Cluster analysis in fibromyalgia: a systematic review.

BACKGROUND: The multifaceted nature of Fibromyalgia syndrome (FM) symptoms has been explored through clusters analysis. OBJECTIVE: To synthesize the cluster research on FM (variables, methods, patient subgroups, and evaluation metrics). METHODS: We performed a systematic review following the PRISMA recommendations. Independent searches were performed on PubMed, Embase, Web of Science, and Cochrane Central, employing the terms "fibromyalgia" and "cluster analysis". We included studies dated to January 2024, using the cluster analysis to assess any physical, psychological, clinical, or biomedical variables in FM subjects, and descriptively synthesized the studies in terms of design, cluster method, and resulting patient profiles. RESULTS: We included 39 studies. Most with a cross-sectional design aiming to classify subsets based on the severity, adjustment, symptomatic manifestations, psychological profiles, and response to treatment, based on demographic and clinical variables. Two to four different profiles were found according to the levels of severity and adjustment to FMS. According to symptom manifestation, two to three clusters described the predominance of pain versus fatigue, and thermal pain sensitivity (less versus more sensitive). Other clusters revealed profiles of personality (pathological versus non-pathological) and psychological vulnerability (suicidal ideation). Additionally, studies identified different responses to treatment (pharmacological and multimodal). CONCLUSION: Several profiles exist within FMS population, which point out to the need for specific treatment options given the different profiles and an efficient allocation of healthcare resources. We notice a need towards more objective measures, and the validation of the cluster results. Further research might investigate some of the assumptions of these findings, which are further discussed in this paper.

Effect of Neurostimulation on Chronic Pancreatic Pain: A Systematic Review.

BACKGROUND: Chronic pancreatic pain is one of the most severe causes of visceral pain, and treatment response is often limited. Neurostimulation techniques have been investigated for chronic pain syndromes once there are pathophysiological reasons to believe that these methods activate descending pain inhibitory systems. Considering this, we designed this systematic literature review to investigate the evidence on neuromodulation techniques as a treatment for chronic pancreatic pain. MATERIALS AND METHODS: We performed a literature search using the databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase until April 2024. The included studies used neurostimulation techniques in participants with chronic pancreatic pain and reported pain-related outcomes, with a focus on pain scales and opioid intake. Two reviewers screened and extracted data, and a third reviewer resolved discrepancies. We assessed the risk of bias using the Jadad scale. The authors then grouped the findings by the target of the neurostimulation, cortex, spinal cord, or peripheral nerves; described the findings qualitatively in the results section, including qualitative data reported by the articles; and calculated effect sizes of pain-related outcomes. RESULTS: A total of 22 studies were included (7 randomized clinical trials [RCTs], 14 case series, and 1 survey), including a total of 257 clinical trial participants. The two outcomes most commonly reported were pain, measured by the visual analogue scale (VAS), numeric rating scale (NRS), and pressure pain threshold scores, and opioid intake. Two RCTs investigated repetitive transcranial magnetic stimulation (rTMS), showing a reduction of 36% (±16) (d = 2.25; 95% CI, 0.66-3.83) and 27.2% (±24.5%) (d = 2.594; 95% CI, 1.303-3.885) in VAS pain scale. In another clinical trial, transcranial direct-current stimulation (tDCS) and transcranial pulsed current stimulation were not observed to effect a significant reduction in VAS pain (χ2 = 5.87; p = 0.12). However, a complete remission was reported in one tDCS case. Spinal cord stimulation (SCS) and dorsal root ganglion stimulation were performed in a survey and 11 case series, showing major pain decrease and diminished opioid use in 90% of participants after successful implantation; most studies had follow-up periods of months to years. Two noninvasive vagal nerve stimulation (VNS) RCTs showed no significant pain reduction in pain thresholds or VAS (d = 0.916; 95% CI, -0.005 to 1.838; and d = 0.17; -0.86 to 1.20; p = 0.72; respectively). Splanchnic nerve stimulation in one case report showed complete pain reduction accompanied by discontinuation of oral morphine and fentanyl lozenges and a 95% decrease in fentanyl patch use. Two RCTs investigated transcutaneous electrical nerve stimulation (TENS). One found a significant pain reduction effect with the NRS (d = 1.481; 95% CI, 1.82-1.143), and decreased opioid use, while the other RCT did not show significant benefit. Additionally, one case report with TENS showed pain improvement that was not quantitatively measured. DISCUSSION: The neuromodulation techniques of rTMS and SCS showed the most consistent potential as a treatment method for chronic pancreatic pain. However, the studies have notable limitations, and SCS has had no clinical trials. For VNS, we have two RCTs that showed a non-statistically significant improvement; we believe that both studies had a lack of power issue and suggest a gap in the literature for new RCTs exploring this modality. Additionally, tDCS and TENS showed mixed results. Another important insight was that opioid intake decrease is a common trend among most studies included and that adverse effects were rarely reported. To further elucidate the potential of these neurostimulation techniques, we suggest the development of new clinical trials with larger samples and adequate sham controls.

