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1.
Cont Lens Anterior Eye ; : 102257, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38969607

RESUMO

PURPOSE: The current subclassifications of dry eye disease (DED) are aqueous deficient (ADDE) and evaporative (EDE) forms, but there lacks consistency in the clinical characteristics used to define each of these. This study used clinical data to inform cut-off values for the subclassification of ADDE and EDE, to allow more consistent study of the epidemiology of both DED subtypes. METHODS: The study enrolled 261 residents from the UK, extracted from a cohort with demographics representing the population (mean 42.4 ± 18.7 years, 56 % females). The TFOS DEWS II diagnostic criteria were used to identify those with DED. Meibomian gland loss/drop-out (from meibography), lipid layer thickness (LLT - from interferometry graded on the Guillon-Keeler scale), and tear meniscus height (TMH - Keratograph 5M) along with tear evaporation (Delfin Vapometer) were used to characterise the subclassification. The Dry Eye Risk Factor Survey was used to assess risk factors associated with each DED subtype. RESULTS: Compared to individuals who were not diagnosed with DED, EDE was characterized by signs of meibomian gland loss of > 28 %, LLT grade < 3 and tear evaporation > 46 g/m2/h. In contrast, ADDE was best characterized by a reduced TMH < 0.2 mm. Based on these criteria, the prevalence of ADDE was 6.2 %, EDE was 64.2 %, and 11.1 % exhibited features of both ADDE and EDE, with 18.5 % unclassified despite having a DED diagnosis. Contact lens wear and computer use were risk factors for ADDE (p < 0.05), whereas age was a positive risk factor for EDE (p < 0.01). Meibomian gland loss (occurring in 27.9 %) was the most commonly observed sign in EDE. CONCLUSIONS: Data driven-classification of DED confirms that the evaporative form is most prevalent and identified that in a generalisable UK population, ADDE alone occurs only in approximately 1 in 16 cases of DED.

2.
Front Sports Act Living ; 6: 1334805, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38645726

RESUMO

Background: Physical activity and sport (PAS) have been related to many health outcomes and social benefits. The main aim of this research is to build a Social Return on Investment (SROI) model of PAS based on experts' opinion to clarify the domains of impact and how to measure and value them. Methods and analysis: A Delphi method will be employed with a systematic review on the SROI framework applied to PAS and initial interviews with experts informing the design of the Delphi survey statements. Three iterative rounds of communication with the expert panel will be carried out. Participants will indicate their level of agreement with each statement on a five-point Likert scale. During the second and third iterative rounds, experts will reappraise the statements and will be provided with a summary of the group responses from the panel. A statement will have reached consensus if ≥70% of the panel agree/strongly agree or disagree/strongly disagree after round 3. Finally, group meetings (3-4 experts) will be conducted to ask about the measurement and valuation methods for each domain. Discussion: The final goal of this project will result in the design of a toolkit for organizations, professionals, and policymakers on how to measure the social benefits of PAS.

3.
Cont Lens Anterior Eye ; 46(3): 101837, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37003925

RESUMO

PURPOSE: Cross-sectional studies on dry eye disease (DED) have relied on different diagnoses hindering conclusions about the disease epidemiology. This study offers an insight into DED epidemiology in the UK using prior and recent diagnostic recommendations. METHODS: Study participants comprised 282 volunteers from Birmingham, UK (median 40 years, range 18-88 years, 56% females). DED was defined by the Tear Film Ocular Surface Dry Eye Workshop II (TFOS DEWS II) criteria, based on a positive symptom score with the Dry Eye Questionnaire (DEQ-5) and Ocular Surface Disease Index (OSDI), and one of the following homeostasis markers: non-invasive tear break-up time of < 10 s (Oculus Keratograph 5M); the highest osmolarity value of ≥ 308 mOsm/L among eyes or an interocular osmolarity difference of > 8 mOsm/L (TearLab Osmolarity System); or > 5 corneal spots, >9 conjunctival spots or lower/upper lid-wiper-epitheliopathy staining of ≥ 2 mm length and ≥ 25% width (Oculus Keratograph 5 M). In addition, the Women's Health Study (WHS) criteria, based on symptoms or a prior dry eye diagnosis, was assessed. DED risk factors were gathered using a self-administered questionnaire. RESULTS: DED prevalence by the TFOS DEWS II criteria was 32.1% (95% confidence interval 25.5-37.7% and 29.5% (95% confidence interval 24.4-35.1% by the WHS criteria. Female sex, systemic and/or ocular health conditions, short sleep duration and prolonged outdoor leisure time spent were significant DED risk factors (p ≤ 0.05). CONCLUSIONS: Approximately one-third of the adult UK population have DED, aligning with the prevalence reported in multiple counties globally. Female sex, systemic/ocular health conditions, short sleep duration and prolonged outdoor leisure time are positive predictors of DED.


