Do parental perceptions and motivations towards genetic testing and prenatal diagnosis for deafness vary in different cultures?

Surveys of attitudes of individuals with deafness and their families towards genetic testing or prenatal diagnosis have mostly been carried out in the West. It is expected that the perceptions and attitudes would vary amongst persons of different cultures and economic background. There is little information on the prevailing attitudes for genetic testing and prenatal diagnosis for deafness in developing countries. Therefore, this study evaluates the motivations of Indian people with inherited hearing loss towards such testing. Twenty‐eight families with history of congenital hearing loss (23 hearing parents with child/family member with deafness, 4 couples with both partners having deafness and 1 parent and child with deafness) participated in a semi‐structured survey investigating their interest, attitudes, and intentions for using genetic and prenatal testing for deafness. Participants opinioned that proper management and care of individuals with deafness were handicapped by limited rehabilitation facilities with significant financial and social burden. Nineteen (68%) opted for genetic testing. Twenty‐six (93%) expressed high interest in prenatal diagnosis, while 19 (73%) would consider termination of an affected fetus. Three hearing couples, in whom the causative mutations were identified, opted for prenatal diagnosis. On testing, all the three fetuses were affected and the hearing parents elected to terminate the pregnancies. This study provides an insight into the contrasting perceptions towards hearing disability in India and its influence on the desirability of genetic testing and prenatal diagnosis. © 2012 Wiley Periodicals, Inc.     

The Akaike information criterion in DCE-MRI: does it improve the haemodynamic parameter estimates?

The Akaike information criterion and the associated Akaike weights (AW) rank pharmacokinetic models on the basis of goodness-of-fit and number of parameters. The usefulness of this information for improving the haemodynamic parameter estimates from DCE-MRI was investigated through two examples. In each of these, the estimates from the two-compartment exchange model (2CXM) were combined on the basis of the AW with those of a simplified model (either the uptake model or the extended Tofts model). Data were simulated using the 2CXM for a range of experimental and tissue conditions. Two multimodel approaches exploiting the AW were investigated: the ‘bestmodel’ approach which selects the parameter estimates from the model with highest AW and the ‘weighted model’ approach in which AW-weighted averages of the estimates from the competing models are calculated. Although these approaches were shown to be beneficial in some cases, they were found to frequently lead to unexpected increases in the bias and/or uncertainty of the resulting parameter estimates. Within the limited scope of this simulation study, the use of the Akaike criterion showed no systematic benefit over a fitting strategy involving only the more complex model.     

The validity of the diagnosis of depression in general practice: is using criteria for diagnosis as a routine the answer?

BACKGROUND: In general practice, making a diagnosis does not follow the same lines as in secondary care because every new diagnosis is made against 'foreknowledge' and could be coloured by it. This could explain low accordance and differences in diagnoses between primary and secondary care, in particular when mental illness such as depression is concerned. When criteria are used for diagnosis there should be no differences. AIM: To establish the accordance with the Diagnostic and Statistical Manual of mental disorders, 4th edition (DSM-IV) criteria of major depressive disorder when the diagnosis of depression has been made by general practitioners (GPs) for whom coding and using criteria for diagnosis is a daily routine (ICHPPC-2 criteria). METHOD: Ninety-nine general practice patients from four general practices belonging to the Continuous Morbidity Registry (CMR) of the University of Nijmegen in The Netherlands were interviewed using the Composite International Diagnostic Interview (auto) 12-month version (DSM-IV criteria). Thirty-three patients had a code for depression; 33 patients a code for chronic nervous functional complaints (CNFC); and 33 had no code for mental illness (the depression and CNFC codes were given in the 12 months prior to the interview). Specificity and accordance with the DSM-IV criteria of major depressive disorder (MDD) were calculated with the results from the interviews. RESULTS: Of the 33 general practice depression cases (all matching ICHPPC-2 criteria), 28 matched DSM-IV criteria: 26 for MDD and 2 for dysthymia. No cases of DSM-IV MDD were found in the control group without a code for a mental disorder, and seven out of 33 were found in the control group with the code for CNFC. CONCLUSION: The specificity of diagnosis of depression made by GPs in a continuous morbidity registry and the accordance with DSM-IV criteria are high. Using criteria for diagnosis, which is a trend, could be one of the solutions towards a better diagnosis. As far as the sensitivity is concerned, GPs should not be distracted from using criteria for the diagnosis of depression when a large variety of complaints is presented.     