The Impact of Obesity as a Peripheral Disruptor of Brain Inhibitory Mechanisms in Fibromyalgia: A Cross-Sectional Study.

Background/Objective: Obesity, characterized by chronic inflammation, may serve as a surrogate marker for more dysfunctional peripheral inflammation, potentially exacerbating FM symptomatology. Given this premise, this study aimed to investigate the effects of obesity as an effect modifier on neural and clinical variables, specifically those indexing pain-compensatory mechanisms in FM symptoms. Methods: A cross-sectional study was conducted with 108 participants who underwent a standardized TMS protocol assessment to measure resting motor threshold (MT), intracortical facilitation (ICF), and intracortical inhibition (ICI). Clinical data were collected using Beck's Depression Index (BDI), PROMIS, the Brief Pain Inventory (BPI), and conditioned pain modulation (CPM). Linear regression models were used to explore the relationship between these variables while examining Body Mass Index (BMI) as a potential effect modifier. If it was found to be a modifier, we stratified the sample into two groups with a BMI cutoff of 30 and performed another regression model within the subgroups. Results: BMI was identified as an effect modifier in the relationships between ICI and BDI, PROMIS fatigue, and CPM and in MT versus CPM. After stratification, non-obese fibromyalgia subjects demonstrated significant correlations between clinical symptoms and CPM and ICI activity. However, these correlations were absent in the obese group, suggesting obesity disrupts pain mechanisms and their compensatory effects. Higher MT values were associated with weaker endogenous pain control, particularly evident in the obese group. Conclusions: Obesity appears to be a significant effect modifier and delineates two patient groups across multiple clinical and neural assessments of fibromyalgia. Additionally, it suggests a role for obesity in exacerbating fibromyalgia symptoms and disrupting physiological pain-inhibitory mechanisms.

Surgery is associated with better long-term outcomes than pharmacological treatment for obesity: a systematic review and meta-analysis.

