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Biomedical subjects

C K Connolly

Publications and source records attributed to C K Connolly.

At least 19 recordsLinked to original sources
PubMed2003

Do newly diagnosed lung cancer patients feel their concerns are being met?

Lung cancer is the leading cause of cancer death worldwide. It has a poor prognosis and the majority of those affected are elderly. Evidence suggests that providing clear, relevant information and addressing patients' concerns can make a worthwhile difference to patients. This study aimed to: explore the concerns of lung cancer patients shortly after diagnosis; and enquire whether these concerns had been discussed by their care teams. Eighty patients with a new diagnosis of primary lung cancer were interviewed 14-28 days after the date on which they were told the diagnosis. Interviews were conducted either in the hospital ward, outpatient clinic or at home. Participants were asked to rate 17 specific items of concern from 1 = 'not a worry' to 5 = 'extremely worried', plus one non-specific item. Patients rated at least two items as worrying them to some degree with a median of nine concerns being reported. Major concerns for patients were the illness itself; the future relating to the illness and concerns about the family. Overall, patients in the study felt that less than half of their concerns (43%) had been discussed by the care team. Although levels of concern about physical symptoms were relatively low, these had been more frequently addressed than the psychosocial issues, which were rated higher by patients. There were some differences in the number of concerns reported between males/females and younger/older age groups, but the pattern of concerns was similar. There were no differences in the level of concerns between treatment groups; the location of the interview nor in the interval between diagnosis and delivery of the checklist. This study supports previous findings that there is a need for health professionals to provide emotional support and respond to the psychosocial needs of patients by eliciting their concerns and attempting to address them in the early stages of the disease process.

Adaptation, Psychological↗
PubMed2003

The approach to the surgical management of cancer in four European countries.

Outcome of lung cancer appears poorer in the UK than elsewhere in Europe. This may be due to a less aggressive approach in treatment. This study investigated whether clinicians' perceptions of their approach differed between European countries. A questionnaire was circulated to cancer specialists in four countries (Belgium, Greece, Switzerland and the UK) asking about management. An aggression score was calculated using the proportion of standard cases that would proceed to operation at different ages and levels of pulmonary function. The principle problems suggested by most of the 314 respondents were inoperability before symptoms (particularly in the UK) and confounding effects of comorbidity. Surgeons particularly blamed delay in referral. The aggression scores (Belgium 54%, UK 49%, Switzerland 47% and Greece 37%) did not suggest the UK is an outlier, but the UK was more conservative in its approach to N2 disease and isolated cerebral metastasis. The aggression scores of surgeons were greater than those of the others (51% versus 42%). Lung cancer was felt to present late with potentially confounding symptoms, but delay in the clinical process was thought to be less important. Although the UK was more conservative with special cases, its approach to typical cases could account for differences in patient survival.

Data Collection↗
PubMed2002

WE-14, a chromogranin a-derived neuropeptide.

The neuropeptide WE-14 is derived from the posttranslational processing of chromogranin A (CgA). While CgA is expressed in a preponderance of neuroendocrine cells, WE-14 is generated in a distinct subpopulation of CgA-immunopositive cells, most notably in the adrenal, pituitary, and parathyroid glands. Physiological and pharmacological studies have demonstrated that CgA is cleaved to generate WE-14 in the adrenal chromaffin cell population and in the enterochromaffin-like (ECL) cells of the oxyntic mucosa. Pathological analyses of neuroendocrine tumors have revealed a heterogeneous pattern of WE-14 immunostaining, with variable concentrations quantified and chromatographically resolved in tissue extracts. Phylogenetic surveys have demonstrated that WE-14 exhibits an ancient lineage, while ontogenetic examination has shown that it is generated at an early stage during fetal development. Putative WE-14 receptor binding sites have been identified in several tissues; however, the physiological role of WE-14 remains enigmatic.

Animals↗
PubMed2002

Mortality in asthmatics over 15 yrs: a dynamic cohort study from 1983-1998.