Assuntos
Síndromes do Olho Seco , Adulto , Humanos , Feminino , Masculino , Estudos Transversais , Síndromes do Olho Seco/diagnóstico , Síndromes do Olho Seco/epidemiologia , Lágrimas , Córnea , Concentração Osmolar , Reino Unido/epidemiologia
4.
NPJ Prim Care Respir Med ; 33(1): 6, 2023 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-36750578

RESUMO

Greater Manchester has a greater prevalence and worse asthma outcomes than the national average. This study aims to evaluate a digital approach to primary care asthma management and in particular the initial impact of implementing Clinical Decision Support System software in the form of a computer-guided consultation (CGC) in the setting of primary care asthma reviews in deprived areas of Greater Manchester. The CGC (LungHealth Ltd) is an intelligent decision support system ensuring accurate guideline-based staging of asthma and assessment of asthma control with the software subsequently prompting guideline-standard management. Patients on asthma registers in Greater Manchester Primary Care Networks were identified and underwent remote review by nursing staff using the CGC linked directly to the GP clinical system. Three-hundred thirty-eight patients (mean age 59 (SD 17) years; 60% Female) were reviewed. The CGC reported the patient's asthma control to be "Good" in 22%, "Partial" in 6% and "Poor" in 72%. ACT scores were significantly higher in those patients exhibiting "Good" and "Partial" control when compared to those with "Poor" control. The number of steroid courses and hospital admissions in the previous 12 months was significantly lower in those patients exhibiting "Good" and "Partial" control when compared to those with "Poor" control. Nineteen percent were found not to have a personalised asthma management plan during CGC review, which was alerted by the CGC and subsequently, all but 3 patients had this created on review completion (McNemar's test; p < 0.001). 5% were found not to have been prescribed regular inhaled steroid therapy resulting in the operator being alerted by the CGC in all cases. Overall, 44% underwent alteration in asthma therapy following the CGC review with 82% of these representing treatment escalation. An end-to-end digital service solution is feasible for Asthma within primary care and the utilisation of a CGC when conducting primary care asthma reviews increases implementation of guideline-level management thus addressing healthcare inequality while enabling identification of "high risk" asthma patients and guiding appropriate therapy escalation and de-escalation.


Assuntos
Asma , Disparidades nos Níveis de Saúde , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Estudos de Viabilidade , Asma/tratamento farmacológico , Encaminhamento e Consulta , Computadores
5.
Mult Scler Relat Disord ; 68: 104121, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36088727

RESUMO

BACKGROUND: Following the outbreak of COVID-19, global healthcare systems have had to rapidly adapt. People with multiple sclerosis (pwMS) were required to make decisions about their individual risk and consequent work and social behaviors. This study aimed to evaluate risk perception and patterns of shielding behavior amongst pwMS at the onset of the COVID-19 pandemic and the subsequent impact on patients' employment and access to disease modifying therapies (DMTs). METHODS: Postal surveys were sent to 1690 people within a UK population-based MS cohort during the first wave of the COVID-19 pandemic. Patients were surveyed on: (i) perceived vulnerability to COVID-19; (ii) isolation behavior; (iii) interruption to DMT; (iv) employment status; (v) level of satisfaction with their current working arrangement. RESULTS: Responses were received from 1000 pwMS. Two thirds of patients reported isolating at home during the first wave of the pandemic. This behavior was associated with increased age (p<0.0001), higher disability (p<0.0001) and use of high-efficacy DMTs (p = 0.02). The majority of patients reported feeling vulnerable (82%) with perceived vulnerability associated with higher EDSS (p<0.0001) and receiving a high-efficacy DMT (p = 0.04). Clinician-defined risk was associated with shielding behavior, with those at high-risk more likely to self-isolate/shield (p<0.0001). Patients on high-efficacy DMTs were more likely to have an interruption to their treatment (50%) during the first wave of the pandemic. Most pwMS experienced a change to their working environment, and most were satisfied with the adjustments. CONCLUSION: This study highlights the risk perception, social behavioral practices and changes to treatment experienced by pwMS during the first wave of the COVID-19 pandemic in a large, well-described UK cohort. The results may help inform management of pwMS during future pandemic waves.


