Community-based Cases Research Articles

Implications of influenza resistance

Antiviral treatment is an important tool in the clinical management of severe or complicated influenza. Two classes of antiviral agents for influenza are available: adamantanes (amantadine and rimantadine), and neuraminidase inhibitors (oseltamivir, zanamivir, peramivir, laninamivir). The currently circulating human influenza viruses, influenza A (H1N1)pdm09, influenza A(H3N2), and influenza type-B, are all resistant to adamantanes, but most are sensitive to neuraminidase inhibitors. From April 2009 to 5 October 2011, a total of 605 cases of oseltamivir-resistant infections with influenza A(H1N1) pdm09 virus have been reported to WHO from 32 countries. All resistant strains carry the H275Y substitution in the neuraminidase glycoprotein, which is known to confer a high level of resistance to oseltamivir. Of 468/605 (77%) cases with available clinical information, 133/468 (28%) occurred among patients who were severely immunocompromised. Of the patients who were not immunocompromised, 211/335 cases (63%) occurred after receiving treatment or prophylaxis with antiviral drugs. Four clusters of oseltamivir-resistant viruses with person-to-person transmission have been reported: 2 occurred among severely immunocompromised patients, while 2 were in healthy adults. Most viruses carrying the H275Y substitution remain sensitive to zanamivir. However reports indicate that other virus variants have emerged resulting in a reduced sensitivity to zanamivir and peramivir. Resistance to neuraminidase inhibitors in influenza A (H3N2) and influenza type-B, has been reported rarely, and has usually been associated with prolonged treatment in immunocompromised patients. The prevalence of resistance to neuraminidase inhibitors is still low, and oseltamivir remains the first line treatment recommended for patients with severe influenza or patients at a high risk of developing severe disease. However zanamivir is a therapeutic alternative for patients infected with a virus that is highly suspected to be resistant to oseltamivir, i.e., immunocompromised patients who have received oseltamivir, but still have evidence of persistent viral replication; or people who develop illness despite taking oseltamivir for a post-exposure prophylaxis. In addition appropriate infection control measures should be implemented to prevent spread of the resistant virus. Although prevalence of resistance to neuraminidase inhibitors remains low, reports of person-to-person transmission, and an increased prevalence of resistant viruses in community-based cases in specific regions, emphase the necessity of virological and epidemiological surveillance.

Involving Stakeholders to Optimize a Study Protocol on Secondhand Tobacco Smoke and Chronic Rhinosinusitis in Adults

Epidemiological evidence evaluating the association between secondhand smoke exposure and diseases of the upper airway in adults is limited by a small number of studies and a lack of established protocols. This study was designed to optimize a research protocol on secondhand tobacco smoke exposure and chronic rhinosinusitis for a future population-based case-control study in Washington County, Maryland, using a participatory research model. We conducted three focus groups with health professionals, community members, and research practitioners for protocol development; 10 one-on-one cognitive testings with community members for protocol refinement; and a pilot testing of the full study protocol (10 cases and 10 controls) for full evaluation of the study protocol. Health professionals recommended, among other themes, enrolling patients with confirmed chronic rhinosinusitis (minimum 12-week symptom duration and objective inflammation). Community members and research practitioners discussed optimal strategies for participant recruitment and interviewing. The protocol, revised with the focus group's feedback, was further evaluated in one-on-one sessions with 10 Washington County residents (3 with chronic rhinosinusitis). In the pilot study, 10 nonsmoking chronic rhinosinusitis cases (5 clinic based and 5 community based) and their community-based age, sex, and former/never smoking-matched controls were recruited. Sinonasal symptoms scores were higher in cases than controls but similar for clinic versus community-based cases. This protocol development framework involving stakeholders resulted in a comprehensive questionnaire that was successfully evaluated during a pilot study and is now ready to be used in population-based and clinical epidemiological studies of chronic rhinosinusitis in adults.

