The healthcare system costs of hip fracture care in South Africa.

Despite rapidly ageing populations, data on healthcare costs associated with hip fracture in Sub-Saharan Africa are limited. We estimated high direct medical costs for managing hip fracture within the public healthcare system in SA. These findings should support policy decisions on budgeting and planning of hip fracture services. PURPOSE: We estimated direct healthcare costs of hip fracture (HF) management in the South African (SA) public healthcare system. METHODS: We conducted a micro-costing study to estimate costs per patient treated for HF in five regional public sector hospitals in KwaZulu-Natal (KZN), SA. Two hundred consecutive, consenting patients presenting with a fragility HF were prospectively enrolled. Resources used including staff time, consumables, laboratory investigations, radiographs, operating theatre time, surgical implants, medicines, and inpatient days were collected from presentation to discharge. Counts of resources used were multiplied by unit costs, estimated from the KZN Department of Health hospital fees manual 2019/2020, in local currency (South African Rand, ZAR), and converted to 2020 US$ prices. Generalized linear models estimated total covariate-adjusted costs and cost predictors. RESULTS: The mean unadjusted cost for HF management was US$6935 (95% CI; US$6401-7620) [ZAR114,179 (95% CI; ZAR105,468-125,335)]. The major cost driver was orthopaedics/surgical ward costs US$5904 (95% CI; 5408-6535), contributing to 85% of total cost. The covariate-adjusted cost for HF management was US$6922 (95% CI; US$6743-7118) [ZAR113,976 (95% CI; ZAR111,031-117,197)]. After covariate adjustment, total costs were higher in patients operated under general anaesthesia [US$7251 (95% CI; US$6506-7901)] compared to surgery under spinal anaesthesia US$6880 (95% CI; US$6685-7092) and no surgery US$7032 (95% CI; US$6454-7651). CONCLUSION: Healthcare costs following a HF are high relative to the gross domestic product per capita and per capita spending on health in SA. As the population ages, this significant economic burden to the health system will increase.

The safety and effectiveness of minor injuries telemedicine.

OBJECTIVES: To determine the safety of minor injuries telemedicine compared with on-site specialist care, current practice, and a robust gold standard, and to assess the clinical effectiveness of this new technique. METHODS: Patients presenting to a peripheral hospital within 10 days of injury were separately assessed by each of: an emergency medicine specialist based at a district general hospital using telemedicine, a second on-site emergency medicine specialist, and an on-site general practitioner (representing current practice). The primary outcome measure was discrepancies between these three medical assessments and a gold standard. All patients were subsequently randomised to follow one of the independent treatment plans generated by the above assessments. Secondary outcomes were recovery and further use of healthcare services measured seven days after recruitment, and consultation duration. RESULTS: 600 patients were recruited over a 12 month period. Overall, 73 discrepancies were identified, with 12 important over-treatments and 11 important under-treatments. No consultation modality was clearly superior to any other, and there were no statistically significant differences in the secondary outcomes of clinical effectiveness measured at seven days. The mean duration of a telemedicine consultation (6.0 min) was almost twice as long as an on-site specialist (3.1 min) or on-site general practitioner consultation (3.4 min) (p<0.0001 in both cases). CONCLUSIONS: Minor injuries telemedicine is safe and clinically effective, providing care that is equivalent to specialist on-site assessment and the current practice of treatment by a general practitioner. There is no evidence that telemedicine provides superior care, and there are a number of process issues that may impede successful implementation of this new technique.

Essential yeast protein with unexpected similarity to subunits of mammalian cleavage and polyadenylation specificity factor (CPSF).

The 3' ends of most eukaryotic messenger RNAs are generated by internal cleavage and polyadenylation. In mammals, there is a strict dependence of both reactions on the sequence AAUAAA, which occurs upstream of polyadenylation [poly(A)] sites and which is recognized by CPSF. In contrast, cis-acting signals for yeast 3'-end generation are highly divergent from those of mammals, suggesting that trans-acting factors other than poly(A) polymerase would not be conserved. The essential yeast protein Brr5/Ysh1 shows sequence similarity to subunits of mammalian CPSF and is required for 3'-end processing in vivo and in vitro. These results demonstrate a structural and functional conservation of the yeast and mammalian 3'-end processing machineries despite a lack of conservation of the cis sequences.

Transcriptional pulse-chase analysis reveals a role for a novel snRNP-associated protein in the manufacture of spliceosomal snRNPs.

Vertebrate spliceosomal snRNAs associate with a conserved set of proteins, the Sm proteins, via a conserved RNA sequence, the Sm site. Assembly of this complex is required for the accumulation of stable snRNPs, hypermethylation of the 5' cap structure and nuclear import of the resultant particles. The function of individual core snRNP proteins is poorly understood, in part because of the difficulty of selectively inactivating individual polypeptides in vivo. Using a transcriptional pulse-chase method we have defined for the first time the steps of snRNP biogenesis in Saccharomyces cerevisiae. We describe a novel component of spliceosomal snRNPs, Brr1, which is distinct in sequence from Sm core proteins and yet which shares many of their properties, as well as a genetic interaction with the yeast homolog of Sm D1 core protein. Through a kinetic analysis of snRNP formation in wild-type and brr1 mutant cells we demonstrate specific defects in a subset of steps in the brr1 mutant: newly synthesized snRNAs are destabilized and 3'-end processing is slowed, whereas the cap hypermethylation reaction is unaffected. Notably, the stability of mature particles, as measured by promoter shut-off experiments, is normal in the absence of the Brr1 snRNP protein.

