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Biomedical subjects

A Higgins

Publications and source records attributed to A Higgins.

At least 19 recordsLinked to original sources
PubMed2026

Tumor genomic landscape of older patients with metastatic breast cancer☆.

BACKGROUND: Metastatic breast cancer (MBC) in older patients has distinct clinical and histologic characteristics. Elucidating the genomic basis of MBC helps identify potential therapeutic targets to improve outcomes for older patients with MBC. PATIENTS AND METHODS: Using a prospective database and targeted DNA sequencing (OncoPanel), we examined MBC's genomic landscape in older patients (age &#x2265;70 years at MBC diagnosis) and compared findings with those in younger (aged <50 years) and middle-aged (aged 50-69 years) patients. After classifying single nucleotide variants (SNVs) and copy number variations (CNVs) as oncogenic (via OncoKB), the frequencies of SNVs and CNVs, tumor mutational burden (TMB), and oncogenic signaling pathways were compared by age group using Fisher's exact tests. We estimated the association between continuous age at MBC diagnosis and mutations via multivariate logistic regression analysis, adjusting for race, stage at initial diagnosis, subtype, histology, and sample tested (primary versus metastatic). RESULTS: Our study included 2379 patients [853 (35%) younger, 1311 (55%) middle-aged, and 215 (9%) older] who underwent OncoPanel testing between 2013 and 2020. The most frequent tumor alterations in older patients were SNVs in PIK3CA (44%), TP53 (33%), CDH1 (22%) and amplifications in CCND1 (18%). After adjustment, older age was associated with higher frequency of SNVs in CDH1 [odds ratio (OR) = 1.43, 95% confidence interval (CI) 1.21-1.68, q < 0.001], MAP3K1 [OR = 1.30, 95% CI 1.10-1.54, q = 0.008], and PIK3CA [OR = 1.21, 95% CI 1.11-1.31, q < 0.001] and fewer SNVs in TP53 [OR = 0.84, 95% CI 0.77-0.91, q < 0.001]. Patients in the older group were more likely to have tumors with &#x2265;10 mutations/megabase than the youngest patients (26% versus 17%, P = 0.003). CONCLUSIONS: In this large cohort of patients with MBC, the tumor genomic landscape differed between older and younger patients even after accounting for tumor subtype. Older patients were more likely to have high-TMB and PIK3CA-mutated tumors, highlighting the importance of genomic testing for treatment applications in this population.

NGS↗
PubMed2006

Iatrogenic sexual dysfunction and the protective withholding of information: in whose best interest?

In recent years a growing body of evidence has highlighted the impact of neuroleptics and antidepressants on sexual function. Research from a service user's perspective suggested that service users are dissatisfied with the information that they received on drugs, and would like more education, in particular, on the side effects of medication that impact on sexual function. This paper reports some of the findings of a grounded theory study that explored how psychiatric nurses responded to issues of sexuality in practice. Emphasis within the paper is given to how nursing staff addressed the side effects of drugs that impact on sexual function. Findings suggested that nurse addressed the issue of prescribed medication and sexual function in practice, using a 'Veiling Sexualities Cycle', which had three subcategories: 'Hanging the Veil', 'Lifting the Veil' and 'Re-veiling'. In the light of contemporary mental health policy, findings from the study are discussed and recommendations for practice and education made.

Attitude of Health Personnel↗
PubMed2006

Sexual health education for people with mental health problems: what can we learn from the literature?

Research into sexual risk behaviour among people with 'severe' mental health problems suggested that they are likely to engage in high-risk sexual behaviour, for a number of reasons, putting them at risk of sexually transmitted diseases. The aim of this review is to describe approaches, content and outcomes of sexual health education programmes, developed and implemented for people with mental health problems. A literature review from 1980 to 2005 was carried out using the electronic databases CINAHL, PsycINFO, British Nursing Index, Pubmed and Medline, and the Cochrane library was also searched. The literature search was confined to papers written in English. The keywords 'sexuality', 'sexual health education', 'sexual health promotion', 'HIV', 'sexually transmitted disease' were combined with 'mental illness', 'chronic mental illness''severe mental illness''persistent mental illness''psychiatry', 'mental disorder', 'education interventions' and 'evaluation'. A vast amount of literature was recovered on sexual risk behaviour in people with severe mental health problems, and sexual dysfunction as a result of prescribed medication. As the focus of the review was on sexual health education, this literature was omitted. Although the literature on sexual health education for people experiencing mental health problems was sparse, 14 studies were located that either described or evaluated sexual health education programmes. Most sex education programmes focused on topics such as HIV and other sexually transmitted diseases, negotiating safe sex and skill development in condom use. Findings suggested that the people who attended benefited from sexual health education programmes, facilitated in a sensitive and supportive manner. Education tended to produce a reduction in sexual risk behaviour as opposed to complete cessation. Nevertheless, it is appropriate to consider integrating such education with service provision. The results of the review provide guidance to service providers and mental health nurses wishing to develop and evaluate sexual health education programmes for service users. Areas for future research are also identified.

