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1.
Dis Esophagus ; 33(1)2020 Jan 16.
Article in English | MEDLINE | ID: mdl-31313807

ABSTRACT

The positive impact on patient comprehension and improved procedural outcomes when multimedia is utilized to convey instructions preprocedurally has been previously shown for gastrointestinal procedures such as colonoscopy. However, in gastroesophageal reflux testing (GERD), we continue to utilize verbal and written instructions to establish this diagnosis when we use BRAVO pH testing. This is arguably a more complex procedure involving stopping medications, placement of a device, and maintaining an accurate diary for the duration of the testing. We hypothesize that by utilizing multimedia to relay complex textual information, patients will have improved comprehension of periprocedural instructions thereby improving data entry and satisfaction of expectations during the procedure. Prospective randomized study of 120 patients undergoing endoscopic placement of the BRAVO pH monitoring capsule for evaluation of GERD receive either written preoperative instructions (control) or written plus video instructions (video group). A composite comprehension score was calculated using procedure-specific parameters of data entry over the 48-hour monitoring period. Patient satisfaction was evaluated on the basis of a five-point Likert scale. Extent of patient satisfaction was defined by the fulfillment of patient expectations. Exclusion criteria included patients who did not have access to the video or did not complete follow-up. Seventy-eight patients completed all follow-up evaluations. The video group (n = 44) had a significantly higher mean comprehension score when compared to the control group (n = 34) (9.6 ± 1.4 vs. 7.4 ± 2.0, P = 0.01). Overall satisfaction with instructions was significantly higher in the intervention group (91% vs. 47%, p 0.01). We detected no significant difference in comprehension or satisfaction scores in subgroup analyses of the video group comparing patients <65 and ≥65 years of age and by education level. Compared to standard written instructions, video instructions improved patient comprehension based on data evaluation, and satisfaction. Therefore, clinicians should consider incorporation of multimedia instructions to enhance patient periprocedural expectations and understanding of reflux pH testing using the BRAVO procedure.


Subject(s)
Esophageal pH Monitoring/psychology , Gastroesophageal Reflux/diagnosis , Patient Acceptance of Health Care/psychology , Patient Education as Topic/methods , Patient Satisfaction/statistics & numerical data , Aged , Comprehension , Female , Humans , Male , Middle Aged , Multimedia , Prospective Studies
2.
Pilot Feasibility Stud ; 4: 122, 2018.
Article in English | MEDLINE | ID: mdl-30002869

ABSTRACT

BACKGROUND: Prescribing for patients taking multiple medicines (i.e. polypharmacy) is challenging for general practitioners (GPs). Limited evidence suggests that the integration of pharmacists into the general practice team could improve the management of these patients. The aim of this study is to develop and test an intervention involving pharmacists, working within GP practices, to optimise prescribing in Ireland, which has a mixed public and private primary healthcare system. METHODS: This non-randomised pilot study will use a mixed-methods approach. Four general practices will be purposively sampled and recruited. A pharmacist will join the practice team for 6 months. They will participate in the management of repeat prescribing and undertake medication reviews (which will address high-risk prescribing and potentially inappropriate prescribing, deprescribing and cost-effective and generic prescribing) with adult patients. Pharmacists will also provide prescribing advice regarding the use of preferred drugs, undertake clinical audits, join practice team meetings and facilitate practice-based education. Throughout the 6-month intervention period, anonymised practice-level medication (e.g. medication changes) and cost data will be collected. A nested Patient Reported Outcome Measure (PROM) study will be undertaken during months 4 and 5 of the 6-month intervention period to explore the impact of the intervention in older adults (aged ≥ 65 years). For this, a sub-set of 50 patients aged ≥ 65 years with significant polypharmacy (≥ 10 repeat medicines) will be recruited from each practice and invited to a medication review with the pharmacist. PROMs and healthcare utilisation data will be collected using patient questionnaires, and a 6-week follow-up review conducted. Acceptability of the intervention will be explored using pre- and post-intervention semi-structured interviews with key stakeholders. Quantitative and qualitative data analysis will be undertaken and an economic evaluation conducted. DISCUSSION: This non-randomised pilot study will provide evidence regarding the feasibility and potential effectiveness of general practice-based pharmacists in Ireland and provide data on whether a randomised controlled trial of this intervention is indicated. It will also provide a deeper understanding as to how a pharmacist working as part of the general practice team will affect organisational processes and professional relationships in a mixed public and private primary healthcare system.

