Overview of Smith-Magenis syndrome

Increased awareness of the phenotype associated with SMS permits early diagnosis and optimal management and intervention. From a management standpoint, the unique constellation of behavioral dysfunction and sleep disturbances has a significant impact on the parents, siblings and relatives of individuals with SMS as well as the professionals involved in their care. Support groups for families of persons with SMS like PRISMS in the US [http://www.prisms.org], provide families with up-to-date information, as well as emotional and peer support, enabling them to better care for their child.     

Requirements for a minimum standard of care for phenylketonuria: the patients’ perspective

Phenylketonuria (PKU, ORPHA716) is an inherited disorder that affects about one in every 10,000 children born in Europe. Early and continuous application of a modified diet is largely successful in preventing the devastating brain damage associated with untreated PKU. The management of PKU is inconsistent: there are few national guidelines, and these tend to be incomplete and implemented sporadically. In this article, the first-ever pan- European patient/carer perspective on optimal PKU care, the European Society for Phenylketonuria and Allied Disorders (E.S.PKU) proposes recommendations for a minimum standard of care for PKU, to underpin the development of new pan-European guideline for the management of PKU. New standards of best practice should guarantee equal access to screening, treatment and monitoring throughout Europe. Screening protocols and interpretation of screening results should be standardised. Experienced Centres of Expertise are required, in line with current European Union policy, to guarantee a defined standard of multidisciplinary treatment and care for all medical and social aspects of PKU. Women of childbearing age require especially intensive management, due to the risk of severe risks to the foetus conferred by uncontrolled PKU. All aspects of treatment should be reimbursed to ensure uniform access across Europe to guideline-driven, evidence-based care. The E.S.PKU urges PKU healthcare professionals caring for people with PKU to take the lead in developing evidence based guidelines on PKU, while continuing to play an active role in serving as the voice of patients and their families, whose lives are affected by the condition.     

Hyperthyroidism and Other Causes of Thyrotoxicosis: Management Guidelines of the American Thyroid Association and American Association of Clinical Endocrinologists

ObjectiveThyrotoxicosis has multiple etiologies, manifestations, and potential therapies. Appropriate treatment requires an accurate diagnosis and is influenced by coexisting medical conditions and patient preference. This article describes evidence-based clinical guidelines for the management of thyrotoxicosis that would be useful to generalist and subspeciality physicians and others providing care for patients with this condition.MethodsThe development of these guidelines was commissioned by the American Thyroid Association in association with the American Association of Clinical Endocrinologists. The American Thyroid Association and American Association of Clinical Endocrinologists assembled a task force of expert clinicians who authored this report. The task force examined relevant literature using a systematic PubMed search supplemented with additional published materials. An evidence-based medicine approach that incorporated the knowledge and experience of the panel was used to develop the text and a series of specific recommendations. The strength of the recommendations and the quality of evidence supporting each was rated according to the approach recommended by the Grading of Recommendations, Assessment, Development, and Evaluation Group.ResultsClinical topics addressed include the initial evaluation and management of thyrotoxicosis; management of Graves’ hyperthyroidism using radioactive iodine, antithyroid drugs, or surgery; management of toxic multinodular goiter or toxic adenoma using radioactive iodine or surgery; Graves’ disease in children, adolescents, or pregnant patients; subclinical hyperthyroidism; hyperthyroidism in patients with Graves’ ophthalmopathy; and management of other miscellaneous causes of thyrotoxicosis.ConclusionsOne hundred evidence-based recommendations were developed to aid in the care of patients with thyrotoxicosis and to share what the task force believes is current, rational, and optimal medical practice.     

