Delivering Rehabilitation Care Around the World: Voices From the Field.

OBJECTIVES: To identify the challenges and common issues that the rehabilitation health workforce experienced in delivering services in different practice settings across the world. These experiences could suggest approaches to improving rehabilitation care to people in need. DESIGN: A semi-structured interview protocol centering on 3 broad research questions was conducted to collect data. The data were analyzed to identify common themes across the cohort interviewed. SETTING: Interviews were conducted using Zoom. Interviewees not able to access Zoom provided written responses to the questions. PARTICIPANTS: Participants included 30 key rehabilitation opinion leaders from different disciplines from 24 countries, across world regions and income levels (N=30). INTERVENTIONS: NA. MAIN OUTCOME MEASURES: Although rehabilitation care deficiencies differ in severity, participants reported that the demand for services consistently outstrips available care, regardless of world region or income level. Access and social barriers, particularly in rural areas and remote regions, are common challenges for those delivering and receiving rehabilitation care. RESULTS: Individual voices from the field reported both challenges and hopeful changes in making rehabilitation services available and accessible. CONCLUSIONS: The descriptive approach undertaken has allowed individual voices, rarely included in studies, to be highlighted as meaningful data. Although the research findings are not generalizable beyond the convenience cohort included without further analysis and validation in specific local practice contexts, the authentic voices that spoke out on these issues demonstrated common themes of frustration with the current state of rehabilitation services delivery but also hopefulness that more solutions are on the horizon.

A Revised Nomenclature for ToxA Haplotypes Across Multiple Fungal Species.

ToxA is one of the most studied proteinaceous necrotrophic effectors produced by plant pathogens. It has been identified in four pathogens (Pyrenophora tritici-repentis, Parastagonospora nodorum, Parastagonospora pseudonodorum [formerly Parastagonospora avenaria f. sp. tritici], and Bipolaris sorokiniana) causing leaf spot diseases on cereals worldwide. To date, 24 different ToxA haplotypes have been identified. Some P. tritici-repentis and related species also express ToxB, another small protein necrotrophic effector. We present here a revised and standardized nomenclature for these effectors, which could be extended to other poly-haplotypic genes found across multiple species.

Advancing Clinical Trial Design for Non-Muscle Invasive Bladder Cancer.

BACKGROUND: Despite recent drug development for non-muscle invasive bladder cancer (NMIBC), few therapies have been approved by the US Food and Drug Administration (FDA), and there remains an unmet clinical need. Bacillus Calmette-Guerin (BCG) supply issues underscore the importance of developing safe and effective drugs for NMIBC. OBJECTIVE: On November 18-19, 2021, the FDA held a public virtual workshop to discuss NMIBC research needs and potential trial designs for future development of effective therapies. METHODS: Representatives from various disciplines including urologists, oncologists, pathologists, statisticians, basic and translational scientists, and the patient advocacy community participated. The workshop format included invited lectures, panel discussions, and opportunity for audience discussion and comment. RESULTS: In a pre-workshop survey, 92% of urologists surveyed considered the development of alternatives to BCG as a high drug development priority for BCG-naïve high-risk patients. Key topics discussed included definitions of disease states; trial design for BCG-naïve NMIBC, BCG-unresponsive carcinoma in situ, and BCG-unresponsive papillary carcinoma; strengths and limitations of single-arm trial designs; assessing patient-reported outcomes; and considerations for assessing avoidance of cystectomy as an efficacy measure. CONCLUSIONS: The workshop discussed several important opportunities for trial design refinement in NMIBC. FDA encourages sponsors to meet with the appropriate review division to discuss trial design proposals for NMIBC early in drug development.

Transcription factor lineages in plant-pathogenic fungi, connecting diversity with fungal virulence.

