Proactive Referral to Behavioral Smoking Cessation Programs by Healthcare Staff: A Systematic Review.

INTRODUCTION: Behavioral smoking cessation programs are an effective tool for quitting smoking, yet remain underused by smokers. Proactive referral may be a promising strategy for healthcare staff to connect smokers to such programs. AIMS AND METHODS: The aim of this study was to gain insight into the effectiveness and implementability of proactive referral of smokers to behavioral smoking cessation programs by healthcare staff. A systematic review was conducted using five databases. Effectiveness of proactive referral was defined as the proportion of referred smokers who enrolled in a behavioral smoking cessation program. To determine the implementability of proactive referral, measures of feasibility, acceptability, adoption, and referral rates were included as variables of interest. Out of 6686 screened records, 34 articles were eligible for review. A narrative synthesis approach was used. RESULTS: The majority of the included studies investigated proactive referral within an e-referral system, combined with one or more intervention components that enhance implementation. Overall, proactive referral resulted in higher enrollment rates, especially among low-income smokers, and was found to be feasible, adoptable, and acceptable to healthcare staff. E-referral systems performed better in terms of implementability compared to fax referral systems. About half of the studies were of good quality. Many studies lacked information which resulted in lower-quality scores. CONCLUSIONS: The literature provides evidence that the proactive referral of smokers to behavioral smoking cessation programs by healthcare staff is effective and implementable across different settings. Based on the results, e-referral systems may be preferable to fax referral systems in terms of implementability. IMPLICATIONS: This systematic review demonstrated that proactive referral has the potential to increase the reach of smoking cessation programs and reduce inequalities in access to such programs. In the selection and implementation of behavioral smoking cessation programs with a proactive referral component, stakeholders (eg, policymakers, healthcare funders, and healthcare professionals) may benefit from taking different aspects of proactive referral systems into account, such as the type of proactive referral system used and additional strategies which can enhance the implementability of the system.

The delivery of Ask-Advise-Connect for smoking cessation in Dutch general practice during the COVID-19 pandemic: results of a pre-post implementation study.

BACKGROUND: The Ask-Advise-Connect approach can help primary care providers to increase the number of smokers that attempt to quit smoking and enrol into cessation counselling. The approach has not yet been implemented in general practice in the Netherlands. The aim of this study was to investigate the influence of a comprehensive implementation strategy on the delivery of Ask-Advise-Connect for smoking cessation within Dutch general practice during the COVID-19 pandemic. METHODS: A pre-post study was conducted between late 2020 and early 2022, and included 106 Dutch primary care providers (GPs, practice nurses and doctor's assistants). Participation lasted nine months: during the first three months participants delivered smoking cessation care as usual (pre-intervention); the implementation strategy came into effect after three months and participants were followed up for another six months (post-intervention). The implementation strategy consisted of two meetings in which participants were educated about Ask-Advise-Connect, made agreements on the implementation of Ask-Advise-Connect and reflected on these agreements. Participants also received online educational materials and a desk card as reminder. The changes in the proportions of 'Ask' and 'Advise' over time were modelled using linear mixed effects models. A descriptive analysis was conducted with regard to referrals to cessation counselling. RESULTS: Participants provided consultations to 29,112 patients (both smokers and non-smokers). Results of the linear mixed effects model show that the proportion of patients that were asked about smoking ('Ask') significantly decreased in the first three months (pre-intervention), but slightly increased again after the implementation strategy came into effect (post-intervention). No significant change over time was found with regard to the proportion of patients advised to quit smoking ('Advise'). Descriptive statistics suggested that more participants proactively (vs. passively) referred patients to cessation counselling post-intervention ('Connect'). CONCLUSIONS: The findings indicate that a comprehensive implementation strategy can support primary care providers in offering smoking cessation care to patients, even under stressful COVID-19 conditions. Additional implementation efforts are needed to increase the proportion of patients that receive a quit advice and proactive referral.

Mentioning smoking cessation assistance during healthcare consultations matters: findings from Dutch survey research.