Assuntos
COVID-19 , Esclerose Múltipla , Humanos , COVID-19/complicações , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/complicações , Pandemias , Atenção à Saúde , Percepção
6.
J Plast Reconstr Aesthet Surg ; 75(7): 2127-2134, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35367161

RESUMO

BACKGROUND: The COVID-19 pandemic created a unique opportunity to explore the use of Technology Enabled Care Services (TECS), which remains novel for many service providers. This study assesses the factors that affect adaptation to remote monitoring of patients after upper-limb trauma injury. A standardised risk-stratified screening tool is further developed here to support clinical staff in both the determination of appropriate use of TECS and the optimisation of patient care. OBJECTIVES: 1: To explore the patient and injury factors that determine the appropriate use of TECS for patients with upper-limb injury. 2: To use these findings to refine a standardised screening tool for the appropriate choice of follow-up format. METHODS: A retrospective review of patient management was undertaken across three NHS upper-limb trauma units during the first UK COVID-19 lockdown. Data were collected, and themes were analysed across a number of predetermined categories. This was underpinned by a review of contemporary policy guidance and literature. RESULTS: A total of 85% of patients were offered an appropriate format of follow-up; this was defined by the ability to achieve desired patient-clinician goals and lack of complications. Key factors in determining appropriate follow-up included extent of injury, mental health considerations, and the need for face-to-face (F2F) assessment and treatment. CONCLUSION: Study findings demonstrate consistency between units in the factors determining the appropriate use of TECS. The refined screening tool provides a risk-stratified, standardised approach to the choice of follow-up format, F2F or TECS. It is hoped that this will support future clinical decision-making processes to ensure optimal patient care.


Assuntos
COVID-19 , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Humanos , Pandemias/prevenção & controle , Estudos Retrospectivos , Tecnologia , Extremidade Superior
7.
Br J Neurosurg ; : 1-5, 2022 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-35042450

RESUMO

Programmable variable pressure valves were introduced in the 1980s, providing a non-invasive solution to post-operative alterations of the valve opening pressure to address problems of under or overdrainage. Since their increased use in the treatment of hydrocephalus, there have been case reports of unintentional alterations of the valve opening pressure following exposure to magnetic fields in everyday environments, from televisions to rollercoasters. Here we describe two cases of patients' programmable valves being altered following audiology assessments. We subsequently discuss some of the available research on the safety of these valves in various magnetic field strengths, alongside interim and updated recommendations made by the British Society of Audiologists with regards to testing of children with programmable shunts in place.

8.
Hernia ; 26(1): 309-323, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33788008

RESUMO

BACKGROUND: Polypropylene (PP) mesh is widely used to reinforce tissues. The foreign body reaction (FBR) to the implant is dominated by innate immune cells, especially macrophages. However, considerable numbers of adaptive immune cells, namely T cells, have also been regularly observed, which appear to play a crucial role in the long-term host response. METHODS: This study investigated the FBR to seven human PP meshes, which were removed from the abdomen for recurrence after a median of one year. Using immunofluorescence microscopy, the FBR was examined for various innate (CD11b+ myeloid, CD68+ macrophages, CD56+ NK) and adaptive immune cells (CD3+ T, CD4+ T-helper, CD8+ cytotoxic, FoxP3+ T-regulatory, CD20+ B) as well as "conventional" immune cells (defined as cells expressing their specific immune cell marker without co-expressing CD68). RESULTS: T-helper cells (19%) and regulatory T-cells (25%) were present at comparable rates to macrophages, and clustered significantly toward the mesh fibers. For all cell types the lowest proportions of "conventional" cells (< 60%) were observed at the mesh-tissue interface, but increased considerably at about 50-100 µm, indicating reduced stimulation with rising distance to the mesh fibers. CONCLUSION: Both innate and adaptive immune cells participate in the chronic FBR to PP meshes with T cells and macrophages being the predominant cell types, respectively. In concordance with the previous data, many cells presented a "hybrid" pattern near the mesh fibers. The complexity of the immune reaction seen within the foreign body granuloma may explain why approaches focusing on specific cell types have not been very successful in reducing the chronic FBR.


