The changing profile of the patient undergoing coronary artery bypass surgery

The first 100 consecutive patients undergoing isolated coronary artery bypass surgery in 1975 were evaluated with respect to the incidence of operative risk factors and outcome. When compared with an identically selected group from 1985, there was significant worsening of the preoperative condition over the decade with regard to mean age (p less than 0.0005), presence of congestive heart failure (p less than 0.05), left ventricular dysfunction (p less than 0.05), severity of coronary artery disease (p less than 0.001) and incidence of emergency operation (p less than 0.05). More patients in 1985 had associated medical diseases such as diabetes (p less than 0.01) and chronic lung disease (p less than 0.005). There was an increase in the occurrence of vascular diseases (hypertension, renal dysfunction, peripheral vascular and cerebrovascular disease) (p less than 0.05). Overall operative mortality increased from 1 to 8% (p less than 0.05) over the decade. Despite the deterioration in the clinical profile of the patient undergoing coronary bypass surgery, elective procedures were still performed with low mortality. The significant increase in overall mortality was chiefly in patients undergoing emergency operation (p less than 0.05). There were also increases in operative morbidity including low output syndrome (p less than 0.01) and respiratory (p less than 0.005) and neurologic (p = 0.06) complications.     

Personality Characteristics of Patients Showing Suboptimal Cognitive Effort

This study examined the relationship between performance on the Portland Digit Recognition Test (PDRT) and the MMPI-2 in a group of veterans who were suspected of having motivation to exaggerate cognitive and/or psychiatric symptoms. Number correct on “easy” trials on the PDRT correlated inversely with MMPI-2 measures of psychopathology, whereas number correct on “hard” trials positively correlated with the same scales. Some individuals performed poorly across both types of PDRT trials and had significant MMPI-2 elevations, whereas others performed poorly only on “hard” PDRT trials and had less extreme MMPI-2 elevations. This study reinforces the need to assess the validity of both cognitive and psychiatric symptom complaints.     

Moving beyond randomized controlled trials in the evaluation of compulsory community treatment

Compulsory community treatment for people with severe mental illness remains controversial due to conflicting research evidence. Recently, there have been challenges to the conventional view that trial‐based evidence should take precedence. This paper adds to these challenges in three ways. First, it emphasizes the need for critiques of trials to engage with conceptual and not just technical issues. Second, it develops a critique of trials centred on both how we can have knowledge and what it is we can have knowledge of. Third, it uses this critique to develop a research strategy that capitalizes on the information in large‐scale datasets.     

Matchmaking facilitates the diagnosis of an autosomal‐recessive mitochondrial disease caused by biallelic mutation of the tRNA isopentenyltransferase (TRIT1) gene

Deleterious variants in the same gene present in two or more families with overlapping clinical features provide convincing evidence of a disease–gene association; this can be a challenge in the study of ultrarare diseases. To facilitate the identification of additional families, several groups have created “matching” platforms. We describe four individuals from three unrelated families “matched” by GeneMatcher and MatchMakerExchange. Individuals had microcephaly, developmental delay, epilepsy, and recessive mutations in TRIT1. A single homozygous mutation in TRIT1 associated with similar features had previously been reported in one family. The identification of these individuals provides additional evidence to support TRIT1 as the disease‐causing gene and interprets the variants as “pathogenic.” TRIT1 functions to modify mitochondrial tRNAs and is necessary for protein translation. We show that dysfunctional TRIT1 results in decreased levels of select mitochondrial proteins. Our findings confirm the TRIT1 disease association and advance the phenotypic and molecular understanding of this disorder.     

Repeat sequences in block 2 of Plasmodium falciparum merozoite surface protein 1 are targets of antibodies associated with protection from malaria

Human antibodies to the block 2 region of Plasmodium falciparum merozoite surface protein 1 (MSP1) are associated with a reduced prospective risk of clinical malaria. Block 2 is highly polymorphic, but all known alleles can be grouped into three major types. Two of these types (the K1-like and MAD20-like types) contain type-specific sequences (found in all alleles of a particular type) that flank polymorphic tripeptide repeats. These repeats contain both type-specific and subtype-specific sequences. To evaluate the antibody recognition of these parts of block 2, a new panel of six recombinant proteins was used (fused type-specific flanking sequences and two representative repeat sequences for each of the K1-like and MAD20-like types separately). Extensive testing of these antigens and full-length block 2 antigens showed that human serum immunoglobulin G antibodies induced by infection can recognize (i) type-specific epitopes in the repeats, (ii) subtype-specific epitopes in the repeats, or (iii) type-specific epitopes in flanking sequences. A large prospective study in The Gambia showed that antibodies to the repeats are strongly associated with protection from clinical malaria. The results are important for design of a vaccine to induce protective antibodies, and they address hypotheses about repeat sequences in malaria antigens.