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1.
J Vet Cardiol ; 42: 43-46, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35709546

ABSTRACT

A nine-year-old male, castrated Pembroke Welsh Corgi presented with a two-month history of lethargy, hyporexia, and occasional vomiting. There was also a two-week history of exercise intolerance; no syncopal episodes were reported. Auscultation revealed bradycardia with an irregular rhythm and otherwise normal heart and lung sounds. Third-degree atrioventricular block was diagnosed. Two-dimensional transthoracic echocardiography revealed a soft tissue structure arising from the atrioventricular junction and interatrial septum. There was scant abdominal effusion. Pacemaker implantation was offered, but the owner elected humane euthanasia due to the unknown prognosis. Necropsy was consistent with cardiac hemangiosarcoma infiltrating the interatrial and interventricular septum.


Subject(s)
Atrioventricular Block , Dog Diseases , Heart Neoplasms , Hemangiosarcoma , Pacemaker, Artificial , Animals , Atrioventricular Block/complications , Atrioventricular Block/veterinary , Dog Diseases/diagnosis , Dog Diseases/therapy , Dogs , Euthanasia, Animal , Heart Neoplasms/complications , Heart Neoplasms/veterinary , Hemangiosarcoma/complications , Hemangiosarcoma/veterinary , Male , Pacemaker, Artificial/veterinary
2.
Int J Drug Policy ; 96: 103359, 2021 10.
Article in English | MEDLINE | ID: mdl-34325969

ABSTRACT

BACKGROUND: Reaching World Health Organization hepatitis C (HCV) elimination targets requires diagnosis and treatment of people who use drugs (PWUD) with direct acting antivirals (DAAs). PWUD experience challenges engaging in HCV treatment, including needing multiple provider and laboratory appointments. Women, minoritized racial communities, and homeless individuals are less likely to complete treatment. METHODS: We implemented a streamlined opt-out HCV screening and linkage-to-care program in two healthcare for the homeless clinics and a medically supported withdrawal center. Front-line staff initiated a single-order reflex laboratory bundle combining screening, confirmation, and pre-treatment laboratory evaluation from a single blood draw. Multinomial logistic regression models identified characteristics influencing movement through each stage of the HCV treatment cascade. Multiple logistic regression models identified patient characteristics associated with HCV care cascade progression and Cox proportional hazards models assessed time to initiation of DAAs. RESULTS: Of 11,035 clients engaged in services between May 2017 and March 2020, 3,607 (32.7%) were screened. Of those screened, 1,020 (28.3%) were HCV PCR positive. Of those with detectable RNA, 712 (69.8%) initiated treatment and 670 (94.1%) completed treatment. Of those initiating treatment, 407 (57.2%) achieved SVR12. There were eight treatment failures and six reinfections. In the unadjusted model, the bundle intervention was associated with increased care cascade progression, and in the survival analysis, decreased time to initiation; these differences were attenuated in the adjusted model. Women were less likely to complete treatment and SVR12 labs than men. Homelessness increased likelihood of screening and diagnosis but was negatively associated with completing SVR12 labs. Presence of opioid and stimulant use disorder diagnoses predicted increased care cascade progression. CONCLUSIONS: The laboratory bundle and referral pathways improved treatment initiation, time to initiation, and movement across the cascade. Despite overall population improvements, women and homeless individuals experienced important gaps across the HCV care cascade.


Subject(s)
Hepatitis C, Chronic , Hepatitis C , Ill-Housed Persons , Algorithms , Antiviral Agents/therapeutic use , Delivery of Health Care , Female , Hepacivirus , Hepatitis C/diagnosis , Hepatitis C/drug therapy , Hepatitis C, Chronic/drug therapy , Humans , Laboratories , Male
3.
Article in English | MEDLINE | ID: mdl-26556778

ABSTRACT

The study examined the impact of using a quality of life (QoL) questionnaire during a clinic to identify QoL issues and to improve QoL. 138 patients were randomised (1:1:1) to either (1) an Intervention group that completed the European Organisation for Research and Treatment of Cancer-Core Quality of Life Questionnaire and Lung Cancer Module (EORTC QLQ-C30 and LC13) at baseline and received feedback during a clinic, (2) an Attention group that completed the questionnaire at baseline without feedback and (3) a Control group that did not complete the questionnaire. All patients completed the same questionnaire 6 weeks later and a contact diary during the study period. There was a significant difference between the Intervention and Control groups for the mean number of QoL issues identified at baseline (4.69 vs. 2.81, P = 0.006) and the mean number of actions taken (4.41 vs. 2.46, P = 0.004). At 6 weeks, there was no difference between the groups in global QoL (Intervention vs. Control group, P = 0.596; Attention vs. Control, P = 0.973). The results suggest that the completion of the EORTC QLQ-C30 LC13 with feedback improves communication and increases the number of QoL issues identified and actions taken. However, the intervention does not impact on QoL per se. Clinicaltrials.gov: NCT01213745.