BACKGROUND: Smoking cessation assistance (SCA) can help smokers to successfully quit smoking. It is unclear to what extent hearing about SCA from a healthcare professional is associated with using SCA during a quit attempt. METHODS: We used pooled survey data from the 2016, 2018 and 2020 'Module Substance Use' survey in the Netherlands (N = 5928). Multivariate logistic regression analyses were used to determine the association between having heard about SCA from one or more healthcare professionals in the last year and the use of SCA during the most recent quit attempt in the last year. We used two models: model 1 included any type of assistance; model 2 included assistance typically recommended by treatment guidelines (i.e. counselling and pharmacotherapy). RESULTS: Hearing about any type of SCA from a healthcare professional in the last year was significantly associated with using any type of SCA during the most recent quit attempt [odds ratio (OR) = 2.96; 95% confidence interval (CI) 2.16-4.06; P < 0.001]. We found the strongest association between hearing about counselling and/or pharmacotherapy and using counselling and/or pharmacotherapy (OR = 5.40; 95% CI 4.11-11.60; P < 0.001). The odds of using SCA was not significantly higher for smokers who had heard about it from two or more healthcare professionals compared to one healthcare professional (OR = 1.38; 95% CI 0.79-2.42; P = 0.26). CONCLUSIONS: Healthcare professionals can play a greater role in stimulating the use of SCA, especially counselling and pharmacotherapy, by mentioning it to smokers during consultations.

The referral of patients to smoking cessation counselling: perceptions and experiences of healthcare providers in general practice.

BACKGROUND: Few European smokers receive professional counselling when attempting to quit smoking, resulting in suboptimal success rates and poor health outcomes. Healthcare providers in general practice play an important role in referring smokers to smoking cessation counselling. We chose the Netherlands as a case study to qualitatively explore which factors play a role among healthcare providers in general practice with regard to referral for smoking cessation counselling organised both inside and outside general practice. METHODS: We conducted four focus groups and 18 telephone interviews, with a total of 31 healthcare providers who work in general practice. Qualitative content analysis was used to identify relevant factors related to referral behaviours, and each factor was linked to one of the three main components of the COM-B behaviour model (i.e., capability, opportunity and motivation) as well as the six sub-components of the model. RESULTS: Dutch healthcare providers in general practice typically refer smokers who want to quit to counselling inside their own general practice without actively discussing other counselling options, indicating a lack of shared decision making. The analysis showed that factors linked to the COM-B main components 'capability' and 'opportunity', such as healthcare providers' skills and patients' preferences, play a role in whether patients are referred to counselling inside general practice. Factors linked to all three COM-B components were found to play a role in referrals to counselling outside general practice. These included (knowledge of) the availability and quality of counselling in the region, patients' requests, reimbursement, and sense of urgency to refer. The identified factors can both act as barriers and facilitators. CONCLUSIONS: The findings of this research suggest that more smokers can be reached with smoking cessation counselling if implementation interventions focus on: (i) equipping healthcare providers with the knowledge and skills needed to refer patients; (ii) creating more opportunities for healthcare providers to refer patients (e.g., by improving the availability and reimbursement of counselling options); and (iii) motivating healthcare providers to discuss different counselling options with patients.

Introducing hepatitis C virus healthcare pathways in addiction care in the Netherlands with a Breakthrough project: a mixed method study.

BACKGROUND: People who inject drugs (PWID) are disproportionally affected by the hepatitis C virus (HCV) infection. In the Netherlands, active HCV transmission in PWID has practically been halted but uptake of HCV testing and linkage to care remains insufficient in this risk group. A national HCV in Addiction Care (HAC) quality improvement project based on the Breakthrough methodology (i.e. Breakthrough project) aimed to secure proper linkage to care in PWID by introducing local HCV healthcare screening and treatment pathways in addiction care units. AIM: To qualitatively appraise the local HCV healthcare pathways; to evaluate the yield in terms of number of PWID screened, diagnosed, referred, and treated; and to identify best practices and barriers to successful participation in the HAC Breakthrough project. METHODS: Between 2013 and 2016, 12 units of addiction care centers throughout the Netherlands participated in two series of a HAC Breakthrough project. Local multidisciplinary teams created HCV healthcare pathways. Quality assessment of HCV healthcare pathways was performed retrospectively and data on screening results was collected. In-depth interviews were conducted to elucidate best practices and essential elements for successful participation. RESULTS: In total, six HCV healthcare pathways were submitted by ten teams of which 83% was judged to be of "good" or "sufficient" quality. Uptake of HCV-antibody screening was 40% (N = 487/1219) and uptake of HCV-RNA in HCV-antibody positives was 59% (N = 107/181). The project resulted in 76 (6%) newly detected cases of persistent HCV viremia. Of all HCV-RNA positives, 92% was referred to a hepatitis treatment center. In 39% (N = 27/70) of those referred, treatment initiation was documented and 82% (N = 22/27) achieved a sustained virological response. Teams identified several best practices including motivational counseling training, oral swabs for anti-HCV testing, facilitating complementary HCV RNA testing, and supervised hospital visits. CONCLUSION: The HAC Breakthrough project has brought about good quality HCV healthcare pathways in the majority of participating addiction care centers and has successfully linked PWID with ongoing HCV viremia to care. Uptake of HCV screening and treatment after referral were identified as the main gaps to be closed in the HCV cascade of care to achieve final HCV elimination in Dutch PWID (i.e. micro-elimination).