Obesity is a highly prevalent disease with numerous complications. Both intensive medical treatment with the use of pharmacological drugs and bariatric surgery are current options. The objective of this meta-analysis was to compare, in the long-term, intensive medical treatment and surgery based on twelve parameters related to weight loss, cardiovascular and endocrine changes. A review of the literature was conducted in accordance with the PRISMA guidelines (PROSPERO: CRD42021265637). The literature screening was done from inception to October 2023 through PubMed, EMBASE and Web of Science databases. We included randomized clinical trials that had separate groups for medical treatment and bariatric surgery as an intervention for obesity. The risk of bias was assessed through RoB2. A meta-analysis was performed with measures of heterogeneity and publication bias. Subgroup analysis for each surgery type was performed. Data is presented as forest-plots. Reviewers independently identified 6719 articles and 6 papers with a total 427 patients were included. All studies were randomized controlled trials, three had a follow up of 5 years and two had a follow up of 10 years. Both groups demonstrated statistical significance for most parameters studied. Surgery was superior for weight loss (- 22.05 kg [- 28.86; - 15.23), total cholesterol (- 0.88 [- 1.59; - 0.17]), triglycerides (- 0.70 [- 0.82; - 0.59]), HDL (0.12 [0.02; 0.23]), systolic pressure (- 4.49 [- 7.65; - 1.33]), diastolic pressure (- 2.28 [- 4.25; - 0.31]), Hb glycated (- 0.97 [- 1.31; - 0.62]), HOMA IR (- 2.94; [- 3.52; - 2.35]) and cardiovascular risk (- 0.08; [- 0.10; - 0.05]). Patient in the surgical treatment group had better long term outcomes when compared to the non-surgical group for most clinical parameters.

Interaction between apolipoprotein E genotypes, excessive daytime sleepiness, and cognitive function in obstructive sleep apnea patients.

BACKGROUND: Some studies show an association between the apolipoprotein E ε4 allele (ApoEε4) and obstructive sleep apnea syndrome (OSAS), and other studies, an association between ApoEε4 and excessive daytime sleepiness (EDS), but there are no data in the literature on the interaction between EDS, cognitive function, and ApoEε4 in patients with OSA. OBJECTIVE: To examine the cognitive function of adults with and without EDS and with and without ApoEε4. METHODS: A total of 21 male and female patients aged between 33 and 79 years, underwent a clinical interview, ApoE genotyping, neuropsychological evaluation, polysomnography, and the application of the Epworth Sleepiness Scale. RESULTS: Excessive daytime sleepiness was associated with lower intelligence quotient (IQ; total performance) and worse immediate visual memory, regardless of the ApoE genotype. Patients carrying the ApoEε3/ε4 genotype had a worse performance in divided attention, constructional praxis, perceptual organization, and cognitive flexibility. A combination of the ε4 allele and EDS potentiates the negative effect on cognition, except for immediate visual memory. In this case, patients had a worse performance in terms of processing speed, selective attention, and visuomotor coordination. CONCLUSIONS: Excessive daytime sleepiness and the ApoEε3/ε4 genotype are associated with worse cognitive performance in OSA patients. The combination of EDS and ε4 allele potentiates cognitive impairment.

ANTECEDENTES: Alguns estudos mostram uma associação entre o alelo ε4 da apolipoproteina E (ApoEε4) e a síndrome da apneia obstrutiva do sono (SAOS), e outros, entre ApoEε4 e a sonolência excessiva diurna (SED), mas não há dados na literatura sobre a interação entre SED, função cognitiva e ApoEε4 em pacientes com SAOS. OBJETIVO: Avaliar a função cognitiva em adultos com SAOS com e sem SED e com e sem ApoEε4. MéTODOS: Ao todo, 21 pacientes, de 33 a 79 anos, homens e mulheres, foram avaliados clinicamente, e submetidos a genotipagem ApoE, avaliação neuropsicológica, polissonografia, e aplicação da Escala de Sonolência de Epworth. RESULTADOS: A SED esteve associada com menor quociente de inteligência (QI; desempenho geral) e pior memória visual imediata, independentemente do genótipo ApoE. Pacientes com genótipo ApoEε3/ε4 apresentaram pior desempenho na atenção dividida, praxe construcional, organização perceptiva e flexibilidade cognitiva. A combinação do alelo ε4 com a SED potencializa esse efeito deletério na cognição, exceto na memória visual imediata. Nesse caso, os pacientes tiveram uma menor velocidade de processamento cognitivo, e piores atenção seletiva e coordenação visiomotora. CONCLUSõES: A SED e o genótipo ApoEε3/ε4 estão associados a um pior desempenho cognitivo em pacientes com SAOS. A combinação de SED e do alelo ε4 potencializa esse efeito.