Subject(s)
Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Mesothelioma/therapy , Quality of Life , Surveys and Questionnaires/standards , Activities of Daily Living , Analysis of Variance , Cancer Care Facilities , Female , Humans , Male , Middle Aged , Treatment Outcome
4.
Parkinsons Dis ; 2013: 572134, 2013.
Article in English | MEDLINE | ID: mdl-23738230

ABSTRACT

Background. It is widely believed that exercise improves mobility in people with Parkinson's disease (PD). However, it is difficult to determine whether a specific type of exercise is the most effective. The purpose of this study was to determine which outcome measures were sensitive to exercise intervention and to explore the effects of two different exercise programs for improving mobility in patients with PD. Methods. Participants were randomized into either the Agility Boot Camp (ABC) or treadmill training; 4x/week for 4 weeks. Outcome measures were grouped by the International Classification of Function/Disability (ICF). To determine the responsiveness to exercise, we calculated the standardized response means. t-tests were used to compare the relative benefits of each exercise program. Results. Four of five variables at the structure/function level changed after exercise: turn duration (P = 0.03), stride velocity (P = 0.001), peak arm speed (P = 0.001), and horizontal trunk ROM during gait (P = 0.02). Most measures improved similarly for both interventions. The only variable that detected a difference between groups was postural sway in ABC group (F = 4.95; P = 0.03). Conclusion. Outcome measures at ICF body structure/function level were most effective at detecting change after exercise and revealing differences in improvement between interventions.

5.
BJOG ; 117(11): 1358-65, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20716251

ABSTRACT

OBJECTIVE: Higher risks of uterine rupture have been reported among women attempting vaginal birth after caesarean (VBAC) particularly following induction with prostaglandins, compared with women who do not labour. This study aimed to estimate these risks as well as that associated with oxytocin use. DESIGN: Population-based retrospective cohort study involving all women who had their first births by caesarean. In their second birth, risks of uterine rupture among women without labour and women who had labour augmented or induced were compared with women who gave birth after spontaneous labour. SETTING: Four Australian states in 1998-2000. POPULATION: Women on pregnancy outcome databases with a second birth after a prior caesarean for their first birth. METHODS: From 29, 008 women identified from the databases, those with uterine rupture were identified and validated using hospital case records. MAIN OUTCOME MEASURE: Uterine rupture. RESULTS: The risk of complete uterine rupture among women without labour was 0.01%. The risk in spontaneous labour without augmentation was 0.15%, considerably higher when there was augmentation with oxytocin (1.91%). The risk with induction of labour was 0.54% for oxytocin alone, 0.68% for prostaglandin alone, 0.63% without either and 0.88% when they were combined. Compared with spontaneous labour, risks were increased three- to five-fold for any induction, six-fold for prostaglandin combined with oxytocin and 14-fold for augmentation with oxytocin. CONCLUSIONS: Careful consideration should be given to the use of oxytocin for augmentation of labour or induction by any method for women with a previous caesarean in view of increased risks of uterine rupture.


Subject(s)
Uterine Rupture/etiology , Vaginal Birth after Cesarean/adverse effects , Adult , Australia/epidemiology , Female , Humans , Labor, Induced/adverse effects , Labor, Induced/statistics & numerical data , Oxytocics/adverse effects , Oxytocin/adverse effects , Pregnancy , Pregnancy Outcome , Retrospective Studies , Risk Factors , Uterine Rupture/epidemiology , Vaginal Birth after Cesarean/statistics & numerical data
6.
Arch Dis Child ; 94(9): 658-62, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19477912