Risk of death due to COVID-19 among current and former smokers in the Netherlands: a population-based quasi-cohort study.

BACKGROUND: Research on smoking as a risk factor for death due to COVID-19 remains inconclusive, with different studies demonstrating either an increased or decreased risk of COVID-19 death among smokers. To investigate this controversy, this study uses data from the Netherlands to assess the relationship between smoking and death due to COVID-19. METHODS: In this population-based quasi-cohort study, we linked pseudonymized individual data on smoking status from the 2016 and 2020 'Health Monitor Adults and Elderly' in the Netherlands (n = 914 494) to data from the cause-of-death registry (n = 2962). Death due to COVID-19 in 2020 or 2021 was taken as the main outcome. Poisson regression modelling was used to calculate relative risks (RRs) and 95% CIs of death due to COVID-19 for current and former smokers compared with never smokers while adjusting for relevant confounders (age, sex, educational level, body mass index and perceived health). RESULTS: Former smokers had a higher risk of death due to COVID-19 compared with never smokers across unadjusted (RR, 2.22; 95% CI, 2.04-2.42), age-sex-adjusted (RR, 1.38; 95% CI, 1.22-1.55) and fully adjusted (RR, 1.30; 95% CI, 1.16-1.45) models. Current smokers had a slightly higher risk of death due to COVID-19 compared with never smokers after adjusting for age and sex (RR, 1.21; 95% CI, 1.00-1.48) and after full adjustment (RR, 1.08; 95% CI, 0.90-1.29), although the results were statistically non-significant. CONCLUSIONS: People with a history of smoking appear to have a higher risk of death due to COVID-19. Further research is needed to investigate which underlying mechanisms may explain this.

Implementation of ask-advise-connect for smoking cessation in Dutch general practice during the COVID-19 pandemic: a mixed-methods evaluation using the CFIR framework.

BACKGROUND: The Ask-Advise-Connect (AAC) approach can help primary care providers to increase the number of people who attempt to quit smoking and enrol into cessation counselling. We implemented AAC in Dutch general practice during the COVID-19 pandemic. In this study we describe how AAC was received in Dutch general practice and assess which factors played a role in the implementation. METHODS: A mixed-methods approach was used to evaluate the implementation of AAC. Implementation took place between late 2020 and early 2022 among 106 Dutch primary care providers (general practitioners (GPs), practice nurses and doctor's assistants). Quantitative and qualitative data were collected through four online questionnaires. A descriptive analysis was conducted on the quantitative data. The qualitative data (consisting of answers to open-ended questions) were inductively analysed using axial codes. The Consolidated Framework for Implementation Research was used to structure and interpret findings. RESULTS: During the study, most participants felt motivated (84-92%) and able (80-94%) to apply AAC. At the end of the study, most participants reported that the AAC approach is easy to apply (89%) and provides advantages (74%). Routine implementation of the approach was, however, experienced to be difficult. More GPs (30-48%) experienced barriers in the implementation compared to practice nurses and doctor's assistants (7-9%). The qualitative analysis showed that especially external factors, such as a lack of time or priority to discuss smoking due to the COVID-19 pandemic, negatively influenced implementation of AAC. CONCLUSIONS: Although AAC was mostly positively received in Dutch general practice, implementation turned out to be challenging, especially for GPs. Lack of time to discuss smoking was a major barrier in the implementation. Future efforts should focus on providing additional implementation support to GPs, for example with the use of e-health.

[Crucial role for healthcare providers in the PURE smoke-free campaign]. / Cruciale rol zorgverleners bij campagne PUUR rookvrij.

Smoking is still one of the leading causes of death in the Netherlands and worldwide. The current pandemic has made the importance of smoking cessation even more visible. With the smoking cessation campaign PURE smoke-free (in Dutch: PUUR rookvrij), the Dutch government aims to encourage smokers to quit smoking. Physicians and other healthcare providers play an indispensable role in stimulating smokers to quit. In practice, potential opportunities to discuss smoking are often missed by healthcare providers; the PURE smoke-free campaign can help with this.

