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What is the long-term outcome of the different subgroups of functional dyspepsia?

BACKGROUND: Functional dyspepsia is often a long-lasting disorder that accounts for substantial healthcare costs. It has been classified into subgroups assuming that it can guide management of dyspepsia. AIM: To evaluate the clinical significance of subgrouping functional dyspepsia in a long-term perspective study. METHODS: Consecutive patients with dyspepsia identified by general practitioners were investigated. Those patients with functional dyspepsia (n=201) were enrolled in this study. Initially, patients were divided into five subgroups (ulcer-like, dysmotility-like, reflux-like, unspecified, and irritable bowel syndrome-like). Patients' medical histories were reviewed after 6-7 years, and the number and outcome of repeated investigations were analysed. At the end of follow-up, patients filled in a questionnaire similar to that at baseline, and were invited for gastroscopy. RESULTS: Only 2% of patients developed peptic ulcer during follow-up, none of them were in the ulcer-like subgroup. When referrals to hospital and examinations during follow-up were registered, no statistically significant differences existed between subgroups. Patients with reflux-like dyspepsia made fewer revisits than others (P=0.02), but had used antidyspepsia drugs during the previous year more often (P=0.036). Stability of the subgroups over time was poor. CONCLUSIONS: Functional dyspepsia is a long-lasting disorder with a very good prognosis. Subgroups of functional dyspepsia play only a minor role in prediction of the long-term outcome, and their usefulness in clinical practice is also hampered by subgroup instability over time.

Adolescent↗

The value of maximum jaw motion measurements for distinguishing between common temporomandibular disorder subgroups.

OBJECTIVE: The purpose of this study was to determine if mandibular motion measurements could be used to distinguish between common temporomandibular disorder (TMD) subgroups that were established on the basis of only clinical signs and symptoms. STUDY DESIGN: Patients were 41 consecutive TMD clinic patients (31 women and 10 men). These patients were divided into 6 typical TMD subgroups. The subgroups were patients with (1) arthromyalgia, (2) arthromyalgia with disk condyle incoordination, (3) disk condyle incoordination only, (4) osteoarthritis, (5) suspected disk displacement without reduction, or (6) other diagnoses. RESULTS: There were no subjects in the other-diagnosis subgroup and only 1 subject with suspected disk displacement without reduction who was dropped without further consideration. The data for mean age showed that the osteoarthritis subgroup (n = 12) was statistically older (17 years) than the disk-condyle-incoordination-only subgroup (n = 11). The mean age of the other 2 groups, arthromyalgia (n = 11) and arthromyalgia with disk condyle incoordination (n = 6), was between the osteoarthritis and the disk-condyle-incoordination-only subgroups. For the 4 TMD subgroups whose data were analyzed, the mean differences between similar jaw opening measurements ranged from 6 to 8 mm with a standard deviation of approximately 8 to 10 mm. The mean left lateral motions were 0.5 to 1.3 mm larger than observed on the right. The widest mean jaw opening (56 mm) occurred in the disk-condyle-incoordination-only group. These differences were not found to be statistically significant. CONCLUSION: Analysis of opening, lateral and protrusive jaw motion data showed these measurements could not reliably differentiate between patients with osteoarthritis, arthromyalgia, arthromyalgia with disk condyle incoordination and disk condyle incoordination only.

Adult↗

Neuropsychological subgroups of patients with Alzheimer's disease: an examination of the first 10 years of CERAD data.

Neuropsychological CERAD data from 960 patients with Alzheimer's disease and 465 controls were subjected to separate yet identical classification procedures. Consistent with past research, three patient subgroups were reliably identified: Subgroup 1 (LAD; n = 312) was characterized by severe naming impairment yet borderline-normal figure-copying skills; Subgroup 2 (RAD; n = 247) displayed average naming ability but moderately-impaired copying performance; Subgroup 3 (GAD; n = 161) evinced profound anomia and constructional dyspraxia. LAD patients were older and less educated than those of the other subgroups. Control subgroups (n = 2) did not resemble the patient subgroups. Initial patterns of performance remained discernible across time for LAD and GAD, but were less consistent for RAD. Members from patient subgroups were present across disease stage.

