Corrigendum: Comparative microbiome analysis of beef cattle, the feedyard environment, and airborne particulate matter as a function of probiotic and antibiotic use, and change in pen environment.

[This corrects the article DOI: 10.3389/fmicb.2024.1348171.].

Comparative microbiome analysis of beef cattle, the feedyard environment, and airborne particulate matter as a function of probiotic and antibiotic use, and change in pen environment.

Introduction: Intensive beef cattle production systems are frequently implicated as a source of bacteria that can be transferred to nearby humans and animals via effluent water, manure used as fertilizer, or airborne particulate matter. It is crucial to understand microbial population dynamics due to manure pack desiccation, antibiotic usage, and antibiotic alternatives within beef cattle and their associated feedyard environment. Understanding how bacterial communities change in the presence of antibiotics can also improve management practices for reducing the spread of foodborne bacteria. Methods: In this study, we aimed to compare the microbiomes within cattle feces, the feedyard environment and artificially produced airborne particulate matter as a function of pen change and treatment with tylosin or probiotics. We utilized 16S rRNA sequencing to compare bacterial communities among sample types, study days, and treatment groups. Results: Bacterial community diversity varied as a function of sampling day and pen change (old or new) within fecal and manure pack samples. Manure pack samples from old pens and new pens contained diverse communities of bacteria on days 0 and 84; however, by day 119 of the study these taxonomic differences were less evident. Particulate matter samples exhibited significant differences in community diversity and predominant bacterial taxa compared to the manure pack they originated from. Treatment with tylosin did not meaningfully impact bacterial communities among fecal, environmental, or particulate matter samples; however, minor differences in bacterial community structure were observed in feces from cattle treated with probiotics. Discussion: This study was the first to characterize and compare microbial communities within feces, manure pack, and airborne particulate matter from the same location and as a function of tylosin and probiotic treatment, and pen change. Although fecal and environmental samples are commonly used in research studies and other monitoring programs to infer public health risk of bacteria and antimicrobial resistance determinants from feedyard environments, our study suggests that these samples may not be appropriate to infer public health risk associated with airborne particulate matter.

Comparison of peripherally inserted central venous catheters (PICC) versus subcutaneously implanted port-chamber catheters by complication and cost for patients receiving chemotherapy for non-haematological malignancies.

PURPOSE: Indwelling central venous catheters (CVCs) have been increasingly used to enable delivery of intravenous chemotherapy. We aimed to compare the safety and cost of two commonly used CVCs, peripherally inserted central venous catheter (PICCs) and ports, in the delivery of chemotherapy in patients with non-haematological malignancies. METHODS: Seventy patients were randomly assigned to receive either a PICC or a port. The primary endpoint was occurrence of major complications, which required removal of the CVC and secondary endpoints included occurrence of any complications. RESULTS: Port devices were associated with fewer complications compared with PICC lines (hazard ratio of 0.25, CI, 0.09-0.86, P = 0.038). Major complication rate was lower in the port arm compared to the PICC arm (0.047 versus 0.193 major complications/100 catheter days, P = 0.034) with 6 versus 20 % of patients experiencing major complications, respectively. Thrombosis, the most common complication, was significantly higher in the PICC arm compared to the port arm (25 versus 0 %, P = 0.013). Quality of life and cost estimates did not differ significantly between the two arms. CONCLUSIONS: Port devices are associated with a lower risk of complications, with no difference in cost, compared to PICC lines in patients with non-haematological malignancies receiving intravenous chemotherapy.

Final results from a randomized phase 3 study of FOLFIRI {+/-} panitumumab for second-line treatment of metastatic colorectal cancer.