A polymorphism in the regulatory region of PRNP is associated with increased risk of sporadic Creutzfeldt-Jakob disease.

BACKGROUND: Creutzfeldt-Jakob disease (CJD) is a rare transmissible neurodegenerative disorder. An important determinant for CJD risk and phenotype is the M129V polymorphism of the human prion protein gene (PRNP), but there are also other coding and non-coding polymorphisms inside this gene. METHODS: We tested whether three non-coding polymorphism located inside the PRNP regulatory region (C-101G, G310C and T385C) were associated with risk of CJD and with age at onset in a United Kingdom population-based sample of 131 sporadic CJD (sCJD) patients and 194 controls. RESULTS: We found no disease association for either PRNP C-101G or PRNP T385C. Although the crude analysis did not show a significant association between PRNP G310C and sCJD (OR: 1.5; 95%CI = 0.7 to 2.9), after adjusting by PRNP M129V genotype, it resulted that being a C allele carrier at PRNP G310C was significantly (p = 0.03) associated with a 2.4 fold increased risk of developing sCJD (95%CI = 1.1 to 5.4). Additionally, haplotypes carrying PRNP 310C coupled with PRNP 129M were significantly overrepresented in patients (p = 0.02) compared to controls. Cases of sCJD carrying a PRNP 310C allele presented at a younger age (on average 8.9 years younger than those without this allele), which was of statistical significance (p = 0.05). As expected, methionine and valine homozygosity at PRNP M129V increased significantly the risk of sCJD, alone and adjusted by PRNP G310C (OR MM/MV = 7.3; 95%CI 3.9 to 13.5 and OR VV/MV = 4.0; 95%CI 1.7 to 9.3). CONCLUSIONS: Our findings support the hypothesis that genetic variations in the PRNP promoter may have a role in the pathogenesis of sCJD.

[Patients who smoke: should we ignore the addiction or take care of the patient?] / Rokers in de spreekkamer.

Smoking cessation yields large health gains, especially in times of COVID-19. Compared to measures to stop COVID-19, tobacco control is lagging behind. We studied smoking-cessation-care in the Netherlands, using qualitative interviews with physicians (N=55) and questionnaires among physicians and other healthcare providers (HCPs; N=883) in 2017. Who is responsible for what? Three actors emerged: the patient who smokes (end responsible for quitting), the HCP (quit-advice, counseling or referral) and the government (create a society that stimulates "smoke-free"). Many HCPs do not ask about smoking, nor advise to quit. The task-division is unclear, as smoking causes multiple diseases that are part of multiple disciplines and specializations. HCPs that see smoking as a serious addiction are more inclined to ensure adequate smoking-cessation-care for their patients. Fortunately, there are positive developments as well, both within healthcare as society, and ways in which you can contribute.

[Complications of contaminated drugs: how to reduce the number of future victims?] / Complicaties van vervuilde drugs.

Serious complications of drug abuse are frequently seen in acute care. When the clinical signs and symptoms of drug use are discordant with the expected clinical features of the intended substance used, it may involve misleading, contaminated and therefore dangerous illicit drugs. In 2014 and 2015, multiple young patients presented to several Dutch emergency departments in Amsterdam with an opioid toxidrome after supposed use of cocaine. However, it required months and multiple patient presentations, including fatalities, to discover that heroin was sold as cocaine, resulting in serious opioid toxidrome complications. The improvement and formalization of local collaboration and the instatement of an accessible central coordinating party enables early pattern recognition, treatment, sample testing and prevention of future cases of serious drug complications. This was demonstrated in a case of accidental fentanyl intoxication after alleged cocaine use in 2018. Extension of such collaborative networks to create a national coverage is desirable.

Seroprevalence of HIV, hepatitis b, and hepatitis c among opioid drug users on methadone treatment in the netherlands.

