Experiences of caregiving and quality of healthcare among caregivers of patients with complex chronic processes: A qualitative study.

Aim To explore the perceptions of main caregivers regarding caring for chronic complex patients in two different regions of Spain. BACKGROUND: Spain is a country with an ageing population and a high number of people with chronic diseases. It is well known that the role of the caregiver is important to ensure quality of life and appropriate care. METHODS: Qualitative design using focus groups. Five focus groups, from two different regions, were conducted with 22 caregivers of people with chronic complex diseases to explore their personal experience, examine the quality of care received by the patient and their family and to develop strategies for the improvement of the quality of health care. The focus groups were audio and video recorded. The transcriptions of the focus group sessions were exported to qualitative software analysis MAXQDA 2018.2. The qualitative content analysis was based on different analytical cycles. RESULTS: In general terms, caregivers would refer to accepting the care of their family members, but they highlight many negative aspects such as tiredness, lack of help and overload of care. They indicated general satisfaction with the health system but indicated that help was insufficient and that strategies to better address the situations of the complex chronic patient should be improved. The main categories observed were: Conclusions. Complex chronic illnesses are increasingly common at present, generating important consequences on the lives of patients and that of their caregivers. The design of any health strategy for facing the dilemma of chronic illnesses, must necessarily include the vision of the caregivers.

Coding Prony's method in MATLAB and applying it to biomedical signal filtering.

BACKGROUND: The response of many biomedical systems can be modelled using a linear combination of damped exponential functions. The approximation parameters, based on equally spaced samples, can be obtained using Prony's method and its variants (e.g. the matrix pencil method). This paper provides a tutorial on the main polynomial Prony and matrix pencil methods and their implementation in MATLAB and analyses how they perform with synthetic and multifocal visual-evoked potential (mfVEP) signals. This paper briefly describes the theoretical basis of four polynomial Prony approximation methods: classic, least squares (LS), total least squares (TLS) and matrix pencil method (MPM). In each of these cases, implementation uses general MATLAB functions. The features of the various options are tested by approximating a set of synthetic mathematical functions and evaluating filtering performance in the Prony domain when applied to mfVEP signals to improve diagnosis of patients with multiple sclerosis (MS). RESULTS: The code implemented does not achieve 100%-correct signal approximation and, of the methods tested, LS and MPM perform best. When filtering mfVEP records in the Prony domain, the value of the area under the receiver-operating-characteristic (ROC) curve is 0.7055 compared with 0.6538 obtained with the usual filtering method used for this type of signal (discrete Fourier transform low-pass filter with a cut-off frequency of 35 Hz). CONCLUSIONS: This paper reviews Prony's method in relation to signal filtering and approximation, provides the MATLAB code needed to implement the classic, LS, TLS and MPM methods, and tests their performance in biomedical signal filtering and function approximation. It emphasizes the importance of improving the computational methods used to implement the various methods described above.

How is post-mortem microbiology appraised by pathologists? Results from a practice survey conducted by ESGFOR.

Post-mortem microbiology (PMM) is an important tool in forensic pathology, assisting to determine the cause and manner of death. However, there is a lack of standardisation of PMM sampling. In order to get a better insight into the methods used, the available technical options and developmental needs, ESCMID Study Group for Forensic and Postmortem Microbiology (ESGFOR) members designed a survey aimed at pathologists regarding common practices of PMM in clinical and forensic autopsies. Multiple choice questions were developed based on Cumulative Techniques and Procedures in Clinical Microbiology (Cumitech). The questionnaire was sent to pathologists mainly across Europe and Turkey using SurveyMonkey. The survey had 147 respondents. Although all pathologists were aware of the existence of PMM, 39% (19/49) of the participants were not using it. The three main indications for PMM were: (i) clinical suspicion of an infection not confirmed antemortem (83%), (ii) infectious signs at autopsy (83%) and (iii) as part of a standard protocol for foetal/perinatal or paediatric death (67%). Almost 80% of the participants using PMM stated taking 1-10 samples per case. Of the requested examinations, a general bacteriological culture (96%) and a specific polymerase chain reaction (PCR) assay for a particular infectious agent (34%) were most popular. The most frequent samples were: heart blood (66%), peripheral femoral blood (49%), spleen (64%) and lung (56%). Eighty-nine percent of the participants considered PMM a useful resource when investigating the cause of death. Although there are some common uses, this survey indicates that there is a need for improvement towards standardising sampling procedures in PMM.