Comparing dextrose prolotherapy with other substances in knee osteoarthritis pain relief: A systematic review.

The objective of this study is to compare the effectiveness of dextrose-prolotherapy with other substances for pain relief in patients with primary knee osteoarthritis. The literature screening was done in January 2021 through Medline (PubMed), EMBASE, and Database of the National Institute of Health based on the following criteria: randomized clinical trials that subjected patients with primary knee osteoarthritis who underwent treatment with dextrose-prolotherapy and other substances for pain relief. Paired reviewers independently identified 3381 articles and included 8 trials that met the eligibility criteria. According to the findings of this review, participants that underwent dextrose-prolotherapy showed improvements between baseline and posterior assessments and when compared to saline injections, but when compared to other substances, the results were not clear. Although dextrose-prolotherapy is a useful treatment method by itself, it is still not possible to clearly affirm that it is superior or inferior to its counterparts. There is an urgent need for further studies to bring more evidence to the field.

Cirrhosis and hernia repair in a cohort of 6352 patients in a tertiary hospital: Risk assessment and survival analysis.

The prevalence of hernias in patient with cirrhosis can reach up to 40%. The pathophysiology of cirrhosis is closely linked to that of the umbilical hernia, but other types are also common in this population. The aim of this study is to evaluate factors that influence in the prognosis after hernia repair in patients with cirrhosis. A historical cohort of 6419 patients submitted to hernia repair was gathered. Clinical, epidemiological data and hernia characteristics were obtained. For patient with cirrhosis, data from exams, surgery and follow-up outcomes were also analyzed. Survival curves were constructed to assess the impact of clinical and surgical variables on survival. 342 of the 6352 herniated patients were cirrhotic. Patient with cirrhosis had a higher prevalence of umbilical hernia (67.5% × 24.2%, P < .001) and a lower prevalence of epigastric (1.8% × 9.0%, P < .001) and lumbar (0% × 0.18%, P = .022). There were no significant differences in relation to inguinal hernia (P = .609). Ascites was present in 70.1% of patient with cirrhosis and its prevalence was different in relation to the type of hernia (P < .001). The survival curve showed higher mortality for emergency surgery, MELD > 14 and ascites (HR 12.6 [3.79-41.65], 4.5 [2.00-10.34], and 6.1 [1.15-20.70], respectively, P < .05). Hernia correction surgery in patient with cirrhosis has a high mortality, especially when performed under urgent conditions associated with more severe clinical conditions of patients, such as the presence of ascites and elevated MELD.

MICRObiota on BILIOpancreatic malignant diseases [MICROBILIO]: A systematic review.

INTRODUCTION: The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA). METHODS: This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases. RESULTS: Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies' results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA. CONCLUSION: There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.

The development of laparoscopic skills using virtual reality simulations: A systematic review.

BACKGROUND: Teaching based on virtual reality simulators in medicine has expanded in recent years due to the limitations of more traditional methods, especially for surgical procedures such as laparoscopy. PURPOSE OF REVIEW: To analyze the effects of using virtual reality simulations on the development of laparoscopic skills in medical students and physicians. DATA SOURCES: The literature screening was done in April 2020 through Medline (PubMed), EMBASE and Database of the National Institute of Health. ELIGIBILITY CRITERIA: Randomized clinical trials that subjected medical students and physicians to training in laparoscopic skills in virtual reality simulators. STUDY APPRAISAL: Paired reviewers independently identified 1529 articles and included 7 trials that met the eligibility criteria. FINDINGS: In all studies, participants that trained in virtual simulators showed improvements in laparoscopic skills, although the articles that also had a physical model training group did not show better performance of one model compared to the other. LIMITATIONS: No article beyond 2015 met the eligibility criteria, and the analyzed simulators have different versions and models, which might impact the results. CONCLUSION: Virtual reality simulators are useful educational tools, but do not show proven significant advantages over traditional models. The lack of standardization and a scarcity of articles makes comparative analysis between simulators difficult, requiring more research in the area, according to the model suggested in this review. SYSTEMATIC REVIEW REGISTRATION NUMBER: Registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020176479.

