Care pathways in atopic dermatitis: a retrospective population-based cohort study.

BACKGROUND: Atopic dermatitis (AD) is a complex disease with variations in severity and healthcare utilization. Examining patient pathways through analyses of longitudinal patient data provides an opportunity to describe real-world clinical patient care and evaluate healthcare access and treatment. OBJECTIVE: To describe longitudinal care pathways including health care management, treatment patterns and disease progression (by proxy measures) in patients with AD. MATERIALS AND METHODS: This was a longitudinal observational study, which used linked data from national and regional healthcare registers in Sweden. Patients with AD were identified through diagnosis in primary or secondary care or by dispensed medications. Descriptive statistics for number of healthcare visits, type of dispensed drug class, rate of - and time to - referral to secondary care and treatment escalation were calculated. RESULTS: A total of 341 866 patients with AD distributed as 197 959 paediatric (age < 12), 36 133 adolescent (age ≥ 12- < 18) and 107 774 adult (age ≥ 18) patients were included in this study. Healthcare visits to primary and secondary care and dispensation of AD-indicated treatments were more common during the year in which managed AD care was initiated. Topical corticosteroids (TCSs) and emollients were the most frequently used treatments across all age cohorts while systemic treatment was uncommon in all age cohorts. Among patients who initiated treatment with TCSs, 18.2% escalated to TCSs with higher potency following the start of managed AD care. CONCLUSIONS: We found that healthcare contacts and use of AD-indicated treatments were concentrated in the year during which managed AD care was initiated and decreased significantly thereafter. Since a significant proportion of patients with AD have flares and persistent AD, our results suggest that patients with AD may be monitored infrequently and are undertreated. There is a need to inform practitioners about adequate treatment options to provide individualized care, in particular for patients with persistent severe AD.

Evaluation of intranasal nafamostat or camostat for SARS-CoV-2 chemoprophylaxis in Syrian golden hamsters.

Successful development of a chemoprophylaxis against SARS-CoV-2 could provide a tool for infection prevention implementable alongside vaccination programmes. Camostat and nafamostat are serine protease inhibitors that inhibit SARS-CoV-2 viral entry in vitro but have not been characterised for chemoprophylaxis in animal models. Clinically, nafamostat is limited to intravenous delivery and while camostat is orally available, both drugs have extremely short plasma half-lives. This study sought to determine whether intranasal dosing at 5 mg/kg twice daily was able to prevent airborne transmission of SARS-CoV-2 from infected to uninfected Syrian golden hamsters. SARS-CoV-2 viral RNA was above the limits of quantification in both saline- and camostat-treated hamsters 5 days after cohabitation with a SARS-CoV-2 inoculated hamster. However, intranasal nafamostat-treated hamsters remained RNA negative for the full 7 days of cohabitation. Changes in body weight over the course of the experiment were supportive of a lack of clinical symptomology in nafamostat-treated but not saline- or camostat-treated animals. These data are strongly supportive of the utility of intranasally delivered nafamostat for prevention of SARS-CoV-2 infection and further studies are underway to confirm absence of pulmonary infection and pathological changes.

Do genetic variations in proximal tubule transporters influence tenofovir-induced renal dysfunction? An exploratory study in a Ghanaian population.

OBJECTIVES: To assess associations between polymorphisms within genes encoding proximal tubule transporters implicated in tenofovir renal clearance and kidney tubular dysfunction (KTD), chronic kidney disease (CKD) and individual biochemical parameters. PATIENTS AND METHODS: The study included a cohort of HIV-positive Ghanaians receiving regimens containing tenofovir disoproxil fumarate (n = 66) for at least 6 months prior to study enrolment. SNPs in ABCC10, ABCC2 and ABCC4 were selected for analysis based on previous published associations. All SNPs were genotyped by real-time PCR allelic discrimination. Creatinine clearance (CLCR), serum and urine creatinine concentrations and biochemical measures of KTD were assessed. Statistical significance was determined through univariate linear or binary logistical regression (P ≤ 0.05). RESULTS: None of the SNPs evaluated was associated with CKD or KTD. A trend between body weight and higher incidence of CKD (P = 0.012, OR = 0.9) was observed. ABCC10 2843T>C (rs2125739) was significantly associated with lower log10 baseline creatinine (P = 0.001, ß= -0.4), higher baseline CLCR (P = 0.008, ß = 65.2) and lower CLCR after 1 year (P = 0.024, ß= -26.6). CONCLUSIONS: This study demonstrates an association of ABCC10 rs2125739 with indicators of declining renal function and builds on current knowledge of this interaction within a Ghanaian cohort.