Plant-pathogenic fungi span diverse taxonomic lineages. Their host-infection strategies are often specialised and require the coordinated regulation of molecular virulence factors. Transcription factors (TFs) are fundamental regulators of gene expression, yet relatively few virulence-specific regulators are characterised in detail and their evolutionary trajectories are not well understood. Hence, this study compared the full range of TFs across taxonomically-diverse fungal proteomes and classified their lineages through an orthology analysis. The primary aims were to characterise differences in the range and profile of TF lineages broadly linked to plant-host association or pathogenic lifestyles, and to better characterise the evolutionary origin and trajectory of experimentally-validated virulence regulators. We observed significantly fewer TFs among obligate, host-associated pathogens, largely attributed to contractions in several Zn2Cys6 TF-orthogroup lineages. We also present novel insight into the key virulence-regulating TFs Ste12, Pf2 and EBR1, providing evidence for their ancestral origins, expansion and/or loss. Ultimately, the analysis presented here provides both primary evidence for TF evolution in fungal phytopathogenicity, as well as a practical phylogenetic resource to guide further detailed investigation on the regulation of virulence within key pathogen lineages.

The novel avirulence effector AlAvr1 from Ascochyta lentis mediates host cultivar specificity of ascochyta blight in lentil.

Ascochyta lentis is a fungal pathogen that causes ascochyta blight in the important grain legume species lentil, but little is known about the molecular mechanism of disease or host specificity. We employed a map-based cloning approach using a biparental A. lentis population to clone the gene AlAvr1-1 that encodes avirulence towards the lentil cultivar PBA Hurricane XT. The mapping population was produced by mating A. lentis isolate P94-24, which is pathogenic on the cultivar Nipper and avirulent towards Hurricane, and the isolate AlKewell, which is pathogenic towards Hurricane but not Nipper. Using agroinfiltration, we found that AlAvr1-1 from the isolate P94-24 causes necrosis in Hurricane but not in Nipper. The homologous corresponding gene in AlKewell, AlAvr1-2, encodes a protein with amino acid variation at 23 sites and four of these sites have been positively selected in the P94-24 branch of the phylogeny. Loss of AlAvr1-1 in a gene knockout experiment produced a P94-24 mutant strain that is virulent on Hurricane. Deletion of AlAvr1-2 in AlKewell led to reduced pathogenicity on Hurricane, suggesting that the gene may contribute to disease in Hurricane. Deletion of AlAvr1-2 did not affect virulence for Nipper and AlAvr1-2 is therefore not an avirulence gene for Nipper. We conclude that the hemibiotrophic pathogen A. lentis has an avirulence effector, AlAvr1-1, that triggers a hypersensitive resistance response in Hurricane. This is the first avirulence gene to be characterized in a legume pathogen from the Pleosporales and may help progress research on other damaging Ascochyta pathogens.

Setting research priorities for management and treatment of hyperhidrosis: the results of the James Lind Alliance Priority Setting Partnership.

BACKGROUND: Hyperhidrosis is a common skin condition characterized by excessive sweating, which can negatively impact on quality of life. It is under-researched compared with other conditions of similar prevalence. AIM: To generate a Top 10 list of research priorities for the treatment and management of hyperhidrosis, with equal input from people with hyperhidrosis and healthcare professionals (HCPs). METHODS: A priority setting partnership (PSP) was established and processes from the James Lind Alliance Handbook were followed. An online survey asked participants what questions they would like research to answer. These questions were grouped into 'indicative questions', which were ranked in a second survey of 45 indicative questions. The top 23 questions were then taken to a final workshop event attended by key stakeholders, and ranked to generate the Top 10 list of research priorities. RESULTS: There were 592 questions submitted by 268 respondents for the first survey. For the second survey, 286 participants ranked the indicative questions in order of priority. At the final workshop, the Top 10 list was generated. The top three priorities were: (i) Are there any safe and effective permanent solutions for hyperhidrosis? (ii) What is the most effective and safe oral treatment (drugs taken by mouth) for hyperhidrosis? and (iii) What are the most effective and safe ways to reduce sweating in particular areas of the body? CONCLUSIONS: There are many unanswered research questions that both people with hyperhidrosis and HCPs would like to see answered. The results from this PSP will help to ensure future research funding can be directed to these areas of priority.

