inflammatory blood parameters. METHODS: The study recruited patients with adolescent idiopathic scoliosis who attended the Rehabilitation Center of the Apostolo Foundation in Merate (LC). The scoliosis curve (Cobb's angle) was used as a severity index to compare with inflammatory blood parameters (white blood cells subpopulations, immunoglobulins, protein electrophoresis). In addition, the study used an overall severity grading called "Scoliosis Score" which includes all spine angles and Risser's score (bone development index). RESULTS: Thirty-four subjects were recruited (mean age 14 years, 2 months), 30 females and 2 males. A significant correlation was found between Cobb's angle and the percentage values of beta-2 globulins in a directly proportional manner (r= 0.42, p= 0.01), and gamma globulins in an inversely proportional manner (r=-0.366, p= 0.04). However, no significant correlation between Cobb's angle and the absolute values of white blood cells and percentage subpopulations was found (r= 0.0821 p= 0.655). A moderate, inverse correlation was found between the Scoliosis Score and the percentage of neutrophils (r=-0.385, p= 0.02), a direct correlation was found between the Scoliosis Score and the percentage of lymphocytes (r= 0.404, p= 0.02). In addition, there was a strong correlation of the Scoliosis Score with alpha-2 globulin (r= 0.564, p= 0.0012), beta-1 globulin (r= 0.478, p= 0.0074), and beta-2 globulin (r= 0.370, p= 0.044) and an inverse relationship with gamma globulin (r=-0.625, p= 0.0002). The main correlations were confirmed by regression analysis. CONCLUSION: The correlation between beta-2 globulins and gamma globulins with Cobb's angle and the Scoliosis Score suggests a link between spinal curvature and inflammation in scoliosis patients, This link may indicate the significance of these parameters for diagnosing, staging the disease, and monitoring therapies.

The Problem of Home Therapy during COVID-19 Pandemic in Italy: Government Guidelines versus Freedom of Cure?

After starting in late 2019, COVID-19 spread worldwide, and Italy was one of the first Western nations to be seriously affected. At that time, both the virus and the disease were little known and there were no Evidence-Based Medicine indications for treatment. The Italian Health Ministry guidelines claimed that, unless oxygen saturation fell to <92%, no pharmacological treatment was necessary during the first 72 hours, other than on a purely symptomatic basis, preferably with paracetamol. As later confirmed, that delay in therapeutic intervention may have been responsible for numerous hospital admissions and a very high lethality (3.5 %). To try to remedy this situation, several volunteer groups were formed, managing to promptlycure thousands of patients at home with non-steroidal anti-inflammatory drugs and a variety of re-purposed drugs (principally hydroxychloroquine, ivermectin) and supplements (such as antioxidants, polyphenols and vitamin D). Although not documented by any randomized controlled studies, these approaches were nonetheless based on the best available evidence, were aimed at addressing otherwise unmet major needs and produced a significant reduction of hospitalizations, of symptom duration, and a complete recovery from the disease compared with late treatment, according to some retrospective observational studies and the clinical experience of many physicians. A prompt discussion, with a clear and open exchange between healthcare Institutions and the said groups of voluntary physicians, could clarify the most effective approaches to reduce the number of hospitalizations and the lethality of this disease.

Retrospective Study of Outcomes and Hospitalization Rates of Patients in Italy with a Confirmed Diagnosis of Early COVID-19 and Treated at Home Within 3 Days or After 3 Days of Symptom Onset with Prescribed and Non-Prescribed Treatments Between November 2020 and August 2021.

BACKGROUND This retrospective study aimed to investigate outcomes and hospitalization rates in patients with a confirmed diagnosis of early COVID-19 treated at home with prescribed and non-prescribed treatments. MATERIAL AND METHODS The medical records of a cohort of 158 Italian patients with early COVID-19 treated at home were analyzed. Treatments consisted of indomethacin, low-dose aspirin, omeprazole, and a flavonoid-based food supplement, plus azithromycin, low-molecular-weight heparin, and betamethasone as needed. The association of treatment timeliness and of clinical variables with the duration of symptoms and with the risk of hospitalization was evaluated by logistic regression. RESULTS Patients were divided into 2 groups: group 1 (n=85) was treated at the earliest possible time (<72 h from onset of symptoms), and group 2 (n=73) was treated >72 h after the onset of symptoms. Clinical severity at the beginning of treatment was similar in the 2 groups. In group 1, symptom duration was shorter than in group 2 (median 6.0 days vs 13.0 days, P<0.001) and no hospitalizations occurred, compared with 19.18% hospitalizations in group 2. One patient in group 1 developed chest X-ray alterations and 2 patients experienced an increase in D-dimer levels, compared with 30 and 22 patients, respectively, in group 2. The main factor determining the duration of symptoms and the risk of hospitalization was the delay in starting therapy (P<0.001). CONCLUSIONS This real-world study of patients in the community showed that early diagnosis and early supportive patient management reduced the severity of COVID-19 and reduced the rate of hospitalization.

