Harmonization of clinical practice guidelines for primary prevention and screening: actionable recommendations and resources for primary care.

BACKGROUND: Clinical practice guidelines (CPGs) synthesize high-quality information to support evidence-based clinical practice. In primary care, numerous CPGs must be integrated to address the needs of patients with multiple risks and conditions. The BETTER program aims to improve prevention and screening for cancer and chronic disease in primary care by synthesizing CPGs into integrated, actionable recommendations. We describe the process used to harmonize high-quality cancer and chronic disease prevention and screening (CCDPS) CPGs to update the BETTER program. METHODS: A review of CPG databases, repositories, and grey literature was conducted to identify international and Canadian (national and provincial) CPGs for CCDPS in adults 40-69 years of age across 19 topic areas: cancers, cardiovascular disease, chronic obstructive pulmonary disease, diabetes, hepatitis C, obesity, osteoporosis, depression, and associated risk factors (i.e., diet, physical activity, alcohol, cannabis, drug, tobacco, and vaping/e-cigarette use). CPGs published in English between 2016 and 2021, applicable to adults, and containing CCDPS recommendations were included. Guideline quality was assessed using the Appraisal of Guidelines for Research and Evaluation (AGREE) II tool and a three-step process involving patients, health policy, content experts, primary care providers, and researchers was used to identify and synthesize recommendations. RESULTS: We identified 51 international and Canadian CPGs and 22 guidelines developed by provincial organizations that provided relevant CCDPS recommendations. Clinical recommendations were extracted and reviewed for inclusion using the following criteria: 1) pertinence to primary prevention and screening, 2) relevance to adults ages 40-69, and 3) applicability to diverse primary care settings. Recommendations were synthesized and integrated into the BETTER toolkit alongside resources to support shared decision-making and care paths for the BETTER program. CONCLUSIONS: Comprehensive care requires the ability to address a person's overall health. An approach to identify high-quality clinical guidance to comprehensively address CCDPS is described. The process used to synthesize and harmonize implementable clinical recommendations may be useful to others wanting to integrate evidence across broad content areas to provide comprehensive care. The BETTER toolkit provides resources that clearly and succinctly present a breadth of clinical evidence that providers can use to assist with implementing CCDPS guidance in primary care.

Chronic disease prevention and screening outcomes for patients with and without financial difficulty: a secondary analysis of the BETTER WISE cluster randomised controlled trial.

OBJECTIVE: Building on Existing Tools To improvE chronic disease pRevention and screening in primary care Wellness of cancer survIvorS and patiEnts (BETTER WISE) was designed to assess the effectiveness of a cancer and chronic disease prevention and screening (CCDPS) programme. Here, we compare outcomes in participants living with and without financial difficulty. DESIGN: Secondary analysis of a cluster-randomised controlled trial. SETTING: Patients of 59 physicians from 13 clinics enrolled between September 2018 and August 2019. PARTICIPANTS: 596 of 1005 trial participants who responded to a financial difficulty screening question at enrolment. INTERVENTION: 1-hour CCDPS visit versus usual care. OUTCOME MEASURES: Eligibility for a possible 24 CCDPS actions was assessed at baseline and the primary outcome was the percentage of eligible items that were completed at 12-month follow-up. We also compared the change in response to the financial difficulty screening question between baseline and follow-up. RESULTS: 55 of 265 participants (20.7%) in the control group and 69 of 331 participants (20.8%) in the intervention group reported living with financial difficulty. The primary outcome was 29% (95% CI 26% to 33%) for intervention and 23% (95% CI 21% to 26%) for control participants without financial difficulty (p=0.01). Intervention and control participants with financial difficulty scored 28% (95% CI 24% to 32%) and 32% (95% CI 27% to 38%), respectively (p=0.14). In participants who responded to the financial difficulty question at both time points (n=302), there was a net decrease in the percentage of participants who reported financial difficulty between baseline (21%) and follow-up (12%, p<0.001) which was similar in the control and intervention groups. The response rate to this question was only 51% at follow-up. CONCLUSION: The BETTER intervention improved uptake of CCDPS manoeuvres in participants without financial difficulty, but not in those living with financial difficulty. Improving CCDPS for people living with financial difficulty may require a different clinical approach or that social determinants be addressed concurrently with clinical and lifestyle needs or both. TRIAL REGISTRATION NUMBER: ISRCTN21333761.