The Darlington and Northallerton long-term asthma study observes outcome in asthmatics in the light of potential explanatory variables recorded prospectively. This paper reports changes in mortality during the study, and assesses the relevant risk factors. All asthmatics attending secondary care were recruited at 5-yr intervals from 1983 and reviewed 5 yrs later. Demographic and functional variables, including a formal estimate of best function were recorded prospectively. The dynamic cohort comprised 1,148 asthmatics with 95% follow-up, enabling 612 observations in the period 1983/1988, 774 in 1988/93 and 823 in 1993/98, with 101, 111 and 100 deaths respectively. Principal risk factors for mortality were lower social class and best forced vital capacity. Mortality relative to 1983 halved by 1993/98 and was reduced against the Darlington population, despite an entry forced expiratory volume in one second of 84.7%. There was no change in predictive value of risk factors during the study period, or with date of entry. This study demonstrates a consistent reduction in mortality, which was not entirely a survivor effect, but may be associated with changes in management. By 1993/98 mortality approximated to that of the local reference population despite a lower than predicted forced expiratory volume in one second.

Asthma↗
PubMed2001

The effect of coculture with nonparenchymal cells on porcine hepatocyte function.

Porcine hepatocytes are currently being investigated as a therapy for patients suffering from acute liver failure. Incorporating hepatocytes in an extracorporeal device that would stabilize a patient until transplantation or recovery could dramatically decrease the mortality rate associated with this disease. The ability to maximize hepatocyte function would contribute significantly to being able to provide the required cell mass in a device of reasonable size. Several approaches have been effective at increasing rat hepatocyte function in vitro, including coculture with nonparenchymal cells. In this study, we investigated the effect of the addition of 3T3 cells to porcine hepatocyte culture and found that while there was an increase in albumin secretion, there was little or no effect on urea synthesis or cytochrome P450 activity.

3T3 Cells↗
PubMed2000

Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer--a randomized trial with quality of life as the primary outcome. UK NSCLC Gemcitabine Group. Non-Small Cell Lung Cancer.

Three hundred patients with symptomatic, locally advanced or metastatic NSCLC not requiring immediate radiotherapy were enrolled into this randomized multicentre trial comparing gemcitabine + BSC vs BSC alone. Patients allocated gemcitabine received 1000 mg/m2 on days 1, 8 and 15 of a 28-day cycle, for a maximum of six cycles. The main aim of this trial was to compare patient assessment of a predefined subset of commonly reported symptoms (SS14) from the EORTC QLQ-C30 and LC13 scales. The primary end-points were defined as (1) the percentage change in mean SS14 score between baseline and 2 months and (2) the proportion of patients with a marked (> or = 25%) improvement in SS14 score between baseline and 2 months sustained for > or =4 weeks. The secondary objectives were to compare treatments with respect to overall survival, and multidimensional QL parameters. The treatment groups were balanced with regard to age, gender, Karnofsky performance status (KPS) and disease stage (40% had metastatic disease). The percentage change in mean SS14 score from baseline to 2 months was a 10% decrease (i.e. improvement) for gemcitabine plus BSC and a 1% increase (i.e. deterioration) for BSC alone (P = 0.113, two-sample t-test). A sustained (> or = 4 weeks) improvement (> or =25%) on SS14 was recorded in a significantly higher proportion of gemcitabine + BSC patients (22%) than in BSC alone patients (9%) (P = 0.0014, Pearson's chi-squared test). The QLQ-C30 and L13 subscales showed greater improvement in the gemcitabine plus BSC arm (in 11 domains) than in the BSC arm (one symptom item). There was greater deterioration in the BSC alone arm (six domains/items) than in the gemcitabine + BSC arm (three QL domains). Tumour response occurred in 19% (95% CI 13-27) of gemcitabine patients. There was no difference in overall survival: median 5.7 months (95% CI 4.6-7.6) for gemcitabine + BSC patients and 5.9 months (95% CI 5.0-7.9) (log-rank, P = 0.84) for BSC patients, and 1 -year survival was 25% for gemcitabine + BSC and 22% for BSC. Overall, 74 (49%) gemcitabine + BSC patients and 119 (79%) BSC patients received palliative radiotherapy. The median time to radiotherapy was 29 weeks for gemcitabine + BSC patients and 3.8 weeks for BSC. Patients treated with gemcitabine + BSC reported better QL and reduced disease-related symptoms compared with those receiving BSC alone. These improvements in patient-assessed QL were significant in magnitude and were sustained.

Adult↗
PubMed1999

Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life.