Association between individual and combined SNPs in genes related to innate immunity and incidence of CMV infection in seropositive kidney transplant recipients.

In this study, we assessed the association between single-nucleotide polymorphisms (SNPs) in seven candidate genes involved in orchestrating the immune response against cytomegalovirus (CMV) and the 12-month incidence of CMV infection in 315 CMV-seropositive kidney transplant (KT) recipients. Patients were managed either by antiviral prophylaxis or preemptive therapy. CMV infection occurred in 140 patients (44.4%), including 13 episodes of disease. After adjusting for various clinical covariates, patients harboring T-allele genotypes of interleukin-28B (IL28B) (rs12979860) SNP had lower incidence of CMV infection (adjusted hazard ratio [aHR]: 0.66; 95% confidence interval [CI]: 0.46-0.96; p-value = 0.029). In the analysis restricted to patients not receiving prophylaxis, carriers of the TT genotype of toll-like receptor 9 (TLR9) (rs5743836) SNP had lower incidence of infection (aHR: 0.61; 95% CI: 0.38-0.96; p-value = 0.035), whereas the GG genotype of dendritic cell-specific ICAM 3-grabbing nonintegrin (DC-SIGN) (rs735240) SNP exerted the opposite effect (aHR: 1.86; 95% CI: 1.18-2.94; p-value = 0.008). An independent association was found between the number of unfavorable SNP genotypes carried by the patient and the incidence of CMV infection. In conclusion, specific SNPs in IL28B, TLR9 and DC-SIGN genes may play a role in modulating the susceptibility to CMV infection in CMV-seropositive KT recipients.

How to optimise the yield of forensic and clinical post-mortem microbiology with an adequate sampling: a proposal for standardisation.

Post-mortem microbiology (PMM) is an important tool in forensic pathology, helping to determine the cause and manner of death, especially in difficult scenarios such as sudden unexpected death (SD). Currently, there is a lack of standardization of PMM sampling throughout Europe. We present recommendations elaborated by a panel of European experts aimed to standardize microbiological sampling in the most frequent forensic and clinical post-mortem situations. A network of forensic microbiologists, pathologists and physicians from Spain, England, Belgium, Italy and Turkey shaped a flexible protocol providing minimal requirements for PMM sampling at four practical scenarios: SD, bioterrorism, tissue and cell transplantation (TCT) and paleomicrobiology. Biosafety recommendations were also included. SD was categorized into four subgroups according to the age of the deceased and circumstances at autopsy: (1) included SD in infancy and childhood (0-16 years); (2) corresponded to SD in the young (17-35 years); (3) comprised SD at any age with clinical symptoms; and (4) included traumatic/iatrogenic SD. For each subgroup, a minimum set of samples and general recommendations for microbiological analyses were established. Sampling recommendations for main bioterrorism scenarios were provided. In the TCT setting, the Belgian sampling protocol was presented as an example. Finally, regarding paleomicrobiology, the sampling selection for different types of human remains was reviewed. This proposal for standardization in the sampling constitutes the first step towards a consensus in PMM procedures. In addition, the protocol flexibility to adapt the sampling to the clinical scenario and specific forensic findings adds a cost-benefit value.

European mitochondrial haplogroups are not associated with hepatitis C virus (HCV) treatment response in HIV/HCV-coinfected patients.