Identification of novel genes required for yeast pre-mRNA splicing by means of cold-sensitive mutations.

Genetic approaches in Saccharomyces cerevisiae have identified 38 genes required for efficient RNA splicing. The majority have been found by screening (high) temperature-sensitive (ts) mutants for those defective in splicing, an approach limited by the presence of ts hotspots and by the fact that many essential genes rarely mutate to the ts phenotype. To identify novel genes, we screened a collection of 340 cold-sensitive (cs) mutants for those that exhibited diminished splicing of several pre-mRNAs. We isolated 12 mutants in nine complementation groups. Four of these affected known genes (PRP8, PRP16, PRP22, PRP28), three of which encode RNA helicase homologues. Five genes are novel (BRR1, BRR2, BRR3, BRR4, BRR5; Bad Response to Refrigeration); mutations in these genes inhibited splicing before the first chemical step of the reaction. Analysis of BRR2 revealed it to encode an essential member of a new class of RNA helicase-like proteins that includes the yeast antiviral protein Ski2. These data validate the use of cs mutants in genetic screens and raise the possibility that RNA helicase family members are particularly prone to mutation to cold sensitivity.

CfT-I: an LTR-retrotransposon in Cladosporium fulvum, a fungal pathogen of tomato.

A retrotransposon from the fungal tomato pathogen Cladosporium fulvum (syn. Fulvia fulva) has been isolated and characterised. It is 6968 bp in length and bounded by identical long terminal repeats of 427 bp; 5 bp target-site duplications were found. Putative first- and second-strand primer binding sites were identified. Three long open reading frames (ORFs) are predicted from the sequence. The first has homology to retroviral gag genes. The second includes sequences homologous to protease, reverse transcriptase, RNAse H and integrase, in that order. Sequence comparisons of the predicted ORFs indicate that this element is closely related to the gypsy class of LTR retrotransposons. Races of the pathogen exhibit polymorphisms in their complement of at least 25 copies of the sequence. Virus-like particles which co-sediment with reverse transcriptase activity were observed in homogenates of the fungus. This is the first report of an LTR retrotransposon in a filamentous fungus.

Ribosomal DNA variation and population differentiation in Salicornia L.

Analysis of nuclear rDNA variation within and between populations of Salicornia from the salt marsh at Stiffkey, Norfolk has detected new patterns of genetic differentiation. Individual plants may have alternative 10.5 and 12 kb repeat units. A strong association between the frequency of particular genetic variants and the environmental gradient of tidal inundation was evident. Salicornia dolichostachya Moss from sandy flats on the lowest parts of the marsh, near to the seaward edge, and S. fragilis Ball & Tutin from deep creeks were both monomorphic for the 12 kb variant; in contrast, S. pusilla J. Woods, characteristic of the highest parts of the tidal range, was monomorphic for the 10-5 kb variant. The more phenotypically variable S. europaea L. and S. ramosissima J. Woods populations that are found in large areas of lower and upper marsh, respectively, were heterogeneous for rDNA variant type. Nevertheless, the frequency of the 12 kb variant was significantly higher in plants from the lower marsh than in those from upper marsh, and in plants from low-lying pans than in those from raised interfluves; the 10.5 kb variant had the converse distribution. Variation in rDNA was not obviously associated with variation in morphology, or with variations in isozyme frequency established previously. Comparison of these results with those for populations from an extensive study, ranging from Anglesey (N. Wales) to S.W. Spain and the Gulf coast of Saudi Arabia, suggested that the rDNA variation and its association with environmental variation are complex and site-dependent. Plants from Anglesey had 10.5 and 11.5 kb variants, whereas only a 10-75 kb variant was detected in material from Spain and Saudi Arabia. rDNA variants were used as genetic markers in order to test the hypothesis that Salicornia is predominantly an inbreeder; conventional breeding experiments have been hampered by its highly specialized morphology and this represents the first direct, sensitive test of an idea that has been suggested mainly on morphological and phenological grounds. Analysis of rDNA in 38 maternal plants from Stiffkey and 2112 of their progeny provided no evidence for out-crossing.

The gamma delta resolvase induces an unusual DNA structure at the recombinational crossover point.

gamma delta resolvase, a transposon-encoded protein active in site-specific recombination, induces a structural change in the DNA at the recombinational crossover point that results in enhanced intercalation of the foot-printing reagent MPE X Fe(II). The structural change correlates with the formation of a bend in the DNA: a mutant resolvase that binds to the crossover site but induces little or no bend does not promote intercalation. The properties of the mutant protein suggest that the induced structural change, which we propose is a localized kink, is required for recombination.