Functional gait disorders: Demographic and clinical correlations.

OBJECTIVE: We aimed to describe the prevalence and clinical-demographical features of patients with functional gait disorders (FGDs) and to compare them to patients with functional motor disorders (FMDs) without FGDs (No-FGDs). METHODS: In this multicenter observational study, we enrolled patients with a clinically definite diagnosis of FMDs in 25 tertiary movement disorders centers in Italy. Each subject with FMDs underwent a comprehensive clinical assessment, including screening for different subtypes of functional gait disorders. Multivariate regression models were implemented in order to estimate the adjusted odds ratio (OR; 95% confidence interval) of having FGDs in relation to sociodemographic and clinical characteristics. RESULTS: Out of 410 FMDs, 26.6% (n = 109) of patients exhibited FGDs. The most frequent FGDs were slow gait (n = 43, 39.4%), astasia-abasia (n = 26, 23.8%), and knee buckling (n = 24, 22%). They exhibited single FGDs in 51.4% (n = 56) or complex FGDs (more than one type of FGDs) in 48.6% (n = 53) of cases. On multivariate regression analysis, the presence of FGDs was more likely associated with older age (OR 1.03, 95% CI 1.01-1.04), functional visual symptoms (OR 2.19, 95% CI 1.08-4.45), and the diagnosis of somatic symptoms disorder (OR 2.97, 95% CI 1.08-8.17). FGDs were also more likely to undergo physiotherapy (OR 1.81, 95% CI 1.08-3.03). CONCLUSIONS: People with FMDs may present with different and overlapping types of FGDs, which may occur in older age. The association of FGDs with functional visual symptoms and somatic symptoms disorder opens up to new avenues to the understanding of the neural mechanisms of these disorders.

Functional motor phenotypes: to lump or to split?

INTRODUCTION: Functional motor disorders (FMDs) are usually categorized according to the predominant phenomenology; however, it is unclear whether this phenotypic classification mirrors the underlying pathophysiologic mechanisms. OBJECTIVE: To compare the characteristics of patients with different FMDs phenotypes and without co-morbid neurological disorders, aiming to answer the question of whether they represent different expressions of the same disorder or reflect distinct entities. METHODS: Consecutive outpatients with a clinically definite diagnosis of FMDs were included in the Italian registry of functional motor disorders (IRFMD), a multicenter data collection platform gathering several clinical and demographic variables. To the aim of the current work, data of patients with isolated FMDs were extracted. RESULTS: A total of 176 patients were included: 58 with weakness, 40 with tremor, 38 with dystonia, 23 with jerks/facial FMDs, and 17 with gait disorders. Patients with tremor and gait disorders were older than the others. Patients with functional weakness had more commonly an acute onset (87.9%) than patients with tremor and gait disorders, a shorter time lag from symptoms onset and FMDs diagnosis (2.9 ± 3.5 years) than patients with dystonia, and had more frequently associated functional sensory symptoms (51.7%) than patients with tremor, dystonia and gait disorders. Patients with dystonia complained more often of associated pain (47.4%) than patients with tremor. No other differences were noted between groups in terms of other variables including associated functional neurological symptoms, psychiatric comorbidities, and predisposing or precipitating factors. CONCLUSIONS: Our data support the evidence of a large overlap between FMD phenotypes.

Functional motor disorders associated with other neurological diseases: Beyond the boundaries of "organic" neurology.

BACKGROUND AND PURPOSE: The aims of this study were to describe the clinical manifestations of functional motor disorders (FMDs) coexisting with other neurological diseases ("comorbid FMDs"), and to compare comorbid FMDs with FMDs not overlapping with other neurological diseases ("pure FMDs"). METHODS: For this multicenter observational study, we enrolled outpatients with a definite FMD diagnosis attending 25 tertiary movement disorder centers in Italy. Each patient with FMDs underwent a detailed clinical assessment including screening for other associated neurological conditions. Group comparisons (comorbid FMDs vs. pure FMDs) were performed in order to compare demographic and clinical variables. Logistic regression models were created to estimate the adjusted odds ratios (95% confidence intervals) of comorbid FMDs (dependent variable) in relation to sociodemographic and clinical characteristics (independent variables). RESULTS: Out of 410 FMDs, 21.7% of patients (n = 89) had comorbid FMDs. The most frequent coexisting neurological diseases were migraine, cerebrovascular disease and parkinsonism. In the majority of cases (86.5%), FMDs appeared after the diagnosis of a neurological disease. Patients with comorbid FMDs were older, and more frequently had tremor, non-neurological comorbidities, paroxysmal non-epileptic seizures, major depressive disorders, and benzodiazepine intake. Multivariate regression analysis showed that diagnosis of comorbid FMDs was more likely associated with longer time lag until the final diagnosis of FMD, presence of tremor and non-neurological comorbidities. CONCLUSIONS: Our findings highlight the need for prompt diagnosis of FMDs, given the relatively high frequency of associated neurological and non-neurological diseases.