Attitude to Health↗
PubMed2005

Influence of NICE guidelines on removal of third molars in a region of the UK.

We investigated compliance in the West Midlands, UK with the guidelines issued by the National Institute of Clinical Excellence (NICE) on the indications for the removal of third molars. We audited the practice at three departments of maxillofacial surgery that take referrals from three districts of the West Midlands. Of a total of 300 referral letters 217 (72%) specified a NICE-compliant diagnosis. A total of 267 patients (89%) were advised to have third molars removed and all three units achieved 100% compliance with NICE guidelines. There was a concordance of diagnosis of 69% between referring general dental practitioners and attending oral surgeons (concordance was 79% if only those referral letters that carried a specific indication were considered). Disease-free wisdom teeth made up a mean of only 6% of all referrals.

Dental Audit↗
PubMed2005

Neuroleptic medication and sexuality: the forgotten aspect of education and care.

Discussing issues of sexuality is a challenging and difficult issue for many health care workers. When it comes to sexuality and people with mental health problems there seems to be a dual taboo. Mental health nurses are ideal members of the health care team to talk to service users about issues as sensitive as sexuality and the side effects of medication that impact on sexual health. However, in both clinical practice and the nursing literature, the side effects of medications that impact on sexual function are often ignored and unspoken about. This paper examines the impact of both conventional and atypical neuroleptic medication on sexual function and discusses the probable causes of such effects. The possible reasons why health care professionals are reluctant to discuss side effects impacting on sexual health with service users are explored and emphasis is placed on the need for mental health nurses to respond to requests from service users for more education and discussion in the area of sexuality and sexual health.

Antipsychotic Agents↗
PubMed2003

First inelastic neutron scattering studies on thin free standing polymer films.

Glass transition studies in free standing polymer films have revealed values of the transition temperature, T(g), which were substantially reduced below the bulk for sufficiently thin films. Here we report on the preparation of two stacks of free standing polystyrene films: 70 films with a thickness of h approximately 107 nm and 140 films with h approximately 55 nm with equivalent total sample thicknesses of approximately 7.5 microm. We have performed the first measurements on such samples using inelastic neutron scattering, and demonstrate that inelastic neutron scattering experiments, performed on the time-of-flight spectrometer IN6 and the backscattering spectrometer IN16 at the Institut Laue-Langevin, are feasible.

Journal Article↗
PubMed2002

Piglets born from centrifuged and vitrified early and peri-hatching blastocysts.

Cryopreservation of zona-intact porcine embryos has been relatively unsuccessful to date, although some success has been obtained with lipid reduced morulae and early blastocysts. This study adapted some vitrification protocols used successfully with late blastocysts for use with early zona-intact blastocysts, using actin depolymerization, centrifugation, and open-pulled (OPS) straws. Initially, Day 6 peri-hatching blastocysts were collected, cultured for 40 min in 7.5 microg/ml cytochalasin B and vitrified in 6.5 M glycerol and 6% BSA (VS1) in either heat-sealed (HS) or open straws (OS). The post-thaw survival of those stored in HS was 15.4% after 24 and 48 h in vitro; storage in OS significantly improved survival (58.8% for both 24 and 48 h). When similar stage blastocysts were cultured in cytochalasin B and vitrified with 8 M ethylene glycol and 7% polyvinylpyrrolidone (PVP; VS2) in OS, survival was 44.4 and 33.3% for 24 and 48 h, respectively. Day 5 late morulae and early blastocysts were collected, cultured with cytochalasin B, and centrifuged or left intact (control), then vitrified with VS1 in HS or OS, or vitrified in VS2 in OS only. None of the intact control embryos survived thawing and 48 h culture in vitro. Centrifuged early blastocysts vitrified with VS1 showed good post-thaw survival in culture when stored in HS (62.8 and 60.5% for 24 and 48 h, respectively), or OS (75 and 63.6%). When vitrified with VS2 in OS, survival improved (80 and 76.7%). Peri-hatching blastocysts were vitrified in VS1, and early blastocysts were vitrified with VS1 and VS2. All blastocysts were stored in OS. The embryos were recovered and transferred to Day 4 and 5 pseudopregnant recipients (for Day 5 and 6 blastocysts, respectively). Of the five recipients receiving peri-hatching blastocysts, two became pregnant and delivered a total of eight piglets. All three recipients of early blastocysts vitrified in VS1 had a delayed return to estrus; while of the four receiving embryos vitrified with VS2, two were delayed in returning to estrus, and one was confirmed pregnant after 45 days. A litter of five piglets, one male and four female, was produced at 116 days of gestation. To our knowledge, this is the first litter of piglets produced from early blastocysts vitrified without micromanipulation to remove polarized lipid droplets.