ABSTRACT

BACKGROUND: Television advertisements for less healthy foods are thought to contribute to overweight and obesity in children. In the UK, new regulations on television food advertising to children came into effect in April 2007. These prohibit advertisements for "less healthy" foods during or around programmes "of particular appeal to" (OPAT) children. In Canada, self-regulated codes of practice on television food advertising to children were recently strengthened. OBJECTIVE: To document the nutritional content of food advertised and number of advertisements OPAT children broadcast in the UK and central Canada before the introduction of the new UK regulations. DESIGN: All food advertisements broadcast on four popular channels in Canada and the three terrestrial commercial channels in the UK during 1 week in 2006 were identified and linked to relevant nutritional data. Food advertisements OPAT children and for "less healthy" products were identified using the criteria in the UK regulations. RESULTS: 2315 food related advertisements broadcast in Canada and 1365 broadcast in the UK were included. 52-61% were for "less healthy" products; 5-11% were OPAT children. Around 5% of food advertisements would have been prohibited under the new UK regulations. There were few differences in the nutritional content of food described in advertisements that were and were not OPAT children. CONCLUSION: There was little evidence that food described in advertisements OPAT children were any less healthy than those that were not. Few food advertisements are likely to be prohibited by the new UK regulations.


Subject(s)
Advertising/legislation & jurisprudence , Food/classification , Television , Advertising/statistics & numerical data , Canada , Child , Diet , Dietary Fats/administration & dosage , Dietary Fiber/administration & dosage , Humans , Legislation, Food , Nutritive Value , Suggestion , United Kingdom
7.
BJOG ; 115(4): 492-500, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18271886

ABSTRACT

OBJECTIVE: To investigate the role of fetal viral infection in the development of a range of adverse pregnancy outcomes (APOs), including pregnancy-induced hypertensive disorders (PIHD), antepartum haemorrhage (APH), birthweight <10th percentile (small for gestational age, SGA) and preterm birth (PTB). DESIGN: Population-based case-control study. SETTING: Laboratory-based study. POPULATION: The newborn screening cards of 717 adverse pregnancy cases and 609 controls. METHODS: Newborn screening cards were tested for RNA from enteroviruses and DNA from herpesviruses using polymerase chain reaction (PCR). The herpesviruses were detected using two PCRs, one detecting nucleic acids from herpes simplex virus (HSV)-1, HSV-2, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and human herpesvirus (HHV)-8, hereafter designated Herpes PCR group A viruses, and the other detecting nucleic acids from varicella-zoster virus (VZV), HHV-6 and HHV-7, hereafter designated Herpes PCR group B viruses. MAIN OUTCOME MEASURE: Odds ratios and 95% CIs for specific APOs. RESULTS: For both term and PTBs, the risk of developing PIHD was increased in the presence of DNA from Herpes PCR group B viruses (OR 3.57, 95% CI 1.10-11.70), CMV (OR 3.89, 95% CI 1.67-9.06), any herpesvirus (OR 5.70, 95% CI 1.85-17.57) and any virus (OR 5.17, 95% CI 1.68-15.94). The presence of CMV was associated with PTB (OR 1.61, 95% CI 1.14-2.27). No significant association was observed between SGA or APH and exposure to viral infection. CONCLUSIONS: Fetal exposure to herpesvirus infection was associated with PIHD for both term and PTBs in this exploratory study. Exposure to CMV may also be associated with PTB. These findings need confirmation in future studies.


Subject(s)
Fetal Diseases/virology , Herpesviridae Infections/complications , Hypertension, Pregnancy-Induced/virology , Postpartum Hemorrhage/virology , Pregnancy Complications, Infectious/virology , Premature Birth/virology , Case-Control Studies , Cohort Studies , DNA, Viral/analysis , Female , Herpesviridae/isolation & purification , Humans , Infant, Newborn , Infant, Small for Gestational Age , Pregnancy
8.
J Anim Sci ; 86(1): 17-24, 2008 Jan.
Article in English | MEDLINE | ID: mdl-17878273