[The newer sedative-hypnotics]. / Novos sedativos hipnóticos.

There has been a search for more effective and safe hypnotic drugs in the last decades. Zolpidem, zaleplon, zopiclone, eszopiclone (the z-drugs) and indiplon are GABA-A modulators which bind selectively α1 subunits, thus, exhibiting similar mechanisms of action, although recent evidence suggests that eszopiclone is not as selective for α1 subunit as zolpidem is. Ramelteon and tasimelteon are new chrono-hypnotic agents, selective for melatonin MT1 and MT2 receptors. On the other hand, the consumption of sedative antidepressant drugs is significantly increasing for the treatment of insomnia, in the last years. As an experimental drug, eplivanserin is being tested as a potent antagonist of serotonin 2-A receptors (ASTAR) with a potential use in sleep maintenance difficulty. Another recent pharmacological agent for insomnia is almorexant, which new mechanism of action involves antagonism of hypocretinergic system, thus inducing sleep. Finally we also discuss the potential role of other gabaergic drugs for insomnia.

[Brazilian guidelines for the treatment of narcolepsy]. / Diretrizes brasileiras para o tratamento da narcolepsia.

This manuscript contains the conclusion of the consensus meeting of the Brazilian Sleep Association with Brazilian sleep specialists on the treatment of narcolepsy based on the review of medical literature from 1980 to 2010. The manuscript objectives were to reinforce the use of agents evaluated in randomized placebo-controlled trials and to issue consensus opinions on the use of other available medications as well as to inform about safety and adverse effects of these medications. Management of narcolepsy relies on several classes of drugs, namely, stimulants for excessive sleepiness, antidepressants for cataplexy and hypnotics for disturbed nocturnal sleep. Behavioral measures are likewise valuable and universally recommended. All therapeutic trials were analyzed according to their class of evidence. Recommendations concerning the treatment of each single symptom of narcolepsy as well as general recommendations were made. Modafinil is the first-line pharmacological treatment of excessive sleepiness. Second-line choices for the treatment of excessive sleepiness are slow-release metylphenidate followed by mazindol. The first-line treatments of cataplexy are the antidepressants, reboxetine, clomipramine, venlafaxine, desvenlafaxine or high doses of selective serotonin reuptake inibitors antidepressants. As for disturbed nocturnal sleep the best option is still hypnotics. Antidepressants and hypnotics are used to treat hypnagogic hallucinations and sleep paralysis.

[Brazilian guidelines for the diagnosis of narcolepsy]. / Diretrizes brasileiras para o diagnóstico da narcolepsia.

This manuscript contains the conclusion of the consensus meeting on the diagnosis of narcolepsy based on the review of Medline publications between 1980-2010. Narcolepsy is a chronic disorder with age at onset between the first and second decade of life. Essential narcolepsy symptoms are cataplexy and excessive sleepiness. Cataplexy is defined as sudden, recurrent and reversible attacks of muscle weakness triggered by emotions. Accessory narcolepsy symptoms are hypnagogic hallucinations, sleep paralysis and nocturnal fragmented sleep. The clinical diagnosis according to the International Classification of Sleep Disorders is the presence of excessive sleepiness and cataplexy. A full in-lab polysomnography followed by a multiple sleep latency test is recommended for the confirmation of the diagnosis and co-morbidities. The presence of two sleep-onset REM period naps in the multiple sleep latency test is diagnostic for cataplexy-free narcolepsy. A positive HLA-DQB1*0602 with lower than 110pg/mL level of hypocretin-1 in the cerebrospinal fluid is required for the final diagnosis of cataplexy- and sleep-onset REM period -free narcolepsy.