3.
Ecology ; 98(7): 1896-1907, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28419436

ABSTRACT

Functional gene approaches have been used to better understand the roles of microbes in driving forest soil nitrogen (N) cycling rates and bioavailability. Ammonia oxidation is a rate limiting step in nitrification, and is a key area for understanding environmental constraints on N availability in forests. We studied how increasing temperature affects the role of ammonia oxidizing archaea (AOA) and bacteria (AOB) in soil N cycling and availability by using a highly constrained natural mean annual temperature (MAT) elevation gradient in a tropical montane wet forest. We found that net nitrate (NO3- ) bioavailability is positively related to MAT (r2  = 0.79, P = 0.0033), and AOA DNA abundance is positively related to both NO3- availability (r2  = 0.34, P = 0.0071) and MAT (r2  = 0.34, P < 0.001). In contrast, AOB DNA was only detected in some soils across the gradient. We identified three distinct phylotypes within the AOA which differed from one another in abundance and relative gene expression. In addition, one AOA phylotype increased in abundance with MAT, while others did not. We conclude that MAT is the primary driver of ecosystem N availability across this gradient, and AOA population size and structure appear to mediate the relationship between the nitrification and N bioavailability. These findings hold important implications for nutrient limitation in forests and feedbacks to primary production under changing climate.


Subject(s)
Ammonia/metabolism , Ecosystem , Nitrogen Cycle , Soil Microbiology , Temperature , Archaea , Nitrification , Nitrogen , Oxidation-Reduction , Soil , Tropical Climate
4.
Ir J Med Sci ; 186(4): 1009-1017, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28283862

ABSTRACT

BACKGROUND: Hypercholesterolaemia is an important modifiable risk factor for cardiovascular disease (CVD) which requires monitoring and management at a population level. AIMS: This study aims to describe the distribution of serum cholesterol in a community living population of older adults in Ireland and to examine the awareness, treatment and control of hypercholesterolaemia according to CVD risk status. METHOD: This is a cross-sectional study in a nationally representative sample of adults aged 50-79 years (n = 5287). Hypercholesterolaemia was defined as low-density lipoprotein cholesterol (LDL-C) in excess of the recommended CVD risk category target and/or on lipid-lowering medication. RESULTS: This study reports a mean total cholesterol (TC) of 5.1 mmol/L (95% CI 5.0-5.1 mmol/L) and a mean LDL-C of 2.9 mmol/L (95% CI 2.8-2.9 mmol/L) in those aged 50-79 years. In a subgroup aged 50-64 years, 73% (95% CI 71.5-74.5%) were hypercholesterolaemic. LDL-C was controlled to the guideline target in 57% of those with CVD and 49% of those with diabetes. Lack of awareness of hypercholesterolaemia was high across the remainder of the population. CONCLUSION: Despite a substantial reduction in population mean TC from a high of 6.0 mmol/L in the 1980s to 5.1 mmol/L, this study reports a failure to control hypercholesterolaemia to recommended risk-stratified targets in the Irish adult population. Recommendations for policy include continued monitoring of those at highest risk and CVD risk assessment in those perceived to be at low risk in order to inform shared decision making in relation to lifestyle modification and medication management.


Subject(s)
Hypercholesterolemia/drug therapy , Aged , Aging , Cross-Sectional Studies , Female , Humans , Ireland , Longitudinal Studies , Male , Middle Aged , Risk Factors
5.
J Public Health (Oxf) ; 38(3): 450-458, 2016 09.
Article in English | MEDLINE | ID: mdl-25922371

ABSTRACT

BACKGROUND: To assess the prevalence, awareness, treatment and control of hypertension among adults in Ireland and to describe the determinants of awareness, treatment and control in order to inform public health policy. METHODS: A cross-sectional study of a nationally representative sample of community living adults aged 50 years and older using data collected from 2009 to 2011 for the first wave of the Irish Longitudinal Study on Ageing (TILDA) (n = 5857). Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg or diastolic BP ≥90 mmHg and/or currently taking antihypertensive medications. RESULTS: The prevalence of hypertension was 63.7% [95% confidence interval (CI) 62.3-65.1%]. Among those with hypertension, 54.5% (95% CI 52.6-56.2%) were aware of their hypertensive status and 58.9% (95% CI 57.1-60.4%) were on antihypertensive medication. Among those on treatment, 51.6% (95% CI 49.3-53.9%) had their BP controlled to below 140/90 mmHg. Respondents facing financial barriers to primary care and medication were less likely to be on antihypertensive treatment compared with those without financial barriers. CONCLUSIONS: A high prevalence of hypertension was identified in this cohort, with low levels of awareness, treatment and control. Population and primary care interventions are required to reduce prevalence and to improve awareness, detection and management of hypertension.