How well does the CSF inform upon pathology in the brain in Creutzfeldt-Jakob and Alzheimer's diseases?

Analysis of lumbar cerebrospinal fluid (CSF) plays a major role in the investigation of central nervous system disease, but how well do the changes in the CSF reflect pathology within the brain and spinal cord parenchyma? Both Creutzfeldt-Jakob (CJD) and Alzheimer's disease (AD) are characterized by the deposition of insoluble beta-pleated sheet peptides [prion protein (PrP) and beta-amyloid (Abeta), respectively] in the extracellular spaces of grey matter in the brain, but there is discordance in both diseases between the peptide levels in the brain and in the CSF. Experimental studies using tracers have shown that interstitial fluid (ISF) drains through very narrow intercellular spaces within grey matter into bulk flow perivascular channels that surround penetrating arteries. ISF then flows to the surface of the brain and joins CSF to drain to cervical lymph nodes. Such drainage of ISF and CSF to regional lymph nodes in the rat plays a significant role in B-cell and T-cell immune reactions within the brain. In man, the pia mater separates the periarterial ISF drainage pathways from the CSF in the subarachnoid space. The almost complete lack of insoluble protease-resistant PrP entering the CSF from the brain in patients with CJD, reported by Wong et al. in this issue of the Journal of Pathology, illustrates the limitations of ISF drainage pathways for the elimination of insoluble peptides from brain tissue. Insoluble Abeta accumulates in the extracellular spaces as plaques in AD and in periarterial ISF drainage pathways as cerebral amyloid angiopathy. Soluble Abeta appears to become entrapped by the insoluble Abeta in the ISF drainage pathways; thus, as the level of soluble Abeta in the brain rises in AD, the level in the CSF falls. Thus, the changes in the CSF do not accurately reflect the accumulation of the abnormal peptides in the brain parenchyma in either CJD or AD. In both diseases, facilitation of ISF drainage and elimination of PrP and Abeta peptides from the extracellular spaces of the brain may lead to practical therapeutic strategies for these devastating disorders.     

Written information to patients in clinical genetics: what's the impact?

In all countries of the European Union, oral information must be given to the patient. Written information is generally optional, but physicians are tending more and more to send a copy of the clinical report to the patient. In this study, we aimed to evaluate the impact on patients of sending them written information after a clinical consultation in a French genetics department. During a period of three months, two geneticists and one genetic counselor offered to send each patient a copy of the letter sent to their general practitioners. A questionnaire was sent with this copy. Three hundred and seventy-five patients were seen and 64% of the questionnaires were sent back. Of these, 99% showed that this practice was considered a good idea, and 80% reported that the letter reflected the clinical aspects well. Seventy-two percent thought that receiving this letter improved their understanding of the clinical situation. In general, patients found the words understandable (83%), too medical (20%) or even shocking (3%). Sixty-three percent said that they would have asked their general practitioner to give them the letter. Their main motivation for wanting a copy of this letter was to remember the information in the future, to have the information to pass on to other physicians involved in their health in the future, or to have information concerning the family. Finally, 58% would have preferred a letter sent specifically to them rather than a copy, and suggestions for the contents of such a letter should be further studied.     

Health information on the internet: patient empowerment or patient deceit?