Animals↗
PubMed2001

Use of precision agriculture technology to investigate spatial variability in nitrogen yields in cut grassland.

Spatial variability in N uptake and utilisation by swards within uniformly managed field units could be responsible for a significant proportion of the NH3, N2O, NO3- and NOx (NO and NO2) 'pollutants' generated by agriculture and released to the environment. An investigation was commenced, therefore, to quantify, map and explain the spatial variability in sward N yield in a 'large' silage field and to assess the potential for managing this variability using some of the latest precision agriculture technology. Sward dry matter (DM) and N yields were predicted from the results of plant tissue analyses using mathematical models. Sward N yields were found to vary greatly across the field seemingly because of differences in net soil N mineralisation, but the pattern of variability appeared to remain constant with time. Conventional soil analysis of a range of soil chemical and physical properties, however, failed to explain this variability. It was concluded that the N-yield distribution map might be used in place of soil analysis as the basis for varying the rates of N application to different parts of the field with the twin objectives of maximising fertiliser use efficiency and minimising N emissions to air and water.

Agriculture↗
PubMed1999

Prophylactic antibiotics for elective laparoscopic cholecystectomy: are they necessary?

HYPOTHESIS: Prophylactic antibiotic treatment in elective laparoscopic cholecystectomy does not lower the already low infection rate associated with this procedure. DESIGN AND SETTING: Prospective double-blind randomized trial at a community-based training hospital. PATIENTS: Four hundred fifty patients undergoing elective laparoscopic cholecystectomy were randomized into 1 of 3 treatment arms: (1) preoperative cefotetan disodium, 1g intravenously; (2) preoperative cefazolin, 1g intravenously; and (3) intravenous placebo. There were no demographic differences between groups in age, smoking history, American Society of Anesthesiologists score, infection risk class, time of antibiotic administration prior to surgery, and type of skin preparation. INTERVENTIONS: Laparoscopic cholecystectomy was attempted in all cases; however, 10 patients required conversion to an open cholecystectomy and they were included in the statistical analysis. Preoperatively, all patients were randomized in a blinded manner and received cefotetan, cefazolin, or placebo intravenously. RESULTS: There were 10 postoperative infections. In the cefotetan group, there were 3 cases of superficial surgical site infections. In the cefazolin group, there were 2 superficial surgical site infections-1 pneumonia and 1 rhinosinusitis. In the placebo group, there were 2 superficial surgical site infections and 1 urinary tract infection. The overall infection rate in this series was 2.4%. Follow-up was performed at routine postoperative visits and by telephone contact. Data were evaluated using the chi2 test and analysis of variance with Duncan post hoc test (P<.05). CONCLUSION: Based on our data, use of prophylactic antibiotics does not decrease the rate of wound infections in elective laparoscopic cholecystectomy.

Antibiotic Prophylaxis↗
PubMed1999

Evidence-based policy-making in the NHS: exploring the interface between research and the commissioning process.

BACKGROUND: The UK National Health Service (NHS) R&D strategy acknowledges the importance of developing an NHS where practice and policy is more evidence-based. This paper is based on a qualitative study which aimed to identify factors which facilitate or impede evidence-based policy-making at a local level in the NHS. METHODS: The study involved a literature review and case studies of social research projects which were initiated by NHS health authority managers or general practitioner (GP) fundholders in one region of the NHS. Data were collected through in-depth interviews with lead policy-makers, GPs and researchers working on each of the case studies and analysis of project documentation. RESULTS: An over-arching theme from the analysis was that of the complexity of R&D in purchasing. The two worlds of research and health services management often sit uncomfortably together. For this reason it was not possible to describe a 'blueprint' for successful R&D, although several important issues emerged. These include sharing an appropriate model for research utilization, the importance of relationships in shaping R&D, the importance of influence and commitment in facilitating evidence-based change, and the resourcing of R&D in purchasing. CONCLUSIONS: These issues have important implications for the strategic development of R&D as well as for individual project application. Moving beyond the rhetoric of evidence-based policy-making is more likely if both policy-makers and researchers openly acknowledge this complexity and give due concern to the issues outlined.

