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"Witcombe, David"
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Strategies for anti-coccidial prophylaxis
by
WITCOMBE, DAVID M.
,
SMITH, NICHOLAS C.
in
Animals
,
antibodies
,
Antibodies, Protozoan - immunology
2014
Coccidiosis, a serious disease resulting from infection with parasitic protozoa of the genus Eimeria, causes significant economic losses to the poultry industry, where intensive rearing facilitates transmission of infectious oocysts via the fecal/oral route. Current control relies primarily on prophylactic drugs in feed but, whilst cost effective, the rise of drug resistance and public demands for residue-free meat has encouraged development of alternative control strategies. Chickens that recover from infection with Eimeria develop solid immunity that is directed against the early asexual stages of the parasite life cycle. This has allowed development of a number of vaccines that utilize deliberate infection with controlled doses of virulent oocysts or reproductively attenuated lines of Eimeria. The latter are immunogenic but non-pathogenic. The realization that both prophylactic drugs and attenuated vaccines control but do not eradicate infection with Eimeria encouraged development of a vaccine based upon maternal immunity. Laying hens exposed to Eimeria are able to transfer protective antibodies to hatchlings via egg yolks and these antibodies have been used to identify parasite proteins that are conserved across the genus. When delivered maternally, these provide an economical means of preventing coccidiosis, offering immediate protection to newly hatched chicks.
Journal Article
The epidemiology, management, and the associated burden of migraine in Australian primary care: a retrospective analysis of electronic health record data
2025
Background
Migraine accounts for more disability than all other neurologic conditions combined. Despite this, more than 40% of people with migraine do not seek medical care. Migraine is associated with a higher risk of comorbidities, adding to the symptom burden. Currently, there is limited epidemiological data available on the prevalence and incidence of migraine in the Australian primary care setting. This study aimed to describe the epidemiology (prevalence and incidence) of diagnosed migraine within the Australian general practice population.
Methods
Electronic health record data captured by national clinical practice management software over a 14-year index period (2010–2024) was analysed. The point prevalence of diagnosed migraine was estimated. The incidence of diagnosed migraine was estimated based on patients with new onset migraine during the index period. Estimates were stratified by age and sex. Differences by sociodemographic groups, patterns of treatment, and referral pathways were also evaluated.
Results
The study encompassed a total of 37,579 eligible migraine prevalent cases. The overall adjusted point prevalence of diagnosed migraine was estimated as 7.02 per 1,000 persons (95% confidence interval (CI) 6.79 to 7.25), which equates to 0.702% after adjusting for the interaction of age and sex. The overall incidence rate (IR) was estimated as 3.48 per 1,000 person-years (95% CI 3.38 to 3.58) after adjusting for the interaction of age and sex. Depression and anxiety were reported four times more frequently in the migraine population. High use of opioids and opioid combinations (54.75%) was noted in the migraine population, as well as a lower-than-expected use of triptans (51.06%). Among those with migraine, 32.03% had been referred to a physiotherapist and 18.64% had been referred to a neurologist.
Conclusions
This is the first study to describe the IR, accounting for life-years, in the Australian general practice population. The point prevalence of diagnosed migraine and incidence were lower than population-based estimates from other regions. The findings indicate that migraines are frequently underdiagnosed in the Australian primary care setting, with a possible lack of awareness of potential presentations for migraine, including neck pain, and highlight the need for further patient and clinician education.
Journal Article
Real-world evaluation of effectiveness, persistence, and usage patterns of tofacitinib in treatment of rheumatoid arthritis in Australia
by
Littlejohn, Geoffrey
,
Witcombe, David
,
Bird, Paul
in
Non-pharmacological intervention
,
Remission
,
Rheumatoid arthritis
2020
IntroductionThe aim of this study was to describe the real-world evidence for effectiveness, treatment persistence, and treatment patterns among patients in the community with rheumatoid arthritis treated with the JAK inhibitor tofacitinib.MethodsThis was a retrospective, non-interventional cohort study that extracted data for new users of tofacitinib or biologic disease-modifying antirheumatic drugs (bDMARDs) from the Australian Optimizing Patient outcomes in Australian RheumatoLogy (OPAL) dataset between March 2015 and September 2018. Patients were propensity score matched at a 1:2 tofacitinib to bDMARD ratio based on age, sex, and selected baseline treatment combinations. Treatment effectiveness was evaluated using disease status measures. Treatment persistence was calculated and the percentage of patients receiving monotherapy or combination therapy at treatment initiation was evaluated.ResultsData from 2810 patients were extracted and 1950 patients were included in the matched population (1300 bDMARD initiators and 650 tofacitinib initiators). Patients were predominantly aged 55 to 74 years (57.8%) and female (81.2%). After 18 months of treatment, 52.4% and 57.8% of patients had achieved disease activity score (DAS) remission in the bDMARD and tofacitinib groups, respectively. The median treatment persistence for tofacitinib was similar to that for bDMARDs: 34.2 months (95% CI 32.2 to not reached) and 33.8 months (95% CI 28.8 to 40.4), respectively. In the overall population, more patients were prescribed tofacitinib as monotherapy (43.4%) compared with bDMARD monotherapy (33.4%).ConclusionsTofacitinib demonstrated treatment effectiveness and persistence similar to bDMARDs. Overall, there was a trend for more use of tofacitinib as monotherapy than bDMARDs.Key Points• This study provides real-world evidence regarding effectiveness, treatment persistence, and treatment patterns, among patients with rheumatoid arthritis (RA) in the community being treated with tofacitinib.• The study suggests that tofacitinib is an effective and enduring intervention in RA with tofacitinib persistence and effectiveness comparable to bDMARDs.
