Biotinidase deficiency: What have we learned in forty years?

BACKGROUND: Biotinidase deficiency (BD) is an autosomal recessively inherited disorder that was first described in 1982. Forty years after its first description, we compiled available clinical data on BD with the aim of generating a more comprehensive picture of this condition. METHODS: A systematic search strategy was performed in relevant databases without limits for publication date or languages. We screened 3966 records and included 144 articles reporting individuals with BD and their clinical presentation as well as the outcomes, when available. RESULTS: This study included 1113 individuals with BD. More than half (51.5%) of these individuals were diagnosed by newborn screening, 43.3% in presence of clinical symptoms and 5.2% due to family screening. We grouped symptomatic individuals into four main clinical presentations: neonatal-onset (<1 month; 7.9%), early childhood-onset (<2 years; 59.2%), juvenile-onset (2-16 years; 25.1%) and adult-onset (>16 years; 7.7%). BD affected five main organ systems: nervous system (67.2%), skin (53.7%), eye (34.4%), auditory (26.9%) and respiratory system (17.8%). Involvement was mainly multisystemic (82.2%) of individuals, whereas isolated system presentation was seen in only 17.2% of individuals. When reported, metabolic acidosis was present in 42.4% of symptomatic individuals and characteristic abnormal organic acid metabolites were found in 57.1%. Biotin treatment led to clinical stability or improvement in 89.2% of individuals. 1.6% of reported individuals with BD died due to non-availability of treatment or late diagnosis. CONCLUSION: Newborn screening has had a major positive impact on the outcome of many individuals with BD. However, undiagnosed and non-treated BD remains a health concern. Given the risk of mortality or complications associated with late or missed diagnosis if newborn screening is not available, a trial of biotin should be considered in undiagnosed infants and adults exhibiting suspected clinical signs. Enzymatic activity and/or analysis of genetic variants can readily confirm the diagnosis of BD.

Psychological impact of an epidemic/pandemic on the mental health of healthcare professionals: a rapid review.

BACKGROUND: Epidemics or pandemics, such as the current Coronavirus Disease 2019 (COVID-19) crisis, pose unique challenges to healthcare professionals (HCPs). Caring for patients during an epidemic/pandemic may impact negatively on the mental health of HCPs. There is a lack of evidence-based advice on what would be effective in mitigating this impact. OBJECTIVES: This rapid review synthesizes the evidence on the psychological impact of pandemics/epidemics on the mental health of HCPs, what factors predict this impact, and the evidence of prevention/intervention strategies to reduce this impact. METHOD: According to rapid review guidelines, systematic searches were carried out in Embase.com , PubMed, APA PsycINFO-Ovid SP, and Web of Science (core collection). Searches were restricted to the years 2003 or later to ensure inclusion of the most recent epidemic/pandemics, such as Severe Acute Respiratory Syndrome (SARS). Papers written in French or English, published in peer-reviewed journals, and of quantitative design using validated measures of mental health outcomes were included. Of 1308 papers found, 50 were included. The full protocol for this rapid review was registered with Prospero (reg.no. CRD42020175985). RESULTS: Results show that exposed HCPs working with patients during an epidemic/pandemic are at heightened risk of mental health problems in the short and longer term, particularly: psychological distress, insomnia, alcohol/drug misuse, and symptoms of posttraumatic stress disorder (PTSD), depression, anxiety, burnout, anger, and higher perceived stress. These mental health problems are predicted by organizational, social, personal, and psychological factors and may interfere with the quality of patient care. Few evidence-based early interventions exist so far. DISCUSSION: HCPs need to be provided with psychosocial support to protect their mental wellbeing if they are to continue to provide high quality patient care. Several recommendations relevant during and after an epidemic/pandemic, such as COVID-19, and in preparation for a future outbreak, are proposed.

Diagnostic accuracy of carotid plaque instability by noninvasive imaging: a systematic review and meta-analysis.