PURPOSE: Chemotherapy for non-small-cell lung cancer (NSCLC) remains controversial. We describe the two largest reported, randomized, parallel trials designed to determine whether the addition of chemotherapy influences duration and quality of life in localized, unresectable (mitomycin, ifosfamide, cisplatin [MIC]1 trial) and extensive (MIC2 trial) disease. PATIENTS AND METHODS: Ambulatory patients with NSCLC, aged 75 years or younger, with localized disease, were randomized in MIC1 to receive up to four cycles of chemotherapy (CT: mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2)) every 21 days, followed by radical radiotherapy (CT + RT) or radiotherapy (RT) alone. Extensive-stage patients were randomized in MIC2 to identical chemotherapy plus palliative care (CT + PC) or palliative care (PC) alone. Short-term change in quality of life (QOL) was assessed in a subgroup of patients. Data from the two trials were combined to allow multivariate and stratified survival analyses. RESULTS: Seven hundred ninety-seven eligible patients were randomized, 446 in MIC1 and 351 in MIC2. MIC CT improved survival in both trials (significantly in MIC2). The median survival time in MIC1 was 11.7 months (CT + RT) versus 9.7 months (RT alone) (P =.14); whereas in MIC2, median survival time was 6.7 months (CT + PC) compared with 4. 8 months (PC alone) (P =.03). QOL, assessed in 134 patients from start of trial to week 6, showed improvement with chemotherapy and deterioration with standard treatment. In the combined analysis of 797 randomized patients, the positive effect of MIC on survival was significant overall (P =.01) and after adjusting for prognostic factors (P =.01). CONCLUSION: MIC chemotherapy prolongs survival in unresectable NSCLC without compromising QOL.

Adult↗
PubMed1998

The Darlington and Northallerton Prospective Asthma Study: best function predicts mortality during the first 10 years.

The Darlington/Northallerton prospective study of asthmatics referred to secondary care started in 1983, with review and new entry at 5-yr intervals. The principal outcome measures are: mortality (presented here), best function and therapeutic step. All adult asthmatics with > or = 15% peak flow (PEF) reversibility to > or = 200 l min-1 were included. Socio-demographic variables, PEF and spirometry were recorded prospectively. Best vital capacity (FVC) and PEF were assessed according to protocol. The mortality of the original cohort after 10 yr was expressed as standardized mortality ratio (SMR) against the local population, with history and pulmonary function at entry as explanatory variables. Ninety-five per cent follow-up was achieved in 628 subjects, with 173 deaths (29.1% of those traced). The excess death rate was nearly 50% (SMR 1.47, 95% CI 1.26-1.71), with 56% of deaths due to respiratory disease (expected 10%). After allowance for age and sex, there was a consistent inverse relationship between mortality and entry best FVC, increased risk of death 1.51 (95% CI 1.33-1.72) per 10% deficit of best FVC predicted. The risk of respiratory death was eight times greater, and of non-respiratory death three times greater, in the lowest compared with the highest quartile of best FVC. There were no interactions with smoking, but possible enhancement of the effect in the socially deprived. Best FVC was a particularly powerful predictor of mortality in subjects < 65 years at entry, in whom 64% of the excess deaths occurred. Most of the excess in respiratory deaths was not due to acute severe asthma but to the development of chronic obstructive pulmonary disease (COPD), as defined functionally, irrespective of smoking habit which made no further contribution to mortality.

Adult↗
PubMed1998

Symptoms and pulmonary function in asthma.

The relationship between symptoms and pulmonary function in asthma is important if the latter is to be held relevant to management guidelines and their audit. Associations between reported symptoms, pulmonary function and therapy were studied in 824 asthmatics (mean FEV1 75.4% predicted; best FEV1 84.6% predicted; and actual/best peak flow (PEF) 87.5%). Bronchodilator usage (reflecting symptomatic wheeze) was evenly distributed up to eight times daily; 22.5% of subjects had nocturnal disturbance and 46.3% persistent daytime symptoms. The univariate relationships between symptoms and function were generally closer with best rather than actual/best. They were further explored using quintiles of function. Symptoms were consistently less as best function increased, but were highly significantly greater in the fifth than in the third and fourth quintiles of actual/best FEV1. There was a trend to a similar U-shaped relationship of actual/best PEF with nocturnal disturbance and daytime symptoms. Best function is a good determinant of expected symptom load in an asthmatic population. Below 85% actual/best function reflects the prevalence of symptoms. In asymptomatic patients a level of at least 85-90% is a useful check of physiological control but will not exclude some symptomatic patients, irrespective of best function.

