Correction: Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

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Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.

Vitamin E protects rat mesenchymal stem cells against hydrogen peroxide-induced oxidative stress in vitro and improves their therapeutic potential in surgically-induced rat model of osteoarthritis.

OBJECTIVE: Oxidative stress is a major obstacle against cartilage repair in osteoarthritis (OA). Anti-oxidant agents can play a vital role in addressing this issue. We evaluated the effect of Vitamin E preconditioning in improving the potential of mesenchymal stem cells (MSCs) to confer resistance against oxidative stress prevailing during OA. METHODS: Vitamin E pretreated MSCs were exposed to oxidative stress in vitro by hydrogen peroxide (H2O2) and also implanted in surgically-induced rat model of OA. Analysis was done in terms of cell proliferation, apoptosis, cytotoxicity, chondrogenesis and repair of cartilage tissue. RESULTS: Vitamin E pretreatment enabled MSCs to counteract H2O2-induced oxidative stress in vitro. Proliferative markers, proliferating cell nuclear antigen (PCNA) and Ki67 were up-regulated, along with the increase in the viability of MSCs. Expression of transforming growth factor-beta (TGFß) was also increased. Reduction of apoptosis, expression of vascular endothelial growth factor (VEGF) and caspase 3 (Casp3) genes, and lactate dehydrogenase (LDH) release were also observed. Transplantation of Vitamin E pretreated MSCs resulted in increased proteoglycan contents of cartilage matrix. Increased expression of chondrogenic markers, Aggrecan (Acan) and collagen type-II alpha (Col2a1) accompanied by decreased expression of collagen type-I alpha (Col1a1) resulted in increased differentiation index that signifies the formation of hyaline cartilage. Further, there was an increased expression of PCNA and TGFß genes along with a decreased expression of Casp3 and VEGF genes with increased histological score. CONCLUSION: Taken together results of this study demonstrated that Vitamin E pretreated MSCs have an improved ability to impede the progression of OA and thus increased potential to treat OA.

Mutations of SGO2 and CLDN14 collectively cause coincidental Perrault syndrome.

Perrault syndrome (PS) is a genetically heterogeneous disorder characterized by primary ovarian insufficiency (POI) in females and sensorineural hearing loss in males and females. In many PS subjects, causative variants have not been found in the five reported PS genes. The objective of this study was to identify the genetic cause of PS in an extended consanguineous family with six deaf individuals. Whole exome sequencing (WES) was completed on four affected members of a large family, and variants and co-segregation was confirmed by Sanger sequencing. All hearing impaired individuals, including the proband, are homozygous for a pathogenic variant of CLDN14, but this only explains the deafness. The PS proband is also homozygous for a frameshift variant (c.1453_1454delGA, p.(Glu485Lysfs*5)) in exon 7 of SGO2 encoding shugoshin 2, which is the likely cause of her concurrent ovarian insufficiency. In mouse, Sgol2a encoding shugoshin-like 2a is necessary during meiosis in both sexes to maintain the integrity of the cohesin complex that tethers sister chromatids. Human SGO2 has not previously been implicated in any disorder, but in this case of POI and perhaps others, it is a candidate for unexplained infertility.

exomeSuite: Whole exome sequence variant filtering tool for rapid identification of putative disease causing SNVs/indels.

Exome and whole-genome analyses powered by next-generation sequencing (NGS) have become invaluable tools in identifying causal mutations responsible for Mendelian disorders. Given that individual exomes contain several thousand single nucleotide variants and insertions/deletions, it remains a challenge to analyze large numbers of variants from multiple exomes to identify causal alleles associated with inherited conditions. To this end, we have developed user-friendly software that analyzes variant calls from multiple individuals to facilitate identification of causal mutations. The software, termed exomeSuite, filters for putative causative variants of monogenic diseases inherited in one of three forms: dominant, recessive caused by a homozygous variant, or recessive caused by two compound heterozygous variants. In addition, exomeSuite can perform homozygosity mapping and analyze the variant data of multiple unrelated individuals. Here we demonstrate that filtering of variants with exomeSuite reduces datasets to a fraction of a percent of their original size. To the best of our knowledge this is the first freely available software developed to analyze variant data from multiple individuals that rapidly assimilates and filters large data sets based on pattern of inheritance.

