A multitude of risk/protective factors for anxiety and obsessive-compulsive disorders have been proposed. We conducted an umbrella review to summarize the evidence of the associations between ...risk/protective factors and each of the following disorders: specific phobia, social anxiety disorder, generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder, and to assess the strength of this evidence whilst controlling for several biases.
Publication databases were searched for systematic reviews and meta-analyses examining associations between potential risk/protective factors and each of the disorders investigated. The evidence of the association between each factor and disorder was graded into convincing, highly suggestive, suggestive, weak, or non-significant according to a standardized classification based on: number of cases (>1000), random-effects p-values, 95% prediction intervals, confidence interval of the largest study, heterogeneity between studies, study effects, and excess of significance.
Nineteen systematic reviews and meta-analyses were included, corresponding to 216 individual studies covering 427 potential risk/protective factors. Only one factor association (early physical trauma as a risk factor for social anxiety disorder, OR 2.59, 95% CI 2.17-3.1) met all the criteria for convincing evidence. When excluding the requirement for more than 1000 cases, five factor associations met the other criteria for convincing evidence and 22 met the remaining criteria for highly suggestive evidence.
Although the amount and quality of the evidence for most risk/protective factors for anxiety and obsessive-compulsive disorders is limited, a number of factors significantly increase the risk for these disorders, may have potential prognostic ability and inform prevention.
We report the findings from the Spanish Society of Neurology's NeuroCOVID-19 Registry.
We performed a multicentre study of patients with neurological manifestations of COVID-19. Participating ...physicians reported demographic, clinical, and paraclinical data and judged the involvement of COVID-19 in causing neurological symptoms.
A total of 233 cases were submitted, including 74 different combinations of manifestations. The most frequently reported were stroke (27%), neuromuscular symptoms (23.6%), altered mental status (23.6%), anosmia (17.6%), headache (12.9%), and seizures (11.6%). The mean age of patients was 61.1 years, with 42.1% being women; a higher proportion of women was recorded among patients with altered mental status, anosmia, and headache. The onset of symptoms differed within categories. Onset of anosmia occurred a mean (standard deviation) of 2.9 (2.5) days after the first general symptom, whereas neuromuscular symptoms appeared after 13.9 (10.1) days. Neurological symptoms were persistent in 33% of patients. General symptoms were present in 97.7% of patients, and results from general laboratory studies were abnormal in 99.4% of patients. Cerebrospinal fluid analysis findings were abnormal in 62.7% of the cases in which this test was performed (n = 51), but positive results for SARS-CoV-2 were only found in one case.
The neurological manifestations of COVID-19 are diverse. Anosmia, myalgia, and headache occur earlier in the course of the disease. Altered mental status, neuromuscular symptoms, and stroke are associated with greater severity. COVID-19 must be incorporated into most clinical and radiological differential diagnoses. COVID-19 may cause persistent and disabling neurological symptoms.
•NeuroCovid-19 is polymorph: Authors reported >70 different combinations of neurological syndromic presentations.•The symptom's timing varies from early (anosmia, headache, myalgia) to later stages (altered mental status, seizures, stroke, neuromuscular).•Some neurological symptoms might persist, as headache or anosmia; while other may cause persistent disability, as stroke or polyneuropathies.•Cerebrospinal fluid was frequently abnormal but direct isolation of SARS-CoV-2 occurred only in 1/233 cases.•Neurologists must be prepared to face the various neurological syndromes that may be associated with Covid-19 infection.
The rarity of lipodystrophies implies that they are not well-known, leading to delays in diagnosis/misdiagnosis. The aim of this study was to assess the natural course and comorbidities of ...generalised and partial lipodystrophy in Spain to contribute to their understanding. Thus, a total of 140 patients were evaluated (77.1% with partial lipodystrophy and 22.9% with generalised lipodystrophy). Clinical data were collected in a longitudinal setting with a median follow-up of 4.7 (0.5-17.6) years. Anthropometry and body composition studies were carried out and analytical parameters were also recorded. The estimated prevalence of all lipodystrophies in Spain, excluding Köbberling syndrome, was 2.78 cases/million. The onset of phenotype occurred during childhood in generalised lipodystrophy and during adolescence-adulthood in partial lipodystrophy, with the delay in diagnosis being considerable for both cohorts. There are specific clinical findings that should be highlighted as useful features to take into account when making the differential diagnosis of these disorders. Patients with generalised lipodystrophy were found to develop their first metabolic abnormalities sooner and a different lipid profile has also been observed. Mean time to death was 83.8 ± 2.5 years, being shorter among patients with generalised lipodystrophy. These results provide an initial point of comparison for ongoing prospective studies such as the ECLip Registry study.