EORTC-SPECTA Arcagen study, comprehensive genomic profiling and treatment adaptation of rare thoracic cancers.

Arcagen (NCT02834884) is a European prospective study aiming at defining the molecular landscape of rare cancers for treatment guidance. We present data from the cohort of rare thoracic tumors. Patients with advanced pleural mesothelioma (PM) or thymic epithelial tumors (TET) underwent genomic profiling with large targeted assay [>300 genes, tumor mutational burden (TMB), microsatellite instability (MSI) status] on formalin-fixed paraffin-embedded (FFPE) or plasma samples. EORTC molecular tumor board (MTB) advised for biomarker-guided treatments. 102 patients recruited from 8 countries between July 2019 and May 2022 were evaluable: 56 with PM, 46 with TET (23 thymomas, 23 thymic carcinomas). Molecular profiling was performed on 70 FFPE samples (42 PM, 28 TET), and 32 cases on ctDNA (14 PM, 18 TET), within a median turnaround time of 8 days from sample reception. We detected relevant molecular alterations in 66 out of 102 patients (65%; 79% PM, 48% TET), 51 of 70 FFPE samples (73%; 90% PM, 46% TET), and 15 of 32 plasma samples (47%; 43% PM, 50% TET). The most frequently altered genes were CDKN2A/B, BAP1, MTAP in PM and TP53, CDKN2A/B, SETD2 in TET. The TMB was low (mean 3.2 Muts/MB), 2 PM had MSI-high status. MTB advised molecular-guided treatment options in 32 situations, for 17 PM and 15 TET patients (75% clinical trial option, 22% off-label drug or compassionate use, 3% early access program). Molecular testing and MTB discussion were feasible for patients with rare thoracic cancers and allowed the broadening of treatment options for 30% of the cases.

Management of pemphigoid vegetans with mycophenolate mofetil: A case report.

Pemphigoid vegetans is a rare variant of bullous pemphigoid. Only 13 cases have been documented in the medical literature. The lesions clinically resemble pemphigus vegetans, but the histology is consistent with bullous pemphigoid. We present the case of a 63-year-old woman with painful vesicular and vegetative lesions progressing for 4 months. Histopathology showed a dermal-epidermal cleavage, epidermal acanthosis and an eosinophilic infiltrate. Direct immunofluorescence showed linear deposition of IgG and IgA at the junctional level. The diagnosis of pemphigoid vegetans was retained and successfully treated with oral corticosteroid, dapsone and mycophenolate mofetil.

Triggers, clinical manifestations and assessment of paediatric fixed drug eruptions: A systematic review of the literature.

Fixed drug eruption (FDE) is a cutaneous drug reaction characterised by recurrent skin lesions occurring at the same site after each exposure to a causative agent. There is currently limited evidence in the paediatric population. The objective of this systematic review is to investigate the clinical features, causative agents and management of paediatric FDE. A systematic search of the English and French literature on paediatric FDE was conducted using the Medline and Embase databases. After full-text article review, 92 articles were included, representing a total of 233 patients. Antibiotics were the most frequent triggering agents, mainly sulfonamides (65.0% of antibiotics). Systemic symptoms were rare, and most patients only received supportive therapy. One hundred and six patients (106) performed a test to confirm the causative agent. Of these, 72.6% had oral provocation tests (OPTs) and 28.3% had patch tests. The patient's age, presence of bullous lesions and mucosal lesions were similar between tested and untested patients. It did not seem to influence the decision to perform OPTs. Paediatric FDE is a non-severe skin drug reaction. Antibiotics were the most reported triggering agents. Drug testing, including oral provocation test, was safely performed in the paediatric population.

Plant-growth promotion by halotolerant black yeast Hortaea sp. strain PMGTC8 associated with salt crystals from solar saltern of Goa, India.