Combination of ADMSCs and chondrocytes reduces hypertrophy and improves the functional properties of osteoarthritic cartilage.

OBJECTIVE: To evaluate the therapeutic efficacy of Adipose derived MSCs (ADMSCs) in combination with chondrocytes in counteracting oxidative stress in chondrocytes in vitro and in rat model of osteoarthritis (OA). METHOD: Cultured chondrocytes were exposed to oxidative stress with 200 µM Hydrogen peroxide (H2O2), followed by co-culture with ADMSCs or chondrocytes or combination of both cell types in a transwell culture system for 36 h. The cytoprotective effect was assessed by immunocytochemistry and gene expression analysis. In vivo study evaluated therapeutic effect of the above mentioned three treatments after transplantation in OA rats. RESULTS: The Combination of ADMSCs + Chondrocytes decreased the extent of oxidative stress-induced damage of chondrocytes. Enhanced expression level of Acan and Collagen type-II alpha (Col2a1) with a correspondingly decreased expression of Collagen type-I alpha (Col1a1) and Matrix metallopeptidase 13 (Mmp13) was maximally observed in this group. Moreover, reduced count of annexin-V positive cells, Caspase (Casp3) gene expression and Lactate dehydrogenase (LDH) release with concomitantly enhanced viability and expression of proliferating cell nuclear antigen (PCNA) gene was observed. In vivo study showed that homing of cells and proteoglycan contents of knee joints were significantly better in ADMSCs + Chondrocytes transplanted rats. Increased expression of Acan and Col2a1 along with decreased expression of Col1a1 and Mmp13 indicated formation of hyaline cartilage in this group. These rats also demonstrated significantly reduced expression of Casp3 while increased expression of PCNA genes than the other cell transplanted groups. CONCLUSIONS: Our results demonstrated that a combination of ADMSCs and chondrocytes may be a more effective therapeutic strategy against OA than the use of ADMSCs or chondrocytes separately.

Burden and distribution of dengue infection in Pakistan (2000-19): a review.

The goal of this study is to review the overall prevalence, burden, and distribution of the dengue disease in Pakistan from 2000 to 2019. Literature was searched using different search engines like Google scholar, PubMed, etc. providing the keywords "Dengue disease/infection, Dengue virus, DENV, DF/DHF/ DSS Pakistan". All the published research papers/reports on the dengue virus over the period 2000 to 2019 were studied and selected data were summarized using MS Excel for windows such as total cases, age wise, gender, DENV serotype distribution, total DHF, and DSS patients. The literature providing insufficient data was excluded. The total number of cases reported during 2000-19 were 201,269. The maximum number of cases during the mentioned literature survey period was reported in Khyber Pakhtunkhwa (KP) (23.3%) followed by Punjab (3.8%) and Sindh (1.9%). The majority of dengue-infected cases were reported as Dengue fever (74.4%) followed by DHF (24.1%) and DSS (1.5%). Overall the deaths during the mentioned literature survey were 1082, of which the maximum mortalities were reported from KP (N=248) followed by Punjab (N=220). DENV remains a major public health problem in Pakistan and seems to remain endemic for a long time. The total prevalence of dengue infection is increased accordingly with time from 2000 to 2019. Moreover, all the four serotypes exist in Pakistan with increased mortalities.

Toxoplasma gondii in lactating animals: potential risk to milk consuming population in Khyber Pakhtunkhwa.