AIMS: There is increasing evidence that plaque instability in the extracranial carotid artery may lead to an increased stroke risk independently of the degree of stenosis. We aimed to determine diagnostic accuracy of vulnerable and stable plaque using noninvasive imaging modalities when compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis. METHODS AND RESULTS: Medline Ovid, Embase, Cochrane Library, and Web of Science were searched for diagnostic accuracy of noninvasive imaging modalities (CT, MRI, US) in the detection of 1) vulnerable/stable plaque, and 2) vulnerable/stable plaque characteristics, compared to histology. The quality of included studies was assessed by QUADAS-2 and univariate and bivariate random-effect meta-analyses were performed. We included 36 vulnerable and 5 stable plaque studies in the meta-analysis, and out of 211 plaque characteristics from remaining studies, we classified 169 as vulnerable and 42 as stable characteristics (28 CT, 120 MRI, 104 US characteristics). We found that MRI had high accuracy [90% (95% CI: 82-95%)] in the detection of vulnerable plaque, similar to CT [86% (95% CI: 76-92%); P > 0.05], whereas US showed less accuracy [80% (95% CI: 75-84%); P = 0.013]. CT showed high diagnostic accuracy in visualizing characteristics of vulnerable or stable plaques (89% and 90%) similar to MRI (86% and 89%; P > 0.05); however, US had lower accuracy (77%, P < 0.001 and 82%, P > 0.05). CONCLUSION: CT and MRI have a similar, high performance in detecting vulnerable carotid plaques, whereas US showed significantly less diagnostic accuracy. Moreover, MRI visualized all vulnerable plaque characteristics allowing for a better stroke risk assessment. REGISTRATION: PROSPERO ID CRD42022329690.

Muscle parameters in fragility fracture risk prediction in older adults: A scoping review.

Half of osteoporotic fractures occur in patients with normal/osteopenic bone density or at intermediate or low estimated risk. Muscle measures have been shown to contribute to fracture risk independently of bone mineral density. The objectives were to review the measurements of muscle health (muscle mass/quantity/quality, strength and function) and their association with incident fragility fractures and to summarize their use in clinical practice. This scoping review follows the PRISMA-ScR guidelines for reporting. Our search strategy covered the three overreaching concepts of 'fragility fractures', 'muscle health assessment' and 'risk'. We retrieved 14 745 references from Medline Ovid SP, EMBASE, Web of Science Core Collection and Google Scholar. We included original and prospective studies on community-dwelling adults aged over 50 years that analysed an association between at least one muscle parameter and incident fragility fractures. We systematically extracted 17 items from each study, including methodology, general characteristics and results. Data were summarized in tables and graphically presented in adjusted forest plots. Sixty-seven articles fulfilled the inclusion criteria. In total, we studied 60 muscle parameters or indexes and 322 fracture risk ratios over 2.8 million person-years (MPY). The median (interquartile range) sample size was 1642 (921-5756), age 69.2 (63.5-73.6) years, follow-up 10.0 (4.4-12.0) years and number of incident fragility fractures 166 (88-277). A lower muscle mass was positively/not/negatively associated with incident fragility fracture in 28 (2.0), 64 (2.5) and 10 (0.2 MPY) analyses. A lower muscle strength was positively/not/negatively associated with fractures in 53 (1.3), 57 (1.7 MPY) and 0 analyses. A lower muscle function was positively/not/negatively associated in 63 (1.9), 45 (1.0 MPY) and 0 analyses. An in-depth analysis shows how each single muscle parameter was associated with each fragility fractures subtype. This review summarizes markers of muscle health and their association with fragility fractures. Measures of muscle strength and function appeared to perform better for fracture risk prediction. Of these, hand grip strength and gait speed are likely to be the most practical measures for inclusion in clinical practice, as in the evaluation of sarcopenia or in further fracture risk assessment scores. Measures of muscle mass did not appear to predict fragility fractures and might benefit from further research, on D3-creatine dilution test, lean mass indexes and artificial intelligence methods.

Outcomes after microsurgical treatment of lymphedema: a systematic review and meta-analysis.

