Low-prevalence Conditions Research Articles

Diagnostic autoantibodies for autoimmune liver diseases.

Autoimmune liver diseases are conditions of low prevalence that comprise the triad of autoimmune hepatitis, primary biliary cholangitis (cirrhosis) and primary sclerosing cholangitis and their poorly characterised overlapping syndromes. Diagnostic autoantibodies are associated with autoimmune hepatitis and primary biliary cholangitis but not with primary sclerosing cholangitis. Autoantibodies are useful disease markers that facilitate early diagnosis of autoimmune hepatitis and primary biliary cholangitis and allow for therapeutic intervention to prevent progression to liver cirrhosis and associated complications. Adult onset type 1 autoimmune hepatitis is associated with F-actin reactive smooth muscle autoantibody, antinuclear autoantibody in 60% of patients, and autoantibody to SLA/LP in 15–20%. Juvenile onset type 2 autoimmune hepatitis is associated with LKM-1 and LC-1 autoantibodies. Primary biliary cholangitis is associated with a mitochondria-associated autoantibody designated M2 in >90% of patients and with disease-specific antinuclear autoantibodies in 50% that bind to antigens in the nuclear core complex and in multiple nuclear dots. Autoantibodies to the nuclear core complex target gp210, nucleoporin p62 and nuclear lamin B receptor. Autoantibodies to multiple nuclear dots target Sp100 and PML antigens. Liver autoantibodies in asymptomatic patients with normal liver function may precede the subsequent development of overt autoimmune liver disease. For routine diagnostic immunology laboratories, initial screening for liver autoantibodies by immunofluorescence remains the method of choice with confirmation for reactivity with their target antigen by enzyme-linked immunosorbent assay (ELISA) or line blot when required.

Performance of a lateral flow immunochromatography test for the rapid diagnosis of active tuberculosis in a large multicentre study in areas with different clinical settings and tuberculosis exposure levels.

Tuberculosis (TB) continues to cause an outsized burden of morbidity and mortality worldwide, still missing efficient and largely accessible diagnostic tools determining an appropriate control of the disease. Serological tests have the potentially to impact TB diagnosis, in particular in extreme clinical settings. The diagnostic performances of the TB-XT HEMA EXPRESS (HEMA-EXPRESS) immunochromatographic rapid test for active TB diagnosis, based on use of multiple Mycobacterium tuberculosis (MTB) specific antigens, have been evaluated in a large study multicentre TB case-finding study, in populations with different exposure level to TB. A total of 1,386 subjects were enrolled in the six participating centres in Peru: 290 active-TB and 1,096 unaffected subjects. The TB prevalence (overall 20.5%) varied between 4.0% and 41.1% in the different study groups. Overall, the HEMA-EXPRESS test had 30.6% sensitivity (range 3.9-77.9%) and 84.6% specificity (range 51.6-97.3%). A significant inverse correlation between test accuracy (overall 73.5%, range 40.4-96.4%) and TB prevalence in the various study populations was observed (Pearson's r=-0.7985; P=0.05). HEMA-EXPRESS, is rapid and relatively inexpensive test suitable for routine use in TB diagnosis. In low TB prevalence conditions, test performance appears in line with WHO Target Product Profile for TB diagnostics. Performances appear suboptimal in high TB prevalence settings. Appropriate set-up in operative clinical settings has to be considered for novel serological tests for TB diagnosis, particularly for formats suitable for point-of-care use.

Pig Abattoir Inspection Data: Can It Be Used for Surveillance Purposes?