Association between biochemical control and comorbidities in patients with acromegaly: an Italian longitudinal retrospective chart review study.

PURPOSE: Achieving biochemical control (normalization of insulin-like growth factor-1 [IGF-1] and growth hormone [GH]) is a key goal in acromegaly management. However, IGF-1 and GH fluctuate over time. The true potential impact of time-varying biochemical control status on comorbidities is unclear and relies on multiple, longitudinal IGF-1 and GH measurements. This study assessed the association between time-varying biochemical control status and onset of selected comorbidities in patients with acromegaly. METHODS: Medical charts of adults with confirmed acromegaly and ≥ 6 months of follow-up at an Italian endocrinology center were reviewed. Patients were followed from the first diagnosis of acromegaly at the center until loss to follow-up, chart abstraction, or death. Biochemical control status was assessed annually and defined as IGF-1 ≤ the upper limit of normal, or GH ≤ 2.5 µg/L in the few cases where IGF-1 was unavailable. Time-varying Cox models were used to assess the association between biochemical control status and comorbidities. RESULTS: Among 150 patients, 47% were female, average age at diagnosis was 43.1, and mean length of follow-up was 10.4 years. Biochemical control was significantly associated with a lower hazard of diabetes (HR = 0.36, 95% CI 0.15; 0.83) and cardiovascular system disorders (HR = 0.54, 95% CI 0.31; 0.93), and a higher hazard of certain types of arthropathy (HR = 1.68, 95% CI 1.04; 2.71); associations for other comorbidities did not reach statistical significance. CONCLUSION: Results further support the importance of achieving biochemical control, as this may reduce the risk of high-burden conditions, including diabetes and cardiovascular system disorders. The association for arthropathy suggests irreversibility of this impairment. Due to limitations, caution is required when interpreting these results.

Erratum: Cost-effectiveness of everolimus for the treatment of advanced neuroendocrine tumours of gastrointestinal or lung origin in Canada.

[This corrects the article on p. 32 in vol. 25, PMID: 29507481.].

Cost-effectiveness of everolimus for the treatment of advanced neuroendocrine tumours of gastrointestinal or lung origin in Canada.

BACKGROUND: In 2016, everolimus was approved by Health Canada for the treatment of unresectable, locally advanced or metastatic, well-differentiated, non-functional, neuroendocrine tumours (NET) of gastrointestinal (GI) or lung origin in adult patients with progressive disease. This analysis evaluated the cost-effectiveness of everolimus in this setting from a Canadian societal perspective. METHODS: A partitioned survival model was developed to compare the cost per life-year (LY) gained and cost per quality-adjusted life-year (QALY) gained of everolimus plus best supportive care (BSC) versus BSC alone in patients with advanced or metastatic NET of GI or lung origin. Model health states included stable disease, disease progression, and death. Efficacy inputs were based on the RADIANT-4 trial and utilities were mapped from quality-of-life data retrieved from RADIANT-4. Resource utilization inputs were derived from a Canadian physician survey, while cost inputs were obtained from official reimbursement lists from Ontario and other published sources. Costs and efficacy outcomes were discounted 5% annually over a 10-year time horizon, and sensitivity analyses were conducted to test the robustness of the base case results. RESULTS: Everolimus had an incremental gain of 0.616 QALYs (0.823 LYs) and CA$89,795 resulting in an incremental cost-effectiveness ratio of CA$145,670 per QALY gained (CA$109,166 per LY gained). The probability of cost-effectiveness was 52.1% at a willingness to pay (WTP) threshold of CA$150,000 per QALY. CONCLUSIONS: Results of the probabilistic sensitivity analysis indicate that everolimus has a 52.1% probability of being cost-effective at a WTP threshold of CA$150,000 per QALY gained in Canada.

Pharmacogenetic considerations for HIV treatment in different ethnicities: an update.