OBJECTIVES: Mitochondria are multifunctional organelles with a key role in the innate immune response against viral infections. Mitochondrial DNA (mtDNA) haplogroups have been related to AIDS progression and CD4 T-cell recovery in HIV-infected patients, and to a delay in the development of liver fibrosis in HIV/hepatitis C virus (HCV)-coinfected patients. We performed a study to investigate whether mtDNA haplogroups may be associated with HCV treatment response in HIV/HCV-coinfected patients on pegylated interferon (pegIFN) plus ribavirin (RBV). METHODS: We performed a retrospective study in 304 patients who completed a course of HCV therapy. mtDNA polymorphisms were genotyped using Sequenom's MassARRAY platform. The interleukin-28B (IL-28B) polymorphism (rs12980275) was genotyped using the GoldenGate® assay. Sustained virological response (SVR) was defined as an undetectable HCV viral load at week 24 after the end of treatment. The statistical analysis was carried out using on-treatment data. RESULTS: The SVR rates were 52.6% (160 of 304) for all patients, and 37.8% (46 of 201) for patients with HCV genotype 1 or 4 vs. 81.4% (83 of 102) for patients with HCV genotype 2 or 3 (P < 0.001). No significant associations were found between mtDNA haplogroup and SVR when all patients were included in the analysis and when patients were stratified by HCV genotype (i.e. those with genotypes 1/4 and 2/3 analysed separately) or IL-28B rs12980275 genotype. CONCLUSIONS: European mtDNA haplogroups were not related to HCV treatment response in HIV/HCV-coinfected patients on pegIFN-α/RBV therapy.

IL28RA polymorphism (rs10903035) is associated with insulin resistance in HIV/HCV-coinfected patients.

Hepatitis C virus (HCV) infection is associated with insulin resistance (IR), although mechanisms leading to IR in these patients are not completely understood. The aim of this study was to evaluate the association of interleukin 28B (IL28B) and interleukin 28 receptor alpha (IL28RA) polymorphisms with IR among human immunodeficiency virus (HIV)/HCV-coinfected patients. We carried out a cross-sectional study on 203 patients. IL28B (rs8099917) and IL28RA (rs10903035) polymorphisms were genotyped by GoldenGate(®) assay. IR was defined as homeostatic model assessment (HOMA) values ≥3.00. Univariate and multivariate generalized linear models (GLM) were used to compare HOMA values and the percentage of patients with IR according to IL28B and IL28RA genotypes. In total, 32% (n = 65/203) of the patients had IR. IL28B rs8099917 TT was not significantly associated with HOMA values and IR. In contrast, rs10903035 AA was significantly associated with high HOMA values taking into account all patients (P = 0.024), as well as the subgroups of patients with significant fibrosis (P = 0.047) and infected with HCV genotype 3 (P = 0.024). Additionally, rs10903035 AA was significantly associated with IR (HOMA ≥3.00) in all patients (adjusted odds ratio (aOR) = 2.02; P = 0.034), in patients with significant fibrosis (aOR = 2.86; P = 0.039) and HCV genotype 3 patients (aOR = 4.89; P = 0.031). In conclusions, IL28RA polymorphism (rs10903035) seems to be implicated in the glucose homeostasis because AA genotype increases the likelihood of IR, but this association was different depending on hepatic fibrosis and HCV genotype.

KIT and melanoma predisposition in pigs: sequence variants and association analysis.

KIT mutations have been detected in different cancer subtypes, including melanoma. The gene also has been extensively studied in farm animals for its prominent role in coat color. The present work aimed at detecting KIT variants in a porcine model of cutaneous melanoma, the melanoblastoma-bearing Libechov Minipig (MeLiM). By sequencing exons and intron borders, 36 SNPs and one indel were identified. Of 10 coding SNPs, three were non-synonymous mutations, likely to affect the protein conformation. A promising variant, located in exon 19 (p.Val870Ala), was genotyped in a MeLiM × Duroc cross, and an association analysis was conducted on several melanoma-related traits. This variant showed a significant association with melanoma development, tumor ulceration and cutaneous invasion. In conclusion, although the KIT gene would not be a major causal gene for melanoma development in pig, its genetic variation could be influencing this trait.

IL28RA polymorphism is associated with early hepatitis C virus (HCV) treatment failure in human immunodeficiency virus-/HCV-coinfected patients.