Assuntos
Polipropilenos , Telas Cirúrgicas , Abdome , Reação a Corpo Estranho/etiologia , Herniorrafia , Humanos , Polipropilenos/efeitos adversos , Telas Cirúrgicas/efeitos adversos
9.
J Nucl Cardiol ; 29(5): 2119-2128, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34169473

RESUMO

BACKGROUND: International guidance recognizes the shortcomings of the modified Duke Criteria (mDC) in diagnosing infective endocarditis (IE) when transoesophageal echocardiography (TOE) is equivocal. 18F-FDG PET/CT (PET) has proven benefit in prosthetic valve endocarditis (PVE), but is restricted to extracardiac manifestations in native disease (NVE). We investigated the incremental benefit of PET over the mDC in NVE. METHODS: Dual-center retrospective study (2010-2018) of patients undergoing myocardial suppression PET for NVE and PVE. Cases were classified by mDC pre- and post-PET, and evaluated against discharge diagnosis. Receiver Operating Characteristic (ROC) analysis and net reclassification index (NRI) assessed diagnostic performance. Valve standardized uptake value (SUV) was recorded. RESULTS: 69/88 PET studies were evaluated across 668 patients. At discharge, 20/32 had confirmed NVE, 22/37 PVE, and 19/69 patients required surgery. PET accurately re-classified patients from possible, to definite or rejected (NRI: NVE 0.89; PVE 0.90), with significant incremental benefit in both NVE (AUC 0.883 vs 0.750) and PVE (0.877 vs 0.633). Sensitivity and specificity were 75% and 92% in NVE; 87% and 86% in PVE. Duration of antibiotics and C-reactive Protein level did not impact performance. No diagnostic SUV cut-off was identified. CONCLUSION: PET improves diagnostic certainty when combined with mDC in NVE and PVE.


Assuntos
Endocardite Bacteriana , Endocardite , Próteses Valvulares Cardíacas , Infecções Relacionadas à Prótese , Antibacterianos , Proteína C-Reativa , Endocardite/diagnóstico por imagem , Endocardite Bacteriana/diagnóstico , Fluordesoxiglucose F18 , Próteses Valvulares Cardíacas/efeitos adversos , Humanos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Infecções Relacionadas à Prótese/diagnóstico por imagem , Estudos Retrospectivos
10.
Ghana med. j ; 56(4): 311-321, 2022. tales, figures
Artigo em Inglês | AIM (África) | ID: biblio-1402090

RESUMO

Objectives: This study sought to assess the level of anti-glycaemic medication-taking and its predictors among adults living with diabetes receiving treatment at Cape Coast Teaching Hospital (CCTH). Design: This was a cross-sectional study carried out among adults living with diabetes and receiving care at CCTH. Data on socio-demographic characteristics and anti-glycaemic medication-taking were gathered using a structured questionnaire. A scale consisting of 4 domains (filling prescribed medication; taking medications appropriately ac-cording to the instructions of healthcare professionals; practising behavioural modifications, and showing up for fol-low-up appointments) and eight items was used to measure the level of anti-glycaemic medication-taking. Descriptive statistics, chi-square test (and Fisher's exact test where appropriate), bivariate and multivariate logistic regression models were used in analysing the data. Setting: The study was carried out in the diabetes clinic in Cape Coast Teaching Hospital. Participants: The total enumerative sampling technique was used to select 250 adults living with diabetes and receiv-ing care at CCTH.Main outcome measures: Anti-glycaemic medication-taking Results: Out of 250 participants studied, 42% had high anti-glycaemic medication-taking. Predictors of anti-glycae-mic medication-taking included; forgetfulness (aOR=0.02, 95% CI: 0.00-0.64, p<0.001), patient's involvement in treatment plan (aOR=0.12, 95% CI: 0.02-0.64, p=0.014) and having good knowledge about one's medication (aOR=2.34, 95% CI: 1.10-4.98, p=0.028). Conclusion: Less than half of the sample population (42%) had high anti-glycaemic medication-taking, with forget-fulness, involvement in the treatment plan and good knowledge about anti-glycaemic medications, predicting medi-cation-taking


Assuntos
Humanos , Família , Atenção à Saúde , Medicina
11.
Br J Oral Maxillofac Surg ; 59(9): 1056-1060, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34620517