Physical illness in patients with severe mental disorders. II. Barriers to care, monitoring and treatment guidelines, plus recommendations at the system and individual level

Physical disorders are, compared to the general population, more prevalent in people with severe mental illness (SMI). Although this excess morbidity and mortality is largely due to modifiable lifestyle risk factors, the screening and assessment of physical health aspects remains poor, even in developed countries. Moreover, specific patient, provider, treatment and system factors act as barriers to the recognition and to the management of physical diseases in people with SMI. Psychiatrists can play a pivotal role in the improvement of the physical health of these patients by expanding their task from clinical psychiatric care to the monitoring and treatment of crucial physical parameters. At a system level, actions are not easy to realize, especially for developing countries. However, at an individual level, even simple and very basic monitoring and treatment actions, undertaken by the treating clinician, can already improve the problem of suboptimal medical care in this population. Adhering to monitoring and treatment guidelines will result in a substantial enhancement of physical health outcomes. Furthermore, psychiatrists can help educate and motivate people with SMI to address their suboptimal lifestyle, including smoking, unhealthy diet and lack of exercise. The adoption of the recommendations presented in this paper across health care systems throughout the world will contribute to a significant improvement in the medical and related psychiatric health outcomes of patients with SMI.     

Accuracy of diagnostic registers and management of chronic obstructive pulmonary disease: the Devon primary care audit

Background

Guidelines on COPD diagnosis and management encourage primary care physicians to detect the disease at an early stage and to treat patients according to their condition and needs. Problems in guideline implementation include difficulties in diagnosis, using spirometry and the disputed role of reversibility testing. These lead to inaccurate diagnostic registers and inadequacy of administered treatments. This study represents an audit of COPD diagnosis and management in primary care practices in Devon.

Methods

Six hundred and thirty two patients on COPD registers in primary care practices were seen by a visiting Respiratory Specialist Nurse. Diagnoses were made according to the NICE guidelines. Reversibility testing was carried out either routinely or based on clinical indication in two sub-samples. Dyspnoea was assessed. Data were entered into a novel IT-based software which computed guideline-based treatment recommendations. Current and recommended treatments were compared.

Results

Five hundred and eighty patients had spirometry. Diagnoses of COPD were confirmed in 422 patients (73%). Thirty nine patients were identified as asthma only, 94 had normal spirometry, 23 were restrictive and 2 had a cardiac disorder. Reversibility testing changed diagnosis of 11% of patients with airflow obstruction, and severity grading in 18%. Three quarters of patients with COPD had been offered practical help with smoking cessation. Short and long-acting anticholinergics and long acting beta-2 agonists had been under-prescribed; in 15–18% of patients they were indicated but not received. Inhaled steroids had been over-prescribed (recommended in 17%; taken by 60%), whereas only 4% of patients with a chronic productive cough were receiving mucolytics. Pulmonary rehabilitation was not available in some areas and was under-used in other areas.

Conclusion

Diagnostic registers of COPD in primary care contain mistakes leading to inaccurate prevalence estimates and inappropriate treatment decisions. Use of pre-bronchodilator readings for diagnosis overestimates the prevalence and severity in a significant minority, thus post bronchodilator readings should be used. Management of stable COPD does often not correspond to guidelines. The IT system used in this study has the potential to improve diagnosis and management of COPD in primary care.     

18F]FHPG positron emission tomography for detection of herpes simplex virus (HSV) in experimental HSV encephalitis

Herpes simplex virus type 1 (HSV-1) is one of the most common causes of sporadic encephalitis. The initial clinical course of HSV encephalitis (HSE) is highly variable, and the infection may be rapidly fatal. For effective treatment with antiviral medication, an early diagnosis of HSE is crucial. Subtle brain infections with HSV may be causally related to neuropsychiatric disorders such as Alzheimer's dementia. We investigated the feasibility of a noninvasive positron emission tomography (PET) imaging technique using [(18)F]FHPG as a tracer for the detection of HSE. For this purpose, rats received HSV-1 (infected group) or phosphate-buffered saline (control group) by intranasal application, and dynamic PET scans were acquired. In addition, the distribution of tracer accumulation in specific brain areas was studied with phosphor storage imaging. The PET images revealed that the overall brain uptake of [(18)F]FHPG was significantly higher for the infected group than for control animals. Phosphor storage images showed an enhanced accumulation of [(18)F]FHPG in regions known to be affected after intranasal infection with HSV. High-performance liquid chromatography metabolite analysis showed phosphorylated metabolites of [(18)F]FHPG in infected brains, proving that the increased [(18)F]FHPG uptake in infected brains was due to HSV thymidine kinase-mediated trapping. Freeze lesion experiments showed that damage to the blood-brain barrier could in principle induce elevated [(18)F]FHPG uptake, but this nonspecific tracer uptake could easily be discriminated from HSE-derived uptake by differences in the tracer kinetics. Our results show that [(18)F]FHPG PET is a promising tool for the detection of HSV encephalitis.     