BACKGROUND: The study 20050181 demonstrated significant improvements in progression-free survival (PFS), objective response, and a nonsignificant trend toward increased overall survival (OS) with panitumumab-FOLFIRI versus FOLFIRI alone for second-line wild-type (WT) KRAS metastatic colorectal cancer (mCRC). Updated long-term data from a prespecified descriptive analysis are reported. PATIENTS AND METHODS: Patients receiving one prior mCRC treatment were randomly assigned (1:1) to panitumumab (6.0 mg/kg)-FOLFIRI versus FOLFIRI every 2 weeks. Co-primary end points (PFS and OS) were prospectively analyzed by tumor KRAS status. RESULTS: One thousand one hundred and eighty-six patients were randomly assigned. In patients with WT KRAS tumors, panitumumab-FOLFIRI significantly improved PFS versus FOLFIRI [median 6.7 versus 4.9 months; hazard ratio (HR) 0.82 [95% confidence interval (CI) 0.69, 0.97]; P = 0.023]. A trend toward longer OS was observed (median 14.5 versus 12.5 months; HR 0.92 [95% CI 0.78, 1.10]; P = 0.37). Response rates improved from 10% to 36% (P < 0.0001). From post hoc analyses in patients receiving prior oxaliplatin-bevacizumab, panitumumab-FOLFIRI improved PFS (median 6.4 versus 3.7 months; HR 0.58 [95% CI 0.37, 0.90]; P = 0.014). PFS and OS appeared longer for worst-grade skin toxicity of 2-4, versus 0-1 or FOLFIRI. Safety results were as previously reported and consistent with the known toxicities with anti-epidermal growth factor receptor therapy. CONCLUSIONS: These data confirm the primary efficacy and safety findings of this trial and support panitumumab-FOLFIRI as a second-line treatment of WT KRAS mCRC.

Prolonged hypocalcemia following denosumab therapy in metastatic hormone refractory prostate cancer.

Prostate cancer is a leading cause of cancer death, frequently associated with widespread bone metastases. We report two cases of hypocalcemia following the first dose of denosumab in metastatic hormone refractory prostate cancer, the first case requiring 26 days of intravenous calcium therapy. This is the first report of prolonged hypocalcemia following denosumab in a patient with normal renal function.

Docetaxel plus cetuximab as second-line treatment for docetaxel-refractory oesophagogastric cancer: the AGITG ATTAX2 trial.

BACKGROUND: Cetuximab can reverse chemotherapy resistance in colorectal cancer. This study evaluated the efficacy and safety of the combination of docetaxel and cetuximab as a second-line treatment in docetaxel-refractory oesophagogastric cancer. METHODS: Patients received docetaxel 30 mg m(-2) on days 1 and 8, every 3 weeks and cetuximab 400 mg m(-2) on day 1, then 250 mg m(-2) weekly. Biomarker mutation analysis was performed. RESULTS: A total of 38 patients were enrolled. Response rates were PR 6% (95% CI 2-19%), s.d. 43% (95% CI 28-59%). Main grade 3/4 toxicities were febrile neutropenia, anorexia, nausea, diarrhoea, stomatitis, and acneiform rash. Median progression-free and overall survival were 2.1 and 5.4 months, respectively. A landmark analysis showed a trend to improved survival times with increased grade of acneiform rash. No KRAS, BRAF or PIK3CA mutations were observed. CONCLUSION: Cetuximab and docetaxel achieve modest responses rates, but maintain comparable survival times to other salvage regimens with low rates of toxicity.

A randomised, double-blind, placebo-controlled phase 2 study of trebananib (AMG 386) in combination with FOLFIRI in patients with previously treated metastatic colorectal carcinoma.

BACKGROUND: This phase 2 study evaluated trebananib (AMG 386), an investigational peptide-Fc fusion protein that neutralises the interaction between angiopoietins-1/2 and the Tie2 receptor, plus FOLFIRI as second-line treatment for patients with metastatic colorectal cancer. METHODS: Patients had adenocarcinoma of the colon or rectum with progression within 6 months of receiving only one prior fluoropyrimidine/oxaliplatin-based chemotherapy regimen for metastatic disease. All patients received FOLFIRI and were randomised 2:1 to also receive intravenous trebananib 10 mg kg(-1) once weekly (QW) (Arm A) or placebo QW (Arm B). The primary end point was investigator-assessed progression-free survival (PFS). RESULTS: One hundred and forty-four patients were randomised (Arms A/B, n=95/49). Median PFS in Arms A and B was 3.5 and 5.2 months (hazard ratio (HR) 1.23; 95% CI, 0.81-1.86; P=0.33) and median overall survival (OS) was 11.9 and 8.8 months, respectively (HR 0.90; 95% CI; 0.53-1.54; P=0.70). Objective response rate (ORR) was 14% and 0% in Arms A and B, respectively. Incidence of grade ≥3 adverse events was similar between treatment arms (Arm A, 61%; Arm B, 65%) and included pulmonary embolism (1%/4%), deep vein thrombosis (5%/2%), and hypertension (1%/0%). CONCLUSION: Administration of trebananib plus FOLFIRI did not prolong PFS compared with placebo plus FOLFIRI. Toxicities were manageable and consistent with those known for FOLFIRI and trebananib.