RESUMO

Historically, patients who received bilateral sagittal split osteotomies (BSSO) required an inpatient admission for at least one night. Since March 2015, the Oral and Maxillofacial Department at the Royal Gwent Hospital has performed bilateral sagittal split osteotomies (BSSO) as a day case procedure for their medically and socially fit patients. Our team's service evaluation by Davies et al (2018) for this procedure, demonstrated that this could be done both routinely and successfully, whilst conforming to national day case procedural standards. The aim of this satisfaction survey was to evaluate this procedure from a patient's perspective, to further consolidate our results from 2018. The forty-five patients who underwent day case BSSO (DCBSSO) between February 2015 and February 2020 were retrospectively identified and deemed eligible for inclusion. Participation involved completion of a 10-part questionnaire via telephone consultation. Patients were asked questions focussing on their experience of discharge timing, management of postoperative symptoms, and overall recovery at home. Twenty-four patients consented to partake in the survey (response rate of 73%). Twenty-three (96%) were extremely happy to be discharged the day of their surgery and felt that the timing of discharge was appropriate. Only 17% of patients experienced discomfort overnight and 96% of these stated they could manage their symptoms at home. From this survey, we can confirm that the majority of patients receiving DCBSSO at the Royal Gwent Hospital were happy to be discharged the day of their surgery and recover at home.


Assuntos
Osteotomia Sagital do Ramo Mandibular , Encaminhamento e Consulta , Humanos , Mandíbula , Avaliação de Resultados da Assistência ao Paciente , Estudos Retrospectivos , Telefone
13.
Anaesthesia ; 76(11): 1482-1491, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33881774

RESUMO

Significant sleep disturbance can occur following major abdominal surgery. We aimed to evaluate the effectiveness of earplugs and eye masks in improving sleep quality and patient satisfaction, reducing nursing demands and in the incidence of delirium in patients after major abdominal surgery. We conducted a randomised controlled trial in 100 patients undergoing major abdominal surgery. We randomly allocated participants to sleep with or without earplugs and eye masks on postoperative days 1-3. The primary outcome measure was sleep quality as measured by the Richards-Campbell Sleep Questionnaire. Secondary outcomes were patient satisfaction, frequency of nursing demand and incidence of delirium measured by the Neelon and Champagne Confusion Scale. Median (IQR [range]) sleep scores were 64 (38-74 [0-100] and 60 (44-82 [18-100]) for the control and intervention groups, respectively (p = 0.310). Age and Pittsburgh Sleep Quality Index scores were found to be significant factors affecting sleep quality. There were no differences in patient satisfaction, reduction in frequency of nursing demands or incidence of delirium on postoperative days 1-3 after major abdominal surgery. The compliance rate in the intervention group was 60-65%. This study has demonstrated that the use of earplugs and eye masks did not contribute to improvements in sleep quality. Of note, sleep quality was moderate, with higher age and worse baseline sleep quality contributing to worse sleep scores. More studies are needed to investigate interventions to improve sleep quality after major abdominal surgery.


Assuntos
Abdome/cirurgia , Dispositivos de Proteção das Orelhas , Dispositivos de Proteção dos Olhos , Sono/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Período Pós-Operatório , Estudos Prospectivos , Método Simples-Cego , Inquéritos e Questionários
14.
J Hosp Infect ; 110: 148-155, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33485969

RESUMO

BACKGROUND: The emergence of multi-drug-resistant (MDR) micro-organisms prompted new interest in older antibiotics, such as colistin, that had been abandoned previously due to limited efficacy or high toxicity. Over the years, several chromosomal-encoded colistin resistance mechanisms have been described; more recently, 10 plasmid-mediated mobile colistin resistance (mcr) genes have been identified. Spread of these genes among MDR Gram-negative bacteria is a matter of serious concern; therefore, reliable and timely mcr detection is paramount. AIM: To design and validate a multiplex real-time polymerase chain reaction (PCR) assay for detection and differentiation of mcr genes. METHODS: All available mcr alleles were downloaded from the National Center for Biotechnology Information Reference Gene Catalogue, aligned with Clustal Omega and primers designed using Primer-BLAST. Real-time PCR monoplexes were optimized and validated using a panel of 120 characterized Gram-negative strains carrying a wide range of resistance genes, often in combination. Melt-curve analysis was used to confirm positive results. FINDINGS: In-silico analysis enabled the design of a 'screening' assay for detection of mcr-1/2/6, mcr-3, mcr-4, mcr-5, mcr-7, mcr-8 and mcr-9/10, paired with an internal control assay to discount inhibition. A 'supplementary' assay was subsequently designed to differentiate mcr-1, mcr-2, mcr-6, mcr-9 and mcr-10. Expected results were obtained for all strains (100% sensitivity and specificity). Melt-curve analysis showed consistent melting temperature results. Inhibition was not observed. CONCLUSIONS: The assay is rapid and easy to perform, enabling unequivocal mcr detection and differentiation even when more than one variant is present. Adoption by clinical and veterinary microbiology laboratories would aid the surveillance of mcr genes amongst Gram-negative bacteria.