•The high interindividual variability of once-monthly long-acting injectable aripiprazole makes it very difficult to predict its optimal dosing. In this context, population pharmacokinetic models ...constitute a valuable tool to characterize the pharmacokinetic properties of a drug and quantifying the sources of variability in drug exposure considering factors such as age, gender or genetics, among others. In addition, these models can also be used to optimize dosages in the clinical setting, since they contribute to guide decision-making and improve patient outcomes.•This is the first population pharmacokinetic model developed for LAI aripiprazole that includes aripiprazole and its main active metabolite, dehydroaripiprazole. It provides a personalized dosage recommendation that maximizes the probability of achieving optimal therapeutic concentrations and minimizes the difficulties associated with trial-and-error therapeutic strategies carried out in clinical practice.•Weight was the factor that most influenced aripiprazole absorption, which were inversely correlated. The CYP2D6 metabolizing phenotype and concomitant treatment with strong CYP2D6 inhibitors are the factors that most influence drug elimination and total drug exposure.
Population pharmacokinetic (popPK) models constitute a valuable tool for characterizing the pharmacokinetic properties of once-monthly long-acting injectable aripiprazole (LAI aripiprazole) and quantifying the sources of variability in drug exposure. Our aim is to develop a popPK model of both aripiprazole and its metabolite dehydro-aripiprazole in patients treated with LAI aripiprazole, and to personalize the dosing regimen of aripiprazole across different sub-groups of patients. This is a prospective study investigating the pharmacokinetics of LAI aripiprazole. A total of 93 patients were included, 21 for model development and 71 for external model evaluation. A one-compartment model with linear absorption and elimination adequately described both aripiprazole and dehydro-aripiprazole concentrations. The weight of the patients has been shown to be the factor that most influences the absorption. However, the metabolizing phenotype for CYP2D6 and the concomitant treatment with strong inhibitors of this cytochrome have been shown to be the covariates that most influence total drug exposure. This is the first popPK model developed for LAI aripiprazole that includes aripiprazole and its main active metabolite, dehydroaripiprazole. It provides a personalized dosage recommendation that maximizes the probability of achieving optimal therapeutic concentrations and minimizes the difficulties associated with trial-and-error therapeutic strategies carried out in clinical practice.
Protein aggregate reactivation in metazoans is accomplished by the combined activity of Hsp70, Hsp40 and Hsp110 chaperones. Hsp110s support the refolding of aggregated polypeptides acting as ...specialized nucleotide exchange factors of Hsp70. We have studied how Apg2, one of the three human Hsp110s, regulates the activity of Hsc70 (HspA8), the constitutive Hsp70 in our cells. Apg2 shows a biphasic behavior: at low concentration, it stimulates the ATPase cycle of Hsc70, binding of the chaperone to protein aggregates and the refolding activity of the system, while it inhibits these three processes at high concentration. When the acidic subdomain of Apg2, a characteristic sequence present in the substrate binding domain of all Hsp110s, is deleted, the detrimental effects occur at lower concentration and are more pronounced, which concurs with an increase in the affinity of the Apg2 mutant for Hsc70. Our data support a mechanism in which Apg2 arrests the chaperone cycle through an interaction with Hsc70(ATP) that might lead to premature ATP dissociation before hydrolysis. In this line, the acidic subdomain might serve as a conformational switch to support dissociation of the Hsc70:Apg2 complex.
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•Human Apg2 supports protein aggregate reactivation acting as nucleotide exchange factor of Hsc70.•Regulation of Hsc70 binding to aggregates by Apg2 correlates with substrate reactivation.•Apg2 stimulates/inhibits the activity of the Hsc70 system in a concentration-dependent manner.•An Hsc70:Apg2 complex arrests the ATPase cycle in the ADP/ATP exchange process.•The acidic subdomain supports dissociation of the Hsc70:Apg2 complex.