Due to the poor rate of response to hepatitis C virus (HCV) with pegylated interferon and ribavirin treatment in HCV/HIV coinfected patients, key factors for predicting failure would be useful. We performed a retrospective study on 291 patients on HCV treatment, who had early virological response (EVR) data. IL28B and IL28RA polymorphisms were performed using the GoldenGate(®) assay. Unfavourable genotypes at IL28B (rs12980275 AG/GG and rs8099917 GT/GG) and an unfavourable allele at IL28RA (rs10903035 G) were associated with early treatment failure. However, only the rs12980275 AG/GG genotype and rs10903035 G allele remained independently associated with early failure in the overall population (OR = 4.15 (95% CI = 1.64-10.54) and OR = 2.00 (95% CI = 1.19-3.36), respectively) as well as in GT1/4 patients (OR = 5.07 (95% CI = 1.81-14.22) and OR = 2.03 (95% CI = 1.13-3.66), respectively). Next, a decision tree showed early treatment failure increased from 37.1% to 65.5% when the unfavourable rs12980275 AG/GG and rs10903035 AG/GG genotypes and HCV-RNA≥ 500.000 IU/mL were taken into account in GT1/4 patients. In contrast, the failure rate decreased from 37.1% to 11.9% when the favourable rs12980275 AA and rs10903035 AA genotypes were detected. The percentage of patients correctly classified was 78.4%, and AUROC was 0.802 ± 0.028. Regarding GT3 patients, the presence of the GCGCA haplotype (all unfavourable alleles) was associated with early treatment failure, while no association was observed for the IL28B polymorphisms. In conclusion, the IL28RA polymorphism was associated with early treatment failure independently of the IL28B SNPs. The combination of IL28B and IL28RA polymorphisms might be a valuable tool for predicting early treatment failure before starting HCV treatment.

C282Y hemochromatosis gene mutation and iron parameters in dialysis patients.

BACKGROUND: Hereditary hemochromatosis is an autosomal recessive condition causing excessive intestinal iron absorption related to C282Y hemochromatosis mutation gene. Dialysis patients receive intravenous iron supplements as treatment for anemia. The gene mutation frequency and its influence on iron deposits and intravenous iron response are unknown in these patients. STUDY DESIGN: Prospective observational. SETTING AND PARTICIPANTS: 290 dialysis patients in Gran Canaria, Spain. OUTCOMES AND MEASUREMENTS: The C282Y hemochromatosis mutation gene was studied. Other active players in iron metabolism have not been included in this study. Red cell parameters, serum iron, transferrin and ferritin concentrations were measured every 2 months for 2 years. RESULTS: No differences in allelic and genotypic frequencies between dialysis patients and the general population were detected. Baseline clinical or analytical parameters were similar in C282Y +/- and C282Y -/- patients. Among those who did not need intravenous iron treatment, C282Y+/- patients maintained constant serum ferritin (302.1 ± 216.7 vs. 319.5 ± 300.5 µg/l after 4 months), whereas C282Y-/- patients showed decreased levels during the same period (306.7 ± 212.2 vs. 221.6 ± 167.8 µg/l, p < 0.001). After 4 months of parenteral iron, serum ferritin increased more intensely in C282Y +/- patients than in C282Y -/- patients (934.2 ± 195.8 vs. 658.7 ± 259.9 µg/l, p < 0.001). A multivariance analysis identified the C282Y allele as the most important factor that explains this difference. CONCLUSIONS: Heterozygosity for the C282Y allele of the hemochromatosis mutation gene could be associated with differences in iron parameters in dialysis patients.

Analysis of candidate genes underlying two epistatic quantitative trait loci on SSC12 affecting litter size in pig.

The previous results from a genome scan for total number of piglets born and number of piglets born alive in a F(2) Iberian by Meishan intercross showed several single and epistatic QTL. One of the most interesting results was obtained for SSC12, where two QTL affecting both traits showed epistatic interaction. In this study, we proposed two genes (SLC9A3R1 and NOS2) as biological and potentially positional candidates underlying these QTL. Both cDNAs were characterized and 23 polymorphisms were detected. A chromosome scan was conducted with 12 markers, plus one SNP in SLC9A3R1 and one in NOS2, covering 110 cM of SSC12. The epistatic QTL (QTL1 at 15 cM and QTL2 at 97 cM) were confirmed, and SLC9A3R1 and NOS2 were mapped around the QTL1 and QTL2 regions respectively. Several SNPs in both genes were tested with standard animal model and marker assisted association tests. The most significant results were obtained with the NOS2 haplotype defined by one missense SNP c.2192C > T (Val to Ala) and a 15 bp duplication at the 3'UTR. This duplication seems to include AU-rich elements, and could be a target site for miRNA, therefore there are statistical and biological indications to consider this haplotype as the potential causal mutation underlying QTL2. SLC9A3R1 results were not conclusive. Although the interaction between the SNPs was not significant, we cannot reject the possibility of interaction of the NOS2 haplotype with other polymorphisms closely linked to the SL9A3R1 SNPs analysed.