Journal Article
Treatment outcomes in patients with seropositive versus seronegative rheumatoid arthritis in Phase III randomised clinical trials of tofacitinib
2019
ObjectivesTofacitinib is an oral JAK inhibitor for the treatment of rheumatoid arthritis (RA). We examined response to tofacitinib 5 or 10 mg two times a day in patients with seropositive vs seronegative RA.MethodsData were pooled from five Phase III studies of conventional synthetic disease-modifying antirheumatic drug (csDMARD)- or biological DMARD-inadequate responders (ORAL Step [NCT00960440]; ORAL Scan [NCT00847613]; ORAL Solo [NCT00814307]; ORAL Sync [NCT00856544]; ORAL Standard [NCT00853385]). ‘Serotype’ subgroups were: anticyclic citrullinated peptide (CCP) and rheumatoid factor (RF) positive (anti-CCP+/RF+); anti-CCP+/RF negative (-); anti-CCP-/RF+; anti-CCP-/RF-. At month 3, ACR20/50/70 response rates, Disease Activity Score (DAS28-4[ESR])-defined remission (DAS28-4[ESR]<2.6) and low disease activity (LDA; DAS28-4[ESR]≤3.2), changes from baseline (CFB) in Health Assessment Questionnaire-Disability Index (HAQ-DI), Short Form-36 Health Survey (SF-36) physical functioning and Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) were evaluated. Safety endpoints were compared.ResultsBaseline demographics/characteristics were similar across subgroups. Tofacitinib significantly improved ACR20/50/70 response rates, DAS28-4(ESR) LDA rates and CFB in HAQ-DI and FACIT-F vs placebo across subgroups. More anti-CCP+/RF+ than anti-CCP-/RF- patients had ACR20/50/70 responses (ACR20/50: both tofacitinib doses; ACR70: 10 mg two times a day). SF-36 physical functioning improved in anti-CCP+/RF+, anti-CCP+/RF- and anti-CCP-/RF+ patients (both tofacitinib doses) and anti-CCP-/RF- patients (10 mg two times a day) vs placebo. More anti-CCP+/RF+ and anti-CCP+/RF- than anti-CCP-/RF- patients achieved DAS28-4(ESR) remission and LDA with tofacitinib 10 mg two times a day. Frequency of adverse events (AEs), serious AEs and discontinuations due to AEs were similar across subgroups.ConclusionGenerally, tofacitinib efficacy (ACR20/50/70 responses) and safety were similar across subgroups. DAS28-4(ESR) remission rates and SF-36 physical functioning appeared lower in anti-CCP- patients.
Journal Article
Ulcerative Colitis Narrative findings: Australian survey data comparing patient and physician disease management views
by
Andrade, Mauricio
,
Sechi, Alexandra
,
Witcombe, David
in
communication
,
Disease management
,
Gastroenterology
2021
Background and Aim The Global Ulcerative Colitis (UC) Narrative Survey aimed to evaluate the impact of UC, perceptions of UC burden, and management approaches. Here, we present data from patients and physicians in Australia. Methods Surveys, fielded by The Harris Poll, were completed by 215 patients with UC and 90 physicians, between August 2017 and February 2018. Surveys included questions on disease characteristics, impact on life, communication with physicians, and patient knowledge of UC. Results are presented descriptively from all respondents (with no imputation for missing data). Results Based on medication history, 84% of patients had moderate to severe UC. Diagnostic delay was on average 1.9 (SD 5.0) years and 48% of patients had waited ≥1 year for diagnosis. Nearly two‐thirds (65%) of patients considered themselves to be in remission, with 97% also reporting a flare in the past year. The majority (92%) of patients were satisfied with their UC medication and, if their treatment made them feel “good enough,” many (75%) would not consider an alternative. Most (90%) patients were satisfied with communication with their physician; however, only 48% felt comfortable raising emotional concerns. Both patients and physicians desired more time during routine appointments. Patients had gaps in their knowledge of UC, which physicians mostly recognized. Conclusions The Australian survey results highlighted the diagnostic delay and burden of UC patients' experience, gaps in patients' knowledge of UC, and challenges in patient–physician communication. Compared with the overall Global UC Narrative Survey, patients in Australia reported a high burden of disease. The Australia‐specific patient and physician results from the Global Ulcerative Colitis Narrative Survey are reported; they highlight a high disease burden, problems of diagnostic delay, and challenges in patient–physician communication. Pfizer Inc funded editorial support and the study.
