Shaping the risk for late-life neurodegenerative disease: A systematic review on prenatal risk factors for Alzheimer's disease-related volumetric brain biomarkers.

Environmental exposures including toxins and nutrition may hamper the developing brain in utero, limiting the brain's reserve capacity and increasing the risk for Alzheimer's disease (AD). The purpose of this systematic review is to summarize all currently available evidence for the association between prenatal exposures and AD-related volumetric brain biomarkers. We systematically searched MEDLINE and Embase for studies in humans reporting on associations between prenatal exposure(s) and AD-related volumetric brain biomarkers, including whole brain volume (WBV), hippocampal volume (HV) and/or temporal lobe volume (TLV) measured with structural magnetic resonance imaging (PROSPERO; CRD42020169317). Risk of bias was assessed using the Newcastle Ottawa Scale. We identified 79 eligible studies (search date: August 30th, 2020; Ntotal=24,784; median age 10.7 years) reporting on WBV (N = 38), HV (N = 63) and/or TLV (N = 5) in exposure categories alcohol (N = 30), smoking (N = 7), illicit drugs (N = 14), mental health problems (N = 7), diet (N = 8), disease, treatment and physiology (N = 10), infections (N = 6) and environmental exposures (N = 3). Overall risk of bias was low. Prenatal exposure to alcohol, opioids, cocaine, nutrient shortage, placental dysfunction and maternal anemia was associated with smaller brain volumes. We conclude that the prenatal environment is important in shaping the risk for late-life neurodegenerative disease.

A validated Screening instrument for Child Abuse and Neglect (SCAN) at the emergency department.

The objective of this study is to develop and validate a screening instrument for the recognition of child maltreatment in the emergency department (ED). Existing data on screening questions and outcomes (diagnosis of child maltreatment) from three large observational screening studies at eight different EDs in the Netherlands were harmonized. A multivariate logistic regression was performed to develop the Screening instrument for Child Abuse and Neglect (SCAN). The SCAN was validated by performing a cross-validation and calculating the discriminative ability. A total of 24,963 patients were included. Out of the potential screening questions the following questions were included in the final instrument: is the injury compatible with the history, and does it correspond to the child's developmental level? (aOR 10.40, 95% CI 5.69-19.02), was there an unnecessary delay in seeking medical help? (aOR 3.45, 95% CI 1.73-6.88) and is the behaviour/interaction of the child and parents (carers) appropriate? (aOR 14.67, 95% CI 7.93-27.13). The SCAN had a pooled AUC of 0.75 (95% CI 0.63-0.87) in the cross-validation. The question "Are there other signals that make you doubt the safety of the child and/or family?" (available in only one of the original datasets, OR 182.9; 95% CI 102.3-327.4) was by consensus added to the final SCAN. CONCLUSION: This validated and brief Screening instrument for Child Abuse and Neglect (SCAN) is designed to improve early recognition of child maltreatment in the ED. A positive screening result of the SCAN warrants a thorough work-up for child maltreatment, including a top-toe examination, if necessary additional diagnostics and adequate safety measures. WHAT IS KNOWN: • Screening instruments increase the detection of possible cases of child maltreatment in the emergency department and support health care professionals to identify these cases. • The application of different screening instruments led to the need for one brief validated instrument. WHAT IS NEW: • This study presents a validated and brief Screening instrument for Child Abuse and Neglect (SCAN), consisting of four questions. • The SCAN supports professionals in detecting signals of child maltreatment, and a positive screening result should lead to a thorough work-up, including a top-toe examination, complete history, additional diagnostic tests and consultation of a child abuse expert.

Classifying atopic dermatitis: a systematic review of phenotypes and associated characteristics.

Atopic dermatitis is a heterogeneous disease, accompanied by a wide variation in disease presentation and the potential to identify many phenotypes that may be relevant for prognosis and treatment. We aimed to systematically review previously reported phenotypes of atopic dermatitis and any characteristics associated with them. Ovid EMBASE, Ovid MEDLINE and Web of Science were searched from inception till 12 February 2021 for studies attempting to classify atopic dermatitis. Primary outcomes are atopic dermatitis phenotypes and characteristics associated with them in subsequent analyses. A secondary outcome is the methodological approach used to derive them. In total, 8511 records were found. By focussing only on certain clinical phenotypes, 186 studies were eligible for inclusion. The majority of studies were hospital-based (59%, 109/186) and cross-sectional (76%, 141/186). The number of included patients ranged from seven to 526 808. Data-driven approaches to identify phenotypes were only used in a minority of studies (7%, 13/186). Ninety-one studies (49%) investigated a phenotype based on disease severity. A phenotype based on disease trajectory, morphology and eczema herpeticum was investigated in 56 (30%), 22 (12%) and 11 (6%) studies respectively. Thirty-six studies (19%) investigated morphological characteristics in other phenotypes. Investigated associated characteristics differed between studies. In conclusion, we present an overview of phenotype definitions used in literature for severity, trajectory, morphology and eczema herpeticum, including associated characteristics. There is a lack of uniform and consistent use of atopic dermatitis phenotypes across studies.