Variability in an effector gene promoter of a necrotrophic fungal pathogen dictates epistasis and effector-triggered susceptibility in wheat.

The fungus Parastagonospora nodorum uses proteinaceous necrotrophic effectors (NEs) to induce tissue necrosis on wheat leaves during infection, leading to the symptoms of septoria nodorum blotch (SNB). The NEs Tox1 and Tox3 induce necrosis on wheat possessing the dominant susceptibility genes Snn1 and Snn3B1/Snn3D1, respectively. We previously observed that Tox1 is epistatic to the expression of Tox3 and a quantitative trait locus (QTL) on chromosome 2A that contributes to SNB resistance/susceptibility. The expression of Tox1 is significantly higher in the Australian strain SN15 compared to the American strain SN4. Inspection of the Tox1 promoter region revealed a 401 bp promoter genetic element in SN4 positioned 267 bp upstream of the start codon that is absent in SN15, called PE401. Analysis of the world-wide P. nodorum population revealed that a high proportion of Northern Hemisphere isolates possess PE401 whereas the opposite was observed in representative P. nodorum isolates from Australia and South Africa. The presence of PE401 removed the epistatic effect of Tox1 on the contribution of the SNB 2A QTL but not Tox3. PE401 was introduced into the Tox1 promoter regulatory region in SN15 to test for direct regulatory roles. Tox1 expression was markedly reduced in the presence of PE401. This suggests a repressor molecule(s) binds PE401 and inhibits Tox1 transcription. Infection assays also demonstrated that P. nodorum which lacks PE401 is more pathogenic on Snn1 wheat varieties than P. nodorum carrying PE401. An infection competition assay between P. nodorum isogenic strains with and without PE401 indicated that the higher Tox1-expressing strain rescued the reduced virulence of the lower Tox1-expressing strain on Snn1 wheat. Our study demonstrated that Tox1 exhibits both 'selfish' and 'altruistic' characteristics. This offers an insight into a complex NE-NE interaction that is occurring within the P. nodorum population. The importance of PE401 in breeding for SNB resistance in wheat is discussed.

Fungicide resistance characterized across seven modes of action in Botrytis cinerea isolated from Australian vineyards.

BACKGROUND: Botrytis bunch rot, caused by Botrytis cinerea, is an economically important disease of grapes in Australia and across grape-growing regions worldwide. Control of this disease relies on canopy management and the application of fungicides. Fungicide application can lead to the selection of resistant B. cinerea populations, which has an adverse effect on the management of the disease. Characterizing the distribution and severity of resistant B. cinerea populations is needed to inform resistance management strategies. RESULTS: In this study, 724 isolates were sampled from 76 Australian vineyards during 2013-2016 and were screened against seven fungicides with different modes of action (MOAs). The resistance frequencies for azoxystrobin, boscalid, fenhexamid, fludioxonil, iprodione, pyrimethanil and tebuconazole were 5%, 2.8%, 2.1%, 6.2%, 11.6%, 7.7% and 2.9%, respectively. Nearly half of the resistant isolates (43.8%) were resistant to more than one of the fungicides tested. The frequency of vineyards with at least one isolate simultaneously resistant to one, two, three, four or five fungicides was 19.7%, 7.9%, 6.6%, 10.5% and 2.6%. Resistance was associated with previously published genotypes in CytB (G143A), SdhB (H272R/Y), Erg27 (F412S), Mrr1 (D354Y), Bos1 (I365S, N373S + Q369P, I365S + D757N) and Pos5 (V273I, P319A, L412F/V). Novel genotypes were also described in Mrr1 (S611N, D616G), Pos5 (V273L) and Cyp51 (P347S). Expression analysis was used to characterize fludioxonil-resistant isolates exhibiting overexpression (6.3-9.6-fold) of the ABC transporter gene AtrB (MDR1 phenotype). CONCLUSION: Resistance frequencies were lower when compared to most previously published surveys of B. cinerea resistance in grape and other crops. Nevertheless, continued monitoring of critical MOAs used in Australian vineyards is recommended. © 2021 Society of Chemical Industry.