BACKGROUND: Injecting drug users (IDU) remain an important population at risk for blood-borne infections such as human immunodeficiency virus (HIV), hepatitis B virus (HBV) and hepatitis C virus (HCV). In the Netherlands, a program is being implemented to offer annual voluntary screening for these infections to opioid drug users (ODUs) screened in methadone care. At two care sites where the program is now operating, our study aimed to estimate the seroprevalence among ODUs screened for HIV, HBV and HCV; to evaluate HBV vaccination coverage; and to assess the feasibility of monitoring seroprevalence trends by using routine annual screening data. METHODS: Opioid drug users on methadone treatment are routinely offered voluntary screening for infectious diseases such as HIV, HBV and HCV. Data on uptake and outcome of anti-HIV, anti-HBc, and anti-HCV screening among ODUs receiving methadone were obtained from two regions: Amsterdam from 2004 to 2008 and Heerlen from 2003 to 2009. FINDINGS: Annual screening uptake for HIV, HBV and HCV varied from 34 to 69%, depending on disease and screening site. Of users screened, 2.5% were HIV-positive in Amsterdam and 11% in Heerlen; 26% were HCV-positive in Amsterdam and 61% in Heerlen. Of those screened for HBV, evidence of current or previous infection (anti-HBc) was found among 33% in Amsterdam and 48% in Heerlen. In Amsterdam, 92% were fully vaccinated for HBV versus 45% in Heerlen. CONCLUSION: Annual screening for infectious diseases in all ODUs in methadone care is not fully implemented in the Netherlands. On average, more than half of the ODUs in methadone care in Heerlen and Amsterdam were screened for HIV, HBV and HCV. In addition, screening data indicate that HBV vaccination uptake was rather high. While the HIV prevalence among these ODUs was relatively low compared to other drug-using populations, the high HCV prevalence among this group underscores the need to expand annual screening and interventions to monitor HIV, HBV and HCV in the opioid drug-using population.

Haemorrhagic stroke related to the use of 4-fluoroamphetamine.

INTRODUCTION: The use of the new psychoactive substance 4-fluoroamphetamine (4-FA) and the number of 4-FA-related intoxications substantially increased in The Netherlands in recent years. We describe two patients with severe 4-FA-related complications and the characteristics of a large sample of 4-FA-intoxicated patients. METHODS: Information on patients with 4-FA-related intoxications between January 2009 and June 2017 was available from the Monitor Drug-related Incidents. Detailed clinical information was obtained of two patients with haemorrhagic stroke after toxicologically confirmed 4-FA use. RESULTS: We report on two patients who presented with headache and mild hypertension after 4-FA use. Patient A developed one-sided weakness and decreased consciousness after a few hours. A computed tomography scan showed a left-sided intracerebral haemorrhage. Because of life-threatening cerebral herniation, haematoma evacuation was performed. Postoperatively, she suffered from a right-sided hemiparalysis and severe aphasia, requiring clinical rehabilitation. Patient B had a subarachnoid haemorrhage without neurological deficits. In total, 939 4-FA-intoxicated patients were registered. These patients used 4-FA alone (44%) or in combination with alcohol (13%) and/or other drugs (43%). DISCUSSION: Patients using 4-FA are at risk for life-threatening health problems, including intracranial haemorrhage. Additional brain imaging should be considered in 4-FA-intoxicated patients, not only in the presence of neurological deficits, but also in the case of severe headache.

Effectiveness and cost-effectiveness of nationwide campaigns for awareness and case finding of hepatitis C targeted at people who inject drugs and the general population in the Netherlands.

BACKGROUND: Hepatitis C virus infection (HCV) is a serious, but underdiagnosed disease that can generally be treated successfully. Therefore, a nationwide HCV awareness campaign was implemented in the Netherlands targeting people who inject drugs (PWID) in addiction care ('PWID intervention') and high-risk groups in the general population ('public intervention'). The objective of this study is to assess the effectiveness and cost-effectiveness of the interventions used in this campaign. METHODS: For the 'PWID' intervention, all addiction care centres in the Netherlands provided proactive individual HCV consultation and testing. The 'public intervention' consisted of health education through mass media and instruction of health care professionals. A Markov chain model was used to estimate incremental cost-effectiveness ratios (ICER, cost per QALY gained). We included a 'DAA treatment' scenario to estimate the effect of these treatment strategies on cost-effectiveness. RESULTS: The 'PWID intervention' identified 257 additional HCV-carriers. The ICER was €9056 (95% CI: €6043-€13,523) when compared to 'no intervention'. The 'public intervention' identified 38 additional HCV-carriers. The ICER was €18,421 (95% CI: €7376-€25,490,119) when compared to 'no intervention'. Probabilistic sensitivity analysis showed that the probability that the 'PWID intervention' was cost-effective was 100%. It also showed a probability of 34% that the 'public intervention' did not exceed the Dutch threshold for cost-effectiveness (€20,000). New treatment regimens are likely to improve cost-effectiveness of this strategy. CONCLUSION: In a nationwide HCV awareness and case finding campaign, the intervention targeting PWID was effective and cost-effective. An intervention targeting risk groups in the general population showed only a modest effect and is therefore less likely to be cost-effective.