The Dutch Multidisciplinary Occupational Health Guideline to Enhance Work Participation Among Low Back Pain and Lumbosacral Radicular Syndrome Patients.

Purpose Based on current scientific evidence and best practice, the first Dutch multidisciplinary practice guideline for occupational health professionals was developed to stimulate prevention and enhance work participation in patients with low back pain (LBP) and lumbosacral radicular syndrome (LRS). Methods A multidisciplinary working group with health care professionals, a patient representative and researchers developed the recommendations after systematic review of evidence about (1) Risk factors, (2) Prevention, (3) Prognostic factors and (4) Interventions. Certainty of the evidence was rated with GRADE and the Evidence to Decision (EtD) framework was used to formulate recommendations. High or moderate certainty resulted in a recommendation "to advise", low to very low in a recommendation "to consider", unless other factors in the framework decided differently. Results An inventory of risk factors should be considered and an assessment of prognostic factors is advised. For prevention, physical exercises and education are advised, besides application of the evidence-based practical guidelines "lifting" and "whole body vibration". The stepped-care approach to enhance work participation starts with the advice to stay active, facilitated by informing the worker, reducing workload, an action plan and a time-contingent increase of work participation for a defined amount of hours and tasks. If work participation has not improved within 6 weeks, additional treatments should be considered based on the present risk and prognostic factors: (1) physiotherapy or exercise therapy; (2) an intensive workplace-oriented program; or (3) cognitive behavioural therapy. After 12 weeks, multi-disciplinary (occupational) rehabilitation therapy need to be considered. Conclusions Based on systematic reviews and expert consensus, the good practice recommendations in this guideline focus on enhancing work participation among workers with LBP and LRS using a stepped-care approach to complement existing guidelines focusing on recovery and daily functioning.

Developing trustworthy recommendations as part of an urgent response (1-2 weeks): a GRADE concept paper.

OBJECTIVES: The aim of this study is to propose an approach for developing trustworthy recommendations as part of urgent responses (1-2 week) in the clinical, public health, and health systems fields. STUDY DESIGN AND SETTING: We conducted a review of the literature, outlined a draft approach, refined the concept through iterative discussions, a workshop by the Grading of Recommendations Assessment, Development and Evaluation Rapid Guidelines project group, and obtained feedback from the larger Grading of Recommendations Assessment, Development and Evaluation working group. RESULTS: A request for developing recommendations within 2 week is the usual trigger for an urgent response. Although the approach builds on the general principles of trustworthy guideline development, we highlight the following steps: (1) assess the level of urgency; (2) assess feasibility; (3) set up the organizational logistics; (4) specify the question(s); (5) collect the information needed; (6) assess the adequacy of identified information; (7) develop the recommendations using one of the 4 potential approaches: adopt existing recommendations, adapt existing recommendations, develop new recommendations using existing adequate systematic review, or develop new recommendations using expert panel input; and (8) consider an updating plan. CONCLUSION: An urgent response for developing recommendations requires building a cohesive, skilled, and highly motivated multidisciplinary team with the necessary clinical, scientific, and methodological expertise; adapting to shifting needs; complying with the principles of transparency; and properly managing conflicts of interest.

European guidelines on achalasia: United European Gastroenterology and European Society of Neurogastroenterology and Motility recommendations.

INTRODUCTION: Achalasia is a primary motor disorder of the oesophagus characterised by absence of peristalsis and insufficient lower oesophageal sphincter relaxation. With new advances and developments in achalasia management, there is an increasing demand for comprehensive evidence-based guidelines to assist clinicians in achalasia patient care. METHODS: Guidelines were established by a working group of representatives from United European Gastroenterology, European Society of Neurogastroenterology and Motility, European Society of Gastrointestinal and Abdominal Radiology and the European Association of Endoscopic Surgery in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. A systematic review of the literature was performed, and the certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Recommendations were voted upon using a nominal group technique. RESULTS: These guidelines focus on the definition of achalasia, treatment aims, diagnostic tests, medical, endoscopic and surgical therapy, management of treatment failure, follow-up and oesophageal cancer risk. CONCLUSION: These multidisciplinary guidelines provide a comprehensive evidence-based framework with recommendations on the diagnosis, treatment and follow-up of adult achalasia patients.

