Online symptom checker diagnostic and triage accuracy for HIV and hepatitis C.

We sought to address the prior limitations of symptom checker accuracy by analysing the diagnostic and triage feasibility of online symptom checkers using a consecutive series of real-life emergency department (ED) patient encounters, and addressing a complex patient population - those with hepatitis C or HIV. We aimed to study the diagnostic and triage accuracy of these symptom checkers in relation to an emergency room physician-determined diagnosis. An ED retrospective analysis was performed on 8363 consecutive adult patients. Eligible patients included: 90 HIV, 67 hepatitis C, 11 both HIV and hepatitis C. Five online symptom checkers were utilised for diagnosis (Mayo Clinic, WebMD, Symptomate, Symcat, Isabel), three with triage capabilities. Symptom checker output was compared with ED physician-determined diagnosis data in regards to diagnostic accuracy and differential diagnosis listing, along with triage advice. All symptom checkers, whether for combined HIV and hepatitis C, HIV alone or hepatitis C alone had poor diagnostic accuracy in regards to Top1 (<20%), Top3 (<35%), Top10 (<40%), Listed at All (<45%). Significant variations existed for each individual symptom checker, as some appeared more accurate for listing the diagnosis in the top of the differential, vs. others more apt to list the diagnosis at all. In regards to ED triage data, a significantly higher percentage of hepatitis C patients (59.7%; 40/67) were found to have an initial diagnosis with emergent criteria than HIV patients (35.6%; 32/90). Symptom checker diagnostic capabilities are quite inferior to physician diagnostic capabilities. Complex patients such as those with HIV or hepatitis C may carry a more specific differential diagnosis, warranting symptom checkers to have diagnostic algorithms accounting for such complexity. Symptom checkers carry the potential for real-time epidemiologic monitoring of patient symptoms, as symptom entries and subsequent symptom checker diagnosis could allow health officials a means to track illnesses in specific patient populations and geographic regions. In order to do this, accurate and reliable symptom checkers are warranted.

Syndromic surveillance and its utilisation for mass gatherings.

Tremendous advancements in syndromic surveillance strategies over the last two decades, and specifically from prior mass gatherings, have been incorporated into day-to-day healthcare analysis worldwide and have left a lasting indirect impact since their inception. Mass gatherings are a daily occurrence worldwide and provide a scenario ripe for public health aims and objectives utilising syndromic surveillance. Europe is less than a decade away from hosting a colossal worldwide gathering (2024 Summer Olympics) in likely a time when the global agreement is in flux. A call to arms is needed for additional surveillance strategies incorporating mobile application symptom checker data, telemedicine, social media and social data sensing. There remains a need for an optimal combination of real-time data sensing that captures the whole population, but to reach that goal we must incorporate new advancements into baseline epidemiologic data monitoring, otherwise we will be tracking real-time mass gathering events on top of inaccurate baseline epidemiologic data.

Inactivation of the luteinizing hormone/chorionic gonadotropin receptor by an insertional mutation in Leydig cell hypoplasia.

We previously identified a nonsense mutation (Cys545Stop) in the paternal human LH/CG receptor (hLHR) allele in a family with two 46,XY children afflicted with Leydig cell hypoplasia. This mutation abolished the signal transduction capability of the affected hLHR. We have now examined all coding exons and the transcript of both alleles of the hLHR gene of the affected children. A 33-bp in-frame insertion was found in the maternal hLHR allele. This insertion occurred between nucleotide 54 and 55 and might be the result of a partial gene duplication. Genomic DNA-PCR showed that this defective maternal hLHR allele was inherited by the two affected children. However, examination of the inheritance of the 935-A/G polymorphism of the hLHR by genomic- and RT-PCR indicated that the maternal hLHR allele was not expressed in cultured fibroblasts of the patients. The effect of the in-frame insertion on the biological activity of the hLHR was examined by expressing the mutated hLHR construct, generated by site-directed mutagenesis, in HEK 293 cells. The expression of the mRNA for the mutant hLHR in HEK 293 cells was not affected. Response of cells expressing the mutated hLHR to hCG stimulation was impaired as demonstrated by reduced intracellular cAMP biosynthesis. This change in signal transduction was the result of a profound reduction in hormone binding at the cell surface due to altered expression and processing of the mutated receptor. We conclude that Leydig cell hypoplasia in this family is the result of compound heterozygous loss-of-function mutations of the hLHR gene.

Chondrodysplasia punctata: another possible X-linked recessive case.

A 22-week fetus who had died in utero had a markedly hypoplastic nose and other facial abnormalities, short fingers, hypoplastic nails, and small phallus. Radiologically there was symmetrical cartilaginous stippling of the vertebral column, femoral heads, calcanei and elbows typical of chondrodysplasia punctata (CP), and metacarpal shortness and tiny pyramidal phalanges. The several causally different forms of CP are tabulated. Differential diagnosis suggests that the present case, which does not have limb shortness, could be a case of X-linked recessive brachytelephalangic chondrodysplasia punctata.

Monozygotic twins discordant for the oculo-oto-radial syndrome (IVIC syndrome).

Monozygotic twins are rarely completely identical despite their origin from a single zygote. The twinning process itself, or the very early intrauterine environment must provide the clues to explain this developmental dilemma. We present here discordant monozygotic twin girls, one of whom was diagnosed having IVIC (Oculo-oto-radial) syndrome on the basis of hand abnormalities and hearing loss but her twin sister has only strabismus. The family has at least 7 apparently and 2 possible affected members (gene carriers) over four generations, the majority being only midly affected. The 2 girls, whose monozygosity has been proved using independent DNA loci, show marked variability in expression, showing that for this gene modification of expression must be epigenetic or environmental rather than genetic.