Adverse neurological events after sodium tetradecyl sulfate foam sclerotherapy - A prospective, observational study of 8056 treatments.

BACKGROUND: Ultrasound guided foam sclerotherapy (UGFS) is a flexible and highly utilised tool in the treatment of varicose veins (VVs), both as a primary treatment and as an adjunct to other treatments. Concern remains regarding the risk of neurological adverse events (AEs) such as migraine, visual disturbance and serious adverse events (SAEs) such as cerebrovascular accident that have been reported after UGFS treatments. AIM: To determine the incidence of neurological AEs and SAEs after UGFS. METHODS: A prospective, multicentre, post-authorisation safety study across Europe (both private and government) was performed between January 2015-2020. Neurological adverse events after UGFS with Fibrovein® (Sodium Tetradecyl Sulfate) 1 and 3% physician generated foam. RESULTS: 8056 patients underwent treatment. There were 46 AE (including 5 SAEs), 30 (65%) SAEs were in female patients. Mean age was 55 years with mean body mass index (BMI) of 27. Univariable logistic regression demonstrate that UGFS only treatment (i.e. no adjunctive treatment), liquid-to-gas ratio, gas type and total foam volume (1% sodium tetradecyl sulfate, STS) were significantly associated with the odds of experiencing the outcome. Multivariable logistic regression model exhibits that migraine and total foam volume (1% STS) maintained statistical significance thus associated with the odds of adverse events. CONCLUSIONS: This study demonstrates that UGFS with Fibrovein is safe with a very low incidence of neurological AEs and SAEs. Past history of migraine, use of physiological gas (O2/CO2) and increasing volumes of 1% foam increase the risk of AEs.

Soliton-effect compression of picosecond pulses on a photonic chip.

We report soliton-effect pulse compression of low energy (∼25pJ), picosecond pulses on a photonic chip. An ultra-low-loss, dispersion-engineered 40-cm-long waveguide is used to compress 1.2-ps pulses by a factor of 18, which represents, to our knowledge, the largest compression factor yet experimentally demonstrated on-chip. Our scheme allows for interfacing with an on-chip picosecond source and offers a path towards a fully integrated stabilized frequency comb source.

Adult resistance genes to barley powdery mildew confer basal penetration resistance associated with broad-spectrum resistance.

Powdery mildew isa major disease of barley (Hordeum vulgare L.) for which breeders have traditionally relied on dominant, pathogen race-specific resistance genes for genetic control. Directional selection pressures in extensive monocultures invariably result in such genes being overcome as the pathogen mutates to evade recognition. This has led to a widespread reliance on fungicides and a single broad-spectrum recessive resistance provided by the mlo gene. The range of resistance genes and alleles found in wild crop relatives and landraces has been reduced in agricultural cultivars through an erosion of genetic diversity during domestication and selective breeding. Three novel major-effect adult plant resistance (APR) genes from landraces, designated Resistance to Blumeria graminis f. sp. hordei (Rbgh1 to Rbgh3), were identified in the terminal regions of barley chromosomes 5HL, 7HS, and 1HS, respectively. The phenotype of the new APR genes showed neither pronounced penetration resistance, nor the spontaneous necrosis and mesophyll cell death typical of mlo resistance, nor a whole epidermal cell hypersensitive response, typical of race-specific resistance. Instead, resistance was localized to the site of attempted penetration in an epidermal cell and was associated with cell wall appositions and cytosolic vesicle-like bodies, and lacked strong induction of reactive oxygen species. The APR genes exhibited differences in vesicle-like body sizes, their distribution, and the extent of localized 3,3-diaminobenzidine staining in individual doubled haploid lines. The results revealed a set of unique basal penetration resistance genes that offer opportunities for combining different resistance mechanisms in breeding programs for robust mildew resistance.

Transcription factor control of virulence in phytopathogenic fungi.