Does the Degree of Trunk Bending Predict Patient Disability, Motor Impairment, Falls, and Back Pain in Parkinson's Disease?

Background: Postural abnormalities in Parkinson's disease (PD) form a spectrum of functional trunk misalignment, ranging from a "typical" parkinsonian stooped posture to progressively greater degrees of spine deviation. Objective: To analyze the association between degree of postural abnormalities and disability and to determine cut-off values of trunk bending associated with limitations in activities of daily living (ADLs), motor impairment, falls, and back pain. Methods: The study population was 283 PD patients with ≥5° of forward trunk bending (FTB), lateral trunk bending (LTB) or forward neck bending (FNB). The degrees were calculated using a wall goniometer (WG) and software-based measurements (SBM). Logistic regression models were used to identify the degree of bending associated with moderate/severe limitation in ADLs (Movement Disorders Society Unified PD Rating Scale [MDS-UPDRS] part II ≥17), moderate/severe motor impairment (MDS-UPDRS part III ≥33), history of falls (≥1), and moderate/severe back pain intensity (numeric rating scale ≥4). The optimal cut-off was identified using receiver operating characteristic (ROC) curves. Results: We found significant associations between modified Hoehn & Yahr stage, disease duration, sex, and limitation in ADLs, motor impairment, back pain intensity, and history of falls. Degree of trunk bending was associated only with motor impairment in LTB (odds ratio [OR] 1.12; 95% confidence interval [CI], 1.03-1.22). ROC curves showed that patients with LTB of 10.5° (SBM, AUC 0.626) may have moderate/severe motor impairment. Conclusions: The severity of trunk misalignment does not fully explain limitation in ADLs, motor impairment, falls, and back pain. Multiple factors possibly related to an aggressive PD phenotype may account for disability in PD patients with FTB, LTB, and FNB.

Validity of the wall goniometer as a screening tool to detect postural abnormalities in Parkinson's disease.

INTRODUCTION: Software-based measurements of postural abnormalities in Parkinson's disease (PD) are the gold standard but may be time-consuming and not always feasible in clinical practice. Wall goniometer (WG) is an easier, quicker, and inexpensive instrument for screening patients with postural abnormalities, but no studies have investigated its validity so far. The aim of this study was to investigate the validity of the WG to measure postural abnormalities. METHODS: A total of 283 consecutive PD outpatients with ≥5° forward trunk, lateral trunk or forward neck bending (FTB, LTB, FNB, respectively) were recruited from seven centers for movement disorders. Postural abnormalities were measured in lateral and posterior view using a freeware program (gold standard) and the WG. Both angles were expressed in degrees (°). Sensitivity and specificity for the diagnosis of camptocormia, Pisa syndrome, and anterocollis were assessed. RESULTS: WG showed good to excellent agreement (intraclass correlation coefficient from 0.80 to 0.98) compared to the gold standard. Bland-Altman plots showed a mean difference between the methods from -7.4° to 0.4° with limits of agreements from -17.7° to 9.5°. Sensitivity was 100% for the diagnosis of Pisa syndrome, 95.74% for anterocollis, 76.67% for upper camptocormia, and 63.64% for lower camptocormia. Specificity was 59.57% for Pisa syndrome, 71.43% for anterocollis, 89.80% for upper camptocormia, and 100% for lower camptocormia. Overall, the WG underestimated measurements, especially in lower camptocormia with an average of -8.7° (90% of cases). CONCLUSION: WG is a valid tool for screening Pisa syndrome and anterocollis, but approximately 10° more should be added for camptocormia.

Vegetable but not animal protein intake is associated to a better physical performance: a study on a general population sample of adults.