ABSTRACT

The feasibility and economic value of DNA paternity identification were investigated and illustrated using Nevada beef cattle operations. A panel of 15 microsatellites was genotyped in 2,196 animals from 8 ranches with a total of 31,571 genotypes. Probabilities of exclusion for each marker within ranch and across ranches were computed. Joint probabilities of exclusion for the 15 microsatellites were also determined, resulting in values over 0.99 for any individual ranch and across ranches. Dropping 1 or 2 microsatellites with the lowest probabilities of exclusion resulted in joint probabilities greater than 0.99 and with marginal reduction compared with the probabilities with 15 microsatellites. Formulas for benefit-cost analysis for a DNA paternity identification program in beef cattle were derived. Genotyping 15 microsatellites with 20 calves per sire resulted in benefits of $1.71 and $2.44 per dollar invested at bull culling rates of 0.20 and 0.30, respectively. The breakpoints for the program to be profitable occurred when the ratio of the price of 1 kg of calf liveweight over the cost of genotyping 1 microsatellite was greater than 1.1 for a bull culling rate of 0.30. Benefit-cost analysis was also derived under incomplete DNA paternity identification using a lower number of DNA markers than necessary to achieve joint probabilities of exclusion of 0.99. Approximately a 20% increase in the benefit-cost ratio was achieved using 10 vs. 12 microsatellites with incomplete paternity identification. The greater the number of bulls in the operation, the lower the benefit-cost ratio of the paternity testing program. Low probabilities of exclusion and a high number of bulls in the beef operation reduced the benefit-cost ratio dramatically. The DNA paternity identification programs are feasible and may be profitable for free-range beef cattle operations.


Subject(s)
Animal Husbandry/economics , Paternity , Alleles , Animals , Breeding/economics , Cattle , DNA/genetics , Heterozygote , Male , Microsatellite Repeats/genetics , Nevada
9.
Ann Oncol ; 17(2): 270-5, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16317014

ABSTRACT

BACKGROUND: Prior phase II trials have demonstrated the therapeutic activity of cytotoxic chemotherapy in mesothelioma. Currently there are few randomised data assessing the role of chemotherapy versus best supportive care (BSC) in the management of patients with stable symptoms after control of any pleural effusion. A policy of observation is often adopted over initial use of chemotherapy. In this prospective randomised trial we assess the use of early versus delayed cytotoxic therapy. The study opened in 1998, and closed in view of a competing national study (MSO 1) in 2003. METHODS: Eligible patients had a performance status3 months and had stable symptoms for at least 4 weeks prior to randomisation. Patients were randomised to receive immediate chemotherapy or initial BSC with the addition of chemotherapy at time of symptomatic progression. All patients received the same platinum-based chemotherapy regimen, MVP [mitomycin C 8 mg/m2 cycles 1, 2, 4 and 6, vinblastine 6 mg/m2, maximum 10 mg, and cisplatin 50 mg/m2 (or carboplatin AUC 5)], every 3 weeks for up to six cycles. RESULTS: A total of 43 patients were recruited, of which 21 were randomised to the early treatment group and 22 to the delayed treatment group. The median ages were 59 years (range 50-78) and 67 years (range 48-75), respectively (P=0.1); other baseline parameters were well matched between the two groups. All 21 patients in the early group received chemotherapy versus 17 patients in the delayed group. Median time to symptomatic progression was 25 weeks in the early group compared with 11 weeks for the delayed group (P=0.1). Median survival was 14 months (1-year survival 66%) for the early group compared with 10 months (1-year survival 36%) for the delayed group (P=0.1). Quality of life was in general better maintained for early treatment and the health resources use was similar in both arms. CONCLUSIONS: In this patient group, presenting with stable symptoms after control of pleural effusion, the early use of chemotherapy provided an extended period of symptom control, and in this small trial a trend to survival advantage.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Mesothelioma/drug therapy , Peritoneal Neoplasms/drug therapy , Pleural Neoplasms/drug therapy , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Carboplatin/administration & dosage , Cisplatin/administration & dosage , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Mitomycins/administration & dosage , Quality of Life , Survival Analysis , Vinblastine/administration & dosage
11.
Ann Oncol ; 15(9): 1406-12, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15319247