The transcription factor 7-like 2 (TCF7L2) gene is associated with Type 2 diabetes in UK community-based cases, but the risk allele frequency is reduced compared with UK cases selected for genetic studies

Common polymorphisms in the transcription factor 7-like 2 (TCF7L2) gene are strongly associated with Type 2 diabetes. Many studies include a large proportion of cases enriched for family history or young age of diagnosis and may therefore provide an overestimation of the general population risk. We aimed to compare the impact of TCF7L2 in UK community-based Type 2 diabetic subjects with that in subjects ascertained for genetic studies. We genotyped the TCF7L2 polymorphism rs7903146 in 1068 cases from two sources: 487 from 10 GP practices and 601 ascertained for genetic studies, and 2099 control subjects from two sources: 1099 parents from a birth cohort (population control subjects) and 300 subjects with normal fasting glucose aged > or = 45 years (community control subjects). When compared with Type 2 diabetes cases ascertained for genetic studies, the risk allele frequency in community-based cases was lower (40 vs. 36%, P = 0.04), but there was no difference in risk allele frequency between community-based control and population-based control subjects (31 vs. 30%, P = 0.61). The T allele of rs7903146 increased Type 2 diabetes risk with an odds ratio (OR) of 1.32 (95% CI: 1.13-1.52; P = 0.0002) in community-based cases, but this OR was lower than the OR of cases enriched for genetic studies [1.58 (95% CI: 1.38-1.80), P = 1.4 x 10(-11)] and the combined OR of meta-analysis of 10 studies to date on rs7903146 [1.48 (95% CI: 1.41-1.54), P < 10(-20)]. Common variation in the TCF7L2 gene contributes to Type 2 diabetes risk in UK patients recruited in general practice, but the risk allele frequency may be lower than that in subjects enriched for genetic effects.

From Community-Based Resource Management to Complex Systems: The Scale Issue and Marine Commons

Most research in the area of common property (common-pool) resources in the last 2-3 decades sought the simplicity of community-based resource management cases to develop theory. This was mainly because of the relative ease of observing processes of self-governance in simple cases. However, this creates a problem. Whether the findings of small- scale, community-based commons can be scaled up to generalize about regional and global commons is much debated. Even though some of the principles from community-based studies are likely relevant across scale, new and different principles may also come into play at different levels. Cross-scale institutions (such as institutions of co- management) have something in common: they provide ways to deal with complex adaptive systems. They all pertain to various aspects of complexity, such as selforganizatio n, uncertainty, and resilience, and deal with the challenges of scale. Communities themselves can be seen as complex systems -- embedded in larger complex systems. Thus, community-based resource management needs to deal with cross-scale governance and external drivers of change, as I illustrate with examples of marine commons.

Progressive dementia after first-ever stroke: A community-based follow-up study

To examine the risk and determinants of a progressive dementia syndrome and cognitive impairment not dementia (CIND) in community-based nonaphasic first-ever stroke cases 1 year after stroke, relative to a matched community-based stroke-free group.Matched cohort design, with cognitive tests given on two occasions 9 months apart to 99 mild-to-moderate first-ever stroke patients and 99 age- and sex-matched people without stroke. At follow-up, progressive dementia or CIND were diagnosed, with judges blinded to stroke/nonstroke status.Progressive dementia was diagnosed in 12.5% of stroke patients and 15.4% of those without strokes (RR 1.1, 95% CI 0.5 to 2.2, p = 0.85). CIND was diagnosed in 37.5% of stroke patients and 17.6% of participants without strokes (RR 2.1, 95% CI 1.2 to 3.4, p = 0.003). In multivariable regression, age (p = 0.04) and baseline cognition (p < 0.001) were independently associated with dementia whereas stroke (p = 0.002), age (p = 0.05), baseline cognition (p = 0.001), and baseline mood (p = 0.03) were independently associated with CIND at follow-up.In this community-based nonaphasic sample, mild-to moderate first-ever stroke was not associated with the presence of progressive dementia 1 year later, but was clearly associated with a greater risk of cognitive impairment not dementia (CIND). Baseline mood impairment remained independently associated with CIND at 1 year after taking into account stroke, age, and baseline cognitive ability.

Progressive dementia after first-ever stroke: a community-based follow-up study.