Statutory recording of carcass lesions at the abattoir may have significant potential as a resource for surveillance of livestock populations. Food Standards Agency (FSA) data in Great Britain are not currently used for surveillance purposes. There are concerns that the sensitivity of detection, combined with other issues, may make the outputs unreliable. In this study we postulate that FSA data could be used for surveillance purposes. To test this we compared FSA data with BPHS (a targeted surveillance system of slaughtered pigs) and laboratory diagnostic scanning surveillance (FarmFile) data, from mid-2008 to mid-2012, for respiratory conditions and tail bite lesions in pigs at population level. We also evaluated the agreement/correlation at batch level between FSA and BPHS inspections in four field trials during 2013. Temporal trends and regional differences at population level were described and compared using logistic regression models. Population temporal analysis showed an increase in respiratory disease in all datasets but with regional differences. For tail bite, the temporal trend and monthly patterns were completely different between the datasets. The field trials were run in three abattoirs and included 322 batches. Pearson’s correlation and Cohen’s kappa tests were used to assess correlation/agreement between inspections systems. It was moderate to strong for high prevalence conditions but slight for low prevalence conditions. We conclude that there is potential to use FSA data as a component of a surveillance system to monitor temporal trends and regional differences of chosen indicators at population level. At producer level and for low prevalence conditions it needs further improvement. Overall a number of issues still need to be addressed in order to provide the pig industry with the confidence to base their decisions on these FSA inspection data. Similar conclusions, at national level, may apply to other livestock sectors but require further evaluation of the inspection and data collection processes.

Using Caffeine Pills for Performance Enhancement. An Experimental Study on University Students' Willingness and Their Intention to Try Neuroenhancements.

Recent research has indicated that university students sometimes use caffeine pills for neuroenhancement (NE; non-medical use of psychoactive substances or technology to produce a subjective enhancement in psychological functioning and experience), especially during exam preparation. In our factorial survey experiment, we manipulated the evidence participants were given about the prevalence of NE amongst peers and measured the resulting effects on the psychological predictors included in the Prototype-Willingness Model of risk behavior. Two hundred and thirty-one university students were randomized to a high prevalence condition (read faked research results overstating usage of caffeine pills amongst peers by a factor of 5; 50%), low prevalence condition (half the estimated prevalence; 5%) or control condition (no information about peer prevalence). Structural equation modeling confirmed that our participants’ willingness and intention to use caffeine pills in the next exam period could be explained by their past use of neuroenhancers, attitude to NE and subjective norm about use of caffeine pills whilst image of the typical user was a much less important factor. Provision of inaccurate information about prevalence reduced the predictive power of attitude with respect to willingness by 40-45%. This may be because receiving information about peer prevalence which does not fit with their perception of the social norm causes people to question their attitude. Prevalence information might exert a deterrent effect on NE via the attitude-willingness association. We argue that research into NE and deterrence of associated risk behaviors should be informed by psychological theory.

Good-quality research in rare diseases: trials and tribulations

Despite the fact that rare diseases affecting the kidney are not as uncommon as generally believed, proper clinical guidelines for guiding therapeutic management are scarce or absent owing to the overall lack of reliable scientific evidence. Although the randomized controlled trial (RCT) is the best study design for dealing with questions of intervention, RCTs under low-prevalence conditions are extremely challenging because of the limited number of patients, the variable phenotypic expression, and the long course of these disorders. In this brief review, we aimed to summarize the main alternative methods to traditional RCTs designed with the intent of minimizing the number of subjects needed for recruitment or maximizing the statistical efficiency of study analyses. Most of these approaches have not yet been extensively employed, may denote crucial limitations to wide applicability, or still lack proper validation in the field of rare diseases. Nevertheless, the growing number of proposed strategies is indicative of the perceived necessity by the scientific community to fill the quality gap between clinical guidelines for common and rare pathological conditions.

Noncirrhotic portal hypertension: Medical and endoscopic management.

Noncirrhotic portal hypertension: Medical and endoscopic management.