ABSTRACT

BACKGROUND: With the rising incidence of malignant mesothelioma (MM), it is important to optimise treatment to control symptoms, maintain quality of life and, if possible, prolong life. We have analysed prospectively collected data to evaluate a frequently used palliative chemotherapy regimen. PATIENTS AND METHODS: Between October 1986 and May 2002 all patients with inoperable pleural mesothelioma were considered for treatment with MVP (mitomycin C 8 mg/m2 every 6 weeks, vinblastine 6 mg/m2 every 3 weeks and cisplatin 50 mg/m2 every 3 weeks) chemotherapy. Symptoms were assessed by physician assessment at baseline and after each cycle of chemotherapy. RESULTS: One hundred and fifty patients were treated with MVP for mesothelioma. Forty-three per cent had a performance status (PS) 2 or worse. The response rate was 15.3%, with 68.6% having stable disease. Sixty-nine per cent reported an improvement in symptoms; in particular there were good responses for pain (71%), cough (62%) and dyspnoea (50%). The most common grade 3/4 toxicity was neutropenia (22%). Median overall survival was 7 months, with 1-year survival 31% and 2-year survival 11%. Median survival for patients with PS 0/1 was 10 months, and was 6 months for patients with PS 2/3. Poor prognostic factors in univariate analysis included poor PS, weight loss, mixed or sarcomatoid histology, low haemoglobin and high white blood cell count. Excluding pathological subtype, the prognostic significance of poor PS and weight loss were retained in multivariate analysis. CONCLUSIONS: Palliation of symptoms in MM is achievable with current cisplatin-based treatments.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Mesothelioma/drug therapy , Pleural Neoplasms/drug therapy , Adult , Aged , Antibiotics, Antineoplastic/adverse effects , Antibiotics, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Cisplatin/adverse effects , Female , Humans , Male , Mesothelioma/mortality , Middle Aged , Mitomycin/administration & dosage , Mitomycin/adverse effects , Multivariate Analysis , Pleural Neoplasms/mortality , Prospective Studies , Survival Analysis , Survival Rate , Treatment Outcome , Vinblastine/administration & dosage , Vinblastine/adverse effects , Weight Loss/drug effects
12.
Br J Cancer ; 90(10): 1905-11, 2004 May 17.
Article in English | MEDLINE | ID: mdl-15138470

ABSTRACT

To examine whether weight loss at presentation influences outcome in patients who received chemotherapy for lung cancer or mesothelioma. Multivariate analysis of prospectively collected data 1994-2001. Data were available for age, gender, performance status, histology, stage, response, toxicity, progression-free and overall survival. The outcomes of patients with or without weight loss treated with chemotherapy for small cell lung cancer (SCLC; n=290), stages III and IV non-small-cell lung cancer (NSCLC; n=418), or mesothelioma (n=72) were compared. Weight loss was reported by 59, 58 and 76% of patients with SCLC, NSCLC and mesothelioma, respectively. Patients with weight loss and NSCLC (P=0.003) or mesothelioma (P=0.05) more frequently failed to complete at least three cycles of chemotherapy. Anaemia as a toxicity occurred significantly more frequently in NSCLC patients with weight loss (P=0.0003). The incidence of other toxicities was not significantly affected by weight loss. NSCLC patients with weight loss had fewer symptomatic responses (P=0.001). Mesothelioma patients with weight loss had fewer symptomatic (P=0.03) and objective responses (P=0.05). Weight loss was an independent predictor of shorter overall survival for patients with SCLC (P=0.003, relative risk (RR)=1.5), NSCLC (P=0.009, RR=1.33) and mesothelioma (P=0.03, RR=1.92) and an independent predictor of progression-free survival in patients with SCLC (P=0.01, RR=1.43). In conclusion, weight loss as a symptom of lung cancer predicts for toxicity from treatment and shorter survival.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Small Cell/drug therapy , Carcinoma, Small Cell/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Mesothelioma/drug therapy , Mesothelioma/pathology , Weight Loss , Adult , Aged , Female , Humans , Male , Middle Aged , Multivariate Analysis , Prognosis , Retrospective Studies , Risk Factors , Survival Analysis
13.
Palliat Med ; 16(5): 403-9, 2002 Sep.
Article in English | MEDLINE | ID: mdl-12380658

ABSTRACT

Our aims were to determine the extent of coverage by designated palliative care services of the population of terminally ill cancer patients in South Australia, and to identify the types of patients who receive these services and the types who do not. All designated hospice and palliative care services in South Australia notified to the State Cancer Registry the identifying details of all their patients who died in 1999. This information was cross-referenced with the data for all cancer deaths (n=3086) recorded on the registry for 1999. We found that the level of coverage by designated palliative services of patients who died with cancer in 1999 was 68.2%. This methodology was previously used to show that the level of coverage had increased from 55.8% for cancer deaths in 1990 to 63.1% for those in 1993. Patients who died at home had the largest coverage by palliative services (74.7%), whereas patients who died in nursing homes had the lowest coverage (48.4%). Patients who did not receive care from these palliative services tended to be 80 years of age or older at death, country residents, those with a survival time from diagnosis of three months or less, and those diagnosed with a prostate, breast, or haematological malignancy. Gender, socioeconomic status of residential area, and race were not related to coverage by a designated palliative service, whereas migrants to Australia from the UK, Ireland, and Southern Europe were relatively high users of these services. We conclude that the high level of palliative care coverage observed in this study reflects widespread support for the establishment of designated services. When planning future care, special consideration should be given to the types of patients who most miss out on these services.