Internet is the biggest medical library in the world. It has transformed the way many health seekers find health information. Seekers on net have exponentially increased from 54 million in 1998 to 110 million in 2002 (U.S. figures) and are ever increasing. Act of looking for health or medical information is the third most popular activities online. Search engines are used by almost 81% of the e-patients to look for the information they want. Internet is fast becoming an influential force as more than 70% consumers say that the information on the net has influenced their treatment decisions. However, the reliability of all the health information available on the Internet is questionable. Numerous studies have indicated deficiencies in the quality of information on the Internet. Due to technical and commercial reasons, the results provided by various search engines can be potentially biased. Only about a quarter of health seekers thoroughly check the source, timeliness of information every time they search for health information. In fact, most adults from USA, Japan, France and Germany who participated in a recent survey thought online health care information to be trustworthy, of good quality, easy to understand and easy to find. Efforts are now being taken to ensure the quality of health information on the Internet. Patients need to be educated about the worthiness of a site and also be prescribed the right sites to be consulted for information.     

The interaction of lexical and sublexical information in spelling: What's the point?

Most theories of spelling propose two major processes for translating between orthography and phonology: a lexical process for retrieving the spellings of familiar words and a sublexical process for assembling the spellings of unfamiliar letter strings based on knowledge of the systematic correspondences between phonemes and graphemes. We investigated how the lexical and sublexical processes function and interact in spelling by selectively interfering with the sublexical process in a dysgraphic individual. By comparing spelling performance under normal conditions and under conditions of sublexical disruption we were able to gain insight into the functioning and the unique contributions of the sublexical process. The results support the hypothesis that the sublexical process serves to strengthen a target word and provide it with a competitive advantage over orthographically and phonologically similar word neighbours that are in competition with the target for selection.     

The interaction of lexical and sublexical information in spelling: What's the point?

Most theories of spelling propose two major processes for translating between orthography and phonology: a lexical process for retrieving the spellings of familiar words and a sublexical process for assembling the spellings of unfamiliar letter strings based on knowledge of the systematic correspondences between phonemes and graphemes. We investigated how the lexical and sublexical processes function and interact in spelling by selectively interfering with the sublexical process in a dysgraphic individual. By comparing spelling performance under normal conditions and under conditions of sublexical disruption we were able to gain insight into the functioning and the unique contributions of the sublexical process. The results support the hypothesis that the sublexical process serves to strengthen a target word and provide it with a competitive advantage over orthographically and phonologically similar word neighbours that are in competition with the target for selection.     

Is genetic analysis useful in the routine management of hydatidiform mole?

Complete hydatidiform mole and partial hydatidiform mole are two abnormal conceptuses that may be identified by clinical, ultrasonographic, gross morphological, histological, and genetic characteristics. Among all these criteria, the specific diagnosis is generally confirmed only upon histological review. However, an accurate diagnosis based on morphological criteria is difficult and several studies have shown that misclassifications are frequent, even for experienced pathologists. An erroneous diagnosis may imply that women are either not enrolled in an adequate beta-hCG follow-up with the risk that hydatidiform mole (HM) progresses to choriocarcinoma, or are enrolled in an unnecessary follow-up. A reliable and complementary method to the pathologic interpretation is a genetic study of the conceptus to eliminate the diagnostic dilemma by distinguishing non-molar spontaneous abortions from HM and to define the type of HM. The aim of our study was to review the genetic basis of HM and discuss its relevance in the routine management of the disorder.     

Hantavirus and acute appendicitis—The diagnosis behind the diagnosis?

A 33-year-old man with a history of acute lower abdominal pain was admitted to the emergency room. After laparoscopic appendectomy and pathological confirmed acute appendicitis the patient developed thrombocytopenia and acute renal failure. Serological testing for hantaviruses revealed a positive result for PUUV IgG and IgM. Immunohistochemical work-up detected PUUV antigen in endothelial cells of capillaries and larger vessels. The high percentage of patients with hantavirus infection and severe abdominal pain is remarkable and, up to now, unexplained. To our knowledge this is the first report demonstrating PUUV antigen in the human intestine. Further studies are warranted whether hantaviruses are setting the stage for a secondary bacterial infection or cause an inflammation itself.     

Presentation of eating disorders in the news media: What are the implications for patient diagnosis and treatment?