Effects of Target Prevalence and Speech Intelligibility on Visual Search Performance

Visual search is commonly performed in the control rooms of several industries such as nuclear power plants, flight control, security screening, and monitoring. In this study, the effects of target prevalence and speech intelligibility on visual search performance were investigated. A 2 (target prevalence: low versus high) × 3 (speech transmission index = 0 versus 0.51 versus 0.69) mixed design experiment was conducted. Target prevalence was a between-subject variable, whereas the speech transmission index was a within-subject variable. A total of 32 participants participated in simulated X-ray screening tasks in different speech intelligibility conditions. Results revealed that both the target prevalence and the speech transmission index level had significant effects on visual search performance. The reaction time was shorter and the miss error rate was higher under low target prevalence condition than in high target prevalence condition. Compared with no speech condition (speech transmission index = 0), the reaction time of the participants increased significantly with the presence of intelligible speech in an acoustic environment. Performance loss was greatest when the speech transmission index was 0.51. The interaction effect of target prevalence and speech transmission index level was also significant. Proper measures should be taken to reduce unfavorable effects of low target prevalence and intelligible speech in acoustic environment on visual search performance in control rooms.

The effect of expert knowledge on medical search: medical experts have specialized abilities for detecting serious lesions.

How does domain-specific knowledge influence the experts' performance in their domain of expertise? Specifically, can visual search experts find, with uniform efficiency, any type of target in their domain of expertise? We examined whether acquired knowledge of target importance influences an expert's visual search performance. In some professional searches (e.g., medical screenings), certain targets are rare; one aim of this study was to examine the extent to which experts miss such targets in their searches. In one experiment, radiologists (medical experts) engaged in a medical lesion search task in which both the importance (i.e., seriousness/gravity) and the prevalence of targets varied. Results showed decreased target detection rates in the low prevalence conditions (i.e., the prevalence effect). Also, experts were better at detecting important (versus unimportant) lesions. Results of an experiment using novices ruled out the possibility that decreased performance with unimportant targets was due to low target noticeability/visibility. Overall, the findings suggest that radiologists do not have a generalized ability to detect any type of lesion; instead, they have acquired a specialized ability to detect only those important lesions relevant for effective medical practices.

Ask when--not just whether--it's a risk: How regional context influences local causes of diarrheal disease.

Contemporary epidemiology is enriched when it incorporates ecological concepts about systems and dependencies. With regard to diarrheal disease, the causes of which are many and interacting, the dynamics of within- and between-community disease transmission have distinct components but are also linked in important ways. However, few investigators have studied how regional-scale disease dynamics affect local patterns of diarrheal disease transmission. Characterizing this dependence is important for identifying local- and regional-level transmission pathways. We used data from active surveillance of diarrheal disease prevalence gathered from February 2004 through July 2007 in 21 neighboring Ecuadorian villages to estimate how disease prevalence in spatially and temporally proximate villages modulates the influences of village-level risk and protective factors. We found that the impact of local, village-level interventions such as improved latrines and water treatment can be quite different under conditions of high and low regional disease prevalence. In particular, water treatment was effective only when regional disease prevalence was low, suggesting that person-to-person spread, not waterborne spread, is probably responsible for most between-village transmission in this region. Additional regional-scale data could enhance our understanding of how regional-scale transmission affects local-scale dynamics.

Infrequent identity mismatches are frequently undetected

The ability to quickly and accurately match faces to photographs bears critically on many domains, from controlling purchase of age-restricted goods to law enforcement and airport security. Despite its pervasiveness and importance, research has shown that face matching is surprisingly error prone. The majority of face-matching research is conducted under idealized conditions (e.g., using photographs of individuals taken on the same day) and with equal proportions of match and mismatch trials, a rate that is likely not observed in everyday face matching. In four experiments, we presented observers with photographs of faces taken an average of 1.5 years apart and tested whether face-matching performance is affected by the prevalence of identity mismatches, comparing conditions of low (10 %) and high (50 %) mismatch prevalence. Like the low-prevalence effect in visual search, we observed inflated miss rates under low-prevalence conditions. This effect persisted when participants were allowed to correct their initial responses (Experiment 2), when they had to verify every decision with a certainty judgment (Experiment 3) and when they were permitted "second looks" at face pairs (Experiment 4). These results suggest that, under realistic viewing conditions, the low-prevalence effect in face matching is a large, persistent source of errors.