Toxoplasma gondii is an intracellular zoonotic protozoan parasite usually infects human and animal worldwide. This study aimed to analyze the sero-prevalence of T. gondii in blood of lactating animals and human living in close proximity and also to detect Toxoplasma DNA in unpasteurized milk of the studied animals. A total of 233 blood and milk samples were collected from lactating animals, and 735 blood samples were taken from humans in District Upper Dir, Khyber Pakhtunkhwa, Pakistan. The blood samples were analyzed through ELISA while the milk samples were analyzed by PCR for the presence of T. gondii DNA. A standard questionnaire was introduced to collect the data from the participants. In animals, the reported sero-prevalence was 32.18% for IgM, 17.16% for IgG, and 6.4% for both IgM and IgG. The reported positivity for T. gondii DNA in milk was 14.44%, 34.8%, 20%, and 26% in sheep, goats, cows, and buffaloes, respectively. In the human blood samples, 9.8% were found positive for IgM and 11.2% for IgG while none of the samples was found positive for both IgM and IgG. Overall sero-prevalence reported in females was significantly higher than the male (p<0.05) poor hygiene condition (p < 0.0001) were the significant risk factors associated with T. gondii infections in animals. In conclusion, T. gondii infection is prevalent in lactating animals and humans using their raw milk in the study area. It is suggested that raw milk should be considered as a vehicle for the transmission of T. gondii to humans. Proper pasteurization of milk is very useful in limiting the transmission of infection. Awareness and control programs should be implemented to prevent the infection.

Effects of transition metal substitutions on the incommensurability and spin fluctuations in BaFe2As2 by elastic and inelastic neutron scattering.

The spin fluctuation spectra from nonsuperconducting Cu-substituted, and superconducting Co-substituted, BaFe(2)As(2) are compared quantitatively by inelastic neutron scattering measurements and are found to be indistinguishable. Whereas diffraction studies show the appearance of incommensurate spin-density wave order in Co and Ni substituted samples, the magnetic phase diagram for Cu substitution does not display incommensurate order, demonstrating that simple electron counting based on rigid-band concepts is invalid. These results, supported by theoretical calculations, suggest that substitutional impurity effects in the Fe plane play a significant role in controlling magnetism and the appearance of superconductivity, with Cu distinguished by enhanced impurity scattering and split-band behavior.

Antibiotic resistance in patients with urinary tract infections in Pakistan.

BACKGROUND: The level of antibiotic resistance of pathogens causing uncomplicated urinary tract infections (UTIs) is increasing. The 2017-2018 GLASS (Global Antimicrobial Resistance and Use Surveillance System) report indicated >70% resistance to ceftriaxone and ciprofloxacin in Escherichia coli in Pakistan. METHODS: A prospective study was conducted in the Médecins Sans Frontières (MSF) supported Timurgara District Hospital, Timurgara, Pakistan, from September 2017 to December 2018. Women aged 18-65 years presenting to the Emergency Department with symptoms of uncomplicated UTI (cystitis/pyelonephritis) were invited to participate. We conducted microbiological culture and sensitivity testing for samples with positive dipstick or nitrite test. RESULTS: Of the 200 patients who participated, 109 (54.5%) were diagnosed with pyelonephritis and 91 (45.5%) with cystitis. Forty-three samples (21.5%) were culture-positive: E. coli was isolated in 27 samples, Enterococcus spp. in 7 and Klebsiella pneumoniae in 6. Overall resistance to ciprofloxacin was observed in 51.8% of E. coli isolates, and ceftriaxone resistance in 66.7% of E. coli isolates and in 33.3% of K. pneumoniae. Resistance to fosfomycin was low (one E. coli isolate). CONCLUSIONS: This study found resistance to first- and second-line antibiotics for treating UTIs as per the MSF protocol. Heightened awareness and potential changes to local prescription practices are necessary to curb the spread of antimicrobial resistance pathogens causing UTIs.