Plant-pathogenic fungi are a significant threat to economic and food security worldwide. Novel protection strategies are required and therefore it is critical we understand the mechanisms by which these pathogens cause disease. Virulence factors and pathogenicity genes have been identified, but in many cases their roles remain elusive. It is becoming increasingly clear that gene regulation is vital to enable plant infection and transcription factors play an essential role. Efforts to determine their regulatory functions in plant-pathogenic fungi have expanded since the annotation of fungal genomes revealed the ubiquity of transcription factors from a broad range of families. This review establishes the significance of transcription factors as regulatory elements in plant-pathogenic fungi and provides a systematic overview of those that have been functionally characterized. Detailed analysis is provided on regulators from well-characterized families controlling various aspects of fungal metabolism, development, stress tolerance, and the production of virulence factors such as effectors and secondary metabolites. This covers conserved transcription factors with either specialized or nonspecialized roles, as well as recently identified regulators targeting key virulence pathways. Fundamental knowledge of transcription factor regulation in plant-pathogenic fungi provides avenues to identify novel virulence factors and improve our understanding of the regulatory networks linked to pathogen evolution, while transcription factors can themselves be specifically targeted for disease control. Areas requiring further insight regarding the molecular mechanisms and/or specific classes of transcription factors are identified, and direction for future investigation is presented.

High frequency of fungicide resistance-associated mutations in the wheat yellow rust pathogen Puccinia striiformis f. sp. tritici.

BACKGROUND: Reliance on fungicides to manage disease creates selection pressure for the evolution of resistance in fungal and oomycete pathogens. Rust fungi (Pucciniales) are major pathogens of cereals and other crops and have been classified as low-risk for developing resistance to fungicides; no case of field failure of fungicides in a cereal rust disease has yet been recorded. Recently, the Asian soybean rust pathogen, Phakopsora pachyrhizi evolved resistance to several fungicide classes, prompting us to screen a large sample of the globally widespread wheat yellow rust pathogen, Puccinia striiformis f. sp. tritici (Pst), for mutations associated with fungicide resistance. RESULTS: We evaluated 363 Pst isolates from Europe, the USA, Ethiopia, Chile, China and New Zealand for mutations in the target genes of demethylase inhibitor (DMI; Cyp51) and succinate dehydrogenase inhibitor (SDHI; SdhB, SdhC and SdhD) fungicides. A high proportion of Pst isolates carrying a Y134F DMI resistance-associated substitution in the Cyp51 gene was found among those from China and New Zealand. A set of geographically diverse Pst isolates was also found to display a substitution in SdhC (I85V) that is homologous to that reported recently in P. pachyrhizi and linked to SDHI resistance. CONCLUSION: The identification of resistance-associated alleles confirms that cereal rusts are not immune to fungicide resistance and that selection for resistance evolution is operating at high levels in certain locations. It highlights the need to adopt fungicide resistance management practices and to monitor cereal rust species for development of resistance. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Global Rehabilitation Health Worker Certification: Global Agenda, Local Imperative.

Rehabilitation, seen as a disability-specific service needed only by few of the world's population, has not been prioritized in countries and is under-resourced. A rehabilitation-ready health workforce is potentially the most important resource for improving functioning and the quality of life for the 2.41 billion people worldwide needing this care. In April 2019, CGFNS International, Inc., and the Association of Schools Advancing Health Professions (ASAHP) partnered to respond to the World Health Organization's Rehab 2030, which emphasizes the need for global action by professional organizations, development agencies, and civil society to develop and maintain a sustainable workforce for rehabilitation under different healthcare models in different economies. The global certification framework presented in this article provides a mechanism to validate rehabilitation knowledge and practice competence of individual health workers. The impact of certification on upgrading rehabilitation education and upskilling the world's rehabilitation health workforce cannot be overstated.

The Addition of Lipid-Based Contrast Medium does not Inactivate the Detergent Sclerosant Sodium Tetradecyl Sulfate in-vitro.