Phase II randomized, double-blind, placebo-controlled study of AMG 386 (trebananib) in combination with cisplatin and capecitabine in patients with metastatic gastro-oesophageal cancer.

BACKGROUND: We evaluated AMG 386, an investigational peptibody that neutralizes the interaction between angiopoietins-1 and -2 and the Tie2 receptor, combined with cisplatin/capecitabine (CX) as first-line treatment for metastatic gastro-oesophageal cancer. PATIENTS AND METHODS: Patients with metastatic gastric, gastro-oesophageal junction, or distal oesophageal adenocarcinoma were randomized 1:1:1 to CX (cisplatin 80 mg/m(2) IV Q3W; capecitabine 1000 mg/m(2) P.O. BID for 14 days Q3W) plus intravenous AMG 386 10 mg/kg QW (Arm A) or 3 mg/kg QW (Arm B), or placebo QW (Arm C). The primary end point was estimated progression-free survival (PFS). RESULTS: A total of 171 patients were enrolled. Median estimated PFS in Arms A, B, and C was 4.2, 4.9, and 5.2 months, respectively (hazard ratio for Arms A+B combined versus Arm C, 0.98; 95% CI 0.67-1.43; P = 0.92). Objective response rates were 27% (Arm A), 43% (Arm B), and 35% (Arm C). Incidence of grade ≥3 adverse events was 80% in Arm A, 84% in Arm B, and 75% in Arm C. There was no evidence of pharmacokinetic interactions. CONCLUSIONS: In this study, PFS and ORR were estimated to be similar with AMG 386 plus CX and placebo plus CX treatment. Compared with placebo, toxicity of AMG 386 plus CX was greater but manageable. PREVIOUS PRESENTATION: The results of this study have not been previously published or submitted for publication elsewhere. The results were presented in part at the Gastrointestinal Cancers Symposium, San Francisco, CA, January 20-22, 2011. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov registration number: NCT00583674.

Risk of arterial thromboembolic events in patients with advanced colorectal cancer receiving bevacizumab.

BACKGROUND: Bevacizumab is an antiangiogenic mAb with efficacy against several cancers, but it is associated with risk of arterial thromboembolism (ATE). Further data are needed to determine the safety of bevacizumab. PATIENTS AND METHODS: We recorded grade 3, 4, or 5 ATE events and other data (including age, baseline cardiovascular risk factors, history of ATE, and aspirin use) from 471 patients with metastatic colorectal cancer in the MAX (Mitomycin, Avastin, Xeloda) trial of capecitabine monotherapy versus capecitabine with bevacizumab with or without mitomycin C. RESULTS: Bevacizumab-treated patients had 12 grade 3, 4, or 5 ATEs (3.8% incidence). ATEs occurred in 2.1% of patients >65 years, 5% of those with a history of ATE, and 5% of those with cardiac risk factors. Age, history of ATE, or vascular risk factors did not increase risk. Aspirin users had a higher incidence than nonusers (8.9% versus 2.7%) but had higher rates of vascular risk factors. CONCLUSIONS: Bevacizumab was associated with a modestly higher risk of ATE, but safety was not significantly worse in older patients or patients with a history of ATE or vascular risk factors. The effect of aspirin in preventing ATE in patients receiving bevacizumab could not be determined from this study.

A phase I trial of Capecitabine+Gemcitabine with radical radiation for locally advanced pancreatic cancer.