Assuntos
Antibacterianos , Colistina , Farmacorresistência Bacteriana Múltipla/genética , Genes Bacterianos , Bactérias Gram-Negativas/genética , Antibacterianos/farmacologia , Colistina/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Plasmídeos , Reação em Cadeia da Polimerase em Tempo Real
17.
Ann Oncol ; 32(2): 269-278, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33130216

RESUMO

BACKGROUND: KRAS is mutated in ∼90% of pancreatic ductal adenocarcinomas, ∼35% of colorectal cancers and ∼20% of non-small-cell lung cancers. There has been recent progress in targeting G12CKRAS specifically, but therapeutic options for other mutant forms of KRAS are limited, largely because the complexity of downstream signaling and feedback mechanisms mean that targeting individual pathway components is ineffective. DESIGN: The protein kinases RAF and SRC are validated therapeutic targets in KRAS-mutant pancreatic ductal adenocarcinomas, colorectal cancers and non-small-cell lung cancers and we show that both must be inhibited to block growth of these cancers. We describe CCT3833, a new drug that inhibits both RAF and SRC, which may be effective in KRAS-mutant cancers. RESULTS: We show that CCT3833 inhibits RAF and SRC in KRAS-mutant tumors in vitro and in vivo, and that it inhibits tumor growth at well-tolerated doses in mice. CCT3833 has been evaluated in a phase I clinical trial (NCT02437227) and we report here that it significantly prolongs progression-free survival of a patient with a G12VKRAS spindle cell sarcoma who did not respond to a multikinase inhibitor and therefore had limited treatment options. CONCLUSIONS: New drug CCT3833 elicits significant preclinical therapeutic efficacy in KRAS-mutant colorectal, lung and pancreatic tumor xenografts, demonstrating a treatment option for several areas of unmet clinical need. Based on these preclinical data and the phase I clinical unconfirmed response in a patient with KRAS-mutant spindle cell sarcoma, CCT3833 requires further evaluation in patients with other KRAS-mutant cancers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Camundongos , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Quinases da Família src/genética
18.
Hernia ; 24(6): 1175-1189, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33030647

RESUMO

BACKGROUND: Mesh implants are widely used to reinforce the abdominal wall, although the inevitable inflammatory foreign body reaction (FBR) at the interface leads to complications. Macrophages are suspected to regulate the subsequent scar formation, but it is still unclear whether adequate fibrous scar formation with collagen deposition depends mainly on the presence of M1 or M2 macrophages. METHODS: This study investigated the FBR to seven human polypropylene meshes, which were removed after a median incorporation time of 1 year due to the primary complaint of recurrence. Using immunofluorescence, the FBR was examined in six regional zones with increasing distance from the mesh fibers up to 350 µm, based on the cell densities, macrophage M1 (CD86) and M2 (CD163, CD206) phenotypes, deposition of collagen-I and -III, and expression of matrix metalloproteinase-2 (MMP-2) and -8 as indicator of collagen degradation. RESULTS: All mesh-tissue complexes demonstrated a decrease in cell density and macrophages with distance to the mesh fibers. Overall, about 60% of the macrophages presented an M2 phenotype, whereas only 6% an M1 phenotype. Over 70% of macrophages showed co-expression with collagen-I or -III and over 50% with MMP-2. CONCLUSIONS: The chronic FBR to polypropylene meshes is associated with an M2 macrophage response, which is accompanied by collagen deposition and MMP-2 expression. These findings challenge the idea that mainly M1 macrophages are related to inflammation and highlights that iatrogenic attempts to polarize these cells towards the M2 phenotype may not be a solution to ameliorate the long-term foreign body reaction.