INTRODUCTION: Variations in the human genome sequence sometimes play an important role in pharmacokinetics and/or pharmacodynamics. Previous studies have demonstrated a high degree of variation both between and within different ethnic populations. Areas covered: This review sought to summarize key SNPs in CYP2B6, CYP3A enzymes, CYP2C enzymes, UGT2 enzymes, ABCB1, ABCC2, SLCO1B1, NR1I2, and NR1I3 that have previously been associated with variability in antiretroviral pharmacokinetics. Additionally, the impact of ethnicity in these pharmacogenetics studies is discussed, and variation in findings between different ethnic groups is reviewed. A literature search of relevant published work was conducted between April 2017 and September 2017 utilizing the following databases: PubMed, Google Scholar, Web of Science, and Ensembl. Keywords used included drug name, rs (SNP identifier) number, and known effect (if applicable). This report highlights the variation observed between different ethnic populations and subsequently the importance of stratification within pharmacogenetic studies. Expert opinion: Utilization of these findings in future pharmacogenetics studies would aid in the understanding of the extent and impact of genetic variants in different populations and the consequences this has for achieving sustained virological response to antiretroviral therapy.

The Effect of Gene Variants on Levonorgestrel Pharmacokinetics When Combined With Antiretroviral Therapy Containing Efavirenz or Nevirapine.

Reduced levonorgestrel concentrations from the levonorgestrel contraceptive implant was previously seen when given concomitantly with efavirenz. We sought to assess whether single nucleotide polymorphisms (SNPs) in genes involved in efavirenz and nevirapine metabolism were linked to these changes in levonorgestrel concentration. SNPs in CYP2B6, CYP2A6, NR1I2, and NR1I3 were analyzed. Associations of participant demographics and genotype with levonorgestrel pharmacokinetics were evaluated in HIV-positive women using the levonorgestrel implant plus efavirenz- or nevirapine-based antiretroviral therapy (ART), in comparison to ART-naïve women using multivariate linear regression. Efavirenz group: CYP2B6 516G>T was associated with lower levonorgestrel log10 Cmax and log10 AUC. CYP2B6 15582C>T was associated with lower log10 AUC. Nevirapine group: CYP2B6 516G>T was associated with higher log10 Cmax and lower log10 Cmin . Pharmacogenetic variations influenced subdermal levonorgestrel pharmacokinetics in HIV-positive women, indicating that the magnitude of the interaction with non-nucleoside reverse transcriptase inhibitors (NNRTIs) is influenced by host genetics.

Budget impact of pasireotide LAR for the treatment of acromegaly, a rare endocrine disorder.

BACKGROUND: Acromegaly is a rare disorder characterized by the over-production of growth hormone (GH). Patients often experience a range of chronic comorbidities including hypertension, cardiac dysfunction, diabetes, osteoarthropathy, and obstructive sleep apnea. Untreated or inadequately controlled patients incur substantial healthcare costs, while normalization of GH levels may reduce morbidity and mortality rates to be comparable to the general population. OBJECTIVE: To assess the 3-year budget impact of pasireotide LAR on a US managed care health plan following pasireotide LAR availability. METHODS: Two separate economic models were developed: one from the perspective of an entire health plan and another from the perspective of a pharmacy budget. The total budget impact model includes costs of drug therapies and other costs for treatment, monitoring, management of adverse events, and comorbidities. The pharmacy cost calculator only considers drug costs. RESULTS: The total estimated budget impact associated with the introduction of pasireotide LAR is 0.31 cents ($0.0031) per member per month (PMPM) in the first year, 0.78 cents ($0.0078) in the second year, and 1.42 cents ($0.0142) in the third year following FDA approval. Costs were similar or lower from a pharmacy budget impact perspective. For each patient achieving disease control, cost savings from reduced comorbidities amounted to $10,240 per year. LIMITATIONS: Published data on comorbidities for acromegaly are limited. In the absence of data on acromegaly-related costs for some comorbidities, comorbidity costs for the general population were used (may be under-estimates). CONCLUSIONS: The budget impact of pasireotide LAR is expected to be modest, with an expected increase of 1.42 cents PMPM on the total health plan budget in the third year after FDA approval. The efficacy of pasireotide LAR in acromegaly, as demonstrated in head-to-head trials compared with currently available treatment options, is expected to be associated with a reduction of the prevalence of comorbidities.

Technical note: A comparison of DNA collection methods in cattle and yaks.