Donepezil improves obstructive sleep apnea in Alzheimer disease: a double-blind, placebo-controlled study.

BACKGROUND: There is an association between Alzheimer disease and sleep-disordered breathing. Donepezil is the drug most frequently used to treat cognitive symptoms in Alzheimer disease. This study evaluates the effects of donepezil on obstructive sleep apnea in patients with Alzheimer disease. METHODS: Randomized, double-blind, placebo-controlled design. Twenty-three patients with mild-to-moderate Alzheimer disease and apnea-hypopnea index (AHI) > 5/h were allocated to two groups: donepezil treated (n = 11) and placebo treated (n = 12). Polysomnography and cognitive evaluation using Alzheimer disease assessment scale-cognitive (ADAS-cog) subscale were performed at baseline and after 3 months. Cognitive and sleep data were analyzed using analysis of variance. RESULTS: AHI and oxygen saturation improved significantly after donepezil treatment compared to baseline and placebo (p < 0.05). Rapid eye movement (REM) sleep duration increased after donepezil treatment (p < 0.05). ADAS-cog scores improved after donepezil treatment, although they did not correlate with REM sleep increase and sleep apnea improvement (p < 0.01). CONCLUSIONS: Donepezil treatment improved AHI and oxygen saturation in patients with Alzheimer disease. Treatment also increased REM sleep duration and reduced ADAS-cog scores. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00480870.

Interaction between apolipoprotein E genotypes, excessive daytime sleepiness, and cognitive function in obstructive sleep apnea patients / Interação entre genótipos da apolipoproteína E, sonolência excessiva diurna e função cognitiva em pacientes com apneia obstrutiva do sono

Abstract Background Some studies show an association between the apolipoprotein E ε4 allele (ApoEε4) and obstructive sleep apnea syndrome (OSAS), and other studies, an association between ApoEε4 and excessive daytime sleepiness (EDS), but there are no data in the literature on the interaction between EDS, cognitive function, and ApoEε4 in patients with OSA. Objective To examine the cognitive function of adults with and without EDS and with and without ApoEε4. Methods A total of 21 male and female patients aged between 33 and 79 years, underwent a clinical interview, ApoE genotyping, neuropsychological evaluation, polysomnography, and the application of the Epworth Sleepiness Scale. Results Excessive daytime sleepiness was associated with lower intelligence quotient (IQ; total performance) and worse immediate visual memory, regardless of the ApoE genotype. Patients carrying the ApoEε3/ε4 genotype had a worse performance in divided attention, constructional praxis, perceptual organization, and cognitive flexibility. A combination of the ε4 allele and EDS potentiates the negative effect on cognition, except for immediate visual memory. In this case, patients had a worse performance in terms of processing speed, selective attention, and visuomotor coordination. Conclusions Excessive daytime sleepiness and the ApoEε3/ε4 genotype are associated with worse cognitive performance in OSA patients. The combination of EDS and ε4 allele potentiates cognitive impairment.

Resumo Antecedentes Alguns estudos mostram uma associação entre o alelo ε4 da apolipoproteina E (ApoEε4) e a síndrome da apneia obstrutiva do sono (SAOS), e outros, entre ApoEε4 e a sonolência excessiva diurna (SED), mas não há dados na literatura sobre a interação entre SED, função cognitiva e ApoEε4 em pacientes com SAOS. Objetivo Avaliar a função cognitiva em adultos com SAOS com e sem SED e com e sem ApoEε4. Métodos Ao todo, 21 pacientes, de 33 a 79 anos, homens e mulheres, foram avaliados clinicamente, e submetidos a genotipagem ApoE, avaliação neuropsicológica, polissonografia, e aplicação da Escala de Sonolência de Epworth. Resultados A SED esteve associada com menor quociente de inteligência (QI; desempenho geral) e pior memória visual imediata, independentemente do genótipo ApoE. Pacientes com genótipo ApoEε3/ε4 apresentaram pior desempenho na atenção dividida, praxe construcional, organização perceptiva e flexibilidade cognitiva. A combinação do alelo ε4 com a SED potencializa esse efeito deletério na cognição, exceto na memória visual imediata. Nesse caso, os pacientes tiveram uma menor velocidade de processamento cognitivo, e piores atenção seletiva e coordenação visiomotora. Conclusões A SED e o genótipo ApoEε3/ε4 estão associados a um pior desempenho cognitivo em pacientes com SAOS. A combinação de SED e do alelo ε4 potencializa esse efeito.