Acromegaly: a Latin American perspective

Acromegaly: a Latin American perspective

PHP15 The Impact of Orphan Drug Incentives on Innovation and Pricing in Niche Therapeutic Markets: A Systematic Review of the Literature

To review the impact orphan drug (OD) legislation has had on innovation and pricing of therapeutic products for rare diseases in the US, EU, and Japan. A systematic literature review was conducted, seeking English-language studies published after the enactment of initial OD legislation in 1983. EMBASE, Medline, and Business Source Complete were searched and results screened for studies specifically assessing the impact of industry-focused policy interventions using 1) measurable innovation- and pricing-related outcomes, and 2) specifying appropriate comparators. In addition to being abstracted for information on research setting, counterfactuals, outcomes, and findings, the methodological quality of included studies was evaluated with an adapted tool. Twenty unique studies met the inclusion criteria: 14 discussing innovation outcomes and 7 discussing pricing outcomes. Increasingly strong study designs have been used to validate that that OD legislation has increased cross-market approvals and suggest the increasing role of small biotechnology companies. Select research also shows a positive relationship between disease prevalence and the likelihood of indicated ODs and is bolstered by well-controlled regression-continuity studies showing sustained innovation in higher prevalence OD markets. However, some concerns are raised regarding innovation in low prevalence conditions and conditions just above OD thresholds. Pricing studies were almost exclusively focused on the EU. A multiple-regression analysis demonstrated that merely having an OD designation leads to a higher price, with 4 weaker studies suggesting an inverse relationship between rare disease prevalence and acquisition price. Despite an abundance of opinion and case study pieces in OD literature, specific studies of high internal validity exist, as do defined and usable comparator group classifications. The reviewed studies ought to serve as valuable information for policymakers considering policy extensions for ultra-orphans, international markets, or other niche therapeutic areas, as well as demonstration of best-practices in designing well-controlled studies evaluating biopharmaceutical policies.

Prevalence Effect in Haptic Search

In visual search tasks, the ratio of target-present to target-absent trials has important effects on miss rates. In this study, we examined whether the target prevalence effect occurs in a haptic search task by using artificial tactile maps. The results indicated that target prevalence has effects on miss rates, sensitivity, and criterion. Moreover, an increase in miss rates in the low-prevalence condition (10%) was strongly correlated with a decrease in search termination times (target-absent reaction times). These results suggest that the prevalence effect on haptic search is caused by a decrease in the search termination time and a shift in decision criterion and a decrease in sensitivity.

Methodological issues associated with collecting sensitive information over the telephone - experience from an Australian non-suicidal self-injury (NSSI) prevalence study

BackgroundCollecting population data on sensitive issues such as non-suicidal self-injury (NSSI) is problematic. Case note audits or hospital/clinic based presentations only record severe cases and do not distinguish between suicidal and non-suicidal intent. Community surveys have largely been limited to school and university students, resulting in little much needed population-based data on NSSI. Collecting these data via a large scale population survey presents challenges to survey methodologists. This paper addresses the methodological issues associated with collecting this type of data via CATI.MethodsAn Australia-wide population survey was funded by the Australian Government to determine prevalence estimates of NSSI and associations, predictors, relationships to suicide attempts and suicide ideation, and outcomes. Computer assisted telephone interviewing (CATI) on a random sample of the Australian population aged 10+ years of age from randomly selected households, was undertaken.ResultsOverall, from 31,216 eligible households, 12,006 interviews were undertaken (response rate 38.5%). The 4-week prevalence of NSSI was 1.1% (95% ci 0.9-1.3%) and lifetime prevalence was 8.1% (95% ci 7.6-8.6).Methodological concerns and challenges in regard to collection of these data included extensive interviewer training and post interview counselling. Ethical considerations, especially with children as young as 10 years of age being asked sensitive questions, were addressed prior to data collection. The solution required a large amount of information to be sent to each selected household prior to the telephone interview which contributed to a lower than expected response rate. Non-coverage error caused by the population of interest being highly mobile, homeless or institutionalised was also a suspected issue in this low prevalence condition. In many circumstances the numbers missing from the sampling frame are small enough to not cause worry, especially when compared with the population as a whole, but within the population of interest to us, we believe that the most likely direction of bias is towards an underestimation of our prevalence estimates.ConclusionCollecting valid and reliable data is a paramount concern of health researchers and survey research methodologists. The challenge is to design cost-effective studies especially those associated with low-prevalence issues, and to balance time and convenience against validity, reliability, sampling, coverage, non-response and measurement error issues.