Standard chemoradiotherapy with infusional 5FU for locally advanced pancreatic cancer (LAPC) has limited efficacy in this disease. The combination of Capecitabine (Cap) and Gemcitabine (Gem) are synergistic and are potent radiosensitisers. The aim of this phase I trial was thus to determine the highest administered dose of the Cap plus Gem combination with radical radiotherapy (RT) for LAPC. Patients had LAPC, adequate organ function, ECOG PS 0-1. During RT, Gem was escalated from 20-50 mg m(-2) day(-1) (twice per week), and Cap 800-2000 mg m(-2) day(-1) (b.i.d, days 1-5 of each week). Radiotherapy 50.4 Gy/28 fractions/5.5 weeks, using 3D-conformal techniques. Three patients were entered to each dose level (DL). Dose-limiting toxicity(s) (DLTs) were based on treatment-related toxicities. Twenty patients were accrued. Dose level (DL) 1: Cap/Gem; 800/20 mg m(-2) day(-1) (3 patients), DL2: 1000/20 (12 patients), DL3: 1300/30 (5 patients). Dose-limiting toxicities were observed in DL3; grade 3 dehydration (1 patient) and grade 3 diarrhoea and dehydration (1 patient). Dose level 2 was the recommend phase 2 dose. Disease control rate was 75%: PR=15%, SD=60%. Median overall survival was 11.2 months. The addition of Cap and Gem to radical RT was feasible and active and achieved at relatively low doses.

Gemcitabine and oxaliplatin followed by paclitaxel and carboplatin as first line therapy for patients with suboptimally debulked, advanced epithelial ovarian cancer. A phase II trial of sequential doublets. The GO-First Study.

OBJECTIVES: Gemcitabine and oxaliplatin are active in epithelial ovarian cancer with minimal overlapping toxicity. We studied the efficacy and toxicity of this combination in patients with advanced ovarian cancer when given prior to carboplatin and paclitaxel. METHODS: Chemonaive patients with epithelial ovarian cancer and measurable disease were eligible for the study. Treatment consisted of gemcitabine 1250 mg/m2 on days 1 and 8 and oxaliplatin 130 mg/m2 on day 8 every 21 days (GO) for 4 cycles. This was followed by carboplatin AUC = 6 and paclitaxel 175 mg/m2 on day 1 every 21 days (CP) for 4 cycles. RESULTS: Twenty patients, median age 62 years (range 39-78), FIGO stages III (16) and IV (4) received treatment. The response rate (RR) after 4 cycles of GO was 80% (95%CI 61-99%) (4 complete responses (CR), 12 partial responses (PR)). Interval debulking surgery was performed in 7 patients (35%). After CP chemotherapy, RR increased to 85% (95%CI 68-100%) (CR = 13, PR = 4). Median time to progression was 14.5 months. Estimated median overall survival was 31.5 months. Toxicities of GO were mild; grade 3/4 nausea in 3 patients (15%) and vomiting in 2 patients (10%), grade 3/4 neutropenia in 5 patients (25%). Grade 2/3 peripheral neuropathy occurred in 5 patients (25%). After sequential administration of CP, grade 2/3 neuropathy occurred in 13 patients (72%). CONCLUSION: The sequential doublet regimen of GO followed by CP resulted in unacceptable neurotoxicity and is not recommended for further study; however, the doublet gemcitabine and oxaliplatin has significant activity in the first line treatment of patients with ovarian cancer.

Use of fluorodeoxyglucose positron emission tomography scans in patients with advanced germ cell tumour following chemotherapy: single-centre experience with long-term follow up.

AIMS: Fluorodeoxyglucose positron emission tomography (FDG-PET) may detect residual or recurrent malignancy in patients with germ cell tumours (GCT) following chemotherapy. The objective of the present study was to evaluate the use of FDG-PET in the setting of advanced GCT, and to determine the influence of FDG-PET on subsequent patient management. METHODS: A computerized search of the patient database of the Department of Medical Oncology, Guy's Hospital, London, United Kingdom, and a manual search of medical records, were conducted. All male patients with metastatic or extragonadal GCT treated with chemotherapy between July 1996 and June 1999 inclusive were identified. Data from patients that had a PET scan following chemotherapy were analysed. Reported PET scan findings were compared with subsequent clinical management and patient outcome. RESULTS: A total of 30 patients with metastatic testicular GCT and three patients with extragonadal GCT were treated with chemotherapy. Of these, 15 patients (12 testicular; three extragonadal; 10 non-seminoma; and five seminoma) were investigated following chemo-therapy with at least one FDG-PET scan. Seven patients had two or more PET scans, and a total of 26 FDG-PET scans was performed. The most frequent indication for PET scan was evaluation of a residual mass (11 patients). Three patients had an FDG-PET to evaluate thymic prominence. Minimum follow up from first PET scan was 18 months. Three of 26 PET scans had false positive findings. Four PET scans yielded findings of equivocal significance with repeat PET scan recommended. Relapse of disease occurred in three patients; two of whom had normal previous PET scans and one had a previous equivocal result. PET had an impact on patient management in only one case where it 'prompted' surgical excision of a residual mass. Normal PET scans provided reassurance in patients with residual small masses but did not alter their subsequent -management. CONCLUSIONS: A residual mass was the most common indication for PET. For the majority of patients PET did not have a discernible influence on clinical management. Oncologists should exercise caution in their interpretation of PET scan findings and guidelines for the appropriate use of PET in testicular cancer management need to be developed. Prospective trials are required to define the clinical role of PET in this setting.