A variety of biological materials are suitable for the analysis of bovine DNA. The objective of this study was to evaluate the ease of collection, storage, and cost as well as quality and quantity of DNA samples obtained from Bos taurus (European cattle) and Bos grunniens (yak) using 2 different sample types: whole blood sampling and nasal swabs. Hair follicle DNA samples from yaks were also analyzed. Deoxyribonucleic acid samples were collected from 1 herd of Black Angus yearling bulls (n = 166) and 1 herd of yaks (n = 24). A NanoDrop Bioanalyzer ND1000 was used to quantify DNA. To assess DNA purity, absorbance ratios were determined at wavelengths of 260 nm relative to 280 nm and 260 nm relative to 230 nm. Single nucleotide polymorphism genotyping was performed using a competitive allele-specific PCR (KASP) genotyping system and the call rates to 3 specific SNP were compared. Using a commercially available nonautomated ethanol DNA extraction technique, nasal swabs yielded a greater quantity of DNA than blood (P < 0.0001) and a greater quality DNA sample than blood (P < 0.0001). Blood and nasal swab performance in SNP genotyping assays were similar (P = 0.5). The greater expense of nasal swabs was offset by their ease of use: less time, skill, and equipment was needed to obtain a sample and the storage of samples was more convenient (room temperature). In yaks, accessing the coccygeal vein, which is relatively straightforward in cattle, was difficult. Nasal swabbing and hair follicle sampling in yaks was performed relatively easily. Yak hair follicles were a poor source of DNA. In conclusion, DNA collection using nasal swabs was more convenient and provided a greater quantity of DNA and better quality sample than blood collection in both Angus and yak. Notably, yak hair was a poor source of DNA, and yak blood was difficult to obtain.

New insights into polar overdominance in callipyge sheep.

The callipyge phenotype in sheep involves substantial postnatal muscle hypertrophy and other changes to carcass composition. A single nucleotide polymorphism in the DLK1-DIO3 imprinted gene cluster alters gene expression of the paternal allele-specific protein-coding genes and several maternal allele-specific long noncoding RNA and microRNA when the mutation is inherited in cis. The inheritance pattern of the callipyge phenotype is polar overdominant because muscle hypertrophy only occurs in heterozygous animals that inherit a normal maternal allele and the callipyge SNP on the paternal allele (+/C). We examined the changes of gene expression of four major transcripts from the DLK1-DIO3 cluster and four myosin isoforms during the development of muscle hypertrophy in the semimembranosus as well as in the supraspinatus that does not undergo hypertrophy. The homozygous (C/C) animals had an intermediate gene expression pattern for the paternal allele-specific genes and two myosin isoforms, indicating a biological activity that was insufficient to change muscle mass. Transcriptome analysis was conducted by RNA sequencing in the four callipyge genotypes. The data show that homozygous animals (C/C) have lower levels of gene expression at many loci relative to the other three genotypes. A number of the downregulated genes are putative targets of the maternal allele-specific microRNA with gene ontology, indicating regulatory and cell signaling functions. These results suggest that the trans-effect of the maternal noncoding RNA and associated miRNA is to stabilize the expression of a number of regulatory genes at a functional, but low level to make the myofibers of homozygous (C/C) lambs less responsive to hypertrophic stimuli of the paternal allele-specific genes.

Budget impact of pasireotide for the treatment of Cushing's disease, a rare endocrine disorder associated with considerable comorbidities.

OBJECTIVES: Cushing's disease (CD) is a rare condition with a prevalence of roughly 39 cases per million in the general population. Healthcare costs are substantial for CD patients with either untreated or inadequately controlled disease. This study assesses the 3-year budget impact of pasireotide on a US managed care health plan following pasireotide (Signifor) availability. METHODS: Two scenarios were evaluated to understand the differences in costs associated with the introduction of pasireotide. The first scenario evaluates the budget impact of pasireotide from the perspective of an entire health plan (total budget impact) and the second from the perspective of the pharmacy budget (pharmacy budget impact). Both scenarios evaluate the annual incremental budget impact with and without pasireotide. Scenario 1 includes costs for medical procedures, drug therapies, monitoring, surgical complications, comorbidities for patients with controlled or uncontrolled CD, and adverse events. Procedures include transsphenoidal surgery, bilateral adrenalectomy, radiotherapy and radiosurgery. Drugs include pasireotide (indicated for CD), mifepristone (indicated to control hyperglycemia secondary to hypercortisolism in patients with Cushing's syndrome) as well as several off-label treatments (ketoconazole, cabergoline, mitotane). Scenario 2 considers costs solely from the perspective of a health plan pharmacy. Costs are in $2013. RESULTS: The estimated total budget impact is $0.0115 per-member per-month (PMPM) in the first year following FDA approval, $0.0184 in the second year, and $0.0194 in the third year. Introduction of pasireotide is expected to increase the pharmacy budget by $0.0257 PMPM in the first year, $0.0363 in the second year, and $0.0360 in the third year. LIMITATIONS: Model inputs rely on the small body of literature available for Cushing's disease. CONCLUSIONS: Cushing's disease is severe disease with debilitating comorbidities and substantial healthcare costs when untreated or inadequately controlled. The inclusion of pasireotide in a health plan formulary appears to have only a small impact on the total health plan or pharmacy budget.