BACKGROUND: The research was conducted in the frame of a population-based, case control study, called Genes Environment Interaction in Respiratory Disease. OBJECTIVE: To assess the association between protein intake and physical performance in a general population sample. DESIGN: Researchers investigated the association between the participants' dietary information and their physical performance using the 6-min walking test and the distance walked in metres (6MWD) as main outcome measure. Information on dietary intake was collected using the validated European Investigation into Cancer and Nutrition food frequency questionnaires (FFQs). Then, daily intake of energy and macronutrients was estimated by means of the NAF software (nutritional analysis of FFQ). Linear regression models were used to evaluate the associations between vegetable, animal and total protein intakes and the 6MWD. The models were adjusted for socio-demographic features, total fats and available carbohydrate intakes. RESULTS: The participants were 223 subjects (57% females) aged between 23 and 68 years. Their mean vegetable and animal proteins intake for gram/kg of body weight/day were, respectively, 0.4 and 0.7. After adjusting for all the potential confounders, there was a significant increase of 20.0 (95% CI 0.8; 39.2) m in the distance walked for an increase in 10 g/day of vegetable proteins and non-significant variations of -1.8 (95% CI -9.3; 5.7) m for an increase in 10 g/day of animal proteins and of 0.5 (95% CI -6.8; 7.7) for an increase in 10 g/day of total proteins. DISCUSSION AND CONCLUSIONS: Our result suggests a positive role of vegetable proteins on physical performance. Whether this result is related to the high protein intake itself or may be a consequence of the other properties of plant-based foods deserves further investigation.

A Pilot Study of Prospective Data Collection by Italian Homeopathic Doctors.

OBJECTIVE: The main purpose of this article is to report the systematic data collection pertaining to the consultations of a group of qualified homeopathic physicians. Studies have been performed concerning: (1) the most frequently treated pathologies; (2) the symptoms reported by patients, with a particular focus on "fear" symptoms; and (3) the evaluation of the outcomes of the treatment, including likelihood ratio (LR) for fear symptoms of mostly prescribed remedies. DESIGN: Prospective observational study. SETTING: Individualized homeopathic treatment at private homeopathic surgeries in Italy. PARTICIPANTS: Adult patients asking for homeopathic therapy for a series of common ailments. OUTCOME MEASURES: Types of diseases and remedies used and clinical parameters (frequency of acute attacks, and their intensity and duration); the overall outcome of the cure was registered using the Outcome Related to Impact on Daily Living (ORIDL) scale. RESULTS: Only 94 patients could be enrolled by eight homeopathic doctors in a 2-year period between 2015 and 2017. Ninety (72 females, 18 males) patients completed the observation period. The most represented pathologies belonged to the group "Anxiety and anxiety disorders" followed by gastrointestinal ailments. The most prescribed remedy was Phosphorus (9 cases), followed by Natrum muriaticum (4 cases) and Ignatia (4 cases). The intensity of the symptoms and the frequency of the attacks decreased during the course of the study. Most patients reported a positive outcome (ORIDL scale). In the "Phosphorus" group, LR values were calculated for fear symptoms: LR+ for fear of dark = 2.25 (95% confidence interval [CI] = 0.56 to 9.02), LR- for fear of crowds = 1.27 (95% CI = 1.13 to 1.42), and LR- for fear of ghosts = 1.12 (95% CI = 1.04 to 1.22). CONCLUSION: The recruited group was smaller than expected, but data from most participants could be collected. Positive clinical outcomes were recorded and LR of a few specific fears contributed to distinguish Phosphorus patients from the remaining population.

Comparison of imaging-based and pathological dimensions in pancreatic neuroendocrine tumors.

AIM: To establish the ability of magnetic resonance (MR) and computer tomography (CT) to predict pathologic dimensions of pancreatic neuroendocrine tumors (PanNET) in a caseload of a tertiary referral center. METHODS: Patients submitted to surgery for PanNET at the Surgical Unit of the Pancreas Institute with at least 1 preoperative imaging examination (MR or CT scan) from January 2005 to December 2015 were included and data retrospectively collected. Exclusion criteria were: multifocal lesions, genetic syndromes, microadenomas or mixed tumors, metastatic disease and neoadjuvant therapy. Bland-Altman (BA) and Mountain-Plot (MP) statistics were used to compare size measured by each modality with the pathology size. Passing-Bablok (PB) regression analysis was used to check the agreement between MR and CT. RESULTS: Our study population consisted of 292 patients. Seventy-nine (27.1%) were functioning PanNET. The mean biases were 0.17 ± 7.99 mm, 1 ± 8.51 mm and 0.23 ± 9 mm, 1.2 ± 9.8 mm for MR and CT, considering the overall population and the subgroup of non-functioning- PanNET, respectively. Limits of agreement (LOA) included the vast majority of observations, indicating a good agreement between imaging and pathology. The MP further confirmed this finding and showed that the two methods are unbiased with respect to each other. Considering ≤ 2 cm non-functioning-PanNET, no statistical significance was found in the size estimation rate of MR and CT (P = 0.433). PBR analysis did not reveal significant differences between MR, CT and pathology. CONCLUSION: MR and CT scan are accurate and interchangeable imaging techniques in predicting pathologic dimensions of PanNET.

Total body fat and central fat mass independently predict insulin resistance but not hyperandrogenemia in women with polycystic ovary syndrome.