Journal Article
Characterisation of the antigenic and immunogenic properties of bacterially expressed, sexual stage antigens of the coccidian parasite, Eimeria maxima
2004
Coccidiosis in poultry is caused by the intestinal parasite
Eimeria; it causes significant financial losses to the commercial poultry industry worldwide. CoxAbic
® is the first commercially available subunit vaccine against coccidiosis. The vaccine consists of affinity purified sexual stage (gametocyte) antigens (APGA) isolated from
Eimeria maxima. Production of this vaccine is time-consuming and laborious and, therefore, a recombinant subunit vaccine substitute for CoxAbic
® is desirable. The genes encoding the two immunodominant components of CoxAbic
®, gam56 and gam82, were cloned into the bacterial expression vector, pTRCHisB, and the proteins expressed and purified. Both recombinant proteins were recognised by protective chicken antibodies that were raised to APGA, by immunoblotting. In a competitive ELISA, a combination of the recombinant proteins inhibited the binding of anti-APGA antibodies to APGA by 76%, which was comparable to the inhibition of 98% observed when APGA was used as the competing protein in the assay. In two breeds of chicken (Australorp and Cobb500), the recombinant proteins alone, or in combination, elicited a dose-dependent, antibody response that recognised APGA by ELISA, and gametocytes by immunoblotting. Together, the results suggested that the development of a recombinant subunit vaccine that maintains the antigenic and immunogenic properties of the native protein vaccine, CoxAbic
®, is feasible.
Journal Article
Real-world evaluation of effectiveness, persistence, and usage patterns of monotherapy and combination therapy tofacitinib in treatment of rheumatoid arthritis in Australia
by
O’Sullivan, Catherine
,
Littlejohn, Geoffrey
,
Witcombe, David
in
Antirheumatic Agents - therapeutic use
,
Arthritis, Rheumatoid - drug therapy
,
Australia
2022
Objective
This study aimed to describe the real-world effectiveness and treatment persistence among patients with rheumatoid arthritis treated with monotherapy and combination therapy tofacitinib and biologic disease-modifying antirheumatic drugs (bDMARDs).
Methods
This was a post hoc analysis of a retrospective, non-interventional study that extracted data for patients treated with tofacitinib or bDMARDs from the Australian OPAL dataset between March 2015 and September 2018. Monotherapy tofacitinib and bDMARDs and combination therapy tofactinib and bDMARDs were propensity score matched and treatment effectiveness and persistence of the groups were evaluated.
Results
In the bDMARD and tofacitinib monotherapy and combination therapy matched populations there were 1300 bDMARD initiators (
n
= 564 monotherapy) and 650 tofacitinib initiators (
n
= 282 monotherapy). In the bDMARD and tofacitinib monotherapy matched groups, 62.9% and 66.7% were in DAS-28 CRP disease remission after 18 months of treatment, respectively. In the combination therapy bDMARD and tofacitinib groups, 50% and 58.9% were in DAS-28 CRP disease remission after 18 months, respectively. The median treatment persistence was similar between the monotherapy bDMARD and tofacitinib treatment groups (36.7 months (95% CI 27.4 to “not reached’) and 34.2 months (95%CI 30.3 to “not reached”) respectively) as well as the combination therapy bDMARD and tofacitinib groups (32.2 months (95% CI 25.7 to 34.4) and 32.7 months (95%CI 28.7 to “not reached”, respectively).
Conclusions
Patients receiving combination therapy with tofacitinib or bDMARDs had higher disease activity scores at index than patients receiving monotherapy. Monotherapy with tofacitinib or bDMARDs, and combination therapy with tofacitinib or bDMARDs demonstrated similar treatment effectiveness and persistence, respectively.
Key Points
•
This study provides real-world evidence regarding effectiveness, treatment persistence, and treatment patterns, among patients with rheumatoid arthritis (RA) treated with monotherapy or combination therapy tofacitinib.