Subject(s)
Neoplasms/therapy , Palliative Care/statistics & numerical data , Patient Acceptance of Health Care/statistics & numerical data , Terminally Ill/statistics & numerical data , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Neoplasms/mortality , Odds Ratio , Registries , South Australia/epidemiology
14.
Br J Cancer ; 83(7): 853-7, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10970684

ABSTRACT

Mycobacterial preparations have been used with limited success against cancer apart from superficial bladder cancer. Recently, a therapeutic vaccine derived from Mycobacterium vaccae has been given to patients with prostate cancer and melanoma indicating a possible beneficial effect on disease activity in such patients. We have recently initiated a series of randomized studies to test the feasibility and toxicity of combining a preparation of heat-killed Mycobacterium vaccae (designated SRL172) with a multidrug chemotherapy regimen to treat patients with inoperable non-small cell lung cancer (NSCLC) and mesothelioma. 28 evaluable patients with previously untreated symptomatic NSCLC and mesothelioma were randomized to receive either 3 weekly intravenous combination chemotherapy alone, or chemotherapy given with monthly intra-dermal injections of SRL172. Safety and tolerability were scored by common toxicity criteria and efficacy was evaluated by survival of patients and by tumour response assessed by CT scanning. The toxicity of chemotherapy was similar in the two groups. SRL172 caused mild inflammation at the injection site. In the group of patients randomized to receive chemotherapy combined with SRL172, there was a trend towards improved response rate (54% vs. 33%) with more patients in the combined arm receiving radical surgery and radiotherapy, improved median survival (9.7 months vs. 7.5 months) and improved 1 year survival (42% vs. 18%). SRL172 appeared to improve sleep (P = 0.08) and improved appetite (P = 0.01). There was no detectable change in serum cytokine levels for gamma-interferon and TNF-alpha before and after treatment. In patients with NSCLC and mesothelioma, there may be a beneficial interaction when chemotherapy is administered in combination with SRL172. Confirmation of this effect and further investigation is underway in a randomized phase III trial and in laboratory models.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bacterial Vaccines/therapeutic use , Cancer Vaccines/therapeutic use , Carcinoma, Non-Small-Cell Lung/therapy , Lung Neoplasms/therapy , Mesothelioma/therapy , Mycobacterium/immunology , Adjuvants, Immunologic/adverse effects , Adjuvants, Immunologic/therapeutic use , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bacterial Vaccines/adverse effects , Bacterial Vaccines/immunology , Cancer Vaccines/adverse effects , Cancer Vaccines/immunology , Carcinoma, Non-Small-Cell Lung/immunology , Cisplatin/administration & dosage , Cisplatin/adverse effects , Combined Modality Therapy , Female , Humans , Immunotherapy, Active , Interferon-gamma/blood , Interleukin-10/blood , Lung Neoplasms/drug therapy , Lung Neoplasms/immunology , Male , Mesothelioma/drug therapy , Mesothelioma/immunology , Middle Aged , Mitomycin/administration & dosage , Mitomycin/adverse effects , Tumor Necrosis Factor-alpha/metabolism , Vaccines, Inactivated/adverse effects , Vaccines, Inactivated/immunology , Vaccines, Inactivated/therapeutic use , Vinblastine/administration & dosage , Vinblastine/adverse effects
15.
Br J Cancer ; 77(11): 1966-70, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9667676