CONTEXT/OBJECTIVE: Obesity is a common feature of women with polycystic ovary syndrome (PCOS). The aim of this study was to assess the role of body fat on insulin resistance and androgen excess in these subjects. PATIENTS/DESIGN: One hundred sixteen consecutive Caucasian women with PCOS, diagnosed by the Rotterdam criteria, underwent accurate assessment of clinical, anthropometric, hormonal, and metabolic features. In particular, total fat mass and fat distribution were assessed by dual-energy x-ray absorptiometry, serum-free T by liquid chromatography mass spectrometry and equilibrium dialysis and insulin sensitivity by the glucose clamp technique. RESULTS: Total fat mass and truncal fat were significantly higher in insulin-resistant than in insulin-sensitive PCOS subjects (+89% and +127%, respectively, both P < .001), and both tended to be higher in hyperandrogenemic than in normoandrogenemic women (+22% and +28%, respectively, P = .087 and P = .090). All parameters of adiposity correlated inversely with insulin sensitivity (P < .001) and directly with serum-free T (P ≤ .001). A statistically significant inverse relationship was observed between insulin sensitivity and serum-free T concentrations (r = -0.527, P < .001). In a multiple regression analysis, either total fat mass or truncal fat, in addition to serum-free T and age, were independent predictors of insulin sensitivity. However, insulin sensitivity, but not total fat mass or truncal fat, was an independent predictor of free T concentrations. CONCLUSIONS: These data suggest that body fat contributes to determining insulin resistance in PCOS women. However, the association between body fat and hyperandrogenism seems to be to a large extent explained by insulin resistance.

A randomized controlled trial of IV immunoglobulin in patients with postpolio syndrome.

OBJECTIVE: To investigate in a single-center randomized control trial whether a single IVIg course improves short-term outcome in patients with postpolio syndrome (PPS). METHODS: Fifty-one patients with PPS were randomly allocated to receive 2g/kg IVIg body weight or placebo infused over 5 consecutive days. The primary endpoint was health-related quality of life (HRQoL) limited to the physical component score (PCS) in the Short-Form-36 (SF-36). Secondary endpoints included the SF-36 mental component score (MCS), 6-minute walk test, visual analog scale, 101-numeric rating, and fatigue severity scale. Muscle strength was graded according to the Medical Research Council scale and by dynamometer. Primary and secondary outcome variables were tested double-blind at baseline, 2months, and 4months. RESULTS: At two months, although SF-36 PCS scores were similar in both arms, the role physical (RP) domain improved significantly in the treatment arm (p=0.05) and so did the composite MCS (p=0.015), and role emotional (RE) subscale (p=0.02). No differences were found in the remaining outcome measures. At 4months, none of the outcome variables differed significantly between groups. CONCLUSIONS: Although the study did not reach the primary endpoint, we showed that a single IVIg course improves HRQoL related to mental activity, as measured by the SF-36 composite MCS, and role limitations including RP and RE SF-36 subscales at 2months, in patients with PPS. A single IVIg course leaves, gait, muscle strength, fatigue and bodily pain unchanged in patients with PPS. CLASSIFICATION OF EVIDENCE: Class I evidence indicates that IVIg did not change SF-36 PCS, and Class II evidence indicates that IVIg improved scores on the SF-36 MCS, RP, and RE.

The TNF-family cytokine TL1A inhibits proliferation of human activated B cells.

Death receptor (DR3) 3 is a member of the TNFR superfamily. Its ligand is TNF-like ligand 1A (TL1A), a member of the TNF superfamily. TL1A/DR3 interactions have been reported to modulate the functions of T cells, NK, and NKT cells and play a crucial role in driving inflammatory processes in several T-cell-dependent autoimmune diseases. However, TL1A expression and effects on B cells remain largely unknown. In this study, we described for the first time that B cells from human blood express significant amounts of DR3 in response to B cell receptor polyclonal stimulation. The relevance of these results has been confirmed by immunofluorescence analysis in tonsil and spleen tissue specimens, which showed the in situ expression of DR3 in antigen-stimulated B cells in vivo. Remarkably, we demonstrated that TL1A reduces B-cell proliferation induced by anti-IgM-antibodies and IL-2 but did not affect B-cell survival, suggesting that TL1A inhibits the signal(s) important for B-cell proliferation. These results revealed a novel function of TL1A in modulating B-cell proliferation in vitro and suggest that TL1A may contribute to homeostasis of effector B-cell functions in immune response and host defense, thus supporting the role of the TL1A/DR3 functional axis in modulating the adaptive immune response.

Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial).