OBJECTIVE: Eating disorder (ED) specialists increasingly see anorexia nervosa and bulimia nervosa as complex mental illnesses with both genetic and social roots. The public, however, tends to view EDs more simply as a manifestation of personal or social problems among female, white, young women. This disconnect potentially prevents timely ED diagnosis and reinforces a stigma that limits treatment availability. We examine the presentation of EDs in daily newspapers, an important contributor to shaping public perception of EDs. METHODS: We analyze 1 year of coverage about EDs by seven daily U.S. newspapers (252 articles), focusing on the messages conveyed about epidemiology, etiology, severity and treatment. RESULTS: The highest proportion of articles about EDs (48%) ran in arts and entertainment sections. Articles primarily covered those who are female, young and white, and mentioned mainly environmental causal factors. Only 8% of patient profiles discussed treatment and recovery within a medical context. CONCLUSION: News coverage rarely presents EDs as complex medical phenomena, but rather simplifies and sensationalizes these conditions. PRACTICE IMPLICATIONS: Educators would benefit from recognizing the news media's role in shaping public perceptions of EDs in ways that differ from clinical perspectives, potentially limiting diagnosis and treatment. Three communication improvements are suggested.     

Deep sequencing of patient genomes for disease diagnosis: when will it become routine?

Next-generation sequencing technologies have greatly lowered the cost of whole-genome sequencing (WGS) and related approaches. Thus, comprehensive sequencing for diagnostic purposes may clear this financial hurdle in the near future. The report by Bainbridge and colleagues in this issue of Science Translational Medicine illustrates the diagnostic power of WGS. In this Perspective, we discuss whether and how genome sequencing might become routine for clinical diagnosis.     

Socio-economic status of the patient and doctor–patient communication: does it make a difference?

This systematic review, in which 12 original research papers and meta-analyses were included, explored whether patients' socio-economic status influences doctor-patient communication. Results show that patients from lower social classes receive less positive socio-emotional utterances and a more directive and less participatory consulting style, characterised by significantly less information giving, less directions and less socio-emotional and partnership building utterances from their doctor. Doctors' communicative style is influenced by the way patients communicate: patients from higher social classes communicate more actively and show more affective expressiveness, eliciting more information from their doctor. Patients from lower social classes are often disadvantaged because of the doctor's misperception of their desire and need for information and their ability to take part in the care process. A more effective communication could be established by both doctors and patients through doctors' awareness of the contextual communicative differences and empowering patients to express concerns and preferences.     

Informed decision-making in prenatal screening for Down's syndrome: What knowledge is relevant?

Objective

To determine the content of decision-relevant knowledge needed for informed decision-making about (non-) participation in prenatal screening for Down's syndrome (DS), in order to develop a knowledge questionnaire for routine application in large-scale programme evaluations.

Methods

A generic list of content domains for knowledge about screening was extracted from the literature. Items reflecting specific knowledge domains were constructed. An expert group of professionals and pregnant women expressed whether domains and items represented decision-relevant information.

Results

All presented domains were scored as (very) important. Options when receiving an ‘increased probability for DS’ test result, the meaning of this result, the aim of the screening, and voluntary nature of the test were scored as most important. The condition being screened for, prevalence, and the screening procedure were scored as relatively less important, with a high amount of expert consensus.

Conclusion

A knowledge measure for prenatal screening for DS was developed, based on domains and items acquired by expert consensus.

Practice implications

This measure of decision-relevant knowledge can be used in routine, large-scale evaluations of the procedure for offering information about prenatal screening for DS.     