A dose-escalating study of oral eniluracil/5-fluorouracil plus oxaliplatin in patients with advanced gastrointestinal malignancies.

BACKGROUND: Oral eniluracil/5-fluorouracil (5-FU) was shown in early clinical studies to have promising activity against gastrointestinal malignancies. Oxaliplatin in combination with 5-FU also has activity against these tumour types. The primary objective of this study was to determine a tolerable dose for oral eniluracil/5-FU in combination with oxaliplatin. PATIENTS AND METHODS: Twenty-three patients with advanced gastrointestinal malignancies were recruited into this open-label study. Patients received a fixed dose of oxaliplatin (130 mg/m(2) on the first day of a 21-day cycle), and the dose intensity of oral eniluracil/5-FU was gradually increased by escalating the number of days of treatment per course. RESULTS: The maximum tolerated dose intensity was eniluracil/5-FU 10.0/1.0 mg/m(2) twice daily for 16 days in combination with oxaliplatin 130 mg/m(2) on the first day of a 21-day cycle. Dose-limiting toxicities included vomiting and diarrhoea. The objective tumour response rate was 26% with a median duration of response of 15.3 weeks (95% confidence interval 8.5-22.1). Twenty-two patients (96%) experienced neurotoxicity (sensory neuropathy or cold-related dysaesthesia), although only two events were severe (grade 3). CONCLUSIONS: The recommended dose for future study in patients with advanced gastrointestinal cancer is 10.0/1.0 mg/m(2) oral eniluracil/5-FU twice daily for 14 days in combination with oxaliplatin 130 mg/m(2) on the first day of each treatment cycle.

Pathologic splenic rupture as the presentation of mantle cell lymphoma.

Pathologic splenic rupture in non-Hodgkin's lymphoma (NHL) is a rare event, with 32 cases previously reported. Initial presentation of NHL with this complication is even rarer. We report such a case in an 80-year-old man with mantle cell lymphoma (MCL). It is notable that of the previously reported cases of pathologic rupture, three have occurred in MCL, suggesting that patients with this uncommon subtype of NHL may be particularly vulnerable to pathologic splenic rupture. Following splenectomy the patient's disease behaved in a high-grade fashion. Despite an initially encouraging response, his disease ran an aggressive course and he succumbed within four months. This case demonstrates the presentation of MCL with pathologic splenic rupture, as well as the potentially highly malignant behaviour of the disease.

A phase II study evaluating the tolerability and efficacy of CAELYX (liposomal doxorubicin, Doxil) in the treatment of unresectable pancreatic carcinoma.

BACKGROUND: Preclinical studies of liposomal doxorubicin (CAELYX) have demonstrated significant inhibition of growth of human pancreatic cancer explants in nude mice. This study evaluated the efficacy of CAELYX in chemotherapy-naïve patients with unresectable, histologically confirmed pancreatic carcinoma. Secondary endpoints were quality of life (QOL). time to progression and overall survival. PATIENTS AND METHODS: Twenty-two patients (median age 65) were enrolled. CAELYX was administered to the first five patients at a dose of 30 mg/m2 three-weekly. Two of these patients were dose escalated to 50 mg/m2 four-weekly. Subsequent patients were all treated on the latter schedule. RESULTS: Two patients died after consenting to enter the study but before treatment was commenced and are not included in the analysis. Sixteen patients were evaluable for response. No objective responses were seen. Six patients had stable disease. One patient experienced grade 4 toxicity with palmar plantar dysaesthesia (PPE), but continued treatment after dose reduction and delay. Four patients experienced grade 3 stomatitis and two grade 3 nausea. Median survival from time of starting chemotherapy was 3.2 months (range 21 days to 19 months) and one year survival was 10%. Eight patients completed at least two EORTC QLQ C-30 questionnaires. There was no significant change in either global QOL or in any functional or symptom subscale score. CONCLUSION: No objective responses were seen with CAELYX in this study. CAELYX was however associated with stable disease, but data were inconclusive with regard to clinical benefit. It warrants further investigation in the context of combination trials.