ABSTRACT

MVP chemotherapy (mitomycin C 8 mg m(-2), courses 1, 2, 4 and 6, vinblastine 6 mg m(-2), cisplatin 50 mg m(-2)) is an active low-toxicity regimen in non-small-cell lung cancer (NSCLC). Based on the single-agent activity of these agents in SCLC, we have conducted a phase II trial of MVP in SCLC. Fifty chemo-naive patients with SCLC were entered in this trial. There were 33 men and 17 women with median age 66 years (range 46-83 years); 18 patients had limited disease (LD) and 32 extensive disease (ED). WHO performance status (PS) was: three patients PS 0, 33 patients PS 1, ten patients PS 2, four patients PS 3. A maximum of six cycles was given in responding patients. On completion of chemotherapy, patients with LD obtaining complete response (CR)/good partial response (PR) received thoracic irradiation and those obtaining CR were offered entry into the ongoing MRC Prophylactic Cranial Irradiation Trial. The overall response was 79% with 17% CR and 62% PR. For LD patients, 38% obtained CR but for ED only one patient achieved CR. Median response duration for LD patients was 8 months and for ED patients 5 months. Median survival was 10 months for LD patients and 6 months for ED patients. There was complete resolution of symptoms in 24%, partial improvement in 68%, no change in 2% and progressive symptoms in 6%. As regards toxicity, 24% developed WHO grade 3/4 neutropenia, 16% grade 3/4 thrombocytopenia and 6% significant hair loss. Two patients died during the first week of treatment with neutropenic infection. Quality of life using the EORTC questionnaire (QLC-C30) with lung cancer module demonstrated significant improvements from baseline levels in emotional and cognitive functioning, global QOL, of pain, dyspnoea and cough. MVP, an effective palliative regimen for NSCLC, is also active against SCLC with low toxicity and merits comparison with more toxic conventional schedules.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Small Cell/drug therapy , Lung Neoplasms/drug therapy , Aged , Aged, 80 and over , Carcinoma, Small Cell/mortality , Carcinoma, Small Cell/psychology , Cisplatin/administration & dosage , Female , Humans , Lung Neoplasms/mortality , Lung Neoplasms/psychology , Male , Middle Aged , Mitomycins/administration & dosage , Pilot Projects , Quality of Life , Survival Rate , Vinblastine/administration & dosage
16.
Ann Oncol ; 9(3): 269-73, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9602260

ABSTRACT

PURPOSE: To evaluate the therapeutic impact of a simple combination chemotherapy regimen on symptoms related to malignant mesothelioma. MATERIALS AND METHODS: Between October 1986 and June 1997, 39 patients with advanced inoperable malignant mesothelioma were treated with palliative MVP (mitomycin-C 8 mg/m2 q. six weeks, vinblastine 6 mg/m2 q. three weeks and cisplatin 50 mg/m2 q. three weeks) chemotherapy and assessed for objective response and relief of symptoms. RESULTS: Eight of 39 patients (20%) achieved an objective partial response with a median duration of nine months: only five patients had progression of disease during chemotherapy. Twenty-four of 39 (62%) had an overall improvement in their symptomology with particularly good responses for pain (79%). These benefits were independent of performance status. Resolution of symptoms was achieved in all responding patients within two treatment cycles. There was no statistically significant difference in duration and incidence of symptom response in those patients achieving radiological PR compared with those with no change and more than 60% of patients with radiological no change obtained useful symptom control. The treatment was well tolerated with only four patients developing grade 3 leucopenia and three with grade 3 nausea. CONCLUSIONS: MVP is a well tolerated regimen and its use in malignant mesothelioma provides useful symptomatic benefit. These results should be the basis for further trials of MVP in the management of mesothelioma with symptom control as a principal endpoint.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Lung Neoplasms/drug therapy , Mesothelioma/drug therapy , Palliative Care , Aged , Analysis of Variance , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Cisplatin/administration & dosage , Female , Humans , Lung Neoplasms/mortality , Male , Mesothelioma/mortality , Middle Aged , Mitomycin/administration & dosage , Multivariate Analysis , Survival Rate , Treatment Outcome , Vindesine/administration & dosage
17.
Br J Cancer ; 73(2): 228-35, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8546911