Comparing dextrose prolotherapy with other substances in knee osteoarthritis pain relief: A systematic review

Abstract The objective of this study is to compare the effectiveness of dextrose-prolotherapy with other substances for pain relief in patients with primary knee osteoarthritis. The literature screening was done in January 2021 through Medline (PubMed), EMBASE, and Database of the National Institute of Health based on the following criteria: randomized clinical trials that subjected patients with primary knee osteoarthritis who underwent treatment with dextrose-prolotherapy and other substances for pain relief. Paired reviewers independently identified 3381 articles and included 8 trials that met the eligibility criteria. According to the findings of this review, participants that underwent dextrose-prolotherapy showed improvements between baseline and posterior assessments and when compared to saline injections, but when compared to other substances, the results were not clear. Although dextrose-prolotherapy is a useful treatment method by itself, it is still not possible to clearly affirm that it is superior or inferior to its counterparts. There is an urgent need for further studies to bring more evidence to the field. HIGHLIGHTS Dextrose injections promote deposition of collagen into injured structures through growth factors and inflammatory cells. Dextrose-prolotherapy is a useful treatment method, but it is not superior or inferior to its counterparts.

MICRObiota on BILIOpancreatic malignant diseases [MICROBILIO]: A systematic review

Abstract Introduction: The increase in the incidence of pancreatic and biliary cancers has attracted the search for methods of early detection of diseases and biomarkers. The authors propose to analyze new findings on the association between microbiota and Pancreatic Ductal Adenocarcinoma (PDAC) or Cholangiocarcinoma (CCA). Methods: This systematic review was carried out according to the items of Preferred Reports for Systematic Reviews and Protocol Meta-Analysis (PRISMA-P). This study was registered by the Prospective Register of Systematic Reviews (PROSPERO), identification code CRD42020192748 before the review was carried out. Articles were selected from the PUBMED, EMBASE, and Cochrane databases. Results: Most studies (86.67%) used 16s rRNA as a sequencing method. The main comorbidities found were diabetes mellitus, systemic arterial hypertension, and dyslipidemia. Many studies were limited by the small number of participants, but the biases were mostly low. There was very little concordance about the composition of the microbiome of different sites, for both case and control groups when compared to other studies' results. Bile sample analysis was the one with a greater agreement between studies, as three out of four studies found Escherichia in cases of CCA. Conclusion: There was great disagreement in the characterization of both the microbiota of cases and control groups. Studies are still scarce, making it difficult to adequately assess the data in this regard. It was not possible to specify any marker or to associate any genus of microbiota bacteria with PDAC or CCA.

The Effect of Donepezil on Arousal Threshold and Apnea-Hypopnea Index. A Randomized, Double-Blind, Cross-Over Study.