To examine the risk and determinants of a progressive dementia syndrome and cognitive impairment not dementia (CIND) in community-based nonaphasic first-ever stroke cases 1 year after stroke, relative to a matched community-based stroke-free group. Matched cohort design, with cognitive tests given on two occasions 9 months apart to 99 mild-to-moderate first-ever stroke patients and 99 age- and sex-matched people without stroke. At follow-up, progressive dementia or CIND were diagnosed, with judges blinded to stroke/nonstroke status. Progressive dementia was diagnosed in 12.5% of stroke patients and 15.4% of those without strokes (RR 1.1, 95% CI 0.5 to 2.2, p = 0.85). CIND was diagnosed in 37.5% of stroke patients and 17.6% of participants without strokes (RR 2.1, 95% CI 1.2 to 3.4, p = 0.003). In multivariable regression, age (p = 0.04) and baseline cognition (p < 0.001) were independently associated with dementia whereas stroke (p = 0.002), age (p = 0.05), baseline cognition (p = 0.001), and baseline mood (p = 0.03) were independently associated with CIND at follow-up. In this community-based nonaphasic sample, mild-to moderate first-ever stroke was not associated with the presence of progressive dementia 1 year later, but was clearly associated with a greater risk of cognitive impairment not dementia (CIND). Baseline mood impairment remained independently associated with CIND at 1 year after taking into account stroke, age, and baseline cognitive ability.

Software to Assist with Programme Planning: Two Community-Based Cases

Software to Assist with Programme Planning: Two Community-Based Cases

Use of hospitalization and pharmaceutical prescribing data to compare the prevaccination burden of varicella and herpes zoster in Australia.

The aims of the study were to compare the burden of varicella and herpes zoster in Australia. No national surveillance exists for varicella or herpes zoster. We used hospital morbidity data from 1993-9 and pharmaceutical prescribing data from 1995-9. In the financial year 1998/99, there were 4718 hospitalizations for zoster compared to 1991 for varicella. For varicella the mean age of patients was 15 years compared to 69 years for zoster. The mean length of stay in hospital was 4.2 days for varicella and 12.7 days for zoster. Varicella accounted for 8396 (3726 with principal diagnosis varicella) bed days compared to 26 266 (5382 with principal diagnosis of zoster) for zoster. The in-hospital case-fatality rate was 0.4% for varicella and 1% for zoster. In 1999, 59 200 community-based cases of zoster were treated with antivirals. We estimate that 157 266 cases of zoster occurred in the community in 1999, a rate of 830 per 100 000 population. Herpes zoster has a higher burden of disease than varicella, and must be a component of disease surveillance in order to determine the full impact of vaccination on the epidemiology of varicella zoster virus (VZV).

A polymorphism in the cystatin C gene is a novel risk factor for late-onset Alzheimer's disease.

To investigate whether or not a coding polymorphism in the cystatin C gene (CST3) contributes risk for AD. A case-control genetic association study of a Caucasian dataset of 309 clinic- and community-based cases and 134 community-based controls. The authors find a signficant interaction between the GG genotype of CST3 and age/age of onset on risk for AD, such that in the over-80 age group the GG genotype contributes two-fold increased risk for the disease. The authors also see a trend toward interaction between APOE epsilon4-carrying genotype and age/age of onset in this dataset, but in the case of APOE the risk decreases with age. Analysis of only the community-based cases versus controls reveals a significant three-way interaction between APOE, CST3 and age/age of onset. The reduced or absent risk for AD conferred by APOE in older populations has been well reported in the literature, prompting the suggestion that additional genetic risk factors confer risk for later-onset AD. In the author's dataset the opposite effects of APOE and CST3 genotype on risk for AD with increasing age suggest that CST3 is one of the risk factors for later-onset AD. Although the functional significance of this coding polymorphism has not yet been reported, several hypotheses can be proposed as to how variation in an amyloidogenic cysteine protease inhibitor may have pathologic consequences for AD.

Gender-specific association of the angiotensin converting enzyme gene with Alzheimer's disease

Epidemiological studies have demonstrated that risk factors for vascular disease are also risk factors for Alzheimer's disease (AD). The gene for the angiotensin converting enzyme (ACE) has recently been reported to be associated with risk for AD. We have investigated the possibility of such an association in 98 clinic-based and 73 community-based AD cases versus 175 community-based controls and find a gender-specific association of ACE genotype with AD in the female clinic population. These data suggest that gender may interact with genetic factors to influence risk for AD. Gender-specific risk for AD has been previously reported, and a biological rationale for involvement of ACE in the AD process is supported by studies exploring the relationship between AD and vascular risk factors such as hypertension. However, the results may also be a consequence of the known anomalies that arise in genetic association studies as a consequence of sample selection.