Aged↗

Extensive sequence variation in the attachment (G) protein gene of avian pneumovirus: evidence for two distinct subgroups.

The putative attachment protein of the avian pneumovirus that causes turkey rhinotracheitis is, by analogy with mammalian pneumoviruses, expected to be the major antigenic determinant. We report the nucleotide sequence of the attachment (G) protein genes of five different continental European isolates and compare them with the previously published sequence of the G gene for the focal variant of a U.K. isolate. The nucleotide sequences and the predicted amino acid sequences indicate that there are at least two distinct subgroups, similar to the grouping described for human respiratory syncytial (RS) virus. The U.K. and French isolates form one group and the isolates from Spain, Italy and Hungary form a second. The two subgroups can be easily distinguished on the basis of restriction enzyme digestion of PCR-generated products representing the full-length gene. Within the subgroups the predicted G proteins were highly conserved (98.5 to 99.7% amino acid identity) compared to the levels of identity of RS virus G proteins in the same subgroup (80 to 95%). Between the avian pneumovirus subgroups described here there was an unexpected degree of divergence, the average amino acid identity between members of the two groups being only 38%. This compares with the 53% conservation seen between members of the RS virus subgroups A and B. Comparison of the predicted amino acid sequences showed that the G proteins of members of the two avian pneumovirus subgroups had similar structural features. All proteins had an amino-terminal membrane anchor and the positions of cysteine residues were highly conserved. The potential importance of the high level of variation between the two subgroups in terms of epidemiology of the disease is discussed.

Amino Acid Sequence↗

Nucleotide sequences of the F, L and G protein genes of two non-A/non-B avian pneumoviruses (APV) reveal a novel APV subgroup.

Sequence analysis was performed of all or part of the genes encoding the fusion (F), polymerase (L) and attachment (G) proteins of two French non-A/non-B avian pneumovirus (APV) isolates (Fr/85/1 and Fr/85/2). The two isolates shared at least 99.7% nt and 99.0% aa sequence identity. Comparison with the F genes from subgroup A, subgroup B or Colorado APVs revealed nt and aa identities of 70.0-80. 5% and 77.6-97.2%, respectively, with the L gene sharing 76.1% nt and 85.3% aa identity with that of a subgroup A isolate. The Fr/85/1 and Fr/85/2 G genes comprised 1185 nt, encoding a protein of 389 aa. Common features with subgroup A and subgroup B G proteins included an amino-terminal membrane anchor, a high serine and threonine content, conservation of cysteine residues and a single extracellular region of highly conserved sequence proposed to be the functional domain involved in virus attachment to cellular receptors. However, the Fr/85/1 and Fr/85/2 G sequences shared at best 56.6% nt and 31.2% aa identity with subgroup A and B APVs, whereas these isolates share 38% aa identity. Phylogenetic analysis of the F, G and L genes of pneumoviruses suggested that isolates Fr/85/1 and Fr/85/2 belong to a previously unrecognized APV subgroup, tentatively named D. G-based oligonucleotide primers were defined for the specific molecular identification of subgroup D. These are the first G protein sequences of non-A/non-B APVs to be determined.

Amino Acid Sequence↗

Genetic diversity and molecular epidemiology of respiratory syncytial virus over four consecutive seasons in South Africa: identification of new subgroup A and B genotypes.

The molecular epidemiology of respiratory syncytial virus (RSV) was studied over four consecutive seasons (1997-2000) in a single tertiary hospital in South Africa: 225 isolates were subgrouped by RT-PCR and the resulting products sequenced. Subgroup A predominated in two seasons, while A and B co-circulated approximately equally in the other seasons. The nucleotide sequences of the C-terminal of the G-protein were compared to sequences representative of previously defined RSV genotypes. South African subgroup A and subgroup B isolates clustered into four and five genotypes respectively. One new subgroup A and three new subgroup B genotypes were identified. Different genotypes co-circulated in every season. Different circulation patterns were identified for group A and B isolates. Subgroup A revealed more variability and displacement of genotypes while subgroup B remained more consistent.