Impact of Speller Size on a Visual P300 Brain-Computer Interface (BCI) System under Two Conditions of Constraint for Eye Movement.

The vast majority of P300-based brain-computer interface (BCI) systems are based on the well-known P300 speller presented by Farwell and Donchin for communication purposes and an alternative to people with neuromuscular disabilities, such as impaired eye movement. The purpose of the present work is to study the effect of speller size on P300-based BCI usability, measured in terms of effectiveness, efficiency, and satisfaction under overt and covert attention conditions. To this end, twelve participants used three speller sizes under both attentional conditions to spell 12 symbols. The results indicated that the speller size had, in both attentional conditions, a significant influence on performance. In both conditions (covert and overt), the best performances were obtained with the small and medium speller sizes, both being the most effective. The speller size did not significantly affect workload on the three speller sizes. In contrast, covert attention condition produced very high workload due to the increased resources expended to complete the task. Regarding users' preferences, significant differences were obtained between speller sizes. The small speller size was considered as the most complex, the most stressful, the less comfortable, and the most tiring. The medium speller size was always considered in the medium rank, which is the speller size that was evaluated less frequently and, for each dimension, the worst one. In this sense, the medium and the large speller sizes were considered as the most satisfactory. Finally, the medium speller size was the one to which the three standard dimensions were collected: high effectiveness, high efficiency, and high satisfaction. This work demonstrates that the speller size is an important parameter to consider in improving the usability of P300 BCI for communication purposes. The obtained results showed that using the proposed medium speller size, performance and satisfaction could be improved.

Post-mortem microbiology in sudden death: sampling protocols proposed in different clinical settings.

BACKGROUND: Autopsies, including minimally invasive autopsies, are a powerful tool for determination of the cause of death. When a patient dies from an infection, microbiology is crucial to identify the causative organism. Post-mortem microbiology (PMM) aims to detect unexpected infections causing sudden deaths; confirm clinically suspected but unproven infection; evaluate the efficacy of antimicrobial therapy; identify emergent pathogens; and recognize medical errors. Additionally, the analysis of the thanatomicrobiome may help to estimate the post-mortem interval. AIMS: The aim was to provide advice in the collection of PMM samples and to propose sampling guidelines for microbiologists advising autopsy pathologists facing different sudden death scenarios. SOURCES: A multidisciplinary team with experts in various fields of microbiology and autopsies on behalf of the ESGFOR (ESCMID - European Society of Clinical Microbiology and Infectious Diseases - study group of forensic and post-mortem microbiology and in collaboration with the European Society of Pathology) developed this narrative review based on a literature search using MedLine and Scopus electronic databases supplemented with their own expertise. CONTENT: These guidelines address measures to prevent sample contamination in autopsy microbiology; general PMM sampling technique; protocols for PMM sampling in different scenarios and using minimally invasive autopsy; and potential use of the evolving post-mortem microbiome to estimate the post-mortem interval. IMPLICATIONS: Adequate sampling is paramount to identify the causative organism. Meaningful interpretation of PMM results requires careful evaluation in the context of clinical history, macroscopic and histological findings. Networking and closer collaboration among microbiologists and autopsy pathologists is vital to maximize the yield of PMM.

[Importance of the forensic autopsy in the diagnosis of septic shock: a case report]. / Importancia de la autopsia forense en el diagnóstico del shock séptico: a propósito de un caso.

Septic shock sometimes starts with unspecific symptoms that hamper the clinical diagnosis and, therefore an appropriate treatment. When the septic shock follows a fulminating course with a fatal outcome, the etiological diagnosis has to be conducted post-mortem. Sudden unexpected deaths in children and young adults are frequently the object of medico-legal autopsies. Some sudden unexpected deaths have an infectious origin, which requires further analyses, including microbiology, to establish the cause of death. Here, the case of a fatal septic shock in a 19-month old male infant is presented. After a mild foot injury, an infection by Streptococcus pyogenes progressed to septic shock with a fatal outcome as post-mortem studies demonstrated.