Assuntos
Parede Abdominal/cirurgia , Macrófagos/metabolismo , Microscopia de Fluorescência/métodos , Polipropilenos/metabolismo , Telas Cirúrgicas/normas , Animais , Humanos
19.
BMJ Mil Health ; 166(6): 373-377, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32345681

RESUMO

INTRODUCTION: Ex SAIF SAREEA 3 was a joint British-Omani military exercise involving approximately 5500 British personnel deployed to Oman over a 6-month period. Role 1 medical care was provided by medical treatment facilities (MTFs) deployed with medical equipment as per the UK 300 medical module. METHOD: Retrospective analysis was undertaken of prospectively collected equipment usage data from two Role 1 MTFs in Duqm (MTF 1) and Muaskar Al Murtafa (MTF 2) camps over a period of 6-8 weeks. Data were analysed alongside routinely collected epidemiological data (EPINATO) during the deployment. Equipment used in addition to the module was also recorded. RESULTS: MTF 1 used 50 out of the 179 different items from the module over the 8-week period. MTF 2 used 45 out of the 179 different items from their module over the 6-week period. The most commonly used items across the sites were non-sterile examination gloves, plastic aprons, tympanic thermometer probe covers, disinfectant wipes and self-adhesive plasters. Extramodular items (blunt fill needle, water pump sprayer, Jelonet gauze and stool specimen pot) accounted for 5% of all equipment used in MTF 1. CONCLUSION: The study showed that the 300 module accommodates 95% of Role 1 patients' needs but highlights the requirement for dedicated equipment for the treatment of heat casualties if deemed likely and blunt fill/filter needles for the administration of parenteral medication. Commanders must perform a thorough medical estimate and risk assessment prior to deployment to ensure that the 300 medical module is likely to provide the necessary equipment and supplement the module if required.


Assuntos
Equipamentos Médicos Duráveis/tendências , Medicina Militar/instrumentação , Ensino/estatística & dados numéricos , Adulto , Equipamentos Médicos Duráveis/provisão & distribuição , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medicina Militar/métodos , Medicina Militar/estatística & dados numéricos , Omã , Estudos Retrospectivos , Reino Unido/etnologia
20.
BMJ Mil Health ; 166(6): 387-390, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32345682

RESUMO

INTRODUCTION: Module 501 provides core medications which are fundamental to the capability of a prehospital treatment team (PHTT). The quantities of each medication in the module inventory undergo regular review, but these do not correspond to a population at risk (PAR) figure or deployment length for which they intend to be used. This article proposes how the quantities of Module 501 drugs can be scaled for a given deployment, in this example using statistics taken from static PHTTs on Exercise Saif Sareea 3 (SS3). METHODS: The statistics were gathered using a custom-built search of electronic records from the Deployed Defence Medical Information Capability Programme in addition to written record-keeping, which were aligned to the weekly PAR at each PHTT location throughout their full operational capability periods. A quotient was then derived for each module item using a formula. RESULTS: Among the 10 most commonly prescribed drugs were four analgesics and three antimicrobials. 42 of the 110 studied drugs were not prescribed during SS3. DISCUSSION: The data from SS3 reflect the typical scope of disease encountered in the deployed land setting. Employing these data, the use of a formula to estimate the drug quantities needed to sustain a Strike Armoured Infantry Brigade over a 28-day period is demonstrated. RECOMMENDATIONS: Further study of Module 501 across varied deployment environments would be valuable in evolving this approach to medicinal scaling if proven effective for the warm desert climate. It could then be applied to other modules to further inform future Strike medical planning. LIMITATIONS: Several considerations when drawing deductions from the data are mentioned, including the inaccuracy of predictor variables taken from the EpiNATO-2 reports. CONCLUSION: The proposed formula provides an evidence-based framework for scaling drug quantities for a deployment planning. This may improve patient safety and confer logistical, storage and fiscal benefits.


Assuntos
Serviços Médicos de Emergência/métodos , Medicina Militar/instrumentação , Padrões de Prática Médica/estatística & dados numéricos , Ensino/estatística & dados numéricos , Serviços Médicos de Emergência/estatística & dados numéricos , Humanos , Medicina Militar/estatística & dados numéricos , Reino Unido
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