Amino Acid Sequence↗

Oncogenicity of avian leukosis viruses of different subgroups and of mutants of sarcoma viruses.

Leukosis viruses of seven subgroups were tested for oncogenicity in chickens susceptible to virus infection and to development of lymphoid leukosis (LL) tumors. All subgroup A viruses and the subgroup B virus tested produced a high incidence of LL and other related neoplasms. Viruses of subgroup C and RAV-61 of subgroup F produced a low level of LL. The RAV-50 of subgroup D produced osteopetrosis. In these tests, the viruses of subgroup E and G and one virus of subgroup F were not pathogenic, possibly because infection was not established in the chickens, the chickens were not susceptible to tumor development by these viruses, or the viruses lacked oncogenicity. All temperature-sensitive mutants of Rous sarcoma virus produced sarcomas, but the level varied. One nontransforming mutant produced sarcomas, and the other three tested produced LL. All three mutants that cause cells to grow as colonies in agar produced a high incidence of sarcomas. Thus, sarcoma viruses, by back-mutation, may lose the ability to transform cells in vitro, to make cells grow in agar colonies, or to induce sarcomas in vivo, yet they retain the ability to produce LL. Conversely, it was previously shown that leukosis viruses may be changed into viruses that transform cells in vitro and produce sarcomas in vivo by suitable passage in chicks.

Animals↗

Enterotoxin production, presence of colonization factor antigen I, and adherence to HeLa cells by Escherichia coli O128 strains belonging to different O subgroups.

Strains of three subgroups of Escherichia coli O128 were studied. Enterotoxin production was observed in 30 (91%) O128ac strains, whereas strains of subgroups O128ab and O128ad were not toxigenic. CFA/I was only found in two serotypes of subgroup O128ac, all of them producing heat-stable enterotoxin except for one which produced both toxins. None of the strains studied produced CFA/II. In a binding test with HeLa cells, localized adherence was found only in strains of subgroup O128ab; diffuse adherence occurred in strains of subgroup O128ac. As flagellar antigens were specific in subgroups ab and ac and toxin production was observed only in subgroup ac, the present results suggest that subgroup and serotype are useful markers for O128 strains that are enterotoxigenic or enteropathogenic.

Antigens, Bacterial↗

Characterization by enzyme-linked immunosorbent assay using subgroup- and serotype-specific monoclonal antibodies of human rotavirus obtained from diarrheic patients in Bangladesh.

By enzyme-linked immunosorbent assay with group A-, subgroup-, and serotype-specific monoclonal antibodies (MAbs), we tested 414 stool specimens collected from pediatric and adult patients hospitalized with acute gastroenteritis between January and June 1988. Of 414 specimens tested, 124 (30%) were positive for group A rotavirus. The subgroup was determined in 110 specimens (88.7%); 16.1% were subgroup I, and 72.6% were subgroup II. Two specimens reacted with both subgroup I- and subgroup II-specific MAbs. Serotype determinations showed that serotype 1 (38.4%) was predominant over serotypes 2 (28.2%), 3 (2.5%), and 4 (23%). Three specimens reacted with more than one serotype-specific MAb. While the frequency of serotype 1 was highest in the two hospitals in Mymensingh, serotype 2 was most prevalent in one hospital in Dhaka. All human rotavirus strains with subgroup I and serotype 2 specificities showed a short electropherotype, and all but one strain with subgroup II and serotype 1, 3, or 4 specificities exhibited a long electropherotype.

Acute Disease↗

The Drosophila montium subgroup species. Phylogenetic relationships based on mitochondrial DNA analysis.