Treatments, complications, and healthcare utilization associated with acromegaly: a study in two large United States databases.

The economic burden of acromegaly in the US has been largely unknown. We describe the prevalence of treatment patterns, complication rates, and associated healthcare utilization and costs of acromegaly in the US. Patients were identified between 1/1/2002 and 12/31/2009 in claims databases. During 1-year after each continuously-enrolled patient's first acromegaly claim, pharmacy and medical claims were used to estimate outcomes. Regression models were used to adjust outcomes. There were 2,171 acromegaly patients (mean age: 45.3 years; 49.7% female); 77.8% received the majority of their care from non-endocrinologists. Pharmacologic treatment was used by 30.8% of patients: octreotide-LAR in 18.6%, dopamine agonists in 9.8%, short-acting octreotide in 4.7%, pegvisomant in 4.1%, and lanreotide in 1.2%; 56% had biochemical monitoring. Comorbidities were common, ranging from 6.6% (colon neoplasms) to 25.6% (musculoskeletal abnormalities). Mean healthcare costs were $24,900. Adjusted analyses indicated comorbidities increased the odds of hospitalization: by 76% for musculoskeletal abnormalities; 193% for cardiovascular abnormalities; and 56% for sleep apnea (p < 0.05). Odds of emergency department visits increased by 87% (musculoskeletal) and 132% (cardiovascular abnormalities) (p < 0.01). After adjustments, colon neoplasms were associated with $8,401 mean increase in costs; musculoskeletal abnormalities with $7,502, cardiovascular abnormalities with $13,331, sleep apnea with $10,453, and hypopituitarism with $6,742 (p < 0.01). Complications are common and increase utilization and cost in acromegaly patients. Cardiovascular complications nearly tripled the odds of hospitalization (OR 2.93) and increased annual mean cost by $13,331. Adequate management of this disease may be able to reduce health care utilization and cost associated with these complications and with acromegaly in general.

Effects of co-grazing dairy heifers with goats on animal performance, dry matter yield, and pasture forage composition.

Mixed livestock grazing can offer an alternative management system for rearing dairy replacement heifers (Bos taurus). A 2-yr study was conducted during 2009 (yr 1) and 2010 (yr 2) to determine the effects of co-grazing Holstein heifers under rotational stocking with Boer × Kiko goats on animal performance, pasture DM yield, and botanical composition. Each year, 24 heifers (134 ± 6 d of age and 147.4 ± 31.2 kg BW in yr 1; 166 ± 11 d of age and 168.0 ± 27.6 kg BW in yr 2) and 6 goats (2 yr old and 39.7 ± 16.2 kg BW in yr 1; 1 yr old and 33.7 ± 7.4 kg BW in yr 2) were divided into 6 paddocks with 4 heifers and 2 goats, where applicable, per group. Low endophyte-infected tall fescue (Festuca arundinacea Schreb.) and white clover (Trifolium repens L.) pastures were used to evaluate 2 grazing strategies (heifers grazed alone [HO] or heifers co-grazed with goats [HG]). In addition, 6 goats were assigned to 2 paddocks and grazed alone (GO) each year to estimate goat pasture forage intake and compare Haemonchus contortus infection to co-grazed goats. Forage samples were taken monthly to assess DM yield and botanical composition. Samples collected for botanical composition were manually sorted into grass, legume, and weed species. Forage DMI was estimated using a rising plate meter before and after grazing. Heifer BW at the conclusion of yr 1 and yr 2 did not differ between HO and HG (P = 0.40 and P = 0.12, respectively). Likewise, overall ADG did not differ between HO and HG, averaging 0.65 kg/d and 0.63 kg/d over both grazing seasons (P = 0.70). Grazing strategy did not affect forage or total DMI in yr 1; however, HO consumed 2.3 kg/d more forage DM than HG (P < 0.01), resulting in greater total DMI for HO in yr 2 (P < 0.01). Heights at the hip and withers were greater for HO than for HG during both grazing seasons (P < 0.05). Weed presence did not differ between grazing strategies over both grazing seasons as determined by manual harvesting, but visual estimation of botanical composition at the end of yr 2 showed that HO paddocks had 3.5 times more weed presence than HG pastures (P < 0.01). Within the confines of this study, co-grazing did not affect overall heifer BW gain, but it decreased DMI, suggesting that dairy heifers can be co-grazed with goats without negative effects on ADG or feed efficiency.

