AIMS:HbA1c and body weight were assessed across selected subgroups of adults with type 2 diabetes receiving oral semaglutide in clinical practice. METHODS:In this non-interventional study, changes in HbA1c and body weight to end of study (EoS) and safety were assessed by subgroup: baseline age, body mass index (BMI), type 2 diabetes duration, participants switching from dipeptidyl peptidase-4 inhibitors, and semaglutide dose at EoS. RESULTS:All subgroups experienced reductions in HbA1c and body weight. Younger participants had greater reductions in HbA1c than older participants (-0.9, -0.7, -0.7, and -0.5 percentage points for participants aged <55, ≥55-<65, ≥65-<75, and ≥75 years, respectively [P = 0.0467]). Shorter type 2 diabetes duration and lower EoS semaglutide dose were associated with greater HbA1c reductions (-0.8, -0.7, and -0.6 percentage points with ≤5, >5-≤10, and >10 years' duration, respectively [P < 0.0001]; -1.2, -0.7, and -0.4 percentage points with 3, 7, and 14 mg, respectively [P < 0.0001]). Changes in HbA1c were not significantly different across other subgroups. Lower EoS semaglutide dose was associated with greater body weight reductions (-3.8, -2.9, and -2.8 kg with 3, 7, and 14 mg, respectively [P < 0.0001]); body weight reductions were not significantly different across other subgroups. Adverse events were similar between subgroups, except that older subgroups experienced more events. CONCLUSIONS:HbA1c and body weight decreased across all subgroups, providing insights into oral semaglutide use in clinical practice for individuals with different characteristics in the real-world setting.
The PIONEER REAL Italy study examined the clinical outcomes associated with oral semaglutide in real-world settings. This was a multicenter, prospective, non-interventional, single-arm study in adults with type 2 diabetes (T2D) who were treatment-naive to injectable glucose-lowering medications. Participants initiated oral semaglutide at doses of 3, 7, or 14 mg, and were followed for 34–44 weeks. The primary endpoint was the change in glycated hemoglobin (HbA1c) from baseline to the end of study (EoS). Secondary endpoints were the change in body weight (BW), the percentage of participants attaining HbA1c < 7
AIMS:This real-world study assessed glycemic levels and further clinical outcomes, following initiation of detemir, in sub populations of people with T2D vulnerable to hypoglycemia. METHODS:This retrospective cohort study included people registered in the United Kingdom Clinical Practice Research Datalink (CPRD) GOLD database who initiated detemir between January 2004 and December 2019. Analyses were stratified by age, previous insulin experience, and history of renal, liver or cardiovascular disease (CVD). RESULTS:In total, 8975 eligible study participants were identified (44.4 %, aged ≥65 years; 23.7 %, renal disease; 15.6 %, CVD; 2.2 %, liver disease; 53.3 %, insulin-naïve). Six months post-index estimated changes (95 % confidence intervals [CI]) in HbA1c and body weight were -1.00 % (-1.1; -0.9) (-11 mmol/mol [-12; -9]) and 0.35 kg (0.03; 0.66), respectively. Rates of hypoglycemia were low, with no increase between pre- and post-index periods. Compared with pre-index, the mean number of oral glucose-lowering therapy prescriptions per person and mean number of people receiving each type of glucose-lowering therapy decreased post-index. CONCLUSIONS:Detemir appears to be an effective and well-tolerated treatment for T2D in older people, and those with CVD, renal disease or liver disease.
Objectives This study compared the effectiveness of first-time use of faster aspart with rapid-acting insulin analogues in patients with type 1 diabetes (T1D) or type 2 diabetes (T2D).Design, setting This retrospective cohort study used data from 1 January 2017 to 8 May 2021 captured in the Clinical Practice Research Datalink Aurum database in the UK.Interventions Patients with T1D or T2D either initiating faster aspart or another rapid-acting insulin analogue (‘new users’) or switching from a rapid-acting insulin analogue to faster aspart or to another rapid-acting insulin analogue (‘switchers’) were included. The index date was the date of first prescription of faster aspart or a rapid-acting insulin analogue, or of switching to a different rapid-acting analogue or to faster aspart.Participants A total of 9695 and 2170 patients were included in the new users (T1D, 1737; T2D, 7958) and switchers cohorts (T1D, 1764; T2D, 406), respectively.Primary and secondary outcome measures Glycated haemoglobin (HbA1c) change at 6 months, occurrence of hypoglycaemia from index to 12 months post-index and treatment persistency from index to discontinuation or censoring.Results Numerically greater reductions were observed with faster aspart than rapid-acting insulins in T1D switchers and new users in change in HbA1c at 6 months. Patients with T1D who switched to faster aspart experienced a significant reduction in rate of hypoglycaemia (p=0.0021). Treatment persistency was higher with faster aspart than with rapid-acting insulins among T1D switchers. No distinction in treatment persistency was observed between the treatment groups for T1D new users or T2D switchers.Conclusions Reductions in HbA1c were numerically larger with faster aspart in three of four subgroups. There was higher treatment persistency with faster aspart vs rapid-acting insulin analogues among T1D switchers.Trial registration number NN1218-4967.