Subject(s)
Health Knowledge, Attitudes, Practice , Hypertension/epidemiology , Aged , Aged, 80 and over , Antihypertensive Agents/therapeutic use , Cross-Sectional Studies , Female , Humans , Hypertension/drug therapy , Hypertension/prevention & control , Hypertension/psychology , Ireland/epidemiology , Longitudinal Studies , Male , Middle Aged , Prevalence
6.
J Med Entomol ; 53(1): 225-9, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26487243

ABSTRACT

We explored the relationship between the diversity and abundance of the soil arthropod predator community and the overwinter survival of engorged larval Ixodes scapularis Say under variable snow cover in a hardwood forest. We reduced the snow cover over 30 soil core field microcosms, simulating predicted changes in snow pack in the northeastern United States. An additional 29 microcosms were used as references with no snow pack manipulation. Each microcosm contained 15 engorged larval I. scapularis. We expected lower soil temperature without insulating snow cover to reduce tick survival. However, we observed that reduced snow cover had no effect, with 44.2 and 44.7% overwintering successfully in the reference and snow-removal plots, respectively. Increasing taxonomic family richness of arthropod predators and the total number of large (>1 mm) arthropod predators significantly reduced the overwinter survivorship of I. scapularis within the microcosms. Small (<1 mm) arthropod predator abundance had no effect. Our results suggest that forests with complex natural arthropod predator communities show reduced tick survival.


Subject(s)
Ixodes/physiology , Soil/parasitology , Animals , Snow
7.
BMC Pediatr ; 15: 119, 2015 Sep 11.
Article in English | MEDLINE | ID: mdl-26362648

ABSTRACT

BACKGROUND: In 2003, the Irish Medicines Board (IMB) warned against the treatment of childhood depression with selective serotonin reuptake inhibitors (SSRIs) due to increased risk of suicide. This study examined the effect of this warning on the prevalence of anti-depressants in Irish children and compared age and gender trends and international comparisons of prescription rates. METHODS: A retrospective cohort study of the Irish Health Service Executive (HSE) pharmacy claims database for the General Medical Services (GMS) scheme for dispensed medication. Data were obtained for 2002-2011 for those aged ≤ 15 years. Prevalence of anti-depressants per 1000 eligible population, along with 95% confidence intervals, were calculated. A negative binomial regression analysis was used to investigate trends and compare rates across years, sex and age groups (0-4, 5-11, 12-15 years). International prescribing data were retrieved from the literature. RESULTS: The prevalence of anti-depressants decreased from 4.74/1000 population (95% CI: 4.47-5.01) in 2002 to 2.61/1000 population (95% CI: 2.43-2.80) in 2008. SSRI rates decreased from 2002 to 2008. Prescription rates for contra-indicated SSRIs paroxetine, sertraline and citralopram decreased significantly from 2002 to 2005, and, apart from paroxetine, only small fluctuations were seen from 2005 onwards. Fluoxetine was the most frequently prescribed anti-depressant and rates increased between 2002 and 2011. Anti-depressant rates were higher for younger boys and older girls. The Irish prevalence was lower than the US, similar to the U.K. and higher than Germany and Denmark. CONCLUSIONS: The direction and timing of these trends suggest that medical practitioners followed the IMB advice.


Subject(s)
Antidepressive Agents/therapeutic use , Depression/drug therapy , Drug Prescriptions/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Selective Serotonin Reuptake Inhibitors/therapeutic use , Adolescent , Age Factors , Child , Child, Preschool , Female , Fluoxetine/therapeutic use , Guideline Adherence , Humans , Infant , Ireland , Male , Practice Guidelines as Topic , Retrospective Studies , Sex Factors
8.
Drug Alcohol Depend ; 154: 139-45, 2015 Sep 01.
Article in English | MEDLINE | ID: mdl-26188997