•
The study suggests that monotherapy and combination therapy tofacitinib is an effective intervention in RA with persistence and effectiveness comparable to bDMARDs.
Journal Article
Real-world evaluation of persistence, effectiveness and usage patterns of tofacitinib in treatment of psoriatic arthritis in Australia
by
Leadbetter, Joanna
,
O’Sullivan, Catherine
,
Butcher, Belinda E
in
Cytokines
,
Interleukin 17
,
Population
2024
ObjectivesTo describe treatment patterns and persistence of tofacitinib, interleukin 17 inhibitors (IL-17Ai) and tumour necrosis factor inhibitors (TNFi), in patients with psoriatic arthritis (PsA).MethodsData from adult patients with PsA and who had received at least one prescription of tofacitinib, IL-17Ai or TNFi between May 2019 and September 2021 were sourced from the Australian OPAL dataset. Persistence, analysed via Kaplan–Meier methods, and propensity score matching between tofacitinib and bDMARD (IL-17Ai and TNFi) groups were conducted.ResultsOf 16,692 patients with PsA, 1486 (n = 406 tofacitinib, n = 416 IL-17Ai and n = 664 TNFi) were included. More females were in the tofacitinib group (75.4%) than in the IL-17Ai (61.1%) and TNFi (64.8%) groups. Overall, 19.2% of tofacitinib patients were first line, compared with 41.8% of IL-17Ai and 62.8% of TNFi patients. In the overall population, the median persistence was 16.5 months (95% CI 13.8 to 19.5 months), 17.7 months (95% CI 15.8 to 19.6 months) and 17.2 months (95% CI 14.9 to 20.5 months) in the tofacitinib, IL-17Ai and TNFi groups, respectively. Persistence was similar in the tofacitinib/IL-17Ai matched population; however, in the tofacitinib/TNFi matched population, persistence was longer in the tofacitinib group (18.7 months, 95% CI 15.6 to 21.4 months) compared with the TNFi group (12.2 months, 95% CI 19.9 to 14.9 months).ConclusionsIn this Australian real-world dataset, tofacitinib was more frequently used in later lines and among a slightly higher proportion of female patients than IL-17Ai or TNFi. Overall, treatment persistence was similar for tofacitinib, IL-17Ai and TNFi, but tofacitinib exhibited longer persistence than TNFi in a matched population.Key Points• This is the first, large real-world study from Australia investigating the demographics, treatment patterns and comparative treatment persistence of patients with psoriatic arthritis (PsA) treated with tofacitinib and biologic disease-modifying drugs (bDMARDs).• The study suggests that tofacitinib is an effective intervention in PsA with at least comparable persistence to bDMARDs: tumour necrosis factor inhibitors (TNFi) and interleukin-17 A inhibitors (IL-17Ai).
Journal Article
Estimated Incidence of Hospitalisations and Deaths Attributable to Respiratory Syncytial Virus Infections in Adults in Australia Between 2010 and 2019
2025
Background Respiratory syncytial virus (RSV) morbidity and mortality in adults are often underestimated due to nonspecific symptoms, limited standard‐of‐care testing and lower diagnostic testing sensitivity compared with children. To accurately evaluate the RSV disease burden among adults in Australia, we conducted a model‐based study to estimate RSV‐attributable cardiorespiratory hospitalisation incidence and mortality rate. Methods A quasi‐Poisson regression model was used to estimate RSV‐attributable cardiorespiratory, respiratory and cardiovascular events, using weekly hospitalisation and mortality data from 2010 to 2019, accounting for periodic and aperiodic time trends and viral activity and allowing for potential overdispersion. The time‐series model compared the variability in confirmed RSV events alongside variability in all‐cause cardiorespiratory events identified from ICD‐10‐AM codes to estimate the number of RSV‐attributable events, including undiagnosed RSV‐related events. Results RSV‐attributable incidence of cardiorespiratory hospitalisations increased with age and was highest among adults ≥ 65 years (329.5–386.6 cases per 100,000 person‐years), nine times higher than in adults 18–64 years. The estimated incidence of RSV‐attributable respiratory hospitalisations in adults ≥65 years (219.7–247.8 cases per 100,000 person‐years) was 35‐fold higher than in adults 18–64 years. RSV‐attributable deaths accounted for 4% to 6% of cardiorespiratory deaths in adults ≥ 65 years, with RSV‐attributable mortality rates ranging from 65.6 to 77.6 deaths per 100,000 person‐years and respiratory mortality rates ranging from 20.3 to 24.0 deaths per 100,000 person‐years, both 70‐fold higher than in adults 18–64 years. Conclusions This study identified substantial RSV‐associated morbidity and mortality among Australian adults and is the first study to report RSV‐attributable mortality rates for Australia that account for untested events.
Journal Article