OBJECTIF: Le taux de résistance aux antibiotiques des pathogènes responsables d'infections urinaires non compliquées (UTI) est en hausse. Le rapport GLASS (Global Antimicrobial Resistance and Use Surveillance System) 2017­2018 a indiqué un taux de résistance >70% à la ceftriaxone et à la ciprofloxacine chez Escherichia coli (Pakistan). MÉTHODES: Une étude prospective a été réalisée dans l'hôpital du district de Timurgara géré par Médecins Sans Frontières (MSF), de septembre 2017 à décembre 2018. Les femmes de 18­65 ans consultant aux Urgences avec des symptômes d'UTI non compliquée (cystite/pyélonéphrite) ont été invitées à participer. Nous avons réalisé une culture microbiologique et un test de sensibilité pour les échantillons positifs à la bandelette urinaire et au test de détection des nitrites. RÉSULTATS: Deux cents patients ont participé, dont 109 (54,5%) avaient un diagnostic de pyélonéphrite et 91 (45,5%) un diagnostic de cystite. Quarante-trois échantillons (21,5%) étaient positifs à la culture ; E. coli a été isolé de 27 échantillons, Enterococcus spp. de sept échantillons et Klebsiella pneumoniae de six échantillons. Une résistance à la ciprofloxacine a été observée chez 51,8% des isolats de E. coli, et une résistance à la ceftriaxone chez 66,7% des isolats de E. coli et chez 33,3% des isolats de K. pneumoniae. La résistance à la fosfomycine était faible (un isolat de E. coli). CONCLUSIONS: Cette étude a rapporté une résistance aux antibiotiques de première et deuxième intention utilisés dans le traitement des UTI, conformément au protocole de MSF. Une sensibilisation accrue et un éventuel changement des pratiques locales de prescription sont nécessaires pour freiner la propagation des pathogènes responsables d'UTI résistants aux antimicrobiens.

Molecular detection and prevalence of Rotavirus with acute gastroenteritis among the children of rural and urban areas.

Rotavirus is the main infective agent of acute gastroenteritis (AGE) in children under the age of five years and causing significant morbidity as well as mortality throughout the world. The study was carried out to detect the prevalence rate, genotypes strain and risk factors of Rotavirus among the children of rural and urban areas of district Bannu Khyber Pakhtunkhwa Pakistan. A total of 180 stool samples were collected from children under the age of 5 years from two major hospitals of Bannu from January to December (2015). The samples were analyzed by Reverse-transcriptase Polymerase Chain Reaction (RT-PCR) for the detection of Rotavirus, positive samples were further processed for genotyping (G and P type) through specific PCR. Of the total, 41 (23%) samples were positive for Rotavirus. The most prevalent G genotypes found were: G3, G8, G9 (each 29%), followed by G10 (15%), and G11 (10%). Whereas the prevalent P genotypes were: P-8 (25%), P-4 and P-10 (each 20%), P-9 (15%), followed by P-6 and P-11 (each 10%). Moreover, Rotavirus infection was more prevalent in summer (23.73%) and winter (22.7%) than spring (20%) and autumn (21.4%). Rotavirus infection exhibited high frequency in June (14%), October (8%) and November (6%). It is concluded that Rotavirus is more prevalent in children and various genotypes (G and P) of Rotavirus are present in the study area. Lack of studies, awareness and rarer testing of Rotavirus are the principal reasons of virus prevalence in district Bannu, Pakistan.

Population distribution and habitat analysis of Rufous treepie (Dendrocitta vagabunda) in Abbottabad, Pakistan.