Evaluation and treatment of functional constipation in infants and children: evidence-based recommendations from ESPGHAN and NASPGHAN.

BACKGROUND: Constipation is a pediatric problem commonly encountered by many health care workers in primary, secondary, and tertiary care. To assist medical care providers in the evaluation and management of children with functional constipation, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the European Society for Pediatric Gastroenterology, Hepatology, and Nutrition were charged with the task of developing a uniform document of evidence-based guidelines. METHODS: Nine clinical questions addressing diagnostic, therapeutic, and prognostic topics were formulated. A systematic literature search was performed from inception to October 2011 using Embase, MEDLINE, the Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials, and PsychInfo databases. The approach of the Grading of Recommendations Assessment, Development and Evaluation was applied to evaluate outcomes. For therapeutic questions, quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. Grading the quality of evidence for the other questions was performed according to the classification system of the Oxford Centre for Evidence-Based Medicine. During 3 consensus meetings, all recommendations were discussed and finalized. The group members voted on each recommendation, using the nominal voting technique. Expert opinion was used where no randomized controlled trials were available to support the recommendation. RESULTS: This evidence-based guideline provides recommendations for the evaluation and treatment of children with functional constipation to standardize and improve their quality of care. In addition, 2 algorithms were developed, one for the infants <6 months of age and the other for older infants and children. CONCLUSIONS: This document is intended to be used in daily practice and as a basis for further clinical research. Large well-designed clinical trials are necessary with regard to diagnostic evaluation and treatment.

Lack of evidence to support policy development for management of contacts of multidrug-resistant tuberculosis patients: two systematic reviews.

BACKGROUND: Existing international guidelines provide different recommendations for the management of contacts of multidrug-resistant tuberculosis (MDR-TB) patients. OBJECTIVE: To conduct two systematic reviews with the aim of identifying chemoprophylactic approaches that are effective in contacts of MDR-TB patients to assist in policy making. DESIGN: We systematically searched the Medline, Embase, Central, LILACS, TRIP and BIOSIS Preview databases for studies on the effectiveness of anti-tuberculosis drugs in preventing active TB in persons at risk of developing MDR-TB. This was done as an update of a systematic review from 2006 using the same methodology. In addition, we searched for studies including persons at risk of developing TB after exposure to non-MDR-TB patients who were treated with anti-tuberculosis drugs other than isoniazid or rifampicin. RESULTS: Of 1195 references assessed in the update, one additional study could be included. As the initial review included two studies, the total number of included studies equals three. One study reported no contacts who developed TB, whether or not they received prophylaxis. The other two studies showed non-significant risk differences of 4% (95%CI -3 to 12), and 5% (95%CI -2 to 11), both in favour of chemoprophylaxis. For the additional review, 2480 references were assessed, but none could be included. CONCLUSION: The attention given to MDR-TB in recent years has not resulted in publications on preventive treatment for contacts of MDR-TB patients. The available evidence is not sufficient to support or reject preventive treatment. Furthermore, the combined available evidence is of very low quality.

Prevalence of inappropriate tuberculosis treatment regimens: a systematic review.

A potential threat to the success of new tuberculosis (TB) drugs is the development of resistance. Using drugs in appropriate regimens, such as those recommended in the World Health Organization (WHO) treatment guidelines, prevents the development of resistance. We performed a systematic review to assess the prevalence of inappropriate prescription of TB drugs for the treatment of TB. MEDLINE, EMBASE and other databases were searched for relevant articles in January 2011. Observational studies published from 2000 that included TB patients receiving treatment were selected. A treatment regimen was considered inappropriate if the regimen was not a WHO recommended regimen. 37 studies were included. Inappropriate treatment regimens were prescribed in 67% of studies. The percentage of patients receiving inappropriate regimens varied between 0.4% and 100%. In 19 studies the quality of treatment regimen reporting was low. Despite the fact that assessment of inappropriate treatment was hampered by low quality of reporting, our data indicate a reasonable amount of inappropriate prescription of TB treatment regimens. Thus, there is a risk that new drugs will be used in inappropriate treatment regimens, even with WHO guidelines in place, introducing the risk of resistance development. This article highlights the need to improve implementation of the WHO treatment of TB guidelines.