To what extent do decision aids for prenatal screening and diagnosis address involvement of partners in decision-making? - An environmental scan

ObjectiveNumerous decision aids (DAs) have been developed to inform pregnant people about prenatal screening as the decision whether or not to accept the prenatal screening offer may be difficult. Currently, little is known about the role of the decisional partner of the pregnant people in this decision-making process and to what extent DAs involve and engage the partner.MethodsA broad search was conducted to identify publicly available DAs in English and/or Dutch regarding prenatal screening and diagnosis. These DAs were analysed on aspects of partner involvement.ResultsTen of the 19 identified DAs (52.6%) contained at least one aspect of partner involvement. Several DAs acknowledged that both partners should be involved in the decision (n = 7). The content that was least likely to contain aspects of partner involvement in the DA was value clarification content (n = 2) and only one DA contained content with plural addressing.ConclusionJust over half of the included DAs included some aspect(s) of partner involvement.Practical implicationsMore research is needed to determine to what extent, and how, the partner should be involved in the decision-making process as expectant people consider the input of their partner as important.     

Primary immunodeficiencies and Bruton's disease genetic analysis: which prospects offers this genetic diagnosis?

Bruton's disease is the most frequently primary X-linked immunodeficiency. Bruton's tyrosine kinase (Btk) is encoded by the XLA gene that when mutated causes bruton's disease. This protein acts in multiple intracellular signaling pathways where the BCR (B-cell receptor) pathway is the most elucidated. Moreover 400 mutations were found and identified as responsible for B-cells differentiation block; consequences are a lack of B-cells in peripheral blood and hypo/agammaglobulinemia. Thus, patients are more susceptible to early and recurring infections occurring before the age of one year. Laboratory testing allow differential diagnosis among primary immunodeficiencies in which others hypogammaglobulinemia. Genetic analyses help physicians for clinical and biological diagnosis, and allow prenatal diagnosis for patient's family. Patient's management is based upon polyclonal immunoglobulin supplementation, infectious diseases prevention and genetic advice.     

What does the future hold for clinical studies in vasculitis?

The era prior to 1990 was a time of careful observation of disease presentation, course, outcomes and meticulous pathology studies. These mainly single-centre studies introduced new life-saving therapies for drugs still used effectively today. In the 1970-1980s, cyclophosphamide (CyP) added to glucocorticosteroids (GCS) was shown to be life-saving. The trade-off was often severe adverse events. Some forms of vasculitis were found not as ominous as thought initially. Some could be treated with safer drugs [e.g. methotrexate (MTX)]. However, whether mild or severe, patients were not cured. From 1990 to the present large collaborative networks have provided studies were not possible heretofore. Randomized controlled trials captured and manipulated vast amounts of data, banked biological specimens and shared these resources and intellectual capital, moving the field forward at an extraordinary pace. We now know that even for severe forms of granulomatosis and polyangiitis [granulomatosis with polyangiitis (GPA), Wegener's granulomatosus (WG)], microscopic polyangiitis (MPA) and Churg-Strauss syndrome (CSS), we do not need to use CyP for extended periods. We have learned recently that rituximab is as effective as CyP for severe WG and MPA. We should never again see the permanent toxicities born from years of chronic CyP use. However, short courses of CyP remain useful and can be life-saving. Step-down therapy from CyP is now a standard of care, perhaps to be replaced by rituximab in the future. If one accepts the premise that there are few cures at present for idiopathic large- and small-vessel vasculitis, we will serve our patients well if we can determine the most effective initial therapy that leads to a maintenance strategy for remission with least risk. Ultimately, we wish to identify causes of vasculitis so they can be used as a wedge to secure cures. Unmet needs and strategies are as follows: (1) to increase the numbers of vasculitis-trained physicians; (2) to define risk-benefit formulae for chronic maintenance therapy versus discontinuation of treatment after remission; (3) to define risk- and cost-benefit formulae for laboratory monitoring; (4) large-scale studies with longer follow-up that explore inhibition of interleukin-5 in CSS; (5) to explore the value of anti-interferon-γ for GCA, Takayasu's and other granulomatous vasculitides; and (6) identification of aetiological factors: cures will probably be linked to knowledge of the antigen driving the disease, plus vulnerabilities of the patient that prepare them to develop an illness phenotype. Improved outcomes using anti-inflammatory/immunosuppressive agents do not rule out infection as a driver for autoimmunity. Techniques that can facilitate pathogen discovery have never been more sophisticated.