ABSTRACT

INTRODUCTION: Drug misuse has been identified as a significant problem in homeless populations. This study examines aspects of physical and mental health, perceived quality of life and health service use among homeless illicit drug users and compares these to non-drug users. METHODS: Participants were recruited through health clinics across Dublin. A questionnaire assessed participants' drug use, health and well-being, health behaviours and use of health services. Descriptive statistics are presented for the entire cohort and drug users separately. Logistic regression analysis was used to examine the relationship between drug use and (i) multimorbidity, (ii) anxiety and/or depression, (iii) perceived quality of life and (iv) use of health services. RESULTS: Of 105 participants recruited, 35 (33%) were current drug users. Current and previous drug users were significantly more likely to have multimorbidity than those who had never taken drugs (OR 4.86, 95% CI 1.00-23.66). There was no significant difference between drug users and non-drug users in the prevalence of anxiety and/or depression. Drug users were five times more likely than non-drug users to have a low perceived quality of life (OR 5.2, 95% CI 1.7-16.0). Health service utilization was high, although some services were used less by drug users (e.g., dentist and psychiatric outpatient services) while others were used more often (e.g., phoneline services and day care centres). CONCLUSION: This study highlights the high levels of drug use in this population and the negative impact of drug use on health and perceived quality of life of a homeless population in Dublin.


Subject(s)
Drug Users/psychology , Health Status , Ill-Housed Persons/psychology , Ill-Housed Persons/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Quality of Life , Substance-Related Disorders/psychology , Adult , Drug Users/statistics & numerical data , Female , Humans , Ireland/epidemiology , Male , Substance-Related Disorders/epidemiology , Surveys and Questionnaires , Young Adult
9.
BMJ Open ; 5(6): e007070, 2015 Jun 09.
Article in English | MEDLINE | ID: mdl-26059522

ABSTRACT

OBJECTIVE: To examine the prevalence and secular trends in benzodiazepine (BZD) prescribing in the Irish paediatric population. In addition, we examine coprescribing of antiepileptic, antipsychotic, antidepressant and psychostimulants in children receiving BZD drugs and compare BZD prescribing in Ireland to that in other European countries. SETTING: Data were obtained from the Irish General Medical Services (GMS) scheme pharmacy claims database from the Health Service Executive (HSE)--Primary Care Reimbursement Services (PCRS). PARTICIPANTS: Children aged 0-15 years, on the HSE-PCRS database between January 2002 and December 2011, were included. PRIMARY AND SECONDARY OUTCOME MEASURES: Prescribing rates were reported over time (2002-2011) and duration (≤ or >90 days). Age (0-4, 5-11, 12-15) and gender trends were established. Rates of concomitant prescriptions for antiepileptic, antipsychotics, antidepressants and psychostimulants were reported. European prescribing data were retrieved from the literature. RESULTS: Rates decreased from 2002 (8.56/1000 GMS population: 95% CI 8.20 to 8.92) to 2011 (5.33/1000 GMS population: 95% CI 5.10 to 5.55). Of those children currently receiving a BZD prescription, 6% were prescribed BZD for >90 days. Rates were higher for boys in the 0-4 and 5-11 age ranges, whereas for girls they were higher in the 12-15 age groups. A substantial proportion of children receiving BZD drugs are also prescribed antiepileptic (27%), antidepressant (11%), antipsychotic (5%) and psychostimulant (2%) medicines. Prescribing rates follow a similar pattern to that in other European countries. CONCLUSIONS: While BZD prescribing trends have decreased in recent years, this study shows that a significant proportion of the GMS children population are being prescribed BZD in the long term. This study highlights the need for guidelines for BZD prescribing in children in terms of clinical indication and responsibility, coprescribing, dosage and duration of treatment.


Subject(s)
Benzodiazepines/therapeutic use , National Health Programs/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Adolescent , Antidepressive Agents/therapeutic use , Antipsychotic Agents/therapeutic use , Central Nervous System Stimulants/therapeutic use , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Ireland , Male , Socioeconomic Factors
10.
Eur J Surg Oncol ; 40(7): 869-74, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24613740