Health-related quality of life in patients with advanced renal cell carcinoma receiving pazopanib or placebo in a randomised phase III trial.

BACKGROUND: In a double-blind, randomised phase III trial of advanced renal cell carcinoma patients, pazopanib 800mg QD (n=290) versus placebo (n=145) significantly prolonged progression-free survival (hazard ratio (HR)=0.46, 95% confidence interval [CI] 0.34-0.62, p-value<0.0001), without important differences in health-related quality of life (HRQoL). This post-hoc analysis evaluated time to HRQoL deterioration and whether tumour response/stabilisation was associated with HRQoL improvement. METHODS: HRQoL was assessed using EORTC QLQ-C30 and EQ-5D. Effect of pazopanib on time to ⩾20% decline from baseline in summary scores was estimated for all patients and by prior treatment. Analyses were conducted for different HRQoL deterioration thresholds. HRQoL changes were stratified by benefit and compared: complete response (CR) or partial response (PR) versus progressive disease (PD); CR/PR versus stable disease (SD), and SD versus PD. RESULTS: There was a trend for pazopanib patients to be less likely than placebo patients to experience ⩾20% HRQoL deterioration in EORTC-QLQ-C-30 global health status/QOL scale (HR=0.77; 95% CI 0.57-1.03, not significant). Results by prior treatment and different HRQoL deterioration thresholds were similar. Patients with CR/PR and SD experienced significantly less HRQoL deterioration than those with PD (p<0.001, p=0.0024, respectively); mean differences between patients with CR/PR and PD exceeded the pre-determined minimally important difference (MID). Differences between patients with SD and PD did not exceed pre-determined MID. Results were generally consistent across treatment and EQ-5D summary scores. CONCLUSION: Results support the favourable benefit-risk profile of pazopanib and suggest patients experiencing tumour response/stabilisation also may have better HRQoL compared to those without this response.

NCCP breast cancer referral guidelines--are breast cancer patients prioritised?

Following centralisation of breast cancer services, the National Cancer Control Programme (NCCP) introduced referral guidelines indicating which patients require urgent, early and routine review. This study prospectively analysed referrals to a symptomatic breast unit over 3 months to measure Primary Care Physician (GP) uptake of the NCCP referral guidelines, compare triage patterns of GP and consultant breast surgeon and evaluate the efficacy of the guidelines at identifying patients with breast cancer. 1044 consecutive referrals were categorised according to NCCP guidelines. 637 (61%) were referred using the NCCP form. GP referrals correlated well with consultant breast surgeon for patients requiring urgent review (r = 0.71, p < 0.001; Pearson). Patients categorised as "urgent" were more likely to have a breast biopsy compared to those categorised as "routine" (p < 0.0001; Chi2). The overall cancer incidence was 34 (3.3%) and significantly higher in the "urgent" group at 10.5%. NCCP guidelines were 91% sensitive for triaging breast cancer patients into the correct (urgent) category. The NCCP guidelines are accurate and should be considered the gold-standard for referral to the symptomatic breast service. Consideration should be given to a GP-delivered service to patients outside the "urgent" category.

Effects of crude glycerin on performance and carcass characteristics of finishing wether lambs.