Evidence-Based Medicine↗
PubMed1998

A randomised, concentration-controlled, comparison of standard (5-day) vs. prolonged (15-day) infusions of etoposide phosphate in small-cell lung cancer.

PURPOSE: This randomised trial was designed to investigate the activity and toxicity of continuous infusion etoposide phosphate (EP), targeting a plasma etoposide concentration of either 3 micrograms/ml for five days (5d) or 1 microgram/ml for 15 days (15d), in previously untreated SCLC patients with extensive disease. PATIENTS AND METHODS: EP was used as a single agent. Plasma etoposide concentration was monitored on days 2 and 4 in patients receiving 5d EP and on days 2, 5, 8 and 11 in patients receiving 15d EP, with infusion modification to ensure target concentrations were achieved. Treatment was repeated every 21 days for up to six cycles, with a 25% reduction in target concentration in patients with toxicity. RESULTS: The study has closed early after entry of 29 patients (14 with 5d EP, 15 with 15d EP). Objective responses were seen in seven of 12 (58%, confidence interval (CI): 27%-85%) evaluable patients after 5d EP, and two of 14 (14%, CI: 4%-42%) evaluable patients after 15d EP (P = 0.038). Grade 3 or 4 neutropenia or leucopenia during the first cycle of treatment was observed in six of 12 patients after 5d EP and 0/14 patients after 15d EP (P = 0.004), with median nadir WBC count of 2.6 x 10(9)/1 after 5d and 5.0 x 10(9)/1 after 15d EP (P = 0.017). Only one of 49 cycles of 15d EP was associated with grade 3 or worse haematological toxicity, compared to 14 of 61 cycles of 5d EP. CONCLUSIONS: Although the number of patients entered into this trial was small, the low activity seen at 1 microgram/ml in the 15d arm suggests that this concentration is below the therapeutic window in this setting. Further concentration-controlled studies with prolonged EP infusions are required.

Adult↗
PubMed1995

Ank3 (epithelial ankyrin), a widely distributed new member of the ankyrin gene family and the major ankyrin in kidney, is expressed in alternatively spliced forms, including forms that lack the repeat domain.

We cloned a novel ankyrin, Ank3, from mouse kidney cDNA. The full-length transcript is predicted to encode a 214-kD protein containing an 89 kD, NH2 terminal "repeat" domain; a 65 kD, central "spectrin-binding" domain; and a 56 kD, COOH-terminal "regulatory" domain. The Ank3 gene maps to mouse Chromosome 10, approximately 36 cM from the centromere, a locus distinct from Ank1 and Ank2. Ank3 is the major kidney ankyrin. Multiple transcripts of approximately 7.5, 6.9, 6.3, 5.7, 5.1, and 4.6 kb are highly expressed in kidney where Ank1 and Ank2 mRNAs are barely detectable. The smaller mRNAs (< or = 6.3 kb) lack the entire repeat domain. These transcripts have a unique 5'untranslated region and NH2-terminal sequence and encode a predicted protein of 121 kD. Two small sequences of 21 and 18 amino acids are alternatively spliced at the junction of the repeat and spectrin-binding domains in the larger (> or = 6.9 kb) RNAs. Alternative splicing of a 588 bp sequence (corresponding to a 21.5-kD acidic amino acid sequence) within the regulatory domain also occurs. Ank3 is much more widely expressed than previously described ankyrins. By Northern hybridization or immunocytochemistry, it is present in most epithelial cells, in neuronal axons, in muscle cells, and in megakaryocytes/platelets, macrophages, and the interstitial cells of Leydig (testis). On immunoblots, an antibody raised to a unique regions of the regulatory domain detects multiple Ank3 isoforms in the kidney (215, 200, 170, 120, 105 kD) and in other tissues. The 215/200 kD and 120/105-kD kidney proteins are close to the sizes predicted for the 7.5/6.9- and 6.3/5.7-kb RNAs (with/without the 588-bp acidic insert). Interestingly, it appears that Ank3 exhibits a polarized distribution only in tissues that express the approximately 7.0-kb isoforms, the only isoforms in the kidney that contain the repeat domain. In tissues where smaller transcripts (< or = 6.3 kb) are expressed. Ank3 is diffusely distributed in some or all cells and may be associated with cytoplasmic structures. We conclude that Ank3 is a broadly distributed epithelial ankyrin and is the major ankyrin in the kidney and other tissues, where it plays an important role in the polarized distribution of many integral membrane proteins.

Alternative Splicing↗