Substance-related disorders (SRD) have been consistently associated with alterations both in cognitive and executive functions, which affect to patients' quality of life. The main objective of this ...work was to test the beneficial cognitive effects on patients with SRD after the implementation of "Trisquel," an intervention program in board game format. To check the effectiveness of Trisquel program, a group of people diagnosed with SRD was randomly assigned either to the experimental group or to the control group. The experimental group performed Trisquel structured sessions twice a week during 3 months, while the control group performed routinely conventional therapeutic activities with the same frequency and duration. Neuropsychological tests were done to both groups before and after the intervention. After the 3 months of intervention the experimental group showed the following statistically significant improvements for WAIS-III subtests: number key, symbol search, arithmetic, direct digits, inverse digits, total digits, letters-numbers in the processing speed index and in the working memory index. Regarding STROOP tests, statistically significant progress was observed in the phonetic fluency letter P, phonetic fluency letter M, phonetic fluency letter R subtests, word-reading and word-color subtests. The control group only obtained improvements for WAIS-III subtests of arithmetic, letters-numbers and in the working memory index. The results of this study confirm that "Trisquel" is an effective intervention program for people diagnosed with SRD, getting improvements in processing speed (psychomotor and reading), attentional subprocesses (focused and sustained) and executive functions (updating and inhibition).
Post-operative hypoparathyroidism is the most frequent complication after total thyroidectomy. The identification of preoperative predictors could be helpful to identify patients at risk. This study ...aimed to evaluate the potential influence of preoperative PTH levels and their perioperative dynamics as a predictor of transient, protracted, and permanent post-operative hypoparathyroidism.
A prospective, observational study that includes 100 patients who underwent total thyroidectomy between September 2018 and September 2020.
Transient hypoparathyroidism was present in 42% (42/100) of patients, 11% (11/100) developed protracted hypoparathyroidism, and 5% (5/100) permanent hypoparathyroidism. Patients who presented protracted hypoparathyroidism had higher preoperative PTH levels. The protracted and permanent hypoparathyroidism rate was higher in groups with greater preoperative PTH 0% group 1 (<40 pg/mL) vs. 5.7% group 2 (40-70 pg/mL) vs. 21.6% group 3 (>70 pg/mL); p = 0.03 and (0 vs. 8.3 vs. 20%; p = 0.442), respectively. The rate of protracted and permanent hypoparathyroidism was higher in patients with PTH at 24 h lower than 6.6 pg/mL and whose percentage of PTH decline was higher than 90%. The rate of transient hypoparathyroidism was higher in patients who showed a PTH decline rate of more than 60%. The percentage of PTH increase one week after surgery in patients with permanent hypoparathyroidism was significantly lower.
The prevalence of protracted hypoparathyroidism was higher in groups with higher preoperative PTH levels. PTH levels 24 h after surgery lower than 6.6 pg/mL and a decline of more than 90% predict protracted and permanent hypoparathyroidism. The percentage of PTH increase a week after surgery could predict permanent hypoparathyroidism.
The ECHO model was developed to expand access to medical care for populations with HCV infection in underserved areas. We aimed to compare HCV treatment outcomes in community‐based clinics with the ...Austral University Hospital (AUH) and to assess improvement in physician knowledge and skills. In October 2015, we established an HCV ECHO clinic at the AUH in Buenos Aires. To evaluate the impact of this programme, we conducted a prospective cohort study comparing treatment for HCV infection at the AUH with healthcare providers from different Argentinean provinces. A survey evaluating skills and competence in HCV care was administered, and results were compared. The primary endpoint was sustained virologic response (SVR) and under direct‐acting antivirals. Since the implementation of ECHO clinics, a total of 25 physicians participated in at least one session (median 10.0; IQR 3.0‐18.0). SVR rates (n = 437 patients) were 94.2% (95% CI 90.4‐96.8) in patients treated at AUH clinic (n = 227/242) and 96.4% (95% CI 92.7‐98.5) in those treated at ECHO sites (n = 188/195), with a nonsignificant difference between sites, 2.2% SVR difference (95% CI −0.24‐0.06; P = 0.4). We also found a significant improvement in all the evaluated skills and abilities. Replicating the ECHO model helped to improve participants' skills in the management of HCV achieving similar SVR rates. ECHO model was demonstrated to be an effective intervention able to multiply and expand HCV treatment, a critical barrier to access to care that needs to be solved if we are committed with WHO goals to eliminate HCV by 2030.
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