Plant-growth-promoting microbes are sustainable alternative to improve the soil fertility and plant-growth facilitating the nutrients uptake in normal and stressed environmental conditions. Among these, halotolerant and halophilic microorganisms with plant- growth-promoting ability are better candidates that could be exploited as bioinoculants in salinity affected agriculture soils. Considering this, the current study aimed to isolate, characterize and determine the plant-growth-promoting potential of the culturable halotolerant black yeast associated with salt crystals from the solar saltern of Goa, India. The results revealed 1.3 × 104 CFU/g of viable number of colonies on 25% NaCl Tryptone Yeast Extract (NTYE) agar after 30-45 days incubation. Among ten morphologically distinct isolates, a black pigmented strain PMGTC8 was characterized as yeast-like and appeared two celled with average size of 4.30 ± 0.14 µm under scanning electron micrograph. Based on phylogenetic analysis using internal transcribed spacer (ITS) marker, the isolate showed maximum similarity to genus Hortaea. Interestingly, Hortaea sp. strain PMGTC8 (OR527117) exhibited plant-growth-promoting characteristics and caused significantly (p < 0.01) higher germination rate (93.33%), vigor index (964.22), shoot (3.95 cm) and root length (6.38 cm), and fresh weight (0.039 g) of Oryza sativa var. Korgut. This halotolerant black yeast may play a role in nutrition of the plants growing in saline soils. Conclusively, the current findings report for the first time the plant-growth-promoting potential of Hortaea sp. strain PMGTC8 associated with salt crystals of solar saltern, Goa, India for its possible use as bio-fertilizers in saline agriculture soils.

Nutraceutical Potential of Grape (Vitis vinifera L.) Seed Oil in Oxidative Stress, Inflammation, Obesity and Metabolic Alterations.

Vitis vinifera L. (grapevine) is a perennial plant of the Vitaceae family that is widely used to produce grapes and wines. Grape seed oil is rich in fatty acids such as linoleic acid (65-75%), vitamin E (50 mg), and phytosterols in addition to phenolic compounds, such as catechins (414 mg), epicatechins (130.4 mg), and gallic acid (77 µg), shows promise as a nutritional compound and is outstanding as a therapeutic substance with active properties for health, detected mainly by in vitro studies, as well as some in vivo studies. The benefits of consuming this oil include modulating the expression of antioxidant enzymes, anti-atherosclerotic and anti-inflammatory effects, and protection against oxidative cell damage and some types of cancer. However, experimental findings confirm that therapeutic functions remain scarce; thus, more studies are needed to determine the mechanisms of action involved in the indicated therapeutic qualities.

Neurological disorders in pregnant women in low- and middle-income countries-Management gaps, impacts, and future prospects: A review perspective.

Neurological disorders during pregnancy are a substantial threat to women's health, particularly in low- and middle-income countries. Furthermore, a critical shortage of mental health workers and neurologists exacerbates the already pressing issue, where a lack of coordination of respective healthcare among multidisciplinary teams involved in managing these conditions perpetuates the current state of affairs. Financial restrictions and societal stigmas associated with neurological disorders in pregnancy amplify the situation. Addressing these difficulties would necessitate a multifaceted approach comprising investments in healthcare infrastructure, healthcare professional education and training, increased government support for research, and the implementation of innovative care models. Improving access to specialized treatment and coordinated management of antenatal neurological diseases will precipitate improved health outcomes for women and their families in low- and middle-income countries.

O-Linked GlcNAcylation mediates the inhibition of proximal tubule (Na++K+)ATPase activity in the early stage of diabetes mellitus.