“A Massive Long Way”: Interconnecting Histories, a “Special Child,” ADHD, and Everyday Family Life

Focusing on one family from a study of dual-earner middle-class families carried out in Los Angeles, California, this article draws on interview and video-recorded data of everyday interactions to explore illness and healing as embedded in the microcultural context of the Morris family. For this family, an important aspect of what is at stake for them in their daily lives is best understood by focusing on 9-year-old Mark, who has been diagnosed with attention-deficit/hyperactivity disorder (ADHD). In this article, we grapple with the complexity of conveying some sense of how Mark’s condition is experienced and relationally enacted in everyday contexts. Through illuminating connections between lives as lived and lives as told, we explore the narrative structuring of healing in relation to Mark’s local moral world with the family at its center. We examine how his parents understand the moral consequences of the child’s past for his present and future, and work to encourage others to give due weight to his troubled beginnings before this child joined the Morris family. At the same time, we see how the Morris parents act to structure Mark’s moral experience and orient to a desired future in which Mark’s “success” includes an appreciation of how he is accountable to others for his actions. Through our analyses, we also seek to contribute to discussions on what is at stake in everyday life contexts for children with ADHD and their families, through illuminating aspects of the cultural, moral and relational terrain that U.S. families navigate in contending with a child’s diagnosis of ADHD. Further, given that ADHD is often construed as a “disorder of volition,” we seek to advance anthropological theorizing about the will in situations where volitional control over behavior is seen to be disordered.     

Diagnostics for herpes simplex virus: is PCR the new gold standard?

Herpes simplex virus (HSV) is one of the most common, yet frequently overlooked, sexually transmitted infections. Since the type of HSV infection affects prognosis and subsequent counseling, type-specific testing to distinguish HSV-1 from HSV-2 is recommended. Although PCR has been the diagnostic standard for HSV infections of the central nervous system, until now viral culture has been the test of choice for HSV genital infection. However, HSV PCR, with its consistently and substantially higher rate of HSV detection, will likely replace viral culture as the gold standard for the diagnosis of genital herpes in people with active mucocutaneous lesions, regardless of anatomic location or viral type. Alternatively, type-specific serologic tests based on glycoprotein G should be the test of choice to establish the diagnosis of HSV infection when no active lesion is present. Given the difficulty in making the clinical diagnosis of HSV, the growing worldwide prevalence of genital herpes and the availability of effective antiviral therapy, there is an increased demand for rapid, accurate laboratory diagnosis of patients with HSV.     

Xeroderma pigmentosum family support group: Helping families and promoting clinical initiatives

The past two decades of research into Xeroderma pigmentosum (XP), an autosomal recessive disease, has been marked by significant progress in understanding the molecular basis of this rare disease. More importantly, especially from the perspective of the affected families, is that this knowledge has been applied to diagnose the condition both in utero as well as in the very early days of life. The eight known XP genes and their different phenotypes present a number of challenges that the XP Workshop sponsored by the NIH in 2010 has highlighted. There is little current treatment specifically designed for any of the XP types other than standard dermatological and neurological evaluations and care. The Xeroderma Pigmentosum Family Support Group (XPFSG) is dedicated to serving families with children and adults with all forms of XP and to help them better understand the condition, to identify practical measures which can be taken by the XP patients and their families to mitigate the effects of the disease, and to serve as patient advocates to help families discuss issues with their physicians. We summarize our efforts in terms of outreach within the US and abroad to affected families and discuss XPFSG-sponsored clinical initiatives that include molecular diagnoses, treatment, and initial proof-of-concept studies that can, if successful, improve the lives of XP patients in the near term.     