UNLABELLED: Although lifestyle interventions are considered the first-line therapy for nonalcoholic fatty liver disease (NAFLD), which is extremely common in people with type 2 diabetes, no intervention studies have compared the effects of aerobic (AER) or resistance (RES) training on hepatic fat content in type 2 diabetic subjects with NAFLD. In this randomized controlled trial, we compared the 4-month effects of either AER or RES training on insulin sensitivity (by hyperinsulinemic euglycemic clamp), body composition (by dual-energy X-ray absorptiometry), as well as hepatic fat content and visceral (VAT), superficial (SSAT), and deep (DSAT) subcutaneous abdominal adipose tissue (all quantified by an in-opposed-phase magnetic resonance imaging technique) in 31 sedentary adults with type 2 diabetes and NAFLD. After training, hepatic fat content was markedly reduced (P < 0.001), to a similar extent, in both the AER and the RES training groups (mean relative reduction from baseline [95% confidence interval] -32.8% [-58.20 to -7.52] versus -25.9% [-50.92 to -0.94], respectively). Additionally, hepatic steatosis (defined as hepatic fat content >5.56%) disappeared in about one-quarter of the patients in each intervention group (23.1% in the AER group and 23.5% in the RES group). Insulin sensitivity during euglycemic clamp was increased, whereas total body fat mass, VAT, SSAT, and hemoglobin A1c were reduced comparably in both intervention groups. CONCLUSION: This is the first randomized controlled study to demonstrate that resistance training and aerobic training are equally effective in reducing hepatic fat content among type 2 diabetic patients with NAFLD.

The early psoriatic arthritis screening questionnaire: a simple and fast method for the identification of arthritis in patients with psoriasis.

OBJECTIVE: Dermatologists usually see patients with psoriasis before arthritis develops, making them well placed to diagnose early PsA (ePsA). This study aimed to develop a rapid and robust screening questionnaire for predicting PsA in patients with psoriasis referred to a specialized joint dermatology-rheumatology combined clinic. METHODS: In all, 228 psoriasis patients naïve to DMARD treatment were administered two screening questionnaire: the new Early ARthritis for Psoriatic patients (EARP) questionnaire and the existing Psoriatic Arthritis Screening and Evaluation (PASE) questionnaire. The diagnostic accuracy of the two questionnaires for the diagnosis of ePsA was compared by receiving operating characteristics curves. RESULTS: After psychometric analysis, a simplified questionnaire of 10 items was found to have good internal reliability (Cronbach's α = 0.83) and was much faster and simpler to administer than the PASE. Both the EARP and PASE questionnaires presented similar receiving operating characteristics curves (specificity 91.6 and 67.2 and sensitivity 85.2 and 90.7, respectively) in identifying ePsA patients by using the cut-off value of 3 for EARP-10 and the standard cut-off value of 44 for PASE. The CASPAR criteria for PsA were present in 61 (26.7%) of the patients at clinical presentation and in 32.9% at 1-year follow-up, and the EARP score of ≥3 correlated with clinically determined arthropathy by a rheumatologist. CONCLUSION: The EARP questionnaire is simple and fast to administer and proved robust for the identification of PsA in the dermatological setting. Dermatologists should consider the EARP for patients attending clinics, as it correlates well with early PsA diagnosis.

Homeopathic Doses of Gelsemium sempervirens Improve the Behavior of Mice in Response to Novel Environments.

Gelsemium sempervirens is used in homeopathy for treating patients with anxiety related symptoms, however there have been few experimental studies evaluating its pharmacological activity. We have investigated the effects of homeopathic doses of G. sempervirens on mice, using validated behavioral models. Centesimal (CH) dilutions/dynamizations of G. sempervirens, the reference drug diazepam (1 mg/kg body weight) or a placebo (solvent vehicle) were intraperitoneally delivered to groups of mice of CD1 strain during 8 days, then the effects were assessed by the Light-Dark (LD) choice test and by the Open-Field (OF) exploration test, in a fully blind manner. In the LD test, the mean time spent in the illuminated area by control and placebo-treated animals was 15.98%, for mice treated with diazepam it increased to 19.91% (P = .047), while with G. sempervirens 5 CH it was 18.11% (P = .341, non-significant). The number of transitions between the two compartments increased with diazepam from 6.19 to 9.64 (P < .001) but not with G. Sempervirens. In the OF test, G. sempervirens 5 CH significantly increased the time spent and the distance traveled in the central zone (P = .009 and P = .003, resp.), while diazepam had no effect on these OF test parameters. In a subsequent series of experiments, G. sempervirens 7 and 30 CH also significantly improved the behavioral responses of mice in the OF test (P < .01 for all tested variables). Neither dilutions of G. sempervirens affected the total distance traveled, indicating that the behavioral effect was not due to unspecific changes in locomotor activity. In conclusion, homeopathic doses of G. sempervirens influence the emotional responses of mice to novel environments, suggesting an improvement in exploratory behavior and a diminution of thigmotaxis or neophobia.