Alzheimers disease is not associated with the hypertension genetic risk factors PLA2 or G protein ?3, either independently or interactively with apolipoprotein e

Growing evidence suggests that hypertension and Alzheimers disease (AD) may share a common etiology. To evaluate the contribution to AD of genetic factors associated with hypertension, we genotyped clinic and community-based AD cases and controls for polymorphisms within the pancreatic PLA(2) gene and the G protein beta3 subunit gene, both of which are located on chromosome 12. Our results do not support an independent association between either of these genes and AD. We further assessed the possibility that either of these genes may interact with the apolipoprotein E gene, a known risk factor for hypertension and AD, on predicting AD. We were unable to find statistical interaction between either the pancreatic PLA(2) or Gbeta3 genes and the apolipoprotein E gene on risk for AD. These results do not support a shared genetic etiology between hypertension and AD. Possibly, a clinical association between these diseases could be due to pathophysiologic interactions.

Alzheimers disease is not associated with the hypertension genetic risk factors PLA2 or G protein β3, either independently or interactively with apolipoprotein e

Growing evidence suggests that hypertension and Alzheimers disease (AD) may share a common etiology. To evaluate the contribution to AD of genetic factors associated with hypertension, we genotyped clinic and community-based AD cases and controls for polymorphisms within the pancreatic PLA2 gene and the G protein β3 subunit gene, both of which are located on chromosome 12. Our results do not support an independent association between either of these genes and AD. We further assessed the possibility that either of these genes may interact with the apolipoprotein E gene, a known risk factor for hypertension and AD, on predicting AD. We were unable to find statistical interaction between either the pancreatic PLA2 or Gβ3 genes and the apolipoprotein E gene on risk for AD. These results do not support a shared genetic etiology between hypertension and AD. Possibly, a clinical association between these diseases could be due to pathophysiologic interactions. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:465–468, 1999. © 1999 Wiley-Liss, Inc.

The alpha-2 macroglobulin gene is not associated with Alzheimer's disease in a case-control sample

Genetic association has recently been reported between alleles in the alpha-2-macroglobulin (A2M) gene and the occurrence of Alzheimer's disease (AD) in familial and sporadic samples. We have investigated the A2M intronic deletion polymorphism in a case-control study of 295 unrelated clinic and community-based AD cases, and compared these to a sample of 113 unrelated control individuals recruited as part of an epidemiological study. Our results show no association between A2M and AD in either case sample. Furthermore, A2M is not predictive of AD in an interactive fashion when considering APOE, race or gender. In a subset of our larger sample we have also investigated the A2M Val1000Ile polymorphism, and again find no evidence for association. We conclude that there is no genetic association between A2M and AD in our case-control sample.

Clinico-neuropathological correlation of Alzheimer's disease in a community-based case series.

Most clinico-neuropathological correlative studies of Alzheimer's Disease (AD) are based on research cohorts that are not necessarily generalizable to patients seen in the general medical community. In this study, we examine the accuracy of the criteria used in diagnosing AD in a community-based case series of patients with memory complaints. Clinical and neuropathological diagnoses were obtained from 134 patients evaluated for dementia who subsequently underwent autopsy. Subjects who exhibited new symptoms of dementia and were enrolled in the University of Washington/Group Health Cooperative Alzheimer's Disease Patient Registry were eligible for this study. Clinico-pathological correlation was performed using NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) and CERAD (Consortium to Establish a Registry for Alzheimer's Disease) criteria. Ninety-five of the 134 cases studied met CERAD neuropathological criteria for AD. The sensitivity of NINCDS-ADRDA "probable AD" was 83% (diagnosing AD correctly) and overall clinical diagnostic accuracy was 75%. However, there was a high rate of additional neuropathological findings. Only 34 of the 94 cases had pure AD on neuropathology, whereas the remainder frequently had coexisting vascular or Parkinson's disease lesions. This study of a large series of community-based incident dementia cases provides a way of judging the adequacy of currently available clinical diagnostic criteria. It also shows that co-existing neuropathological findings are common in community-based AD.

Mild cognitive impairment--an early stage of Alzheimer's disease?