Differential Reliance on Autophagy for Protection from HSV Encephalitis between Newborns and Adults

Newborns are more susceptible to severe disease from infection than adults, with maturation of immune responses implicated as a major factor. The type I interferon response delays mortality and limits viral replication in adult mice in a model of herpes simplex virus (HSV) encephalitis. We found that intact type I interferon signaling did not control HSV disease in the neonatal brain. However, the multifunctional HSV protein γ34.5 involved in countering type I interferon responses was important for virulence in the brain in both age groups. To investigate this observation further, we studied a specific function of γ34.5 which contributes to HSV pathogenesis in the adult brain, inhibition of the cellular process of autophagy. Surprisingly, we found that the beclin binding domain of γ34.5 responsible for inhibiting autophagy was dispensable for HSV disease in the neonatal brain, as infection of newborns with the deletion mutant decreased time to mortality compared to the rescue virus. Additionally, a functional beclin binding domain in HSV γ34.5 did not effectively inhibit autophagy in the neonate, unlike in the adult. Type I IFN responses promote autophagy in adult, a finding we confirmed in the adult brain after HSV infection; however, in the newborn brain we observed that autophagy was activated through a type I IFN-independent mechanism. Furthermore, autophagy in the wild-type neonatal mouse was associated with increased apoptosis in infected regions of the brain. Observations in the mouse model were consistent with those in a human case of neonatal HSV encephalitis. Our findings reveal age-dependent differences in autophagy for protection from HSV encephalitis, indicating developmental differences in induction and regulation of this innate defense mechanism after HSV infection in the neonatal brain.     

Multiplex real-time PCR for the simultaneous detection of herpes simplex virus, human herpesvirus 6, and human herpesvirus 7

A simultaneous detection system to quantify HSV, HHV-6, and HHV-7 DNA via multiplex real-time PCR using different fluorochromes was developed. The minimum quantitative level established via this multiplex assay was four copies per reaction for HSV type 1, four copies for HHV-6, and three copies for HHV-7, respectively. The dynamic range encompassed at least six orders of magnitude. The system was specific and reproducible even in the presence of large amounts of other viral DNA. We then applied this multiplex real-time PCR assay to 105 CSF specimens obtained from subjects less than 15 years old in whom a diagnosis of viral encephalitis/encephalopathy was suspected on clinical grounds. The detection rate for each viral DNA was 6.7% for HSV, 9.5% for HHV-6, and 1.9% for HHV-7. These results indicate that our system is reliable and may be useful for the rapid diagnosis of viral encephalitis/encephalopathy.     

Weiqu,structural injustice and caring for sick older people in rural Chinese families: An empirical ethical study

This paper examines caregiving for sick older family members in the context of socio-economic transformations in rural China, combining empirical investigation with normative inquiry. The empirical part of this paper is based on a case study, taken from fieldwork in a rural Chinese hospital, of a son who took care of his hospitalized mother. This empirical study highlighted family members’ weiqu (sense of unfairness)—a mental status from experiencing mistreatment and oppression in family care, yet with constrained power to explicitly protest or make care-related choices. Underpinning people’s weiqu and constrained choice, as informed by the conception of structural injustice, is the impact of unjust social structures, organized by unfavourable norms, discriminatory social policies and institutions targeting rural populations. By restraining individual choices and capacities in supporting health care for aging populations, these unjust structures create additional difficulties for and discriminations against rural families and their older members. Some policy recommendations are proposed to mitigate structural injustice so as to empower families and promote care for older people in rural settings.     

Effects of childhood cancer on long-term survivors and their families.

Problems experienced by families of long-term survivors of acute lymphatic leukaemia and Wilms''s tumour were investigated to find out the best way of using limited resources to improve management of such patients. All patients had received treatment at Alder Hey Children''s Hospital, and all had completed treatment at least two years before the study. A social worker interviewed the parents of each child. The results showed that various aspects of management needed improvement, including: information given to parents at diagnosis of their child''s illness and during subsequent treatment; continuity of care and multidisciplinary teamwork among those caring for the child; greater understanding by school teachers that such children have the same educational needs as others; wider communication by hospital staff with the child''s other relatives, particularly grandparents; financial help for parents; and marital counselling. To help implement these proposals full-time social workers were attached to the hospital. Preliminary results were encouraging, though it is too early to evaluate the long-term effects of the changes.     