Adult↗
PubMed1998

A new method for measuring aerosol nebulizer output using radioactive tracers.

Reproducibility and comparability of bronchial challenge tests depends critically on accurate assessment of nebulizer output. Evaporation during nebulization means that simple weighing is inaccurate, overestimating the delivered dose of active ingredient. We wanted to quantify this effect in the context of intermittent nebulization, using a dosimeter as used in bronchial provocation tests. Output of three types of nebulizer, from the MEFAR dosimeter, was measured by radioactive tracer, using a standard solution of technetium-99m-pertechnetate (1.5 kBq x mL(-1)) in 4 mL of normal saline. The aerosol was impacted by suction onto a microfilter, and the radioactivity measured. Nebulizers were weighed before and after nebulization. Ratio of nebulized volume calculated from the radioactivity on the filter, to the total volume loss by weight, was expressed as nebulized ratio. The effect on output of two concentrations of methacholine, two tracers of different weights, and change in temperature, were assessed. Nebulized ratio varied between 44.1-71.6%. Results were more consistent within the same type of nebulizer than between different makes. Neither changes in molar concentration nor molecular weight affected nebulizer output or nebulized ratio. Mean nebulized ratio was 58.5%, showing that calibration by weighing, overestimates the delivered dose by a factor of approximately two. Measuring radioactivity eluted from a microfilter, onto which nebulized output had been impacted proved to be a satisfactory method of calibration.

Aerosols↗
PubMed1998

Management and control of asthma as assessed by actual/best function and corticosteroid use 1980-1993/4.

This study aimed to determine whether the changes in practice in the management of asthma since the early 1980s have improved standards (as assessed by higher actual/best function) and reduced the need for oral corticosteroids. All asthmatic outpatients were reviewed in 1980, 1983, 1988/89 and 1993/94. Therapeutic step, defined by suppressive medication alone, actual and best peak expiratory flow (PEF) were recorded. Cohorts from 1980, 1983 and 1988/89 were identified in whom best function was established on all subsequent occasions. Changes in practice demonstrated by cross-sectional review of all subjects were interpreted with the aid of longitudinal analysis of the cohorts. Attendance increased from 463 in 1980 to 772 in 1993/94. Between 1983 and 1993/94, the proportion maintained on inhaled corticosteroids increased from 49 to 84% with increased use of higher doses. Mean actual/best PEF rose from 80 to 87%, improving at each therapeutic step. The proportion needing rescue oral corticosteroids fell from 47 to 35% and maintenance oral corticosteroids from 20 to 9%. In the cohorts, there was a similar reduction in use of rescue corticosteroids, but not of maintenance oral corticosteroids. The study confirmed an increase in the use and dose of inhaled corticosteroids, and a better outcome at all treatment steps. The fall in the proportion of subjects dependent on oral corticosteroids was due to attrition, rather than weaning in later years.

Administration, Inhalation↗
PubMed1997

Carcinoma of the bronchus in the Yorkshire region of England 1976-1990: trends since 1984.

We wished to confirm that, in patients with lung cancer, trends in demography and histology, together with modest improvements in survival, first seen in the 1976-1983 cohorts, continued to 1990. All lung cancer patients resident in Yorkshire are notified to the Cancer Registry, whose database was analysed for this report. A total of 38,275 patients were notified. There was no change in annual notification for males but an increase from 513 to 815 annual notifications in females between 1976 and 1990. Mean age increased by 3 yrs, in males to 67.4 yrs and in females to 67.2 yrs. Histological confirmation rate increased from 43% to 60% (mean age from 60.8 to 64.5 yrs). Annual notifications of adenocarcinoma increased consistently from 108 to 253. Two year surgical survival improved from 37.4 to 44.3%, doubling in subjects aged > or = 70 yrs to 43.8%. Over the 15 year period, there was no improvement in survival aged < 60 yrs, but a significant improvement in the 60-69 and > or = 70 yrs age groups. Analysis of survival by quartiles showed significant improvement at all levels (first interval 20 to 24 days, median 79 to 91 days, third interval 224 to 266 days). The modest improvement in outlook was confirmed, confined to older subjects after 1983, and partially masked by increasing age. Survival after surgery is now independent of age.

Adenocarcinoma↗