The dopamine D4 receptor gene 48-base-pair-repeat polymorphism and mood disorders: a meta-analysis.

BACKGROUND: We conducted a meta-analysis to re-evaluate the role of the dopamine D4 receptor gene 48-base-pair- repeat (DRD4) polymorphism in mood disorders. METHODS: DRD4 allele frequencies were compared between 917 patients with unipolar (UP) or bipolar affective disorder (BP) and 1164 control subjects from 12 samples, using the Cochrane Review Manager. RESULTS: An association was found between all mood disorder groups and DRD4.2. After correcting for multiple testing, the association between DRD4.2 and BP dropped to insignificance; however, the evidence of an association between the DRD4.2 allele and UP (p < .001) and the combined group (p < .001) remained. There was no evidence for heterogeneity or publication bias. CONCLUSIONS: These findings suggest that the DRD4.2 allele is a risk allele for depression symptomatology. Meta-analysis may be a valuable objective tool for a quantitative summary of evidence for association studies in psychiatric genetics.

[Electronic cigarettes: use, health risks, and effectiveness as a cessation method]. / De elektronische sigaret: Gebruik, gezondheidsrisico's, en effectiviteit als stopmethode.

The use of electronic cigarettes (e-cigarettes) among adults in the Netherlands is increasing but is still relatively low. Increasing numbers of young people abroad are experimenting with e-cigarettes but no trend data for the Netherlands are available to date. Young people who experiment with e-cigarettes are principally those young people who already smoke conventional cigarettes or have done so in the past; the same applies to adults. There are no indications that experimenting with e-cigarettes can lead to tobacco addiction. Although the vapour from e-cigarettes contains substances that are harmful to health, the health risks from the use of e-cigarettes are far smaller than those from smoking conventional cigarettes. Too few research data are available to be able to conclude that e-cigarettes are an effective aid to smoking cessation.

Polymorphisms in the prion protein gene and in the doppel gene increase susceptibility for Creutzfeldt-Jakob disease.

The prion protein gene (PRNP) plays a central role in the origin of Creutzfeldt-Jakob disease (CJD), but there is growing interest in other polymorphisms that may be involved in CJD. Polymorphisms upstream of PRNP that may modulate the prion protein production as well as polymorphisms in the prion-like doppel gene (PRND) have been studied, with inconsistent findings. We investigated the role of a single-nucleotide polymorphism (SNP 1368) located upstream of PRNP and three polymorphisms in PRND (T26M, P56L and T174M) in CJD. The study included a population-based sample of 52 patients with sporadic CJD and 250 controls. We analysed our data as single markers and haplotypes. Further, we conducted a meta-analysis on PRND T174M comparing the data of the four studies conducted to date. For SNP 1368 and PRNP M129V, we found significant evidence for linkage disequilibrium. No evidence was found for a relation of SNP 1368 to CJD independent of PRNP M129V. We further found a significant increased prevalence of M homozygotes at PRND T174M among sporadic CJD patients, when adjusting the analyses for the other genotypes. In the haplotype analyses, the association was strongest for persons homozygous for PRNP 129M and PRND 174M (odds ratio 4.35, 95% confidence interval 1.05-8.09; P=0.04). The meta-analysis on the PRND T174M polymorphism did not show a consistent effect across studies, raising the question as to whether PRND 174M is causally related to CJD, or whether the PRND allele is in linkage disequilibrium with another polymorphism related to CJD.

Genetic testing has no place as a routine diagnostic test in sporadic and familial cases of Alzheimer's disease.

The challenges inherent in diagnosing and treating patients with Alzheimer's disease are increasing. Early diagnosis and modification of risk factors have received growing attention from the media in recent years. As a result, the general public, and patients and family members, are increasingly better informed about the disease, its genetic background, and the possibilities for treatment. The physician is often faced with questions about hereditary patterns within the family and with requests to perform genetic testing. Children, with increasing frequency, ask for a separate appointment with the treating physician, during the patient's life or after the patient has died, to discuss whether they are likely to get the disease and whether genetic tests should be performed. In this paper, some of the clinical and ethical questions that physicians face are explored. Arguments as to why we think routine genetic assessment should not be part of the diagnostic examination of the patient suspected of Alzheimer's disease are given.