PURPOSE: To investigate if the detergent sclerosant sodium tetradecyl sulfate (STS) is deactivated by the lipid-based contrast agent ethiodised oil. METHOD: 3% STS was mixed with ethiodised oil and room air in a 2:1:4 ratio in two luer lock syringes and a three way connector and agitated to make foam (the Tessari technique) to replicate the clinical use of the products. The assay of STS in the mixture was assessed using the British Pharmacopoeia method. Briefly this is a manual titration method where the solution of STS is mixed with an indicator solution and titrated with hyamine solution of known concentration; the concentration of the STS can then be calculated with the titration results. To further mimic the clinical environment with the presence of blood, the effect of adding increasing amounts of albumin to the STS-ethiodised oil mixture was assessed. RESULTS: The assay of STS in the solution after mixing with ethiodised oil was 3% indicating that the ethiodised oil did not deactivate the STS. The addition of albumin to the STS-contrast mixture resulted in near linear neutralisation of the STS with increasing concentrations in the same quantities as with STS alone. CONCLUSIONS: The mixture of the lipid-based contrast agent ethiodised oil with the detergent sclerosant STS did not affect the availability of the sclerosant. The continued use of STS-ethiodised oil in the management of vascular malformations can be supported.

Rapid in situ quantification of the strobilurin resistance mutation G143A in the wheat pathogen Blumeria graminis f. sp. tritici.

As the incidence of fungicide resistance in plant pathogens continues to increase, control of diseases and the management of resistance would be greatly aided by rapid diagnostic methods. Quantitative allele-specific PCR (ASqPCR) is an ideal technique for the in-field analysis of fungicide resistance as it can quantify the frequency of mutations in fungicide targets. We have applied this technique to the fungal pathogen Blumeria graminis f. sp. tritici (Bgt), the causal agent of wheat powdery mildew. In Australia, strobilurin-resistant Bgt was first discovered in 2016. Molecular analysis revealed a nucleotide transversion in the cytochrome b (cytb) gene in the cytochrome bc1 enzyme complex, resulting in a substitution of alanine for glycine at position 143 (G143A). We have developed an in-field ASqPCR assay that can quantify both the resistant (A143) and sensitive (G143) cytb alleles down to 1.67% in host and Bgt DNA mixtures, within 90 min of sample collection. The in situ analysis of samples collected during a survey in Tasmania revealed A143 frequencies ranging between 9-100%. Validation of the analysis with a newly developed laboratory based digital PCR assay found no significant differences between the two methods. We have successfully developed an in-field quantification method, for a strobilurin-resistant allele, by pairing the ASqPCR assay on a lightweight qPCR instrument with a quick DNA extraction method. The deployment of these type of methodologies in the field can contribute to the effective in-season management of fungicide resistance.

Septoria Nodorum Blotch of Wheat: Disease Management and Resistance Breeding in the Face of Shifting Disease Dynamics and a Changing Environment.

The fungus Parastagonospora nodorum is a narrow host range necrotrophic fungal pathogen that causes Septoria nodorum blotch (SNB) of cereals, most notably wheat (Triticum aestivum). Although commonly observed on wheat seedlings, P. nodorum infection has the greatest effect on the adult crop. It results in leaf blotch, which limits photosynthesis and thus crop growth and yield. It can also affect the wheat ear, resulting in glume blotch, which directly affects grain quality. Reports of P. nodorum fungicide resistance, the increasing use of reduced tillage agronomic practices, and high evolutionary potential of the pathogen, combined with changes in climate and agricultural environments, mean that genetic resistance to SNB remains a high priority in many regions of wheat cultivation. In this review, we summarize current information on P. nodorum population structure and its implication for improved SNB management. We then review recent advances in the genetics of host resistance to P. nodorum and the necrotrophic effectors it secretes during infection, integrating the genomic positions of these genetic loci by using the recently released wheat reference genome assembly. Finally, we discuss the genetic and genomic tools now available for SNB resistance breeding and consider future opportunities and challenges in crop health management by using the wheat-P. nodorum interaction as a model.