PIONEER REAL Japan was a non-interventional prospective study of oral semaglutide in adults with type 2 diabetes in Japanese clinical practice. Adults naïve to injectable glucose-lowering therapies initiated oral semaglutide in routine clinical practice and were followed for 34–44 weeks. The primary endpoint was change in glycated hemoglobin (HbA 1c ) from baseline to end of study; the co-primary endpoint was number of adverse events (AEs). Secondary endpoints included change in bodyweight from baseline to end of study. Analyses were also carried out for subgroups aged <75 and ≥75 years. A total of 624 participants initiated oral semaglutide; 578 completed the study. Mean baseline HbA 1c and bodyweight were 7.7% and 72.4 kg, respectively. At end of study, estimated change (95% confidence interval [CI]) in HbA 1c from baseline was −0.7 percentage points (−0.77, −0.61) overall, −0.8 percentage points (−0.86, −0.67) in the <75 years subgroup and −0.5 percentage points (−0.68, −0.41) in the ≥75 years subgroup (all P < 0.0001). Estimated change (95% CI) in bodyweight was −2.8 (−3.19, −2.50) kg overall, −2.9 (−3.38, −2.49) kg in the <75 years subgroup and − 2.7 (−3.18, −2.14) kg in the ≥75 years subgroup (all P < 0.0001). AEs occurred in 161 (25.8%) participants: 99 of 423 (23.4%) and 62 of 201 (30.8%) participants in the <75 and ≥75 years subgroups, respectively. Gastrointestinal AEs were the AEs most frequently leading to oral semaglutide discontinuation. In routine clinical practice, HbA 1c and bodyweight were significantly reduced from baseline in adults initiating oral semaglutide, including those aged ≥75 years, with no new safety concerns.
Oral semaglutide provides an alternative to injectable glucagon-like peptide-1 receptor agonists (GLP-1RAs) for treatment of type 2 diabetes (T2D). The PIONEER REAL studies evaluate clinical outcomes of oral semaglutide treatment of T2D in a real-world setting. PIONEER REAL UK focused on adults living with T2D in the UK. The multi-centre, prospective and non-interventional single-arm study enrolled 333 participants and followed them for 34–44 weeks. Participants were treated as part of routine clinical practice and had not been previously treated with injectable glucose-lowering medication. The primary endpoint was change in glycated haemoglobin (HbA1C) from baseline to end of study (EOS). Secondary endpoints included change in body weight, proportion of participants with HbA1C < 7
Real-world data provide insight into how medications perform in clinical practice. The PIONEER REAL Switzerland study aimed to understand clinical outcomes with oral semaglutide in adults with type 2 diabetes (T2D). PIONEER REAL Switzerland was a 34–44-week, multicentre, prospective, non-interventional, single-arm study of adults with T2D naïve to injectable glucose-lowering medication who were initiated on oral semaglutide in routine clinical practice. The primary endpoint was change in glycated haemoglobin (HbA1c) from baseline (BL) to end of study (EOS); secondary endpoints included change in body weight (BW) from BL to EOS and the proportion of participants achieving HbA1c < 7.0
Oral semaglutide is a glucagon-like peptide 1 receptor agonist (GLP-1RA) approved for improving glycemic control in adults with type 2 diabetes (T2D). The PIONEER REAL program evaluates clinical and patient-reported outcomes of oral semaglutide treatment as part of routine clinical practice across 13 countries. Here, data from Canada, Denmark, Italy, the Netherlands, Sweden, Switzerland, and the UK are pooled and analyzed to address treatment satisfaction as well as glycated hemoglobin (HbA1C) and body weight changes in relevant subgroup analyses. This pooled analysis encompasses seven country-specific, non-interventional, multicenter, phase 4, prospective, single-arm clinical studies assessing the use of oral semaglutide in adults with T2D. Primary endpoint was the change in HbA1C from baseline to end of study (EOS), and secondary endpoints included changes in body weight and treatment satisfaction. For the analyses, results were stratified by age, T2D duration, and oral semaglutide dose at EOS as well as baseline HbA1C, body weight, and body mass index. Oral semaglutide treatment was initiated by 1615 participants. At EOS, 1222 (76
Parasite aggregation within hosts is a fundamental feature of parasite distributions, whereby the majority of parasites are harboured by a minority of hosts. Parasite aggregation can influence their transmission and hence control. In this narrative review, possible sources of aggregation of Taenia solium cysticerci in pigs are discussed, along with implications for control of the parasite. While heavy T. solium infections in pigs could most likely be associated with ingestion of high doses of infective parasite eggs, consistent with coprophagic behaviour of pigs, lighter infections indicate a role of indirect routes of transmission to pigs, mostly from lower infection doses. Light infections are likely to be missed by commonly used diagnostic methods - tongue examination or meat inspection - and end up in the food chain. Hence, they entail a 'hidden' risk and are of a particular public health concern, especially in areas where meat is consumed raw or undercooked. To be effective and sustainable, control strategies against T. solium likely require a broader understanding of, and consideration for parasite transmission dynamics. More importantly, a holistic One Health approach incorporating interventions on humans, pigs and the environment will likely have a larger, more successful and sustainable impact.