Shut-In? Impact of Chronic Conditions on Community Participation Restriction among Older Adults

Community participation may be especially important for older adults, who are often at risk for unwanted declines in participation. We estimated the prevalence of community participation restriction (PR) due to perceived environmental barriers among older adults (≥50 years) and compared the impact among those with selected chronic conditions. Individuals with low-prevalence conditions reported high community PR (9.1–20.4%), while those with highly prevalent conditions (e.g., arthritis) had relatively low community PR (5.1–10.0%) but represented the greatest absolute numbers of condition-associated burden (>1 million). Across all conditions, more than half of those with community PR reported being restricted “always or often.” Community PR most often resulted from modifiable environmental barriers. Promising targets to reduce community PR among adults ≥50 years with chronic conditions, particularly arthritis, include building design, sidewalks/curbs, crowd control, and interventions that improve the built environment.

Decision curve analysis to compare 3 versions of Partin Tables to predict final pathologic stage

ObjectiveTo perform a decision curve analysis (DCA) to compare the Partin Tables 1997, 2001, and 2007 for their clinical applicability. Material and methodsClinical and pathologic data of 687 consecutive patients treated with open radical prostatectomy for clinically localized prostate cancer between 2003 and 2008 at a single institution were used. DCA quantified the net benefit relating to specific threshold probabilities of extraprostatic extension (EPE), seminal vesicle involvement (SVI), and lymph node involvement (LNI). ResultsOverall, EPE, SVI, and LNI were recorded in 17.8, 6.0, and 1.2%, respectively. For EPE predictions, the DCA favored the 2007 version vs. 1997 for SVI vs. none of the versions for LNI. ConclusionsDCA indicate that for very low prevalence conditions such as LNI (1.2%), decision models are not useful. For low prevalence rates such as SVI, the use of different versions of the Partin Tables does not translate into meaningful net gains differences. Finally, for intermediate prevalence conditions such as EPE (18%), despite apparent performance differences, the net benefit differences were also marginal. In consequence, the current analysis could not confirm an important benefit from the use of the Partin Tables and it could not identify a clearly better version of any of the 3 available iterations.

The Limits and Intensity of Plasmodium falciparum Transmission: Implications for Malaria Control and Elimination Worldwide

BackgroundThe efficient allocation of financial resources for malaria control using appropriate combinations of interventions requires accurate information on the geographic distribution of malaria risk. An evidence-based description of the global range of Plasmodium falciparum malaria and its endemicity has not been assembled in almost 40 y. This paper aims to define the global geographic distribution of P. falciparum malaria in 2007 and to provide a preliminary description of its transmission intensity within this range.Methods and FindingsThe global spatial distribution of P. falciparum malaria was generated using nationally reported case-incidence data, medical intelligence, and biological rules of transmission exclusion, using temperature and aridity limits informed by the bionomics of dominant Anopheles vector species. A total of 4,278 spatially unique cross-sectional survey estimates of P. falciparum parasite rates were assembled. Extractions from a population surface showed that 2.37 billion people lived in areas at any risk of P. falciparum transmission in 2007. Globally, almost 1 billion people lived under unstable, or extremely low, malaria risk. Almost all P. falciparum parasite rates above 50% were reported in Africa in a latitude band consistent with the distribution of Anopheles gambiae s.s. Conditions of low parasite prevalence were also common in Africa, however. Outside of Africa, P. falciparum malaria prevalence is largely hypoendemic (less than 10%), with the median below 5% in the areas surveyed.ConclusionsThis new map is a plausible representation of the current extent of P. falciparum risk and the most contemporary summary of the population at risk of P. falciparum malaria within these limits. For 1 billion people at risk of unstable malaria transmission, elimination is epidemiologically feasible, and large areas of Africa are more amenable to control than appreciated previously. The release of this information in the public domain will help focus future resources for P. falciparum malaria control and elimination.