Mitochondrial DNA (mtDNA) restriction site maps for three Drosophila montium subgroup species of the melanogaster species group, inhabiting Indian and Afrotropical montium subgroup territories, were established. Taking into account previous mtDNA data concerning six oriental montium species, a phylogeny was established using distance-matrix and parsimony methods. Both genetic diversity and mtDNA size variations were found to be very narrow, suggesting close phylogenetic relationships among all montium species studied. The phylogenetic trees that were constructed revealed three main lineages for the montium subgroup species studied: one consisting of the Afrotropical species Drosophila seguyi, which is placed distantly from the other species, one comprising the north-oriental (Palearctic) species, and one comprising the southwestern (south-oriental, Australasian, Indian, and Afrotropical) species. The combination of the mtDNA data presented here with data from other species belonging to the melanogaster and obscura subgroups revealed two major clusters: melanogaster and obscura. The melanogaster cluster is further divided into two compact lineages, comprising the montium subgroup species and the melanogaster complex species; the species of the other complex of the melanogaster subgroup, yakuba, disperse among the obscura species. The above grouping is in agreement with the mtDNA size variations of the species. Overall, among all subgroups studied, the species of the montium subgroup seem to be the most closely related.

Animals↗

Genomic analysis of clinical samples with serologic ABO blood grouping discrepancies: identification of 15 novel A and B subgroup alleles.

Since the cloning in 1990 of complementary DNA corresponding to messenger RNA transcribed at the blood group ABO locus, polymorphisms and phenotype-genotype correlations have been reported by several investigators. Exons 6 and 7, constituting 77% of the gene, have been analyzed previously in samples with variant phenotypes but for many subgroups the molecular basis remains unknown. This study analyzed 324 blood samples involved in ABO grouping discrepancies and determined their ABO genotype. Samples from individuals found to have known subgroup alleles (n = 53), acquired ABO phenotypes associated with different medical conditions (n = 65), probable chimerism (n = 3), and common red blood cell phenotypes (n = 109) were evaluated by ABO genotype screening only. Other samples (n = 94) from apparently healthy donors with weak expression of A or B antigens were considered potential subgroup samples without known molecular background. The full coding region (exons 1-7) and 2 proposed regulatory regions of the ABO gene were sequenced in selected A (n = 22) or B (n = 12) subgroup samples. Fifteen novel ABO subgroup alleles were identified, 2 of which are the first examples of mutations outside exon 7 associated with weak subgroups. Each allele was characterized by a missense or nonsense mutation for which screening by allele-specific primer polymerase chain reaction was performed. The novel mutations were encountered in 28 of the remaining 60 A and B subgroup samples but not among normal donors. As a result of this study, the number of definable alleles associated with weak ABO subgroups has increased from the 14 previously published to 29.

ABO Blood-Group System↗

Guidelines on how to assess the validity of results presented in subgroup analysis of clinical trials.

In observational studies, identification of associations within particular subgroups is the usual method of investigation. As an exploratory method, it is the bread and butter of epidemiological research. Nearly everything that has been learned in epidemiology has been derived from the analysis of subgroups. In a randomized clinical trial, the entire purpose is the comparison of the test subjects and the controls, and when there is particular interest in the results of treatment in a certain section of trial participants, a subgroup analysis is performed. These subgroups are examined to see if they are liable to a greater benefit or risk from treatment. Thus, analyzing patient subsets is a natural part of the process of improving therapeutic knowledge through clinical trials. Nevertheless, the reliability of subgroup analysis can often be poor because of problems of multiplicity and limitations in the numbers of patients studied. The naive interpretation of the results of such examinations is a cause of great confusion in the therapeutic literature. We emphasize the need for readers to be aware that inferences based on comparisons between subgroups in randomized clinical trials should be approached more cautiously than those based on the main comparison. That is, subgroup analysis results derived from a sound clinical trial are not necessarily valid; one must not jump to conclusions and accept the validity of subgroup analysis results without an appropriate judgment.

Guidelines as Topic↗

Health outcomes among Hispanic subgroups: data from the National Health Interview Survey, 1992-95.

