Large scale screening for haemoglobin disorders in southern Vietnam: implications for avoidance and management.

In order to obtain an approximate assessment of the public health burden that will be posed by the inherited disorders of haemoglobin in southern Vietnam, several thousand individuals were screened for these conditions. A smaller sample was screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency. The important haemoglobin disorders identified were beta thalassaemia, haemoglobin E and a variety of different forms of alpha thalassaemia. There were sufficient G6PD-deficient individuals to materially affect malaria control programme design. The most remarkable finding was wide variation in the gene frequencies of these conditions among the ethnic groups sampled. The approximate number of babies expected to be born with clinically significant haemoglobin disorders in Vietnam was estimated from the gene-frequency data. This study emphasizes the importance of wide-scale population screening, including ethnic subgroups, to establish the requirements for inherited haemoglobin disorder programmes in resource-limited settings.

Breast cancer malpractice litigation: A 10-year analysis and update in trends.

PURPOSE: The purpose of this study is to evaluate factors contributing to medical malpractice claims relating to breast cancer and the field of breast imaging. METHOD AND MATERIALS: A retrospective analysis of jury verdict and settlement reports in US state and federal courts on the Westlaw legal database was performed. The database was searched for 'malpractice' and 'breast cancer' related terms from 2005 to 2015. 253 cases were evaluated for factors including case outcome, award amounts, type of physician defendants, plaintiff age, stage at diagnosis, length of delay in diagnosis, and symptomatology, among other factors. Data were summarized using descriptive statistics. Logistic regression was used to evaluate associations between factors and plaintiff award. RESULTS: Median plaintiff age was 46 (IQR 39, 56). In cases that resulted in plaintiff payment, the award amount was $978,858 ± 2,308,598. Delay in diagnosis was cited as a reason for claimed negligence in 82% of cases. Mean length of delay was 17 ± 13 months. Named defendants were radiologists (43%), surgeons (27%), obstetrician/gynecologists (26%), and internal medicine/family practice (15%). Age, defendant type, and cancer stage were not significant predictors of case outcome. Failure to refer to a surgeon was twofold (OR [95% CI]: 2.44 [1.085, 5.489]) more likely to be resolved with payment compared to those cases without that factor. Cases with a delay in diagnosis of ≥12 months were twofold (OR [95% CI]: 2.129 [1.086, 4.175]) more likely to be resolved with payment compared to a delay <12 months. Patients who failed to follow up as recommended were twofold (OR [95% CI]: 2.31 [1.05, 5.10]) less likely to have their case be resolved with payment. CONCLUSION: Plaintiffs involved in breast cancer imaging related medical malpractice cases tend to be younger than the median age of diagnosis of breast cancer for US women (62 per NCI Surveillance, Epidemiology and End Results data). Breast cancer imaging suits involve physicians from multiple specialties, radiology being the most common. Delay in diagnosis ≥12 months, lack of surgeon referral, and lack of recommended follow up are related to plaintiff payments and may be areas of professional practice to target as radiology professionals. CLINICAL RELEVANCE/APPLICATION: Medical malpractice relating to breast cancer and breast imaging remains very prevalent and costly for all involved. Radiologists are being named in these lawsuits more frequently than in the past.

Neurologic Injury Predicts Plaintiff Award in Federal Cardiac Surgery Trials.