Parallel evolution of multiple mechanisms for demethylase inhibitor fungicide resistance in the barley pathogen Pyrenophora teres f. sp. maculata.

The fungal pathogen Pyrenophora teres f. sp. maculata (Ptm), responsible for spot-form of net blotch (SFNB), is currently the most significant disease of barley in Australia and a major disease worldwide. Management of SFNB relies heavily on fungicides and in Australia the demethylase inhibitors (DMIs) predominate. There have been sporadic reports of resistance to DMIs in Ptm but the mechanisms remain obscure. Ptm isolates collected from 1996 to 2019 in Western Australia were tested for fungicide sensitivity levels. Decreased sensitivity to DMIs was observed in isolates collected after 2015. Resistance factors to tebuconazole fell into two classes; moderate resistance (MR; RF 6-11) and high resistance (HR; RFs 30-65). Mutations linked to resistance were detected in the promoter region and coding sequence of the DMI target gene Cyp51A. Solo-LTR insertion elements were found at 5 different locations in the promoter region. Three different non-synonymous mutations encoded an altered protein with a phenylalanine to leucine substitution at position 489, F489L (F495I in the archetype CYP51A of Aspergillus fumigatus). F489L mutations have also been found in DMI-resistant strains of P. teres f. sp. teres. Ptm isolates carrying either a LTR insertion element or a F489L allele displayed the MR1 or MR2 phenotypes, respectively. Isolates carrying both an insertion element and a F489L mutation displayed the HR phenotype. Multiple mechanisms acting both alone and in concert were found to contribute to DMI resistance in Ptm. Moreover, these mutations have emerged repeatedly in Western Australian Ptm populations by a process of parallel evolution.

Prospective cohort study of elderly patients with coronary artery disease: impact of frailty on quality of life and outcome.

BACKGROUND: Elderly, frail patients are often excluded from clinical trials so there is lack of data regarding optimal management when they present with symptomatic coronary artery disease (CAD). OBJECTIVE: The aim of this observational study was to evaluate an unselected elderly population with CAD for the occurrence of frailty, and its association with quality of life (QoL) and clinical outcomes. METHODS: Consecutive patients aged ≥80 years presenting with CAD were prospectively assessed for frailty (Fried frailty phenotype (FFP), Edmonton frailty scale (EFS)), QoL (Short form survey (SF-12)) and comorbidity (Charlson Comorbidity Index (CCI)). Patients were re-assessed at 4 months to determine any change in frailty and QoL status as well as the clinical outcome. RESULTS: One hundred fifty consecutive patients with symptomatic CAD were recruited in the study. The mean age was 83.7±3.2 years, 99 (66.0%) were men. The clinical presentation was stable angina in 68 (45.3%), the remainder admitted with an acute coronary syndrome including 21 (14.0%) with ST-elevation myocardial infarction. Frailty was present in 28% and 26% by FFP and EFS, respectively, and was associated with a significantly higher CCI (7.5±2.4 in frail, 6.2±2.2 in prefrail, 5.9±1.6 in those without frailty, p=0.005). FFP was significantly related to the physical composite score for QoL, while EFS was significantly related to the mental composite score for QoL (p=0.003). Treatment was determined by the cardiologist: percutaneous coronary intervention in 51 (34%), coronary artery bypass graft surgery in 15 (10%) and medical therapy in 84 (56%). At 4 months, 14 (9.3%) had died. Frail participants had the lowest survival. Cardiovascular symptom status and the mental composite score of QoL significantly improved (52.7±11.5 at baseline vs 55.1±10.6 at follow-up, p=0.04). However, overall frailty status did not significantly change, nor the physical health composite score of QoL (37.2±11.0 at baseline vs 38.5±11.3 at follow-up, p=0.27). CONCLUSIONS: In patients referred to hospital with CAD, frailty is associated with impaired QoL and a high coexistence of comorbidities. Following cardiac treatment, patients had improvement in cardiovascular symptoms and mental component of QoL.