ABSTRACT

BACKGROUND: This study was to evaluate the clinicopathological and prognostic features of follicular thyroid carcinoma (FTC) in our institute over a 15-year period. METHODS: The clinical features, management and outcome of 134 consecutive patients were analyzed according to the time of diagnosis: Group I (1997-2001), Group II (2002-2006), and Group III (2007-2011). RESULTS: As time advanced, the ratio of FTC to papillary thyroid carcinoma decreased from 8.7% in group I to 4.3% in group III (p = 0.000). The percentage of patients undergoing total thyroidectomy seemed to be more commonly used in the later periods - from 10.5% in group I to 21.8% in group II and 18.9% in group III. The median diameter of tumors in group I was 4.2 cm and it showed a sharp decrease to 2.8 cm in group II and 2.9 cm in group III respectively. There was a trend towards a higher stage in patients from Group I vs. patients from Groups II and III (stage IV, 15.8% vs. 2.2% and 4.3%, p = 0.072). The outcome was improved in terms of disease-free survival (DFS). The 3-year DFS rate improved from 77.8% in group I to 93.7% in group II and 100% in group III (p = 0.008). CONCLUSIONS: The clinical features, management and outcome of FTC patients changed over 15-year period. Patients diagnosed after 2001 had a better prognosis. This improvement was probably related to earlier diagnosis with smaller tumor size and presentation at earlier tumor stage.


Subject(s)
Adenocarcinoma, Follicular/mortality , Adenocarcinoma, Follicular/pathology , Lymph Nodes/pathology , Thyroid Neoplasms/mortality , Thyroid Neoplasms/pathology , Adenocarcinoma, Follicular/surgery , Adolescent , Adult , Aged , Biopsy, Needle , Chi-Square Distribution , China , Cohort Studies , Disease-Free Survival , Female , Hospitals, University , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Lymph Nodes/surgery , Male , Middle Aged , Neoplasm Invasiveness/pathology , Neoplasm Staging , Postoperative Care/methods , Prognosis , Retrospective Studies , Risk Assessment , Survival Analysis , Thyroid Neoplasms/surgery , Thyroidectomy/methods , Time Factors , Treatment Outcome , Young Adult
12.
BMJ Open ; 3(7)2013.
Article in English | MEDLINE | ID: mdl-23869100

ABSTRACT

OBJECTIVES: The aim of this systematic review was to examine the epidemiology of malpractice claims in primary care. DESIGN: A computerised systematic literature search was conducted. Studies were included if they reported original data (≥10 cases) pertinent to malpractice claims, were based in primary care and were published in the English language. Data were synthesised using a narrative approach. SETTING: Primary care. PARTICIPANTS: Malpractice claimants. PRIMARY OUTCOME: Malpractice claim (defined as a written demand for compensation for medical injury). We recorded: medical misadventure cited in claims, missed/delayed diagnoses cited in claims, outcome of claims, prevalence of claims and compensation awarded to claimants. RESULTS: Of the 7152 articles retrieved by electronic search, a total of 34 studies met the inclusion criteria and were included in the narrative analysis. Twenty-eight studies presented data from medical indemnity malpractice claims databases and six studies presented survey data. Fifteen studies were based in the USA, nine in the UK, seven in Australia, one in Canada and two in France. The commonest medical misadventure resulting in claims was failure to or delay in diagnosis, which represented 26-63% of all claims across included studies. Common missed or delayed diagnoses included cancer and myocardial infarction in adults and meningitis in children. Medication error represented the second commonest domain representing 5.6-20% of all claims across included studies. The prevalence of malpractice claims in primary care varied across countries. In the USA and Australia when compared with other clinical disciplines, general practice ranked in the top five specialties accounting for the most claims, representing 7.6-20% of all claims. However, the majority of claims were successfully defended. CONCLUSIONS: This review of malpractice claims in primary care highlights diagnosis and medication error as areas to be prioritised in developing educational strategies and risk management systems.

13.
Ecol Appl ; 23(3): 621-42, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23734490

ABSTRACT

Nitrogen (N) and phosphorus (P) are tightly cycled in most terrestrial ecosystems, with plant uptake more than 10 times higher than the rate of supply from deposition and weathering. This near-total dependence on recycled nutrients and the stoichiometric constraints on resource use by plants and microbes mean that the two cycles have to be synchronized such that the ratio of N:P in plant uptake, litterfall, and net mineralization are nearly the same. Disturbance can disrupt this synchronization if there is a disproportionate loss of one nutrient relative to the other. We model the resynchronization of N and P cycles following harvest of a northern hardwood forest. In our simulations, nutrient loss in the harvest is small relative to postharvest losses. The low N:P ratio of harvest residue results in a preferential release of P and retention of N. The P release is in excess of plant requirements and P is lost from the active ecosystem cycle through secondary mineral formation and leaching early in succession. Because external P inputs are small, the resynchronization of the N and P cycles later in succession is achieved by a commensurate loss of N. Through succession, the ecosystem undergoes alternating periods of N limitation, then P limitation, and eventually co-limitation as the two cycles resynchronize. However, our simulations indicate that the overall rate and extent of recovery is limited by P unless a mechanism exists either to prevent the P loss early in succession (e.g., P sequestration not stoichiometrically constrained by N) or to increase the P supply to the ecosystem later in succession (e.g., biologically enhanced weathering). Our model provides a heuristic perspective from which to assess the resynchronization among tightly cycled nutrients and the effect of that resynchronization on recovery of ecosystems from disturbance.