Aims: This study investigated the ethnic differences in glycaemic levels and clinical characteristics among insulin-naive people with type 2 diabetes (T2D) initiating biphasic insulin aspart 30/70 (BIAsp 30) in primary practice in England.Materials and Methods: Retrospective, observational cohort study utilizing data from the Clinical Practice Research Datalink Aurum database, including White, South Asian, Black and Chinese insulin-naive adults with T2D, initiating BIAsp 30. The index date was that of the first BIAsp 30 prescription. Endpoints included change in glycated haemoglobin (HbA1c) and body mass index (BMI) 6 months post index.Results: In total, 11 186 eligible people were selected (9443 White, 1116 South Asian, 594 Black, 33 Chinese). HbA1c decreased across all subgroups 6 months post index: estimated %-point changes [95% CI of -2.32 (-2.36; -2.28) (White); -1.91 (-2.02; -1.80) (South Asian); -2.55 (-2.69; -2.40) (Black); and -2.64 (-3.24; -2.04) (Chinese)]. The BMI increased modestly 6 months post index in all subgroups [estimated changes (95% CI) kg/m(2): White, 0.92 (0.86; 0.99); South Asian, 0.60 (0.41; 0.78); Black, 1.41 (1.16; 1.65); and Chinese, 0.32 (-0.67; 1.30)]. In the overall population, hypoglycaemic event rates increased from 0.92 events per 100 patient-years before the index to 3.37 events per 100 patient-years post index; event numbers were too low to be analysed by subgroup.Conclusions: Among insulin-naive people with T2D initiating BIAsp 30, clinically meaningful HbA1c reductions in all ethnicities were observed. Some ethnic groups had larger reductions than others, but differences were small. In all groups, small BMI increases were seen, with small differences observed between groups. Hypoglycaemia rates were low.
People with type 2 diabetes (T2D) often require complex treatment regimens, including insulin, to achieve glycaemic goals.1 A basal–bolus insulin regimen combines basal insulin injections (at morning and/or night) and mealtime insulin injections. Although this is effective,2 it can prove burdensome,3 which may be a particular concern in older people. It is important to evaluate simplified regimens that may provide outcomes that are as effective as those achieved with a basal–bolus regimen while reducing treatment burden.4 Biphasic insulin aspart 30/70 (BIAsp 30) is a premixed combination of rapid-acting and intermediate-acting insulin aspart, administered via prefilled pen.5 This combination requires fewer pens and injections (typically 2–3 injections daily) compared with a basal–bolus regimen (usually ≥4 injections daily). However, real-world evidence of the effect of adding BIAsp 30 to a patient's treatment regimen is limited.6 We aimed to address this gap by evaluating glycaemic levels in people with T2D after adding or switching to treatment with BIAsp 30 in real-world clinical practice. We conducted a retrospective, observational study using anonymized patient data from the Clinical Practice Research Datalink (CPRD) GOLD database, which captures routine electronic medical records from UK primary care practices.7 The index date was defined as the date of each patient's first prescription of BIAsp 30. We followed patients from index date to 12 months post-index, database transfer-out date, death, or last collection date (whichever came first; BIAsp 30 discontinuation was also used as a timepoint in analysis of treatment persistence, alongside those mentioned previously). Key study design elements are shown in Supplementary Figure S1. Data were extracted from all CPRD GOLD patients with research-acceptable data (based on quality markers). The study population consisted of adults with T2D (18–75 years old at index) with ≥2 BIAsp 30 prescriptions between March 18, 2002 and December 31, 2019. Furthermore, included patients were required to have ≥2 basal and ≥2 bolus insulin prescriptions in the 12-month period prior to index. Pregnant women and patients with type 1 diabetes were excluded. Full details of inclusion criteria and data extraction are shown in Supplementary Figure S2. Change in glycated haemoglobin (HbA1c) and body mass index (BMI) at 6 months post-index were estimated. Additional endpoints were hypoglycaemic events (defined as records of hypoglycaemia diagnoses) within 12 months