[The increase in the use of drug treatment for diabetes mellitus in the Netherlands, 1998-2003]. / Toenemend gebruik van geneesmiddelen voor diabetes mellitus in Nederland, 1998-2003.

OBJECTIVE: To describe trends in the use of diabetes treatment from 1998-2003 and to compare prescribing in daily practice with the practice guideline 'Diabetes mellitus type 2' issued by the Dutch College of General Practitioners. DESIGN: Descriptive. METHOD: Prescribing data over the period 1998-2003 were taken from the database of the Drug Information Project of the Dutch Health Care Insurance Board. The database contains information on drugs prescribed extramurally and dispensed either by pharmacists or dispensing general practitioners, and reimbursed by health insurance funds. The data are aggregated into volume and cost variables for the general population and individual users were identified to monitor individual use of the medication and co-medication over a period of time. RESULTS: From 1998-2003 the use of medication for treating diabetes in the Netherlands increased from 2.8% to 3.6%. There were 565,000 users of diabetes medication in 2003. The rate of prescription of oral blood-glucose lowering drugs increased more than that for insulin. The rate of concurrent use of an oral drug as well as insulin rose sharply as did the use of more than one type of oral drugs and the use of co-medication, notably cholesterol reducers. With respect to the guidelines, nearly all newly diagnosed type-2 diabetics were initially prescribed metformin or a sulfonamid-urea derivative. In one-third of new patients, a second drug was also prescribed, the combination most used was metformin or a sulfonamid-urea derivative. Combinations of three or more drugs were rarely prescribed. The total cost of diabetes treatment increased from euros 122 million to euros 183 million. The increased use of thiazolidinediones played an important role in this increase. CONCLUSION: The use of oral blood-glucose lowering drugs and thiazolidinediones specifically, increased rapidly between 1998-2003. Individual treatment became more intensive, due to increased use of co-medication, combination therapy and the combined use of insulin and oral drugs. The compliance rate with the general practitioners' practice guidelines was high.

Possibilities and barriers in the implementation of a preconceptional screening programme for cystic fibrosis carriers: a focus group study.

OBJECTIVE: This qualitative study aimed to explore possibilities and barriers in the implementation of a nationwide preconceptional cystic fibrosis (CF) carrier screening programme. METHODS: Sessions were held with two focus groups of CF patients and CF relatives, one focus group of people from the target population (couples planning a pregnancy), and two focus groups of potential providers (general practitioners (GPs) and municipal health service workers). RESULTS: Important barriers in the implementation of a preconceptional CF carrier screening programme included the problem of reaching the target population, the heavy workload of GPs, the limited public knowledge about CF in general, and the absence of a preconceptional consultation setting. In general, there was a positive attitude among the participants towards CF carrier screening. CONCLUSION: This study revealed some important barriers in the implementation of CF carrier screening programmes. More research is needed to specify and quantify the importance of the various barriers. Eventually, different intervention strategies should be included in an implementation plan to overcome the most important barriers in the organization and execution of screening.

The impact of harm-reduction-based methadone treatment on mortality among heroin users.

OBJECTIVES: The purpose of this study was to investigate the impact of harm-reduction-based methadone programs on mortality among heroin users. METHODS: A prospective cohort investigation was conducted among 827 participants in the Amsterdam Cohort Study. Poisson regression was used to identify methadone maintenance treatment characteristics (dosage, frequency of program attendance, and type of program) that are significantly and independently associated with mortality due to natural causes and overdose. RESULTS: From 1985 to 1996, 89 participants died of natural causes, and 31 died as a result of an overdose. After adjustment for HIV and underweight status, there was an increase in natural-cause mortality among subjects who left methadone treatment (relative risk [RR] = 2.38, 95% confidence interval [CI] = 1.28, 4.55). Leaving treatment was also related to higher overdose mortality, but only among injection drug users (RR = 4.55, 95% CI = 1.89, 10.00). CONCLUSIONS: Harm-reduction-based methadone treatment, in which the use of illicit drugs is tolerated, is strongly related to decreased mortality from natural causes and from overdoses. Provision of methadone in itself, together with social-medical care, appears more important than the actual methadone dosage.

[Shigellosis in Amsterdam, 1991-1998: incidence and results of contact tracing]. / Shigellose in Amsterdam, 1991-1998: vóórkomen en resultaten van contactonderzoek.