PET and PLAP in suspected testicular cancer relapse: beware sarcoidosis.

A 31-year-old man previously treated with chemotherapy for metastatic testicular cancer presented with new mediastinal lymphadenopathy and peripheral lung opacities. Serum tumour markers were not elevated and a PET (positron emission tomography) scan revealed increased FDG (fluoro-deoxyglucose) uptake in the lungs and mediastinum consistent with testis cancer relapse. A biopsy of a mediastinal lymph node was performed and the pathology was that of sarcoidosis. Immunohistochemistry however was positive for PLAP (placental alkaline phosphatase) and negative for EMA (epithelial membrane antigen). This immunohistochemical profile raised concerns that the observed pathology represented a sarcoid reaction to micro-metastatic testicular cancer relapse. We performed immunohistochemical pathology analysis on four known cases of sarcoidosis and found the same immunohistochemical-staining pattern. This case highlights the problem of specificity when interpreting the significance of PET scans and immunohistochemical analysis in this situation. Sarcoidosis, a condition that has been associated with testicular cancer, should always be considered in the differential diagnosis.

Immunomodulation therapy in colorectal carcinoma.

There has been much progress in the understanding of the relationship between the immune system and colorectal cancer. This has led to the use of immunomodulatory therapy in the adjuvant and palliative treatment of the condition. Although attempts at the use of non-specific immunomodulation with agents such as levamisole, cimetidine, alpha interferon and Bacillus Calmette-Guerin (BCG) have not produced significant clinical benefits when tested in randomized trials in both the adjuvant setting and for metastatic disease, promising results are being obtained with more specific therapy. Edrecolomab [corrected], a murine monoclonal antibody targeting the 17-1A antigen on malignant colorectal cells has produced a reduction in relapse and mortality rates when used as adjuvant treatment following surgery for Dukes' C colon cancer. Active specific therapy with autologous tumour vaccine administered with BCG has produced similar benefits in Dukes' B cancer. Both 3H1 anti-idiotypic antibody against carcinoembryonic antigen and 105AD7 antibody to gp72 glycoprotein have demonstrated in-vitro and in-vivo immune activation against tumour. Non-randomized studies postulate prolongation of survival using these antibodies in advanced disease. These agents are all currently being tested in randomized studies powered to detect meaningful survival differences and clinical benefit. Immune therapy offers the potential of low toxicity therapy in colorectal cancer and may have a role as an adjunct to conventional chemotherapy.

Increased survival in patients diagnosed with Hodgkin's disease in Tasmania, 1972-1992.

BACKGROUND: It has been shown that in certain populations the prognosis of Hodgkin's disease (HD) has improved markedly since the late 1960s. This has not been formally demonstrated in an Australian population. AIMS: To review all patients in Tasmania diagnosed with HD between 1972 and 1992, and to ascertain whether variation in survival is evident in this group over this period. METHODS: Tasmanian patients with HD diagnosed from 1978 to 1992 were identified retrospectively from the Tasmanian Cancer Registry database. Identification of those diagnosed prior to 1978 was obtained from a previously published data set. To be valid for inclusion, subjects were required to have been diagnosed between January 1972 and December 1992, enabling a minimum four year follow up period. Survival was assessed by contacting patients' medical practitioners and by examining the most current electoral roll, medical records, and the register of births, deaths and marriages. Univariate and multivariate analyses were performed of the influence on prognosis of age, sex, histological subtype and epoch of diagnosis; information concerning stage of disease was not available. RESULTS: During the period of this study 206 patients were newly diagnosed as having HD. Comparisons of cases diagnosed in the successive seven-year epochs 1972-8, 1979-85 and 1986-92 revealed a significant increase in survival duration (p = 0.023), with ten year survival rates of 46%, 55% and 73% respectively. In a multivariate analysis adjusting for age, sex and histology, each successive epoch was associated with an estimated 28% reduction in the death rate relative to the preceding epoch (p = 0.022). CONCLUSIONS: There was a significant improvement in the survival duration of patients diagnosed with HD in Tasmania over the period 1972-92, which was possibly due to a combination of better diagnostic techniques and more effective treatments.