Effects of high-dilutions in behavioural models: a commentary on critical issues, from reproducibility to plausibility

As part of a rigorous investigation into the effects of Gelsemium sempervirens on laboratory mice, we performed two complete series of experiments and published three scientific papers. A recent commentary has, however, called into question the reproducibility and validity of these findings. In this article we discuss the major issues raised by this critique within the framework of methodological aspects and the interpretation of results of high-dilution and homeopathic research. The charge of non-reproducibility is shown to be unfounded, because a same homeopathic medicine displayed the same direction of effects in two well-validated models (light-dark and open-), albeit with nonlinear patterns. The double-blind protocols and statistics by means of ANOVA were performed appropriately and the difference between dilutions of Gelsemium (5cH, 7cH, 9cH and 30cH with variations according to model) and placebo was statistically highly significant. Our investigations brought to light some problems related with the lack of activity of buspirone and diazepam (conventional anxiolytic drugs used as control) on some behavioural parameters, suggesting that Gelsemium may have broader action, and raising doubts as to the reliability of benzodiazepines as positive controls for homeopathic treatments. Concerning the plausibility of experiments in this , disputed on the grounds of alleged lack of dose-response effect, we note that the latter is not at all uncommon, and can be accounted for by a host of possible reasons. In conclusion, our research line showed reproducible and consistent effects of Gelsemium in laboratory mice.(AU)

Como parte da investigação rigorosa sobre os efeitos do Gelsemium sempervirens em camundongos de laboratório, realizamos dois conjuntos completos de experimentos o que deu origem a três artigos sobre o tema. Porém, uma crítica recentemente publicada questionou a reprodutibilidade e validade desses resultados. Neste artigo, discutimos os pontos principais levantados pelos críticos, com base em aspectos metodológicos e a interpretação de resultados de pesquisas em altas diluições e homeopatia. Mostramos que a crítica sobre a não reprodutibilidade é infundada porque um mesmo medicamento sempre gerou efeitos na mesma direção, em dois modelos bem validados (claro-escuro e campo aberto), embora com padrões não-lineares. Os protocolos duplo-cegos e a estatística ANOVA foram devidamente realizados e as diferenças estatísticas entre as diluições de Gelsemiun semprevirens (5cH, 7cH, 9cH e 30cH, com variações de acordo com o modelo) e o placebo foram altamente significativa. Nossas pesquisas trouxeram a tona alguns problemas relacionados com a atividade da buspirona e diazepam (drogas anxiolíticas convencionais usadas como controle) em alguns parâmetros comportamentais, sugerindo que Gelsemiun pode ter uma ação mais ampla, levantando dúvidas sobre o uso de benzodiazepinas como controle positivo para tratamentos homeopáticos. Em relação a plausividade dos experimentos nessa area e a alegada falta de efeito dose-resposta, notamos que estas não são de todo incomuns, e podem ser explicadas por uma série de possíveis razões. Em conclusão, nossa linha de pesquisa mostrou reprodutibilidade e efeitos consistentes, para os efeitos do Gelsemiun em camundongos de laboratório.(AU)

Como parte de una rigurosa investigación de los efectos de Gelsemium sempervirens en ratones de laboratorio, realizamos dos series completas de experimentos y publicamos tres artículos científicos. Sin embargo, un comentario reciente critica la reproductibilidad y validad de nuestros resultados. En este artículo discutimos los aspectos principales de esta crítica en relación a los aspectos metodológicos e interpretativos de la investigación en homeopatía y altas diluciones. La acusación de falta de reproductibilidad carece de fundamentos, pues los efectos de un mismo medicamento homeopático mostraron una misma dirección en dos modelos bien validados (luz/oscuridad y campo abierto), empero, con respuestas no lineares. Los protocolos doble ciego y cálculos estadísticos mediante ANOVA fueron ejecutados correctamente y la diferencia entre diluciones de Gelsemium (5cH, 7cH, 9cH y 30cH según el modelo) y placebo fueron notablemente significativas. Nuestra rigurosa investigación evidenció problemas relacionados con la inactividad de buspirona y diazepam (drogas ansiolíticas convencionales utilizadas como control) en algunos parámetros conductuales, lo que indica que Gelsemium puede tener una acción más amplia y que la confiabilidad de las benzodiazepinas como controles positivos de tratamientos homeopáticos debe ser cuestionada. Con respecto a la plausibilidad de los experimentos en este campo, cuestionados con base en la supuesta ausencia de efecto dosis-respuesta, recordamos que no se trata de nada poco común y que puede ser explicada por innúmeros factores. Concluyendo, nuestra línea de investigación demostró que Gelsemium causa efectos reproducibles y consistentes en ratones de laboratorio.(AU)

Effects of high-dilutions in behavioural models: a commentary on critical issues, from reproducibility to plausibility / Efeitos de altas diluições em modelos comportamentais: comentários sobre temas críticos, da reprodutibilidade a plausibilidade / Efectos de las altas diluciones em modelos comportamentales: comentários respecto a temas críticos, da reprodutibilidad a la plausibilidad