A new lethal chondrodysplasia with platyspondyly, long bone angulation and mixed bone density.

A fetus diagnosed by sonography at 20 weeks' gestation had multiple skeletal abnormalities. The main features were absent ossification of the skull and cervical and upper thoracic vertebral bodies; short, angulated femora, tibiae, radii and ulnae but normal humeri; platyspondyly; trident-shaped acetabular roofs; sclerotic bands on the iliac wings and scapulae; clavicular hooks; and overall, mixed bone density. We suggest that this is a new chondrodysplasia which, since the parents are first cousins, could follow autosomal recessive inheritance.

Four cases of amelia of the upper limb associated with anal atresia--is this VACTERL with extreme limb involvement?

Amelia is an extremely rare abnormality with a highest reported incidence of 1 in 67,500 liveborn infants. We now report four cases in each of which amelia involving one upper limb occurred in association with anal atresia. The pattern of other abnormalities present in these cases suggests that this combination of amelia and anal atresia falls within the spectrum of the VACTERL association.

Chromosomal abnormalities in Dupuytren's contracture and carpal tunnel syndrome.

The cytogenetics of cell cultures derived from Dupuytren's tissue, adjacent palmar fascia and palmar skin from patients undergoing fasciectomy have been examined and the results compared to cell cultures established from palmar fascia, flexor retinaculum and palmar skin of patients undergoing carpal tunnel decompression. Chromosomal abnormalities were detected in cell cultures from Dupuytren's tissue in eight of the nine patients studied. Clones of cells trisomic for chromosome 8 were found in five of the nine patients. Trisomy 8 was also present in two of five flexor retinaculum cultures from carpal tunnel syndrome cases. These findings in both Dupuytren's contracture and carpal tunnel syndrome suggest the presence of chromosomal instability in the palmar fascia. The significance of the chromosomal abnormalities is however unclear, but they indicate a possible common pathway in the onset of pathological fibrosis.

Venous ulceration in males with sex chromosome abnormalities.

Two patients with Klinefelter's syndrome and three with 47,XYY who had venous ulcers, and one patient with 47,XYY and a post thrombotic limb are described. Sex chromosome abnormalities should be suspected in tall males with leg ulcers, especially those who have no progeny and are relatively young. Venous ulcers may be more common in males with 47,XYY.

The anthropological value of minor variants of the dental crown.

The incidences of 31 minor variants of the dental crown were scored from dental casts of samples taken from six European populations. Although several variants showed significant sex bias in one or other sample, only one (pits instead of furrow on premolar2) consistently favoured one sex. Associations between the variants were sought. Although few consistent associations were demonstrated, there was a possible tendency for extra cusps to occur together throughout the dentition. Distance statistics calculated between the samples were compatible with the expected genetical relationships of the samples, but only modern samples could be used since variants were destroyed by attrition in archeological samples. Before such distances can be considered reliable, it is necessary to know: (i)the extent to which environmental factors such as diet influence variant expression. (ii)whether or not variant bearing teeth are selectively destroyed by caries, which in civilised populations render a high proportion of most dentitions unscoreable.

Factors affecting the incidence of non-metrical skeletal variants.

Non-metrical variants of the human cranium have been studied in 186 London crania of known age, sex and date of birth. The incidence of several variants was different in the two sexes, and these results were compared with those of other workers from different parts of the world. Few variants persistently favoured one sex: the majority behaved inconsistently. Age dependency was only demonstrated for one variant, while year of birth, presence of rickets, and spina bifida occulta, showed negligible influence on variant incidence. 20% of vertebral columns examined included an anomalous vertebra, usually sacral spina bifida occulta. Although family studies were largely inconclusive, this investigation provides no reason to doubt the basic genetical control of these variants.

Familial transmission of a non-Robertsonian translocation dicentric.

A second family showing transmission of a dicentric through three generations involving chromosomes 13 and 18 is presented. Features of non-Robertsonian dicentric chromosomes are presented and discussed.

A child with partial monosomy 6q secondary to a maternal direct insertional event.

We report a child, now aged two years, who is monosomic for the region 6q23.1----q24.2. Her mother, older sister, and twin sister have a balanced chromosome complement with this region of 6q being inserted into 11q.

Three children with partial trisomy 1q and partial monosomy 3p.

We report a kindred in which three children suffer from partial trisomy 1q and partial monosomy 3p, transmitted by a balanced translocation which is maternal in one family and paternal in the other. The clinical features of the three children are similar and include severe mental handicap and severe scoliosis in the older two.

Unknown syndrome: congenital heart disease, choanal stenosis, short stature, developmental delay, and dysmorphic facial features in a brother and sister.

We report a brother and sister born to non-consanguineous parents. They both had an atrial septal defect and ventricular septal defect. In addition they had short stature, microcephaly, developmental delay, and the same dysmorphic facial appearance of a short nose, epicanthic folds, a long philtrum, and narrow upper lip. The boy had bilateral choanal hypoplasia and stenosis.

A new X linked syndrome with mental retardation and craniofacial dysmorphism?

We present a syndrome manifested in two half brothers and their two maternal aunts which is characterised in the two boys by severe mental retardation and craniofacial dysmorphism (broad, coarse features and marked plagiocephaly with flattened occiput), and in the aunts merely by moderate mental retardation without dysmorphic features. The brothers do not seem to fall into any previously described X linked syndrome with mental retardation.