The hypothesis that mild cognitive impairment (MCI) represents an early stage of Alzheimer's disease (AD) was investigated by reviewing recent research from three sources: asymptomatic and symptomatic individuals carrying mutations that cause AD, hospital-samples of non-demented patients with MCI at the initial examination that are followed longitudinally, and community-based incident cases of AD. Studies with asymptomatic mutation carriers of the amyloid precursor protein and presenilin 1 gene have shown a linear and disease-related decline in most cognitive functions that begins approximately 10 years before the expected clinical onset of AD. However, there is considerable overlap between the level of impairment for mutation carriers and non-carriers of the same age during the early preclinical stage of AD. Hospital-based longitudinal studies have shown that non-demented individuals with isolated mild episodic memory impairment may develop clinically diagnosed AD with widespread cognitive deficits in a few years time. Community-based epidemiological studies on the incidence of AD demonstrate that indices of episodic memory, in addition to measures of general cognitive functioning, are useful in predicting early AD. In contrast, subjective memory impairment or age-associated memory impairment are less powerful predictors of future dementia development. In summary, there is converging evidence to demonstrate that preclinical AD is characterized by a common behavioral phenotype, with cognitive decline in several domains, predominantly in episodic memory. The decline appears to start many years before the clinical onset of AD. Moreover, the progression of the impairment appears to be continuous. Finally, this pattern of performance generalizes across etiology of AD (familial or sporadic), clinical onset (early or late), sample composition (hospital or community), and method of assessment.

High Prevalence of Rheumatoid Factor in Community-based Series of Patients with Rheumatoid Arthritis Meeting the New (1987) ARA Criteria: RF-negative non-erosive rheumatoid arthritis is very rare

The aim of the study was to assess the prevalence of rheumatoid factor (RF) in a community-based rheumatoid arthritis (RA) series. The subjects of the series represented prevalent RA cases in the Kuusamo community in Northern Finland with 13,000 adult inhabitants. The patients were selected from the official Finnish data registers and from among the subjects who had consulted the local general practitioners due to rheumatic complaints in the recent years, using the American Rheumatism Association (ARA) 1987 classification criteria for inclusion. For this study, ninety-five out of the 103 RA patients so found were RF-tested by immunoturbidimetry. At the time of the study, 71 (75%) of the 95 cases were RF positive, 83 (87%) being 'ever' positive (in one case the early RF status was unclear). Our result contrasts with the much lower prevalence figures (25-60%) obtained from the earlier cross-sectional population-based RA studies, which have used the ARA 1958 definite RA as the inclusion criterion of the subjects. All the eleven patients with RF-negative RA had erosive joint disease. The RF-negative RA patients had a significantly lower frequency of HLA-DR4 (18%) than the RF-positive ones (58%), p<0.05. We found a high frequency of RF among prevalent community-based RA cases meeting the ARA criteria. According to our results, RF-negative non-erosive RA is very rare among cases selected with the above methods.

Proceedings: Effect of corticotrophin and oral corticosteroids on nocturnally released growth hormone.

<b><i>Objective:</i></b> To investigate whether or not a coding polymorphism in the cystatin C gene (<i>CST3</i>) contributes risk for AD. <b><i>Design:</i></b> A case-control genetic association study of a Caucasian dataset of 309 clinic- and community-based cases and 134 community-based controls. <b><i>Results:</i></b> The authors find a signficant interaction between the GG genotype of <i>CST3</i> and age/age of onset on risk for AD, such that in the over-80 age group the GG genotype contributes two-fold increased risk for the disease. The authors also see a trend toward interaction between <i>APOE</i> ε4-carrying genotype and age/age of onset in this dataset, but in the case of <i>APOE</i> the risk <i>decreases</i> with age. Analysis of only the community-based cases versus controls reveals a significant three-way interaction between <i>APOE</i>, <i>CST3</i> and age/age of onset. <b><i>Conclusion:</i></b> The reduced or absent risk for AD conferred by <i>APOE</i> in older populations has been well reported in the literature, prompting the suggestion that additional genetic risk factors confer risk for later-onset AD. In the author’s dataset the opposite effects of <i>APOE</i> and <i>CST3</i> genotype on risk for AD with increasing age suggest that <i>CST3</i> is one of the risk factors for later-onset AD. Although the functional significance of this coding polymorphism has not yet been reported, several hypotheses can be proposed as to how variation in an amyloidogenic cysteine protease inhibitor may have pathologic consequences for AD.