Chapter 20: Issues in planning cervical cancer screening in the era of HPV vaccination

Human Papillomavirus (HPV) vaccines will likely have an impact as a preventive strategy for cervical cancer. Screening for precancerous lesions cannot be discontinued because vaccination will not protect against HPV types not included in the first generation of vaccines. Moreover, protection for the target types, 16 and 18, which are responsible for most cases of cervical precancerous lesions and cancer, and 6 and 11, which are responsible for a substantial proportion of low-grade lesions, cannot be expected to be absolute, and the likely implementation of HPV vaccination in young women will not impact older groups initially. Cervical cancer control programs will need to be re-evaluated because the addition of HPV vaccination will make the existing approach of high-frequency screening by cytology too costly and inefficient for most public health budgets. Simply making cytology screening less frequent may not be a viable strategy in light of potential problems that may plague cytology performance in conditions of low lesion prevalence. HPV testing has the performance characteristics that would make it an ideal primary screening test in such conditions. Cytology should be reserved for triage of HPV-positive cases because it is more likely to perform with sufficient accuracy in high-prevalence conditions. Another advantage of using HPV testing as a primary screening tool is the opportunity to create infection registries that can link test results from the same women over time, thus allowing an efficient and low-cost strategy to monitor long-term protection among vaccinated women.

Effect of different recruitment sources on the composition of a bipolar disorder case registry.

Conducting research on low-prevalence conditions presents an ongoing challenge for clinical and services researchers. Recruitment through health professionals versus other forms of self-referral may affect study group composition. We compared members of a voluntary case registry for bipolar disorder who were recruited through a variety of sources including health professionals, support groups, an Internet website, and mailings, brochures, and other general public relations activities. We also compared the cost of recruitment methods. We hypothesized that self-referred registry members would be of higher socioeconomic status and less likely to be in treatment compared to members recruited through health professionals. Registrants referred through the Internet and patient support groups were better educated and more likely to be married than other registrants. However, Internet registrants were younger, had fewer lifetime hospitalizations and were more likely to be working. Nearly all registrants were in treatment with a psychiatrist. Local registrants were predominantly recruited through health professionals and public presentations. Registrants outside of the local region most often learned about the registry from patient support groups and the Internet. Local registrants were less likely to be using non-lithium mood stabilizers. Recruitment through public relations efforts was the most expensive method of recruitment, and the Internet website was the cheapest. Diverse recruitment methods can expand the population available for clinical trials. For services research, the Internet and patient support groups are less expensive ways to identify persons served in diverse settings and health plans, but these recruitment methods yield a sample that is better educated than the remainder of the population. It remains a difficult task to identify minorities and persons not in treatment.

Prevalence and Impact of Parent‐Reported Disabling Mental Health Conditions Among U.S. Children

To provide a current national profile of the prevalence and impact of parent-reported disabling mental health conditions in U.S. children. A cross-sectional descriptive analysis of 99,513 children younger than 18 years old included in the 1992-1994 National Health Interview Survey (NHIS). The response rate exceeded 94% in each year. Disability is defined as the long-term reduction in a child's ability to perform social role activities, such as school or play, as a result of his/her mental health condition. On average, 2.1% of U.S. children were reported to suffer from a disabling mental health condition in 1992-1994. The most common reported causes of disability include mental retardation, attention-deficit hyperactivity disorder, and learning disabilities. While national prevalence estimates were produced for some low-prevalence conditions such as autism (38/100,000), for many specific diagnoses the reported prevalence rates were too low for accurate national population estimates using this data set. Logistic regression analysis demonstrates that prevalence of a disabling mental health condition was higher for older children; males; children from low-income, single-parent families; and those with less education. These conditions are also associated with high rates of special education participation (approximately 80%) and health system use. The NHIS provides a useful and untapped resource for estimating the prevalence of disabling mental health conditions. These conditions are increasingly prevalent and have a profound impact on children and the educational and health care systems.