EGFR inhibition for metastasized cutaneous squamous cell carcinoma in dystrophic epidermolysis bullosa

The ACTA2 gene encodes for smooth muscle specific α-actin, a critical component of the contractile apparatus of the vascular smooth muscle cell. Pathogenic variants in the ACTA2 gene are the most frequently encountered genetic cause of non-syndromic hereditary thoracic aortic disease (HTAD). Although thoracic aortic aneurysm and/or dissection is the main clinical manifestation, a variety of occlusive vascular disease and extravascular manifestations occur in ACTA2-related vasculopathy. Current data suggest possible mutation-specific manifestations of vascular and extra-aortic traits.

Despite its relatively high prevalence, comprehensive recommendations on the care of patients and families with pathogenic variants in ACTA2 have not yet been established. We aimed to develop a consensus document to provide medical guidance for health care professionals involved in the diagnosis and treatment of patients and relatives with pathogenic variants in ACTA2.

The HTAD Working Group of the European Reference Network for Rare Vascular Diseases (VASCERN) convened to review current literature and discuss expert opinions on clinical management of ACTA2 related vasculopathy. This consensus statement summarizes our recommendations on diagnosis, monitoring, treatment, pregnancy, genetic counselling and testing in patients with ACTA2-related vasculopathy. However, there is a clear need for additional prospective multicenter studies to further define proper guidelines.

     

Report of the Canadian Hypertension Society's consensus conference on the management of mild hypertension.

Since the publication in 1977 of joint recommendations by the Canadian Cardiovascular Society, the Canadian Heart Foundation and the Ontario Council of Health on the detection and management of hypertension in Canada, several clinical trials on the efficacy of antihypertensive drug treatment in patients with mild hypertension have been undertaken. The Canadian Hypertension Society (CHS) felt that the results of these trials should be reviewed to determine whether existing recommendations on treatment should be changed. Three expert panels appointed by the CHS reviewed evidence on the clinical efficacy of antihypertensive therapy, the diagnosis of hypertension and the treatment of mild hypertension, and formulated recommendations on the care of mildly hypertensive patients in Canada. A consensus conference of biomedical scientists, practising physicians and government representatives reviewed and reached agreement on the panels'' recommendations. The final recommendations of the conference are presented in this report.     

Comparison of real-time and nested PCR assays for detection of herpes simplex virus DNA

We performed a real-time PCR assay to detect herpes simplex virus (HSV) DNA, and compared it prospectively with a nested PCR assay in 164 clinical samples (109 cerebrospinal fluid and 55 sera) from patients suspected of having neonatal HSV infection or HSV encephalitis. In 25 of 164 samples, HSV DNA was detected by the nested PCR assay. All samples positive for HSV DNA in the nested PCR assay were also positive in the real-time PCR assay, and all but two samples negative for HSV DNA in the nested assay were negative in the real-time assay. The real-time PCR assay thus had a sensitivity of 100% and a specificity of 99%, when compared with the nested assay. Sequential assays in a case of disseminated HSV showed that a decrease in HSV DNA paralleled clinical improvement. Quantification of HSV DNA by real-time PCR was useful for diagnosing and monitoring patients with HSV encephalitis and neonatal HSV infection.     

Protection against discrimination in national dementia guideline recommendations: A systematic review