BACKGROUND: Microsurgical treatment options for lymphedema consist mainly of lymphovenous anastomosis (LVA) and vascularized lymph node transfers (VLNTs). There are no standard measurements of the effectiveness of these interventions and reported outcomes vary among studies. METHODS: A systematic review and meta-analysis were performed based on a structured search in Embase, Medline, PubMed, Cinahl, Cochrane, and ProQuest in October 2020, with an update in February 2022. Firstly, a qualitative summary of the main reported outcomes was performed, followed by a pooled meta-analysis of the three most frequently reported outcomes using a random effects model. Randomized controlled trials, prospective cohorts, retrospective cohorts, and cross-sectional and case-control studies that documented outcomes following microsurgery in adult patients were included. Studies of other surgical treatments (liposuction, radical excision, lymphatic vessel transplantation) or without reported outcomes were excluded. The study protocol was registered on PROSPERO (International Prospective Register of Systematic Reviews) (ID: CRD42020202417). No external funding was received for this review. RESULTS: One hundred fifty studies, including 6496 patients, were included in the systematic review. The qualitative analysis highlighted the three most frequently reported outcomes: change in circumference, change in volume, and change in the number of infectious episodes per year. The overall pooled change in excess circumference across 29 studies, including 1002 patients, was -35.6% [95% CI: -30.8 to -40.3]. The overall pooled change in excess volume across 12 studies including 587 patients was -32.7% [95% CI: -19.8 to -45.6], and the overall pooled change in the number of cutaneous infections episodes per year across 8 studies including 248 patients was -1.9 [95% CI: -1.4 to -2.3]. The vast majority of the studies included were case series and cohorts, which were intrinsically exposed to a risk of selection bias. CONCLUSION: The currently available evidence supports LVA and vascularized lymph node transfers as effective treatments to reduce the severity of secondary lymphedema. Standardization of staging method, outcomes measurements, and reporting is paramount in future research in order to allow comparability across studies and pooling of results.

Influence of smoking on the healing of conservatively treated displaced midshaft clavicle fractures.

Aims: Tobacco, in addition to being one of the greatest public health threats facing our world, is believed to have deleterious effects on bone metabolism and especially on bone healing. It has been described in the literature that patients who smoke are approximately twice as likely to develop a nonunion following a non-specific bone fracture. For clavicle fractures, this risk is unclear, as is the impact that such a complication might have on the initial management of these fractures. Methods: A systematic review and meta-analysis were performed for conservatively treated displaced midshaft clavicle fractures. Embase, PubMed, and Cochrane Central Register of Controlled Trials (via Cochrane Library) were searched from inception to 12 May 2022, with supplementary searches in Open Grey, ClinicalTrials.gov, ProQuest Dissertations & Theses, and Google Scholar. The searches were performed without limits for publication date or languages. Results: The meta-analysis included eight studies, 2,285 observations, and 304 events (nonunion). The random effects model predicted a pooled risk ratio (RR) of 3.68 (95% confidence interval 1.87 to 7.23), which can be considered significant (p = 0.003). It indicates that smoking more than triples the risk of nonunion when a fracture is treated conservatively. Conclusion: Smoking confers a RR of 3.68 for developing a nonunion in patients with a displaced middle third clavicle fracture treated conservatively. We know that most patients with pseudarthrosis will have pain and a poor functional outcome. Therefore, patients should be informed of the significantly higher risks of nonunion and offered smoking cessation efforts and counselling. Moreover, surgery should be considered for any patient who smokes with this type of fracture.

Factors influencing diabetes self-management in adults: an umbrella review of systematic reviews.