BACKGROUND: Diabetic kidney disease (DKD) is a severe complication of diabetes mellitus (DM). It has been proposed that modifications in the function of proximal tubule epithelial cells (PTECs) precede glomerular damage during the onset of DKD. This study aimed to identify modifications in renal sodium handling in the early stage of DM and its molecular mechanism. METHODS: Streptozotocin (STZ)-induced diabetic BALB/c mice (STZ group) and LLC-PK1 cells, a model of PTECs, were used. All parameters were assessed in the 4th week after an initial injection of STZ. RESULTS: Early stage of DKD was characterized by hyperfiltration and PTEC dysfunction. STZ group exhibited increased urinary sodium excretion due to impairment of tubular sodium reabsorption. This was correlated to a decrease in cortical (Na++K+)ATPase (NKA) α1 subunit expression and enzyme activity and an increase in O-GlcNAcylation. RNAseq analysis of patients with DKD revealed an increase in expression of the glutamine-fructose aminotransferase (GFAT) gene, a rate-limiting step of hexosamine biosynthetic pathway, and a decrease in NKA expression. Incubation of LLC-PK1 cells with 10 µM thiamet G, an inhibitor of O-GlcNAcase, reduced the expression and activity of NKA and increased O-GlcNAcylation. Furthermore, 6-diazo-5-oxo-L-norleucine (DON), a GFAT inhibitor, or dapagliflozin, an SGLT2 inhibitor, avoided the inhibitory effect of HG on expression and activity of NKA associated with the decrease in O-GlcNAcylation. CONCLUSION: Our results show that the impairment of tubular sodium reabsorption, in the early stage of DM, is due to SGLT2-mediated HG influx in PTECs, increase in O-GlcNAcylation and reduction in NKA expression and activity.

Results from the BETTER WISE trial: a pragmatic cluster two arm parallel randomized controlled trial for primary prevention and screening in primary care during the COVID-19 pandemic.

BACKGROUND: Cancer and chronic diseases are a major cost to the healthcare system and multidisciplinary models with access to prevention and screening resources have demonstrated improvements in chronic disease management and prevention. Research demonstrated that a trained Prevention Practitioner (PP) in multidisciplinary team settings can improve achievement of patient level prevention and screening actions seven months after the intervention. METHODS: We tested the effectiveness of the PP intervention in a pragmatic two-arm cluster randomized controlled trial. Patients aged 40-65 were randomized at the physician level to an intervention group or to a wait-list control group. The intervention consisted of a patient visit with a PP. The PP received training in prevention and screening and use of the BETTER WISE tool kit. The effectiveness of the intervention was assessed using a composite outcome of the proportion of the eligible prevention and screening actions achieved between intervention and control groups at 12-months. RESULTS: Fifty-nine physicians were recruited in Alberta, Ontario, and Newfoundland and Labrador. Of the 1,005 patients enrolled, 733 (72.9%) completed the 12-month analysis. The COVID-19 pandemic occurred during the study time frame at which time nonessential prevention and screening services were not available and in-person visits with the PP were not allowed. Many patients and sites did not receive the intervention as planned. The mean composite score was not significantly higher in patients receiving the PP intervention as compared to the control group. To understand the impact of COVID on the project, we also considered a subset of patients who had received the intervention and who attended the 12-month follow-up visit before COVID-19. This assessment demonstrated the effectiveness of the BETTER visits, similar to the findings in previous BETTER studies. CONCLUSIONS: We did not observe an improvement in cancer and chronic disease prevention and screening (CCDPS) outcomes at 12 months after a BETTER WISE prevention visit: due to the COVID-19 pandemic, the study was not implemented as planned. Though benefits were described in those who received the intervention before COVID-19, the sample size was too small to make conclusions. This study may be a harbinger of a substantial decrease and delay in CCDPS activities under COVID restrictions. TRIAL REGISTRATION: ISRCTN21333761. Registered on 19/12/2016. http://www.isrctn.com/ISRCTN21333761 .

Evidence for a protective role of Protein Disulfide Isomerase-A1 against aortic dissection.