BACKGROUND: Within the next 50 years, Hispanics will become the largest minority group in the United States. The largest Hispanic subgroups are those of Mexican, Cuban, and Puerto Rican descent. The Hispanic population is heterogeneous in terms of culture, history, socioeconomic status (SES) and health status. In this report, various health status measures are compared across Hispanic subgroups in the United States. METHODS: National Health Interview Survey (NHIS) data aggregated from 1992 through 1995 were analyzed. NHIS is one of the few national surveys that has a sufficiently large sample size to adequately compare the different subgroups. Data are presented for four Hispanic origin subgroups--Mexican, Cuban, Puerto Rican, and "other Hispanic" persons--for the Hispanic population as a whole and for the non-Hispanic white and non-Hispanic black populations. These groups are compared with respect to several health status outcomes, providing both age-adjusted and unadjusted estimates. RESULTS: The health indicators for Puerto Rican persons are significantly worse than for the other Hispanic origin subgroups. For example, about 21% of Puerto Rican persons reported having an activity limitation, compared with about 15% of Cuban and Mexican persons and 14% of "other Hispanic" persons. In contrast, the health indicators of Cuban persons are often better than those of the other subgroups. For example, Cuban persons reported an average of 3 days per year lost from school or work, compared with about 6 days for Mexican and Puerto Rican persons and 7 days for "other Hispanic" persons. Mexican persons fare better than Puerto Rican persons on measures such as restricted activity days, bed disability days and hospitalizations. CONCLUSION: These data demonstrate clear differences in health status as well as indicators of socioeconomic status across Hispanic subgroups in the United States. Data on Hispanic subgroups facilitate the planning of public health services for various underserved populations.

Adolescent↗

Symptomatic human rotavirus subgroups, serotypes & electropherotypes in Hyderabad, India.

A total of 352 stool specimens obtained from children under 2 yr of age with acute diarrhoea, between January 1998 and March 1999, were screened for the presence of rotavirus by RNA-PAGE. Symptomatic human rotaviruses were detected in 57 of 352 (16.19%) specimens by RNA-PAGE. These 57 samples were tested for rotavirus double stranded RNA pattern and among these, 46 samples were tested for subgroup and serotype specificities. Among the 46 strains tested, 29 strains were found to be subgroup II and remaining 17 strains were subgroup I, indicating that subgroup II strains are more predominant than subgroup I strains. Subgroup I and II strains were circulating concurrently throughout the study period. Seventeen strains with 'short' RNA pattern and subgroup I specificity could not be assigned as serotype 2 strains as they exhibited cross-reactivity to MAbs specific for more than one serotype. Of the 29 subgroup II strains with 'long' RNA pattern, 16 (55.17%) were serotype 1, 8 (27.58%) were serotype 4. Five (17.24%) showed dual reactivity to serotypes 1 and 3. Our results indicated that serotype 1 and G2-like strains are predominant in Hyderabad. None of the virus strains showed an unusual RNA pattern.

DNA, Viral↗

A randomised controlled trial of four management strategies for dyspepsia: relationships between symptom subgroups and strategy outcome.

BACKGROUND: The first step in the management of uncomplicated dyspepsia in primary care often consists of prescribing empirical therapy, but in certain cases prompt endoscopy might be preferred. Any decision is usually based on the patient's symptoms and the presumed underlying pathology that causes these symptoms. AIM: To assess the relationship between symptom subgroups and the effect of management strategies on primary care patients with dyspepsia. DESIGN OF STUDY: Randomised controlled trial. SETTING: All patients presenting successively with a new episode of dyspepsia between January 1995 and November 1997. METHOD: The results of four management strategies in dyspeptic primary care patients were compared and the value of subgrouping within this trial was estimated. Patients were allocated to one of either (a) empirical treatment in which therapy was based on the presented symptoms, or empirical treatment with (b) omeprazole or (c) cisapride regardless of the presented symptoms, or (d) prompt endoscopy followed by the appropriate treatment. Patients were retrospectively classified into the subgroups for each strategy using baseline data. The yield of each strategy was measured by counting the number of strategy failures in the first year. RESULTS: Of the 349 included patients, 326 were analysed. No statistically significant difference could be demonstrated between the strategies or between the symptom subgroups. However, patients in the reflux-like subgroup showed a trend towards a better outcome in all empirical strategies. Ulcer-like dyspepsia seemed to benefit from omeprazole. The non-specific subgroup seemed to benefit from cisapride but also had the highest proportion of strategy failure. Prompt endoscopy did not appear especially useful in any subgroup. CONCLUSION: Although this study has relatively low power, we conclude that the use of symptom subgroups seems to be a sensible approach when choosing empirical therapy in dyspepsia. Patients with reflux-like symptoms seem to have the best prognosis in the first year in every strategy.