The objective of this study was to evaluate the effects of crude glycerin on performance and carcass characteristics in finishing wether lambs. Thirty black-faced, Suffolk-cross wether lambs (44.1 +/- 5.6 kg initial BW) were stratified and blocked by BW to 1 of 5 individually fed, isocaloric, isonitrogenous dietary treatments containing 0, 5, 10, 15, or 20% crude glycerin (88% pure) on a DM basis. Diets were fed once daily for ad libitum consumption and contained 15% chopped hay, approximately 25% dried distillers grains with solubles, and the specified treatment combination of cracked corn replaced with increasing amounts of crude glycerin. Wethers were weighed on 14-d intervals and were selected for slaughter when they reached an approximate 12th-rib fat depth of 0.51 cm (28 to 84 d on trial). Carcass characteristics were collected after a 48-h chill. Dry matter intake (linear, P = 0.004) and ADG (quadratic, P = 0.05) increased with increasing concentrations of glycerin in the diet during the first 14 d of the feeding period. Similarly, G:F tended to increase quadratically (P = 0.06) with increasing concentrations of crude glycerin in the diet during the first 14 d. However, there were no differences among treatments for final BW, days on feed, or cumulative DMI, cumulative ADG, and cumulative G:F (P >or= 0.11). Body wall thickness, dressing percent, HCW, LM area, flank streaking, leg score, conformation score, quality grade, yield grade, and percent boneless, closely trimmed retail cuts did not differ (P >or= 0.21). Adding up to 15% crude glycerin to finishing wether diets improved feedlot performance, particularly during the first 14 d, without any concomitant effect on carcass characteristics.

Improving patient care and quality of life after laryngectomy/glossectomy.

Patients undergoing total laryngectomy/glossectomy are left without a voice at least temporarily in the early postoperative stage, since their larynx and/or tongue has been removed. Those patients rendered permanently speechless usually acquire a form of mechanical speech through electronic devices. However, the life-changing nature of this surgery should not be underrated as effectively these people have lost their normal voice. It can be argued that this patient group is also without a voice in a political sense - theirs seems to be a forgotten cancer, as other forms of cancer appear to attract greater attention for research priorities and funding. In some ways this research attempts to redress the balance through exploring the patient experience postoperatively, in particular the issues related to communication for this patient group. The results also highlight the emotional trauma experienced by patients and the mechanisms healthcare staff employ to support these patients. This research is multidisciplinary, involving patients and all those health workers that come into contact with them on the ward. The patient experience forms a major part of this article, allowing their stories to form much of the content. The results draw attention to deficiencies in service delivery that, as a direct result of this research, have been and are being addressed so that patients' care is improved and their quality of life is restored. Such change has been driven by patient comment such as: 'But then when you wake up after that operation that's the pits when you are laying there and you think "I'm dead". And then when you wake up properly that's the bit I always say you wish you were dead. That's when you wish you had died.'

Cost-effectiveness of oral ibandronate compared with intravenous (i.v.) zoledronic acid or i.v. generic pamidronate in breast cancer patients with metastatic bone disease undergoing i.v. chemotherapy.

BACKGROUND: Ibandronate is the first third-generation bisphosphonate to have both oral and intravenous (i.v.) efficacy. An incremental cost-effectiveness model compared oral ibandronate with i.v. zoledronic acid and i.v. generic pamidronate in female breast cancer patients with metastatic bone disease, undergoing i.v. chemotherapy. METHODS: A global economic model was adapted to the UK National Health Service (NHS), with primary outcomes of direct healthcare costs and quality-adjusted life years (QALYs). Efficacy, measured as relative risk reduction of skeletal-related events (SREs), was obtained from clinical trials. Resource use data for i.v. bisphosphonates and the cost of managing SREs were obtained from published studies. Hospital management and SRE treatment costs were taken from unit cost databases. Monthly drug acquisition costs were obtained from the British National Formulary. Utility scores were applied to time with/without an SRE to adjust survival for quality of life. Model design and inputs were validated through expert UK clinician review. RESULTS: Total cost, including drug acquisition, was pound 386 less per patient with oral ibandronate vs. i.v. zoledronic acid and pound 224 less vs. i.v. generic pamidronate. Oral ibandronate gained 0.019 and 0.02 QALYs vs. i.v. zoledronic acid and i.v. pamidronate, respectively, making it the economically dominant option. At a threshold of pound 30,000 per QALY, oral ibandronate was cost-effective vs. zoledronic acid in 85% of simulations and vs. pamidronate in 79%. CONCLUSIONS: Oral ibandronate is a cost-effective treatment for metastatic bone disease from breast cancer due to reduced SREs, bone pain, and cost savings from avoidance of resource use commonly associated with bisphosphonate infusions.