BACKGROUND AND AIMS: Redox signaling is involved in the pathophysiology of aortic aneurysm/dissection. Protein Disulfide Isomerases and its prototype PDIA1 are thiol redox chaperones mainly from endoplasmic reticulum (ER), while PDIA1 cell surface pool redox-regulates thrombosis, cytoskeleton remodeling and integrin activation, which are mechanisms involved in aortic disease. Here we investigate the roles of PDIA1 in aortic dissection. METHODS: Initially, we assessed the outcome of aortic aneurysm/dissection in transgenic PDIA1-overexpressing FVB mice using a model of 28-day exposure to lysyl oxidase inhibitor BAPN plus angiotensin-II infusion. In a second protocol, we assessed the effects of PDIA1 inhibitor isoquercetin (IQ) against aortic dissection in C57BL/6 mice exposed to BAPN for 28 days. RESULTS: Transgenic PDIA1 overexpression associated with ca. 50% (p = 0.022) decrease (vs.wild-type) in mortality due to abdominal aortic rupture and protected against elastic fiber breaks in thoracic aorta. Conversely, exposure of mice to IQ increased thoracic aorta dissection-related mortality rates, from ca. 18%-50% within 28-days (p = 0.019); elastic fiber disruption and collagen deposition were also enhanced. The structurally-related compound diosmetin, which does not inhibit PDI, had negligible effects. In parallel, stretch-tension curves indicated that IQ amplified a ductile-type of biomechanical failure vs. control or BAPN-exposed mice aortas. IQ-induced effects seemed unassociated with nonspecific antioxidant effects or ER stress. In both models, echocardiographic analysis of surviving mice suggested that aortic rupture was dissociated from progressive dilatation. CONCLUSIONS: Our data indicate a protective role of PDIA1 against aortic dissection/rupture and potentially uncovers a novel integrative mechanism coupling redox and biomechanical homeostasis in vascular remodeling.

The current landscape of intracranial aneurysms in Africa: management outcomes, challenges, and strategies-a narrative review.

Intracranial aneurysms (IAs) pose complex and potentially life-threatening challenges in Africa, where limited resources, restricted access to specialised healthcare facilities, and disparities in healthcare provision amplify the difficulties of management. Timely diagnosis and treatment are pivotal in preventing complications, including subarachnoid haemorrhage. Treatment options encompass observation, surgical clipping, endovascular coiling, and flow diversion. Positive outcomes observed in IA management in Africa include high survival rates, favourable functional outcomes, successful treatment techniques, and the absence of complications in some cases. However, negative outcomes such as postoperative complications, reduced quality of life, perioperative mortality, and the risk of recurrence persist. Challenges in IA management encompass limited access to diagnostic tools, a scarcity of specialised healthcare professionals, and an unequal distribution of services. Addressing these challenges requires interventions focused on improving access to diagnostic tools, expanding the number of trained professionals, and establishing specialised IA treatment centres. Collaboration, research, and capacity-building efforts hold significant importance in improving patient outcomes and reducing disparities in IA management across Africa.

Facilitators and Barriers to the Implementation of BETTER WISE, a Chronic Disease and Prevention Intervention in Canada: A Qualitative Study.

The aim of the BETTER WISE intervention is to address cancer and chronic disease prevention and screening (CCDPS) and lifestyle risks in patients aged 40-65. The purpose of this qualitative study is to better understand facilitators and barriers to the implementation of the intervention. Patients were invited for a 1-h visit with a prevention practitioner (PP), a member of a primary care team, with specific skills in prevention, screening, and cancer survivorship. We collected and analyzed data from 48 key informant interviews and 17 focus groups conducted with 132 primary care providers and from 585 patient feedback forms. We analyzed all qualitative data using a constant comparative method informed by grounded theory and then employed the Consolidated Framework for Implementation Research (CFIR) in a second round of coding. The following key elements were identified: (1) Intervention characteristics-relative advantage and adaptability; (2) Outer setting-PPs compensating for increased patient needs and decreased resources; (3) Characteristics of individuals-PPs (patients and physicians described PPs as compassionate, knowledgeable, and helpful); (4) Inner setting-network and communication (collaboration and support in teams or lack thereof); and (5) Process-executing the implementation (pandemic-related issues hindered execution, but PPs adapted to challenges). This study identified key elements that facilitated or hindered the implementation of BETTER WISE. Despite the interruption caused by the COVID-19 pandemic, the BETTER WISE intervention continued, driven by the PPs and their strong relationships with their patients, other primary care providers, and the BETTER WISE team.

Opportunities to improve quality of care for cancer survivors in primary care: findings from the BETTER WISE study.