BACKGROUND: Cardiothoracic surgery is one of the more highly litigated medical specialties. The incidence and outcomes of federal cases related to cardiac surgery have not been previously explored. METHODS: A legal research service was queried for cardiac surgery-related terms. Citations and related documents were reviewed for relevance and case details. Inclusion criteria were federal district court cases involving cardiac operations. Exclusion criteria were rulings on solely procedural matters. Associations were explored using the Fisher exact test. RESULTS: Of 354 unique citations from 1956 to 2017, 19.2% (n = 68) met criteria. The highest number of cases (25% [n = 17]) were litigated in the Third Circuit. Operations involved coronary artery bypass grafting in 33.8% (n = 23), valves in 32.4% (n = 22), and congenital operations in 19.1% (n = 13). Litigation was prompted by media reporting in 10.3% (n = 7) and involved neurologic injury in 17.6% (n = 12), death in 33.8% (n = 23), and informed consent issues in 29.4% (n = 20). Findings were summary judgment for the defendant in 45.6% (n = 31), partial summary judgment in 17.6% (n = 12), dismissal in 27.9% (n = 19), and ruling for the plaintiff in 7.4% (n = 5). Of the rulings for the plaintiffs, damages had a median dollar amount of $591,300 (interquartile range, $214,2673.50 to $5,807,687.00]. In Fisher's exact test analysis, neurologic injury was significantly associated with ruling for the plaintiff (p < 0.01); death, surgeon defendant, surgical decision-making/conduct, and adult cardiac case type were not associated. CONCLUSIONS: Federal cardiac malpractice court cases are rare. Rulings in favor of the plaintiff, although also rare, are associated with neurologic injury. A comprehensive picture of cardiac surgery-related litigation will require advances in data abstraction techniques and codification.

Polythermal structure of a Himalayan debris-covered glacier revealed by borehole thermometry.

Runoff from high-elevation debris-covered glaciers represents a crucial water supply for millions of people in the Hindu Kush-Himalaya region, where peak water has already passed in places. Knowledge of glacier thermal regime is essential for predicting dynamic and geometric responses to mass balance change and determining subsurface drainage pathways, which ultimately influence proglacial discharge and hence downstream water availability. Yet, deep internal ice temperatures of these glaciers are unknown, making projections of their future response to climate change highly uncertain. Here, we show that the lower part of the ablation area of Khumbu Glacier, a high-elevation debris-covered glacier in Nepal, may contain ~56% temperate ice, with much of the colder shallow ice near to the melting-point temperature (within 0.8 °C). From boreholes drilled in the glacier's ablation area, we measured a minimum ice temperature of -3.3 °C, and even the coldest ice we measured was 2 °C warmer than the mean annual air temperature. Our results indicate that high-elevation Himalayan glaciers are vulnerable to even minor atmospheric warming.

Identification and differentiation of European and African/Australian strains of Mycoplasma mycoides subspecies mycoides small-colony type using polymerase chain reaction analysis.

Mycoplasma mycoides subspecies mycoides small-colony type (M. m. m. SC) is the cause of the economically important contagious bovine pleuropneumonia. Isolates from Africa and Australia have previously been documented to have a fragment of approximately 8.84 kb, which is absent in European strains. A set of polymerase chain reaction (PCR) primers over this region was designed to identify M. m. m. SC isolates and separate European strains from those of Africa/Australia. Specificity of the PCR assay was achieved through the positioning of an oligonucleotide within the insertion sequence IS1296, upstream of this deletion, which then was paired with a reverse primer, upstream of the deletion, within the 8.84 kb-deleted region or downstream of the deletion, generating fragments of 1.1 kb (all M. m. m. SC strains), 1.4 kb (African/Australian strains only) and 1.3 kb (European strains only), respectively. Identification and differentiation was specific for DNA from M. m. m. SC with no amplification of DNA from other cluster members or closely related species. The PCR products did not require differentiation by use of a restriction endonuclease, and have potential for use in detection of this organism in clinical samples.

Insertion sequence profiling of UK Mycoplasma bovis field isolates.

The presence and distribution of insertion sequences ISMbov2 and ISMbov3 within Mycoplasma bovis were investigated. Analysis was carried out by Southern blotting using specific probes of 221 bp and 185 bp, to detect ISMbov2 and ISMbov3, respectively, amplified from the homologous sequences ISMmy1 and IS1634 within Mycoplasma mycoides subspecies mycoides small colony type. We present data obtained from 49 field isolates of M. bovis, originating from pneumonic lungs, collected within the United Kingdom between 1996 and 2002. Hybridisation profiles show considerable variation between strains. ISMbov2 sequences are present between 2 and 17 copies while there are between 3 and 14 copies of the IS1634 homologue ISMbov3. These data also provide support for previous analysis by random amplified polymorphic DNA (RAPD) and amplified fragment length polymorphism (AFLP).