Subject(s)
Computer Simulation , Ecosystem , Models, Theoretical , Nitrogen Cycle , Nitrogen/chemistry , Phosphorus/chemistry , Conservation of Natural Resources , Nitrogen/metabolism , Phosphorus/metabolism , Plants/metabolism , Time Factors , Trees
15.
Pharmacoepidemiol Drug Saf ; 21(9): 945-52, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22231929

ABSTRACT

PURPOSE: Little is known about antibiotic prescribing in Irish children. This study aims to examine antibiotic prescribing patterns in Irish children and associated costs and to compare this with European findings. METHODS: A retrospective analysis of the Irish Health Services Executive (HSE) pharmacy claims database 2004-2009 for the General Medical Services (GMS) scheme for dispensed medications. This represents 28% of Irish children but over-represents lower socio-economic groups. Overall prescribing rates were reported over time (2004-2009), age (0-4, 5-11, 12-15 years) and gender. Statistical comparison is made using negative binomial regression. Overall prescribing rates for the most commonly prescribed drugs were calculated. Associated cost of prescribing also was calculated. European prescribing data were retrieved from the literature. RESULTS: Rates remained stable from 2004 (631/1000 GMS population; 95%CI 628-634) to 2009 (621/1000; 95%CI 618-624). An interaction effect emerged between gender and age. Rates were generally higher for girls, except for the boys aged 0-4 years. The preferred choice of agents changed across years, with co-amoxiclav becoming the most prescribed drug in 2009 (308/1000; 95%CI 306-310). The total cost of antibiotics increased from €4.4 million in 2004 to €6.0 million in 2009. Higher overall rates of antibiotic prescribing emerged compared with available European data. Differences were observed between prescribing of some first-line and second-line drugs. CONCLUSIONS: Age and gender trends are consistent with international literature. However, Ireland has higher overall prescribing rates relative to some European countries. This suggests that a quality improvement in prescribing intervention is warranted.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Practice Patterns, Physicians'/statistics & numerical data , Quality of Health Care , Adolescent , Age Factors , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/economics , Child , Child, Preschool , Databases, Factual , Drug Costs , Female , Humans , Infant , Ireland , Male , Practice Patterns, Physicians'/standards , Regression Analysis , Retrospective Studies , Sex Factors , Time Factors
16.
Oncogene ; 31(41): 4490-8, 2012 Oct 11.
Article in English | MEDLINE | ID: mdl-22266856

ABSTRACT

Differentiation is central to development, while dedifferentiation is central to cancer progression. Hence, a quantitative assessment of differentiation would be most useful. We propose an unbiased method to derive organ-specific differentiation indices from gene expression data and demonstrate its usefulness in thyroid cancer diagnosis. We derived a list of thyroid-specific genes by selecting automatically those genes that are expressed at higher level in the thyroid than in any other organ in a normal tissue's genome-wide gene expression compendium. The thyroid index of a tissue was defined as the median expression of these thyroid-specific genes in that tissue. As expected, the thyroid index was inversely correlated with meta-PCNA, a proliferation metagene, across a wide range of thyroid tumors. By contrast, the two indices were positively correlated in a time course of thyroid-stimulating hormone (TSH) activation of primary thyrocytes. Thus, the thyroid index captures biological information not integrated by proliferation rates. The differential diagnostic of follicular thyroid adenomas and follicular thyroid carcinoma is a notorious challenge for pathologists. The thyroid index discriminated them as accurately as did machine-learning classifiers trained on the genome-wide cancer data. Hence, although it was established exclusively from normal tissue data, the thyroid index integrates the relevant diagnostic information contained in tumoral transcriptomes. Similar results were obtained for the classification of the follicular vs classical variants of papillary thyroid cancers, that is, tumors dedifferentiating along a different route. The automated procedures demonstrated in the thyroid are applicable to other organs.