The Rufous treepie (Dendrocitta vagabunda) belongs to family corvidae, order Passeriformes which includes about 100 species. The current study was conducted to gather information about the Population distribution and habitat analysis of D. vagabunda at District Abbottabad, Pakistan. The data were collected on monthly basis both morning and evening times (2018-2019). "The ''Point count Method" was used for population estimation and ''Quadrates Method" for habitat analysis of study area. The result shows an average month-wise population density of D. vagabunda was maximum at Jhangra 0.14±0.039/ha, whereas minimum at Havelian 0.11±0.022/ha. There was no significant difference (p>0.05) among monthly population densities of D. vagabunda, however, a significant difference (p<0.05) was found between morning and evening times population of the specie. The present study revealed that importance value index (IVI) of plants species at Sherwan, Bakot, Havelian, Langra and Jhangra were 59.6±12.6, 50.1±6.9, 53.4±6.3, 66.8±10 and 60.1±7.7. Likewise, the frequency of shrubs at Sherwan, Bakot, Havelian, Langra and Jhangra were 33.3±4.2, 45±9.4, 46.7±8.2, 55.6±22.2 and 37.5±8.5. Similarly, the frequency of herbs at Sherwan, Bakot, Havelian, Langra and Jhangra were 40.4±6.0, 37.5±5.6, 53.3±7.4, 48.5±5.2 and 46.9±7.4 respectively. Our results show the study area as suitable habitat for D. vagabunda.

Comparison of different diagnostic modalities for isolation of Mycobacterium Tuberculosis among suspected tuberculous lymphadenitis patients.

Tuberculosis is a communicable disease with high morbidity and mortality rates in developing countries. The study's primary objective is to compare conventional methods such as acid-fast bacillus (AFB) culture and microscopy with rapid diagnostic methods. The secondary objective is to compare histopathological and microbiological findings in suspected patients with tubercular lymphadenitis. A total of 111 samples (August 2018 to September 2019) of lymph nodes were processed for AFB microscopy, AFB cultures, drug-susceptibility testing (DST), histopathology, and Xpert Mycobacterium Tuberculosis (MTB)/resistance to Rifampin (RIF) assays. Out of 111 lymph node samples, 6 (5.4%) were positive for AFB smear microscopy, 84 (75.6%) were positive for AFB culture, 80 (70.7%) were positive on Gene Xpert, and 102 (91.8%) were indicative of tuberculosis for histopathology studies. Mycobacteria growth indicator tube (MGIT) culture positivity was 84 (75.6%) higher than solid Lowenstein-Jensen (LJ) culture 74 (66.6%). Positive cultures underwent phenotypic DST. Two cases were Multidrug-resistant (MDR) on DST, while three cases were Rifampicin resistant on Gene Xpert. The sensitivity of Genexpert was (62%) against the conventional AFB culture method. The poor performance of conventional lymphadenitis diagnostic methods requires early and accurate diagnostic methodology. Xpert MTB/RIF test can help in the treatment of multidrug-resistant TB cases. Nonetheless, rapid and conventional methods should be used for complete isolation of Mycobacterium tuberculosis.

Current trends of Hepatitis C virus genotypes and associated risk factors in hemophilia patients in Pakistan.

Hemophilia is a rare bleeding disorder that needs plasma or clotting factor concentrate transfusion. Therefore chances of blood-borne pathogens like HCV transmission increase due to high prevalence in healthy donors. This study was aimed to determine the prevalence of HCV genotypes and associated risk factors in hemophilia patients of Khyber Pakhtunkhwa, Pakistan. Blood samples and data were collected from 672 hemophiliacs after proper consent obtained from each patient. Samples were analyzed for anti-HCV, HCV RNA and HCV genotype/s detection. Of the total, 22.32% (150) were anti-HCV positive, of which HCV RNA was detected in 18.45% (124) individuals. HCV genotype 3a was found with significantly higher prevalence (p<0.05) (19.35%) as compared to 2a (16.13%) and 1a (12.90%). HCV-3b and HCV-4 were found each in 3.22% samples. Dual infection of genotypes was found in 22.58% of individuals and 22.58% HCV RNA positive sampels were not typed. A total of 572 (85.12%) subjects had hemophilia A and 100 (14.88%) had hemophilia B. In hemophiliacs A the most dominant genotype was 3a (19.27%) while in hemophilia B, genotype 1a was prevalent (26.67%). Whole blood and plasma transfusion were observed as the main risk factors of HCV. It is concluded that HCV genotype 3a and 2a are prevalent in hemophilia patients of Khyber Pakhtunkhwa Pakistan and the main risk factor observed was an unscreened whole blood transfusion.