OBJECTIVE: The objective of this review was to identify and describe the factors influencing diabetes self-management in adults by summarizing the available evidence concerning their types, categories, and relative importance. INTRODUCTION: A wide range of factors, acting simultaneously, influence diabetes self-management and interfere with its actual application by patients. There is a variety of systematic reviews of these factors; however, a more thorough examination of their influences was lacking. INCLUSION CRITERIA: Systematic reviews of qualitative or quantitative literature focusing on factors influencing adult diabetes self-management in general or on individual behaviors (ie, management of oral antidiabetic medication and insulin injections, self-monitoring of blood glucose, foot care, healthy eating, regular exercise, and smoking cessation) will be included. METHODS: We performed an extensive search of 11 bibliographic databases, including gray literature, up to June 2019. Quantitative and qualitative findings were summarized separately and labeled according to their types (eg, facilitator/barrier, strength and direction of association), categories (eg, demographic, social), and frequency of occurrence. RESULTS: We identified 51 types of factors within 114 systematic reviews, which mostly addressed medication-taking behavior. Thirty-two (62.7%) factors were reported in both qualitative and quantitative literature. The predominant influences were psychological factors and behavioral attributes/skills factors. The most frequently reported facilitators of diabetes self-management were motivation to diabetes self-management, a favorable attitude to diabetes self-management, knowledge about the disease, medication and behaviors associated with diabetes self-management, skills, and self-efficacy/perceived behavioral control. The predominant barriers were the presence of depression, and polypharmacy or drug regimen complexity. The demographic factor of female sex was frequently reported for its negative influence on diabetes self-management, whereas older age was a positive factor. The social/cultural and physical environment were the least-studied categories. Other factors such as social support from family, friends, or networks; interventions led by health professionals; and a strong community environment with good social services favoring diabetes self-management were reported as major facilitators of diabetes self-management. CONCLUSIONS: Essential components of interventions to promote effective diabetes self-management should aim to help adults manage the effects of specific factors related to their psychological and practical self-management experience. Screening for depression, in particular, should become an integral part of the support for adult diabetes self-management, as depression is a particular obstacle to the effectiveness of diabetes self-management. Future studies should more deeply examine the influence of factors identified in the sociocultural and physical environment categories. Research should properly consider and invest efforts in strengthening social support and innovative community care approaches, including pharmacist- and nurse-led care models for encouraging and improving adult diabetes self-management. Finally, researchers should examine non-modifiable factors - age, sex, or socioeconomic status - in the light of factors from other categories in order to deepen understanding of their real-world patterns of action on adult diabetes self-management. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42018084665.

Malaria standby emergency treatment (SBET) for travellers visiting malaria endemic areas: a systematic review and meta-analysis.

BACKGROUND: Malaria prevention methods for travellers to low or moderate malaria risk areas vary and remain controversial. Standby emergency treatment (SBET) for malaria is one possible strategy increasingly recommended since 1988 with little evidence on its effectiveness or how it is truly being used. METHODS: A systematic review and meta-analysis were performed based on a structured search in Embase, Medline, PubMed, Cochrane and Web of Science on 7 September 2018. The primary outcome was the overall prevalence of SBET use in travellers, and secondary outcomes were the proportion carrying SBET, the response to fever [use of SBET, health facility attendance and use of malaria rapid diagnostic test (mRDT)], adverse events to SBET and the proportion using SBET incorrectly (incorrect dosage/duration). The pooled SBET use prevalence was analysed using a random effects model. A descriptive summary was done to present secondary outcomes. The study protocol was registered with PROSPERO CRD42018103703. RESULTS: A total of 11 studies were eligible for inclusion among the 1027 titles identified by our search. The studies included 7/11 prospective cohort studies that recruited pre-travel clinic attendees in Europe and 4/11 cross-sectional studies, of which 3 recruited travellers at airports before their return home from Southeast Asia and Africa and 1 from an employee registry including long-term travellers. The overall pooled prevalence of SBET use among the 26 403 travellers was 2.5% (95% confidence interval, 1.1-4.3%; range, 0.4-10.8%). There was significant variation in the proportion of travellers carrying SBET medication (40-100%), the proportion of travellers with appropriate response to fever (23-100%), adverse events (0-33%) and incorrect dosage/duration of SBET (0-100%). CONCLUSION: Adherence to the proposed recommendations for SBET use, notably the response to fever, was poor. If the use of SBET is to be pursued, modifications to the current SBET strategy should be considered, such as better selection of travellers at higher risk for malaria and the potential addition of mRDTs.