BackgroundNational dementia guidelines provide recommendations about the most effective approaches to diagnosis and interventions. Guidelines can improve care, but some groups such as people with minority characteristics may be disadvantaged if recommended approaches are the same for everyone. It is not known if dementia guidelines address specific needs related to patient characteristics. The objectives of this review are to identify which countries have national guidelines for dementia and synthesise recommendations relating to protected characteristics, as defined in the UK Equality Act 2010: age, disability, gender identity, marriage and civil partnership, pregnancy and maternity, race, religion or belief, sex, and sexual orientation.Methods and findingsWe searched CINAHL, PsycINFO, and Medline databases and the Guideline International Network library from inception to March 4, 2020, for dementia guidelines in any language. We also searched, between April and September 2020, Google and the national health websites of all 196 countries in English and in each country’s official languages. To be included, guidelines had to provide recommendations about dementia, which were expected to be followed by healthcare workers and be approved at a national policy level. We rated quality according to the iCAHE guideline quality checklist. We provide a narrative synthesis of recommendations identified for each protected characteristic, prioritising those from higher-quality guidelines. Forty-six guidelines from 44 countries met our criteria, of which 18 were rated as higher quality. Most guidelines (39/46; 85%) made at least one reference to protected characteristics, and we identified recommendations relating to age, disability, race (or culture, ethnicity, or language), religion, sex, and sexual orientation. Age was the most frequently referenced characteristic (31/46; 67%) followed by race (or culture, ethnicity, or language; 25/46; 54%). Recommendations included specialist investigation and support for younger people affected by dementia and consideration of culture when assessing whether someone had dementia and providing person-centred care. Guidelines recommended considering religion when providing person-centred and end-of-life care. For disability, it was recommended that healthcare workers consider intellectual disability and sensory impairment when assessing for dementia. Most recommendations related to sex recommended not using sex hormones to treat cognitive impairment in men and women. One guideline made one recommendation related to sexual orientation. The main limitation of this study is that we only included national guidelines applicable to a whole country meaning guidelines from countries with differing healthcare systems within the country may have been excluded.ConclusionsNational guidelines for dementia vary in their consideration of protected characteristics. We found that around a fifth of the world’s countries have guidelines for dementia. We have identified areas of good practice that can be considered for future guidelines and suggest that all guidelines provide specific evidence-based recommendations for minority groups with examples of how to implement them. This will promote equity in the care of people affected by dementia and help to ensure that people with protected characteristics also have high-quality clinical services.

Tiffeny James and team investigate which countries have national guidelines for dementia, and synthesise recommendations relating to protected characteristics as defined in the UK Equality Act 2010.     

Encephalitis resulting from reactivation of latent herpes simplex virus in mice.

Herpes simplex virus (HSV) encephalitis was produced in mice from reactivation of latent virus. Two experimental models were used: the trigeminal model after corneal inoculation of HSV, and the hypoglossal model after tongue inoculation of HSV. In the trigeminal model, cyclophosphamide treatment induced reactivation of latent virus in ganglia but not in central nervous system tissue. Spread of the reactivated virus from ganglia to brain occurred only in mice deficient in anti-HSV antibody. In the hypoglossal model, sectioning of the hypoglossal nerve provoked chromatolysis in the corresponding central nervous system motor neurons and occasionally reactivated latent HSV in the brains of mice. These results suggest that HSV encephalitis can result from the spread of reactivated virus from ganglia to brain and also from in situ reactivation in brain.     

Oral implants in dependent elderly persons: blessing or burden?

doi:10.1111/j.1741‐2358.2009.00314.x
Oral implants in dependent elderly persons: blessing or burden? Background: Implant‐supported (partial) dentures may raise problems in patients who have become dependent on others for daily oral health care. Dental hygienists and general dental practitioners, as well as care providers, volunteer aiders and even health care insurance companies, should anticipate the growing demand for specific oral health care for patients provided with implant‐supported (partial) dentures. Objective: To report three cases of dependent patients and to present recommendations to prevent or resolve implant‐related oral problems. Materials and methods: The three case reports are demonstrating that implant insertion in (dependent) elderly people needs careful consideration. Discussion: When considering implant treatment, some questions should be raised: (1) Is the treatment appropriate in contributing to the patient’s well‐being and quality of life? (2) Is the treatment the most suitable treatment? (3) Does the treatment integrate with the patient’s oral health care plan? (4) Is the patient sufficiently cooperative? (5) Is the patient supported by a well‐functioning oral (self) care assisting network? (6) Is it possible for the patient to regular see an oral health care professional and is oral health care easily accessible in cases of an emergency? Conclusion: Dependent elderly people can benefit from oral implants, providing that adequate oral health care and aftercare can be provided. When indicated, removal of the anchorage structure is easily performed by putting the implants to sleep. All implant patients should be provided with an ‘implant passport’. Regular information and instruction for care providers about the oral condition of the patient are essential.