Prevalence and antibiotic susceptibility pattern of uropathogens in outpatients at a tertiary care hospital.

Globally, urinary tract infection (UTI) is considered a major public health concern and the second most common bacterial infection affecting individuals of different ages. Bacteria are responsible for about 95% of UTIs. The emergence of antimicrobial resistance in uropathogens may lead to poor treatment outcomes in individuals with UTIs. The knowledge of the microorganism involves and antibiograms are important for the empirical treatment of UTIs. A cross-sectional study was carried out over 7 months (January to July 2019) with a focus on the identification of bacterial pathogens causing UTI and the evaluation of their antibiogram. In total, 804 urine samples were collected from individuals with suspected UTIs and inoculated on recommended media. Isolation and identification of the bacterial strains were performed using standard microbiological protocols. Antibiotic susceptibility was carried out following CLSI recommended guidelines. Among the tested specimens, 290 (36.1%) had significant bacterial growth and 147 (50.7%) of the strains were isolated from female patients. The frequently identified isolates were Escherichia coli (68.9%), followed by Klebsiella pneumoniae (8.9%) and Staphylococcus aureus (6.7%). The highest percentages of resistance have been observed against tested antibiotics. The majority of the isolates were extended-spectrum ß-lactamase producers (85.2%) and multidrug-resistant (98.3%). We observed that Gram-negative bacteria were the main cause of UTIs where the predominant microorganism was E. coli.

USH1H, a novel locus for type I Usher syndrome, maps to chromosome 15q22-23.

Usher syndrome (USH) is a hereditary disorder associated with sensorineural hearing impairment, progressive loss of vision attributable to retinitis pigmentosa (RP) and variable vestibular function. Three clinical types have been described with type I (USH1) being the most severe. To date, six USH1 loci have been reported. We ascertained two large Pakistani consanguineous families segregating profound hearing loss, vestibular dysfunction, and RP, the defining features of USH1. In these families, we excluded linkage of USH to the 11 known USH loci and subsequently performed a genome-wide linkage screen. We found a novel USH1 locus designated USH1H that mapped to chromosome 15q22-23 in a 4.92-cM interval. This locus overlaps the non-syndromic deafness locus DFNB48 raising the possibility that the two disorders may be caused by allelic mutations.

Novel effect of plant lectins on the inhibition of Streptococcus mutans biofilm formation on saliva-coated surface.

AIMS: Dental caries is caused by the disturbance in oral homeostasis, marked by a notable increase in the population of Streptococcus mutans. Lectins are a group of plant proteins that are capable of recognizing the glycoconjugates present on the bacterial surface. The aim of this study was to evaluate the effect of seven plant lectins on the growth and initial adhesion of S. mutans. METHODS AND RESULTS: Lectins of different carbohydrate specificities were isolated from plant sources by conventional methods of protein purification. The effect on growth of S. mutans was evaluated following CLSI guidelines. None of the lectins used in this study inhibited the bacterial growth and multiplication. The adherence and biofilm formation of bacteria to saliva-coated polystyrene plates was tested in the presence of plant lectins. All the plant lectins tested, inhibited both the adherence and biofilm in a concentration dependent manner. Confocal microscopy and scanning electron microscopy were employed to assess the biofilm formation in the presence of plant lectin (glucose/mannose-specific) at sub-minimal inhibitory concentrations. These evaluations revealed that lectins inhibited the clumping and attachment of S. mutans. CONCLUSIONS: Lectins tested here inhibited initial biofilm formation by S. mutans. Glucose/Mannose-specific lectin altered the adhesion arrangement of the bacteria on the saliva-coated surfaces. SIGNIFICANCE AND IMPACT OF THE STUDY: The plant lectins used in this study may offer a novel strategy to reduce development of dental caries by inhibiting the initial adhesion and subsequent biofilm formation of S. mutans.