PURPOSE: The BETTER WISE (Building on Existing Tools to Improve Chronic Disease Prevention and Screening in Primary Care for Wellness of Cancer Survivors and Patients) intervention is an evidence-based approach to prevention and screening for cancers and chronic diseases in primary care that also includes comprehensive follow-up for breast, prostate and colorectal cancer survivors. We describe the process of harmonizing cancer survivorship guidelines to create a BETTER WISE cancer surveillance algorithm and describe both the quantitative and qualitative findings for BETTER WISE participants who were breast, prostate or colorectal cancer survivors. We describe the results in the context of the COVID-19 pandemic. METHODS: We reviewed high-quality survivorship guidelines to create a cancer surveillance algorithm. We conducted a cluster randomized trial in three Canadian provinces with two composite index outcome measured 12 months after baseline, and also collected qualitative feedback on the intervention. RESULTS: There were 80 cancer survivors for whom we had baseline and follow-up data. Differences between the composite indices in the two study arms were not statistically significant, although a post hoc analysis suggested the COVID-19 pandemic was a key factor in these results. Qualitative finding suggested that participants and stakeholders generally viewed BETTER WISE positively and emphasized the effects of the pandemic. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: BETTER WISE shows promise for providing an evidence-based, patient-centred, comprehensive approach to prevention, screening and cancer surveillance for cancer survivors in the primary care setting. TRIAL REGISTRATION: ISRCTN21333761. Registered on December 19, 2016, http://www.isrctn.com/ISRCTN21333761 .

Evolution of nutritional status and associated factors among formula-fed infants with cow's milk protein allergy in a government program.

BACKGROUND: Cow's milk protein allergy (CMPA) is a common allergy in infants and can affect proper growth and development. This study verified factors associated with the evolution of the nutritional status (NS) among infants with CMPA fed with hypoallergenic formulas (HF). METHODS: This is a longitudinal study of infants (n = 1036) participating on a governmental program in Brazil. Researchers assessed Nutritional status before HF treatment (T1) and after HF treatment (T2). The causality of exposure variables on the evolution of NS was verified by Multinomial Logistic Regression (MLR). RESULTS: We observed an increase in anthropometric indexes analyzed with statistically significant results (p < 0.01). The weight/age and height/age scores showed a significant reduction in infants with nutritional deficit. The Body Mass Index (BMI) showed a decrease in the number of infants with nutritional deficit (< -2 z-score). On the other hand, there was an increase in those classified as at risk of overweight, overweight and obese. MLR showed that those who remained < 12 months in the program had a lower odds ratio (95% CI = 0.355-0.906; p = 0.018) to have inadequate NS with increasing BMI. Preterm infants were 4 times more likely (CI 95% = 1.520-10.694; p = 0.005) to have their BMI decreased and those who received nutritional counseling had a lower odds ratio (CI 95% = 0.411-0.953; p = 0.029) to maintain adequate NS. CONCLUSION: The program has a significant impact on the NS of infants with CMPA. The constant management and implementation of differentiated criteria according to the evolution of NS for the supply of HF is fundamental in the continuity of this public policy.

Species and antifungal susceptibility profile of agents causing vulvovaginal candidiasis in a military population: a cross-sectional study.

Military women on active duty are exposed to constant physical and mental demands, which may predispose them to some infection risks, including vulvovaginal candidiasis (VVC), a pathology considered a global public health problem. To monitor the prevalent and emerging pathogens in VVC, this study aimed to evaluate the distribution of yeast species and their in vitro antifungal susceptibility profile. We studied 104 vaginal yeast specimens obtained during routine clinical examinations. The population was attended at the Medical Center of the Military Police, São Paulo, Brazil, and was divided into two groups: infected patients (VVC) and colonised patients. Species were identified by phenotypic and proteomic methods (MALDI-TOF MS) and susceptibility to eight antifungal drugs, including azoles, polyenes, and echinocandins, was determined using microdilution broth. Candida albicans stricto sensu was found to be the most frequently isolated species (55%), but we observed a considerable rate of other Candida species isolates (30%), including Candida orthopsilosis stricto sensu only in the infected group. There were also other rare genera such as Rhodotorula, Yarrowia, and Trichosporon (15%), of which Rhodotorula mucilaginosa was the most prevalent in both groups. Fluconazole and voriconazole had the highest activity against all species in both groups. Candida parapsilosis was the most susceptible species, except for amphotericin-B in the infected group. Of note, we observed unusual resistance in C. albicans. Our results have allowed us to compile an epidemiological database on the etiology of VVC to support the empirical treatment and improve the health care of military women.