Subject(s)
Adenoma/diagnosis , Carcinoma/diagnosis , Cell Transformation, Neoplastic/genetics , Thyroid Neoplasms/diagnosis , Adenoma/genetics , Adenoma/pathology , Algorithms , Area Under Curve , Carcinoma/genetics , Carcinoma/pathology , Carcinoma, Papillary , Cell Dedifferentiation , Cell Proliferation , Decision Trees , Diagnosis, Differential , Oligonucleotide Array Sequence Analysis , Organ Specificity , Proliferating Cell Nuclear Antigen/genetics , Proliferating Cell Nuclear Antigen/metabolism , ROC Curve , Support Vector Machine , Thyroid Cancer, Papillary , Thyroid Carcinoma, Anaplastic , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Thyrotropin/physiology , Transcriptome
17.
Ann Surg Oncol ; 19(3): 973-80, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21879273

ABSTRACT

BACKGROUND: Intercellular adhesion molecule-1 (ICAM-1) is implicated in carcinogenesis. In this study we examined the expression of ICAM-1 in papillary thyroid cancer (PTC). We hypothesized that ICAM-1 correlates with indicators of tumor aggressiveness in PTC. METHODS: Thirty-five primary and metastatic PTCs, five follicular adenomas, five Hashimoto thyroiditis, five nodular hyperplasia, and eight normal thyroid tissue samples were analyzed for ICAM-1 gene expression using quantitative reverse-transcription polymerase chain reaction (RT-PCR). ICAM-1 gene expression was analyzed at protein level by immunohistochemistry (IHC) using a semiquantitative score. Gene expression and intensity levels were correlated with markers of tumor aggressiveness including BRAF V600E mutation, tumor size, extrathyroidal extension (ETE), angiolymphatic invasion, and lymph node metastasis. RESULTS: ICAM-1 gene expression was higher in PTC (p = 0.01) and lymph node metastases (p = 0.03) when compared with benign tumors and Hashimoto's. Furthermore, PTCs exhibiting BRAF V600E mutation (p = 0.01), ETE (p < 0.01), and lymph node metastasis (p = 0.02) were associated with higher ICAM-1 levels. Gene expression correlated with protein levels on IHC. Additionally, poorly differentiated thyroid carcinoma had a higher ICAM-1 intensity score compared with well-differentiated carcinoma (p = 0.03). CONCLUSIONS: ICAM-1 expression is upregulated in papillary thyroid carcinoma. Furthermore, ICAM-1 upregulation correlated with aggressive tumor features such as BRAF V600E mutation, ETE, and lymph node metastasis, suggesting that ICAM-1 plays a role in thyroid cancer progression.


Subject(s)
Carcinoma, Papillary/metabolism , Gene Expression Regulation, Neoplastic , Intercellular Adhesion Molecule-1/metabolism , Thyroid Neoplasms/metabolism , Up-Regulation , Adolescent , Adult , Aged , Carcinoma, Papillary/genetics , Carcinoma, Papillary/pathology , Female , Hashimoto Disease/genetics , Hashimoto Disease/metabolism , Humans , Intercellular Adhesion Molecule-1/genetics , Lymphatic Metastasis , Male , Middle Aged , Mutation , Protein Array Analysis , Proto-Oncogene Proteins B-raf/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Young Adult
18.
BMJ Qual Saf ; 20(3): 275-81, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21209143

ABSTRACT

OBJECTIVES: To compare the prevalence of use of potentially inappropriate medicines (PIMs) between older patients living in their own homes versus those living in nursing or residential homes, and to test the association between exposure to PIMs and mortality. DESIGN: Cohort study stratified by place of residence. SETTING: Tayside, Scotland. PARTICIPANTS: All people aged between 66 and 99 years who were resident or died in Tayside from 2005 to 2006. MAIN OUTCOME MEASURES: The exposure variable was PIM use as defined by Beers' Criteria. All cause mortality was the main outcome measure. RESULTS: 70,299 people were enrolled in the cohort of whom 96% were exposed to any medicine and 31% received a PIM. Place of residence was not associated with overall risk of receiving PIMs, adjusted OR 0.94, 95% CI 0.87 to 1.01. Exposure to five of the PIMs (including long-acting benzodiazepines) was significantly higher in nursing homes whereas exposure to five other PIMs (including amitriptyline and NSAIDs) was significantly lower. Exposure to PIMs was similar (20-46%) across all 71 general practices in Tayside and was not associated with increased risk of mortality after adjustment for age, gender and polypharmacy (adjusted OR 0.98, 95% CI 0.92 to 1.05). CONCLUSIONS: The authors question the validity of the full list of PIMs as an indicator of safety of medicines in older people because one-third of the population is exposed with little practice variation and no significant impact on mortality. Future studies should focus on management of a shorter list of genuinely high-risk medicines.