Paramedic-led prehospital thrombolysis is safe and effective: the East Anglian experience.

INTRODUCTION: Prehospital thrombolysis has been shown to improve patient outcomes in clinical trials and this has been confirmed in the ongoing large national myocardial infarction registry (Myocardial Infarction National Audit Project; MINAP) reports. This paper describes a system to improve the delivery of prehospital thrombolysis and the associated governance requirements to gain maximum patient benefit. METHODS: Demographic data were prospectively collected on all patients treated by the East Anglian Ambulance Trust with bolus thrombolytics for a presumed diagnosis of ST elevation myocardial infarction between November 2003 and February 2007. Survival status was determined from the NHS strategic tracing service. RESULTS: 1062 patients (mean age 64.0 years (SD 10.6), 795 men) were treated in this time period. There were 71 deaths in this group, with actuarial survival of 93.9% (SE 0.9%) at 30 days, 91.7% (SE 1.0%) at 6 months and 90.8% (SE 1.1%) at 12 months after treatment. Age and cardiac arrest were most strongly associated with mortality (both p<0.001). Twelve (1.2%) patients received thrombolysis that on review was considered inappropriate. There were no deaths in this subgroup. CONCLUSIONS: Prehospital thrombolysis can be administered safely by ambulance staff supported by a Trust clinical support system with excellent clinical outcomes.

Revision of an infected total hip arthroplasty: the need for the adjustment of risk in bundled payment models for revision arthroplasty.

AIMS: The aim of this study was to investigate the differences in 30-day outcomes between patients undergoing revision for an infected total hip arthroplasty (THA) compared with an aseptic revision THA. PATIENTS AND METHODS: This was a retrospective review of prospectively collected data from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database, between 2012 and 2017, using Current Procedural Terminology (CPT) codes for patients undergoing a revision THA (27134, 27137, 27138). International Classification of Diseases Ninth Revision/Tenth Revision (ICD-9-CM, ICD-10-CM) diagnosis codes for infection of an implant or device were used to identify patients undergoing an infected revision THA. CPT-27132 coupled with ICD-9-CM/ICD-10-CM codes for infection were used to identify patients undergoing a two-stage revision. A total of 13 556 patients were included; 1606 (11.8%) underwent a revision THA due to infection and there were 11 951 (88.2%) aseptic revisions. RESULTS: Patients undergoing an infected revision had a significantly greater length of stay of more than three days (p < 0.001), higher odds of any 30-day complication (p < 0.001), readmission within 30 days (p < 0.001), 30-day reoperations (p < 0.001), and discharge to a destination other than the patient's home (p < 0.001). CONCLUSION: The findings suggest the need for enhanced risk adjustment based on the indication of revision THA prior to setting prices in bundled payment models of total joint arthroplasty. This risk adjustment should be used to reduce the chance of financial disincentives in clinical practice. Cite this article: Bone Joint J 2019;101-B:547-551.

Balloon Pulmonary Angioplasty for Chronic Thromboembolic Pulmonary Hypertension.

Chronic thromboembolic pulmonary hypertension (CTEPH) is a potentially lethal outcome of pulmonary embolism. Balloon pulmonary angioplasty (BPA) is aimed at improving pulmonary perfusion and pulmonary hemodynamics and has gained a lot of interest recently in patients either unsuitable for or refractory to surgical pulmonary endarterectomy. This article outlines the clinical features and diagnostic criteria, imaging evaluation, current medical and surgical treatment options for CTEPH. BPA is discussed in detail, focusing on the rationale, patient selection, technical details, post-procedural care and outcomes.