Anti-Ulcer Agents↗

Tobacco use among racial and ethnic population subgroups of adolescents in the United States.

INTRODUCTION: Limited data on cigarette smoking among population subgroups hinder the development and implementation of intervention strategies for those subgroups. Because of small sample sizes or inadequate study formats, cigarette smoking among youths has been studied mostly among broad racial or ethnic categories (e.g., Asian, Hispanic) instead of subgroups (e.g., Vietnamese, Cuban). The objective of this study was to evaluate cigarette smoking among U.S. youths by racial and ethnic subgroups. METHODS: The study used a nationally representative sample of youths aged 12 to 17 years who participated in the National Survey on Drug Use and Health in 1999, 2000, or 2001. Outcomes measured include prevalence of cigarette smoking, mean age of smoking initiation, and susceptibility to start smoking. RESULTS: The prevalence of smoking among youths aged 12 to 17 years varied among racial and ethnic subgroups, ranging from 27.9% for American Indians and Alaska Natives to 5.2% for Japanese. Among youths aged 12 to 17 years, the age of smoking initiation ranged from 11.5 years (American Indians and Alaska Natives) to 13.2 years (Japanese); the overall mean age of initiation was 12.3 years. White and African American youths were the only groups that showed a significant sex difference in age of initiation among all 14 subgroups; white and African American boys initiated smoking a few months earlier than white and African American girls. One of every four never-smokers aged 12 to 17 years was classified as susceptible to becoming a smoker. CONCLUSION: The prevalence of cigarette smoking among youths varies widely by racial and ethnic subgroup. There is a need for sustained, culturally appropriate interventions to prevent and control cigarette smoking among youths, particularly within racial and ethnic subgroups with a high prevalence of cigarette smoking.

Adolescent↗

Determination of subgroup, serotype and electropherotype of human rotaviruses obtained from diarrheic patients in the Philippines.

A total of 40 rotavirus specimens obtained from infants with acute gastroenteritis in Metro Manila, Philippines, were analyzed for their subgroup and serotype specificities and RNA electropherotype. A half (50%) of the specimens contained subgroup I human rotaviruses (HRVs), while 45% of them contained subgroup II HRVs. All subgroup II HRVs were determined to be serotype 1, except one specimen belonging to serotype 3, by an enzyme-linked immunosorbent assay with serotype specific monoclonal antibodies. However, serotype specificity of all subgroup I specimens failed to be determined. In polyacrylamide gel electrophoresis, RNAs extracted from HRVs of either subgroup showed long electropherotype. At least two electropherotypes were distinguished in subgroup I viruses, while five different patterns of viral RNA were found in subgroup II viruses.

Child, Preschool↗

Analysis and interpretation of treatment effects in subgroups of patients in randomized clinical trials.

A key principle for interpretation of subgroup results is that quantitative interactions (differences in degree) are much more likely than qualitative interactions (differences in kind). Quantitative interactions are likely to be truly present whether or not they are apparent, whereas apparent qualitative interactions should generally be disbelieved as they have usually not been replicated consistently. Therefore, the overall trial result is usually a better guide to the direction of effect in subgroups than the apparent effect observed within a subgroup. Failure to specify prior hypotheses, to account for multiple comparisons, or to correct P values increases the chance of finding spurious subgroup effects. Conversely, inadequate sample size, classification of patients into the wrong subgroup, and low power of tests of interaction make finding true subgroup effects difficult. We recommend examining the architecture of the entire set of subgroups within a trial, analyzing similar subgroups across independent trials, and interpreting the evidence in the context of known biologic mechanisms and patient prognosis.

Cardiovascular Diseases↗