Rapid detection of Mycoplasma dispar and M. bovirhinis using allele specific polymerase chain reaction protocols.

We describe an allele specific PCR based approach for the rapid detection of two bovine Mycoplasma species associated with respiratory disease. Specific and universal oligonucleotides were used in combination to detect the presence of single nucleotide polymorphisms within the 16S ribosomal DNA sequence. Presence of Mycoplasma 16S rDNA is indicated by the production of a single control fragment, whilst positive samples generate an alternative smaller specific product over the same region. This technique provides a reliable and sensitive method which, although widely used in human genetic screening, has not been documented for diagnosis of bacterial infection.

Biofilm formation by mycoplasma species and its role in environmental persistence and survival.

Although mycoplasmas possess a very limited genome, little is known about their virulence mechanisms and methods of persistence in the host. Examination of a wide range of mycoplasma species found considerable variation in their ability to form a biofilm. Mycoplasma putrefaciens, M. cottewii, M. yeatsii, M. agalactiae and M. bovis produced prolific biofilms. Conversely, the highly pathogenic mycoplasma and causative agent of contagious bovine pleuropneumonia, Mycoplasma mycoides subsp. mycoides SC, was unable to produce a biofilm. Biofilms were found to be considerably more resistant to stress, including heat and desiccation, than planktonic cells. A link between the biofilm phenotype and genotype as determined by molecular typing was found for M. bovis. Analysis of biofilms using fluorescent staining combined with confocal microscopy demonstrated that mycoplasma biofilms formed a highly differentiated structure with stacks and channels. Biofilm formation may indicate that mycoplasmas are capable of surviving in the environment.

Hb G-Makassar [beta6(A3)Glu-->Ala; codon 6 (GAG-->GCG)]: molecular characterization, clinical, and hematological effects.

We report a Thai family in which five members are Hb G-Makassar heterozygotes and one member is, in addition, a heterozygote for beta0-thalassemia (IVS-I-1, G-->T). We confirm that the previously presumed mutation at codon 6 of the beta-globin gene is GAG-->GCG. Hb G-Makassar heterozygotes are asymptomatic and hematologically normal. The Hb G-Makassar/beta0-thalassemia compound heterozygote has features of thalassemia minor. A simple and rapid polymerase chain reaction-restriction fragment length polymorphism for the detection of Hb G-Makassar is described.

Hemochromatosis gene (HFE) mutations in South East Asia: a potential for iron overload.

Hereditary hemochromatosis (HH) is an autosomal recessive disease caused by mutations in the HFE gene that mainly affects populations of European descent. Recently a novel mutation (IVS5+1 G-->A) has been described in a Vietnamese patient with HH that was not detected in a European control population. We have developed a novel method to screen for this mutation based on restriction enzyme digestion of a PCR product using a modified forward primer. We have screened 314 Vietnamese people from several ethnic groups and 154 people from Thailand for this mutation and have detected two heterozygotes in the Vietnamese subjects (allele frequency 0.003). Analysis of these heterozygotes indicates that the mutation is on the same haplotype as that found in the original proband. Screening for the widely distributed HFE mutation, H63D, gave an allele frequency of 0.049 in the Vietnamese subjects and 0.032 in the subjects from Thailand. This is the first report of H63D allele frequencies in these populations. We suggest that the presence of the IVS5+1 G-->A and H63D mutations should be considered when investigating iron overload in Vietnamese patients and those of mixed origin as co-inheritance of both mutations is likely to be a risk factor for iron overload.