Subject(s)
Independent Living/statistics & numerical data , Nursing Homes/statistics & numerical data , Prescription Drugs/administration & dosage , Age Factors , Aged , Aged, 80 and over , Cohort Studies , Drug Utilization , Female , Humans , Male , Medication Errors/prevention & control , Medication Errors/statistics & numerical data , Polypharmacy , Prevalence , Scotland/epidemiology , Sex Factors
19.
Int J Sports Med ; 32(3): 229-33, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21271497

ABSTRACT

Intrinsic body fluid regulation is critical for optimizing endurance performance. Aquaporins (AQPs) are a family of transmembrane proteins that transport water and glycerol across cellular membranes. A recent report revealed an association between a single nucleotide polymorphism (SNP) in the 3' untranslated region of the aquaporin-1 (AQP1) gene and endurance performance. The purpose of the study was to explore the association between the AQP1 SNP and acute body fluid loss in long distance runners. The subjects (N=91, Age=26±3 yrs; Ht=170±11 cm; Wt=61±5 kg; mean±SD) were biologically unrelated male long distance runners. Data were collected before and after an international 10 km road race. Body fluid loss was determined by the difference between nude body weight before and after the 10 km run. The AQP1 (G→C) gene variation was detected by the ARMS-PCR procedure. Genotypes were determined by PCR product size. Carriers of the AQP1 SNP had a significantly greater adjusted body fluid loss (3.7±0.9 kg) than non-carriers (1.5±1.1 kg) (P<0.05). In conclusion, our study found an association between the AQP1 SNP and acute body fluid loss in long distance runners.


Subject(s)
Aquaporin 1/genetics , Exercise Tolerance/genetics , Polymorphism, Single Nucleotide , Running/physiology , Sweating/physiology , Adult , Body Fluids/physiology , Body Temperature Regulation , Chromosomes, Human, Pair 7/genetics , Exercise Tolerance/physiology , Genetic Variation , Genotype , Health Services Accessibility , Humans , Male , Task Performance and Analysis , Time Factors
20.
QJM ; 104(5): 403-10, 2011 May.
Article in English | MEDLINE | ID: mdl-21186178

ABSTRACT

BACKGROUND: Annual foot checks are recommended in patients with diabetes mellitus (DM) to identify those at risk of foot ulceration. Systematic reviews have found few studies evaluating the predictive value of tests in community-based diabetic populations. AIM: To quantify the predictive value of clinical risk factors in relation to foot ulceration in a community population. METHODS: A cohort of 1192 people with diabetes receiving care in community settings was recruited and a screening procedure, covering symptoms, signs and diagnostic tests was conducted at baseline. At an average 1-year follow-up patients who developed a foot ulcer were identified by an independent blind assessor. Multivariable analysis was performed to identify clinical predictors of foot ulceration. FINDINGS: The incidence of foot ulceration was 1.93% [95% confidence interval (CI) 1.27-2.89). Three time-independent clinical predictors with five factors were selected: previous amputation [odds ratio (OR) 14.7, 95% CI 3.1-69.5), use of insulin before 3 months with inability to distinguish between cool and cold temperatures (OR 2.97, 95% CI 1.9-4.5) and failure to obtain at least one blood pressure reading for the calculation of ankle-brachial index with the failure to feel touch with a 10-g monofilament (OR 1.7, 95% CI 1.3-2.2). INTERPRETATION: Recommendations for annual diabetic foot check in low-risk, community-based patients should be reviewed as absolute events of ulceration are low. The accuracy of foot risk assessment tools to predict ulceration requires evaluation in randomized controlled trials with concurrent economic evaluations.


Subject(s)
Diabetes Mellitus, Type 2/complications , Diabetic Foot/diagnosis , Mass Screening/standards , Adult , Aged , Aged, 80 and over , Delivery of Health Care/standards , Diabetic Foot/epidemiology , Diabetic Foot/etiology , Diabetic Neuropathies/diagnosis , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Risk Factors , Scotland/epidemiology
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