OBJECTIVE: To determine the incidence of reported shigellosis in Amsterdam (1991-1998) and the factors related to the secondary attack rate of shigellosis. DESIGN: Retrospective. METHODS: From an automated data bank data were collected on all registered shigellosis patients in Amsterdam in the period 1991-1998, and their contacts found by contact tracing. RESULTS: 567 Patients with shigellosis had been reported and a Shigella infection has been diagnosed in 96 of the 983 contacts. The annual incidence decreased statistically significantly from 13 to 8/100.000. 329 males and 334 females were infected. The highest number of cases was found in children from 0-4 years and among adults from 20-34 years. Of the 663 patients 106 (16%) required hospitalization; for children under 7 this proportion was 30% (32/108). Among the contacts (excluding the 14 contacts with the same foreign source and the same first sickness day as the index patient) the secondary attack rate was 8%. Young age, of both the patient and the contact was independently related to a higher secondary attack rate. CONCLUSION: With contact tracing for shigellosis a large number of secondary infections were found. Given the high infection rate and large number of hospitalisations among children, contact tracing should focus at this young age group.

Methadone maintenance and cessation of injecting drug use: results from the Amsterdam Cohort Study.

AIMS: To assess relationships between characteristics of methadone maintenance treatment and long-term cessation of injecting (> or = 1 year). DESIGN AND PARTICIPANTS: The incidence of cessation of injecting and relapse from non-injecting to injecting was estimated among 488 participants of the Amsterdam cohort study among drug users. We used a nested matched case-control design to identify methadone treatment characteristics significantly and independently related to cessation of injecting. To ensure detailed and valid assessment of methadone treatment, data of the Central Methadone Register were linked with cohort data. For 339 of 488 subjects of the initial study group methadone data were available. FINDINGS: The incidence of cessation of injecting increased from 2.2/100 person years in 1985-89 to 5.5/100 per year in 1995-97 (Ptrend = 0.005). Relapse to injecting was high: 17.2/100 person years (no trend). Methadone dosage and frequency of methadone programme attendance in themselves were not significantly related to cessation of injecting. However, an individual increase of 5 mg or more per year (OR 4.20, 95% CI 1.54-11.46) and receiving methadone mainly via the outpatient clinic for drug-abusing prostitutes and foreigners (OR 0.18, 95% CI 0.05-0.59) were independent predictors of cessation of injecting. After cessation of injecting, there were no HIV-seroconversions during the period of non-injecting (129 person years). After relapse to injecting there was one seroconverter; however, follow-up was small (23 person years). The HIV-incidence of those who continued injecting was 3.2/100 per year. CONCLUSIONS: Steadily increasing the methadone dosage in a harm reduction setting may be useful in supporting injecting drug users in the process of cessation of injecting and reducing the spread of HIV-infection.

Methadone maintenance treatment modalities in relation to incidence of HIV: results of the Amsterdam cohort study.

STUDY OBJECTIVE: To evaluate methadone maintenance treatment modalities, prescribed within the concept of harm reduction, in relation to incidence of HIV infection among drug users with a history of methadone treatment in Amsterdam, The Netherlands. DESIGN: Prospective observational cohort study among 582 HIV-negative drug users. To ensure valid and detailed assessment of methadone treatment, data from the Central Methadone Register in Amsterdam were linked to the Amsterdam cohort study among drug users. METHODS: Poisson regression analysis was used to identify independent and significant predictors of incidence of HIV. MAIN RESULTS: During 1906 person years, 58 drug users seroconverted, the overall incidence of HIV being 3.0 per 100 person years with a declining trend for current injectors. An increase in frequency of methadone programme attendance [relative risk (RR), 2.4; 95% confidence interval (CI), 1.2-4.6, compared with no change] and increase in methadone dosage (RR, 0.8; 95% CI, 0.6-1.0, per category of change of 10 mg/day) were significantly associated with incidence of HIV in multivariate analysis. Methadone dosage and frequency of programme attendance in itself were not significant predictors. Other multivariate significant risk factors were homelessness, current injecting and in-patient hospital care. CONCLUSIONS: Among drug users who receive methadone maintenance treatment in a harm-reduction setting, which includes ancillary services such as needle-exchange programmes and HIV testing and counselling, prescription of high methadone dosages is not sufficient to stop the spread of HIV. However, an individual increase of the methadone dosage and measures to achieve high treatment retention could contribute to the prevention of HIV among drug users.