Vulvovaginal candidiasis (VVC) is an infection caused by fungi, mainly Candida albicans. Our results show that fungi other than C. albicans can cause VVC. So, our findings may help to choose the most appropriate treatment, as some may be resistant, to improve the quality of life of military women.

Relationship between nocturnal enuresis and sleep in children and adolescents.

BACKGROUND: Nocturnal enuresis (NE) is a multifactorial and complex condition. One less understood factor in its pathophysiology is the enuretic inability to wake up when the bladder is full (impaired arousal). OBJECTIVE: We aimed to investigate the relationship between sleep and NE in children and adolescents. METHODS: A systematic review was performed following the PRISMA guidelines, and the electronic databases MEDLINE (via PubMed) and SCOPUS were searched until March 2022. Eligibility criteria were studies that recruited patients aged five-17 years with a diagnosis of NE according to the International Child Continence Society (ICCS), Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5), or International Classification Criteria of Sleep Disorders-Third edition (ICSD-3) who had their sleep assessed using validated questionnaires and/or polysomnography. The tool used to analyze the risk of bias in the included studies was the risk of bias in non-randomized studies of exposure. RESULTS: Of 1582 citations screened, nine were included, giving 1685 participants, 581 with NE. All studies were observational and half had a low risk of bias. Four studies evaluated sleep by questionnaires only; two used questionnaires and polysomnography; two used only polysomnography, and one used sleep logs and actigraphy. Sleep questionnaires showed that children with enuresis had more sleep problems than controls, especially parasomnias, breathing disorders, and daytime sleepiness. Among the polysomnography parameters, the sleep stage architecture and periodic limb movements during sleep had conflicting data between the two studies. LIMITATIONS: The studies evaluated sleep through heterogeneous tools. They used different questionnaires; even those considered by polysomnography did not record the same channels. CONCLUSION: It seems that enuretic children and adolescents sleep differently from those who are non-enuretic. More studies are needed to clarify the best way to assess sleep and better understand this relationship. The review protocol was registered with PROSPERO, CRD42021266338. There was no funding.

The relevance of the socio-emotional deficits in cerebral small vessels disease (CSVD): An exploratory study with sporadic CSVD and CADASIL patients.

Background: Cerebral Small Vessels Disease (CSVD) is categorized in different forms, the most common being the sporadic form and a genetic variant - Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL). Amongst the most frequent clinical manifestations are the neuropsychological changes of cognitive, behavioral, and emotional nature, whose features are still under debate. Objective: This exploratory study aimed to compare the neuropsychological profile of a sporadic CSVD sample and a CADASIL sample with an age, education, and gender matched control group, between the ages of 30-65 YO (total sample mean age=51.16; SD=4.31). Methods: 20 patients with sporadic CSVD, 20 patients with CADASIL and 20 matched controls completed a neuropsychological assessment battery. Global cognitive state, processing speed, working memory, attention, executive dysfunction, episodic memory, social cognition, impulsivity, apathy, alexithymia, depression, and anxiety were measured. White matter hyperintensities (WMH) volume were quantified and measured as lesion burden. Results: The cognitive differences found between the clinical groups combined (after confirming no differences between the two clinical groups) and matched controls were restricted to speed processing scores (d = 0.32 95 % CI [.12-.47]). The socio-emotional and behavioral profile revealed significantly higher levels of depression (d = 0.21, 95 % CI [.16-.33]). and anxiety (d = 0.25 95 % CI [.19-.32]) in CADASIL and sporadic CSVD groups, and the same for the alexithymia score (d = 0.533 95 % CI [.32-.65]) were the clinical groups revealed impoverished emotional processing compared to controls. WMH only significantly correlated with the cognitive changes and age. Conclusions: In our study, CADASIL and sporadic cSVD patients combined, present multiple emotional-behavioral symptoms - alexithymia, anxiety, depression, and in a lower extent apathy and impulsivity - suggesting for the presence of emotion dysregulation behaviors, present independently of age and of the presence of cognitive deficits. Despite of the small sample size that could underpower some findings, this exploratory research supported that these symptoms may have a significant impact in disease monitoring, progression, and prognosis, requiring further investigation regarding their neurophysiological substrates.