As part of a rigorous investigation into the effects of Gelsemium sempervirens on laboratory mice, we performed two complete series of experiments and published three scientific papers. A recent commentary has, however, called into question the reproducibility and validity of these findings. In this article we discuss the major issues raised by this critique within the framework of methodological aspects and the interpretation of results of high-dilution and homeopathic research. The charge of non-reproducibility is shown to be unfounded, because a same homeopathic medicine displayed the same direction of effects in two well-validated models (light-dark and open-), albeit with nonlinear patterns. The double-blind protocols and statistics by means of ANOVA were performed appropriately and the difference between dilutions of Gelsemium (5cH, 7cH, 9cH and 30cH with variations according to model) and placebo was statistically highly significant. Our investigations brought to light some problems related with the lack of activity of buspirone and diazepam (conventional anxiolytic drugs used as control) on some behavioural parameters, suggesting that Gelsemium may have broader action, and raising doubts as to the reliability of benzodiazepines as positive controls for homeopathic treatments. Concerning the plausibility of experiments in this , disputed on the grounds of alleged lack of dose-response effect, we note that the latter is not at all uncommon, and can be accounted for by a host of possible reasons. In conclusion, our research line showed reproducible and consistent effects of Gelsemium in laboratory mice.(AU)

Como parte da investigação rigorosa sobre os efeitos do Gelsemium sempervirens em camundongos de laboratório, realizamos dois conjuntos completos de experimentos o que deu origem a três artigos sobre o tema. Porém, uma crítica recentemente publicada questionou a reprodutibilidade e validade desses resultados. Neste artigo, discutimos os pontos principais levantados pelos críticos, com base em aspectos metodológicos e a interpretação de resultados de pesquisas em altas diluições e homeopatia. Mostramos que a crítica sobre a não reprodutibilidade é infundada porque um mesmo medicamento sempre gerou efeitos na mesma direção, em dois modelos bem validados (claro-escuro e campo aberto), embora com padrões não-lineares. Os protocolos duplo-cegos e a estatística ANOVA foram devidamente realizados e as diferenças estatísticas entre as diluições de Gelsemiun semprevirens (5cH, 7cH, 9cH e 30cH, com variações de acordo com o modelo) e o placebo foram altamente significativa. Nossas pesquisas trouxeram a tona alguns problemas relacionados com a atividade da buspirona e diazepam (drogas anxiolíticas convencionais usadas como controle) em alguns parâmetros comportamentais, sugerindo que Gelsemiun pode ter uma ação mais ampla, levantando dúvidas sobre o uso de benzodiazepinas como controle positivo para tratamentos homeopáticos. Em relação a plausividade dos experimentos nessa area e a alegada falta de efeito dose-resposta, notamos que estas não são de todo incomuns, e podem ser explicadas por uma série de possíveis razões. Em conclusão, nossa linha de pesquisa mostrou reprodutibilidade e efeitos consistentes, para os efeitos do Gelsemiun em camundongos de laboratório.(AU)

Como parte de una rigurosa investigación de los efectos de Gelsemium sempervirens en ratones de laboratorio, realizamos dos series completas de experimentos y publicamos tres artículos científicos. Sin embargo, un comentario reciente critica la reproductibilidad y validad de nuestros resultados. En este artículo discutimos los aspectos principales de esta crítica en relación a los aspectos metodológicos e interpretativos de la investigación en homeopatía y altas diluciones. La acusación de falta de reproductibilidad carece de fundamentos, pues los efectos de un mismo medicamento homeopático mostraron una misma dirección en dos modelos bien validados (luz/oscuridad y campo abierto), empero, con respuestas no lineares. Los protocolos doble ciego y cálculos estadísticos mediante ANOVA fueron ejecutados correctamente y la diferencia entre diluciones de Gelsemium (5cH, 7cH, 9cH y 30cH según el modelo) y placebo fueron notablemente significativas. Nuestra rigurosa investigación evidenció problemas relacionados con la inactividad de buspirona y diazepam (drogas ansiolíticas convencionales utilizadas como control) en algunos parámetros conductuales, lo que indica que Gelsemium puede tener una acción más amplia y que la confiabilidad de las benzodiazepinas como controles positivos de tratamientos homeopáticos debe ser cuestionada. Con respecto a la plausibilidad de los experimentos en este campo, cuestionados con base en la supuesta ausencia de efecto dosis-respuesta, recordamos que no se trata de nada poco común y que puede ser explicada por innúmeros factores. Concluyendo, nuestra línea de investigación demostró que Gelsemium causa efectos reproducibles y consistentes en ratones de laboratorio.(AU)