RATIONALE: Obstructive sleep apnea (OSA) has multiple pathophysiological causes. A low respiratory arousal threshold (ArTh) and a high loop gain (unstable ventilatory control) can contribute to recurrent respiratory events in patients with OSA. Prior studies have shown that donepezil, an acetylcholinesterase inhibitor, might improve OSA, but the mechanism is unknown. OBJECTIVES: To determine whether a single dose of donepezil lowers the apnea-hypopnea index by modulating the ArTh or loop gain. METHODS: In this randomized, double-blind, crossover trial, 41 subjects with OSA underwent two polysomnograms with ArTh and loop gain evaluated, during which 10 mg of donepezil or placebo was administered. MEASUREMENTS AND MAIN RESULTS: Compared with placebo, sleep efficiency (77.2 vs. 71.9%; P = 0.015) and total sleep time decreased with donepezil (372 vs. 351 min; P = 0.004). No differences were found in apnea-hypopnea index (51.8 vs. 50.0 events/h; P = 0.576) or nadir oxygen saturation as determined by pulse oximetry (80.3 vs. 81.1%; P = 0.241) between placebo and donepezil, respectively. ArTh was not significantly changed (-18.9 vs. -18.0 cm H2O; P = 0.394) with donepezil. As a whole group, loop gain (ventilatory response to a 1-cycle/min disturbance) did not change significantly (P = 0.089). CONCLUSIONS: A single dose of donepezil did not appear to affect the overall severity of OSA in this patient group, and no consistent effects on ArTh or loop gain were observed. Donepezil may have minor effects on sleep architecture. Clinical trial registered with www.clinicaltrials.gov (NCT02264353).

[Sleep in psychiatric disorders]. / O sono em transtornos psiquiátricos.

Altered sleep patterns are prominent in the majority of psychiatric disorders. This article examines the psychiatric disorders that are most often associated to sleep dysfunction as it is related in clinical practice and describes the polysomnographic findings. Patient's main complaints are related to difficulty in initiating and maintaining sleep (initial or middle insomnia, respectively) and poor quality of sleep. Early awakening or terminal insomnia is most described in the depressive conditions. Hypersomnia may be the main symptom in some depressive disorders, as seasonal depression, depression with atypical features or depressive episodes in bipolar disorder. Polysomnographic evaluation shows, in general, a significative reduction in the efficiency and total time of sleep, in detriment to the amount of slow wave sleep. The reduction of rapid eye movement (REM) sleep latency is mainly described for the depression, but has also been reported in other psychiatric disorders.

Brazilian consensus on guidelines for diagnosis and treatment for restless legs syndrome.

The Consensus on restless legs syndrome is an effort of neurologists from several Brazilian states, which tirelessly reviewed the literature of recent years in search of evidence, both in regard to diagnosis and treatment, according to the Oxford Centre for Evidence-based Medicine.

Effects of aging on sleep structure throughout adulthood: a population-based study.

OBJECTIVE: Although many studies have shown the evolution of sleep parameters across the lifespan, not many have included a representative sample of the general population. The objective of this study was to describe age-related changes in sleep structure, sleep respiratory parameters and periodic limb movements of the adult population of São Paulo. METHODS: We selected a representative sample of the city of São Paulo, Brazil that included both genders and an age range of 20-80 years. Pregnant and lactating women, people with physical or mental impairments that prevent self-care and people who work every night were not included. This sample included 1024 individuals who were submitted to polysomnography and structured interviews. We subdivided our sample into five-year age groups. One-way analysis of variance was used to compare age groups. Pearson product-moment was used to evaluate correlation between age and sleep parameters. RESULTS: Total sleep time, sleep efficiency, percentage of rapid eye movement (REM) sleep and slow wave sleep showed a significant age-related decrease (P<0.05). WASO (night-time spent awake after sleep onset), arousal index, sleep latency, REM sleep latency, and the percentage of stages 1 and 2 showed a significant increase (P<0.05). Furthermore, apnea-hypopnea index increased and oxygen saturation decreased with age. The reduction in the percentage of REM sleep significantly correlated with age in women, whereas the reduction in the percentage of slow wave sleep correlated with age in men. The periodic limb movement (PLM) index increased with age in men and women. CONCLUSIONS: Sleep structure and duration underwent significant alterations throughout the aging process in the general population. There was an important correlation between age, sleep respiratory parameters and PLM index. In addition, men and women showed similar trends but with different effect sizes.