ABSTRACT

The purpose of this study was to determine the effect of the first rat monoclonal antibody (MAb ICR62) to the epidermal growth factor receptor (EGFR) in a phase I clinical trial in patients with unresectable squamous cell carcinomas. This antibody effectively blocks the binding of EGF, transforming growth factor (TGF)-alpha and HB-EGF to the EGFR, inhibits the growth in vitro of tumour cell lines which overexpress the EGFR and eradicates such tumours when grown as xenografts in athymic mice. Eleven patients with squamous cell carcinoma of the head and neck and nine patients with squamous cell carcinoma of the lung, whose tumours expressed EGFR, were recruited. Groups of three patients were treated with 2.5 mg, 10 mg, 20 mg or 40 mg of ICR62 and a further eight patients received 100 mg. All patients were evaluated for toxicity using WHO criteria. Patients' sera were tested for the clearance of MAb ICR62 and the development of human anti-rat antibodies (HARA). No serious (WHO Grade III-IV) toxicity was observed in patients treated with up to 100 mg of antibody ICR62. Antibody ICR62 could be detected at 4 h and 24 h in the sera of patients treated with 40 mg or 100 mg of ICR62. Only 4/20 patients showed HARA responses (one at 20 mg, one at 40 mg and two at 100 mg doses) and of these only the former two were anti-idiotypic responses. In four patients receiving doses of ICR62 at 40 mg or greater, biopsies were obtained from metastatic lesions 24 h later and examined for the localisation of ICR62 using anti-rat antibody reagent. In these patients we showed the localisation of MAb ICR62 to the membranes of tumour cells; this appeared to be more prominent at the higher dose of 100 mg. On the basis of these data we conclude that MAb ICR62 can be administered safely to patients with squamous cell carcinomas and that it can localise efficiently to metastases even at relatively low doses.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Carcinoma, Squamous Cell/therapy , ErbB Receptors/immunology , Head and Neck Neoplasms/therapy , Lung Neoplasms/therapy , Adult , Aged , Animals , Antibodies, Heterophile/blood , Antibodies, Monoclonal/pharmacokinetics , Antibodies, Monoclonal/toxicity , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/metabolism , Cell Membrane/metabolism , ErbB Receptors/metabolism , Female , Head and Neck Neoplasms/immunology , Head and Neck Neoplasms/metabolism , Humans , Immunotherapy , Lung Neoplasms/immunology , Lung Neoplasms/metabolism , Male , Middle Aged , Neoplasm Metastasis , Rats
19.
J Paediatr Child Health ; 31(5): 446-50, 1995 Oct.
Article in English | MEDLINE | ID: mdl-8554867

ABSTRACT

OBJECTIVE: To assess changes in perinatal mortality and risk factors for births to Aboriginal mothers in South Australia in 1981-92. METHODOLOGY: All 4013 singleton Aboriginal births in the South Australian perinatal data collection were included. Trends in proportions with specific maternal and infant characteristics, and perinatal mortality by year of birth, were investigated by logistic regression analysis. RESULTS: Changes found included an increase in the proportion of mothers aged 35 years and over, preterm births and births of very low birthweight (< 1500 g), but a decrease in the proportions of births to women under 20 years of age, and of births with a birth defect. There was no statistically significant change in the crude perinatal mortality rate nor in the risk of perinatal death after adjusting for risk factors. CONCLUSIONS: The perinatal mortality rate among Aboriginal births, which is three times higher than the rate for all South Australian births, is not declining, in contrast to the State rate overall. This highlights the need for a concerted approach to Aboriginal perinatal health.


Subject(s)
Infant Mortality , Native Hawaiian or Other Pacific Islander , Adult , Analysis of Variance , Congenital Abnormalities/epidemiology , Female , Humans , Infant, Low Birth Weight , Infant, Newborn , Infant, Premature , Logistic Models , Maternal Age , Odds Ratio , Parity , Pregnancy , Pregnancy, High-Risk , Risk Factors , South Australia/epidemiology
20.
Br J Cancer ; 71(6): 1315-8, 1995 Jun.
Article in English | MEDLINE | ID: mdl-7779730

ABSTRACT

A pilot study of continuous infusional 5-fluorouracil 200 mg m-2 per 24 h by ambulatory pump and Hickman line for the entire treatment cycle with mitomycin C 8 mg m-2 i.v. on day 1 and cisplatin 75 mg m-2 i.v. on day 1, both repeated every 28 days, was carried out in 31 previously untreated patients with advanced non-small-cell lung cancer (NSCLC). Of 31 patients assessable for response, one attained a complete remission and eight a partial remission, an overall response rate of 29%. Haematological toxicity was minimal, with only 3% of patients developing WHO grade III/IV neutropenia and 13% grade III/IV thrombocytopenia. Significant side-effects included moderate to severe emesis (41%), mucositis (34%), diarrhoea (31%) and palmar-plantar syndrome (14%). Seven patients (23%) had Hickman line complications requiring line removal. Continuous infusional chemotherapy with this regimen is active in advanced non-small-cell lung cancer, but its complexity and associated treatment toxicity offer little advantage over equally active but simpler and less toxic cisplatin-based regimens.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/drug therapy , Adenocarcinoma/drug therapy , Adenocarcinoma/pathology , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Large Cell/drug therapy , Carcinoma, Large Cell/pathology , Carcinoma, Non-Small-Cell Lung/pathology , Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/pathology , Cisplatin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Injections, Intravenous , Lung Neoplasms/pathology , Male , Middle Aged , Mitomycins/administration & dosage , Neoplasm Staging , Pilot Projects
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