pre- and post-index, and treatment persistence based on rate of BIAsp 30 discontinuation within 12 months post-index and to the end of available data for patients. Clinical characteristics were summarized descriptively. A mixed model of repeated measures (MMRM) was used to estimate mean HbA1c using data from index date to 12 months post-index. We fitted both crude and adjusted models (age, sex and BMI). A quadratic relationship between HbA1c and time was established by fitting spline functions with an increasing number of knots. Two sensitivity analyses of HbA1c were also conducted (Supplementary Figure S3). Change in HbA1c at 6 months post-index was estimated together with the associated two-sided 95% confidence interval (CI) and an adjusted two-sided P value using the MMRM. Mean BMI was analysed from index date to 12 months post-index and change in BMI at 6 months post-index was analysed using the same approach as that described for HbA1c. Time to discontinuation of BIAsp 30 was evaluated using the Kaplan–Meier estimator. For hypoglycaemic events, rate (number of events/time at risk) and incidence rate (number of persons with at least one event/time at risk) were calculated. Overall, 502 patients (49% female) were included in the study, with a mean age of 61 years and a mean diabetes duration of 13.1 years (time from first recorded T2D code). Respectively, 473 and 463 patients had sufficient data for HbA1c and BMI model estimation. Patient demographic and clinical characteristics are presented in Supplementary Table S1. Pre-index, 70.5% of patients were prescribed an oral glucose-lowering drug, reducing to 64.5% at 12 months post-index. The proportion of patients with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in their treatment regimen after addition/switch to BIAsp 30 increased from 7.6% to 12% (Table 1). The quadratic MMRM-estimated mean HbA1c was 9.85% at index and 9.40% at 6 months post-index (HbA1c change: −0.453% [95% CI −0.622;−0.285]). Adjusting the model for age, sex and BMI did not lead to significant changes (−0.446% [95% CI −0.615;−0.277]). Estimated mean BMI was 32.1 kg/m2 at index and 31.8 kg/m2 6 months post-index. The quadratic MMRM estimated a change in BMI of −0.277 kg/m2 (95% CI –0.512;–0.042). Model adjustment did not lead to significant changes (−0.279 kg/m2 [95% CI −0.514;−0.044]). Nine and 15 patients had records of hypoglycaemic events pre- and post-index, respectively. The rate of hypoglycaemic events was 1.79 (95% CI 0.82;3.14) per 100/patient-years in the pre-index period compared with 3.72 (95% CI 2.16;5.68) per 100/patient-years in the post-index period. Treatment persistence was high, with 77% (95% CI 73;81) of patients remaining on BIAsp 30 1 year after addition/switch and 50% (95% CI 45;56) remaining after 5.4 years (Figure 1). The mean follow-up time was 4.6 years. This study contributes to the body of real-world evidence on the impact of adding or switching to BIAsp 30 in clinical practice.8-10 Following the addition of or switch to BIAsp 30, we observed a small reduction in HbA1c 6 months post-index, with a minor change in BMI. These findings align with those reported in the observational, multinational IMPROVE study and the prospective, multinational PRESENT study.11, 12 Given the older mean age of the population and the presence of comorbidities, large HbA1c reductions were not expected. However, the stable weight indicates that BIAsp 30 is a viable alternative to basal–bolus therapy. This is also supported by the relatively high treatment persistence. It should be noted that several factors could have contributed to the modest change in HbA1c such as changes in oral glucose-lowering therapy or GLP-1RA usage, although use in this population was relatively low (64.5% and 12.0%, respectively, at 12 months post-index). It should be noted that many patients remained with poor glycaemic control following addition of/switch to BIAsp 30 and may have benefitted from addition of GLP-1RAs or formulations containing them. Likewise, the minor BMI changes observed may be attributable to other factors, including other health conditions, lifestyle changes, and changes in oral glucose-lowering therapy or GLP-1RA usage. This study is limited by its selection criteria. Information on medication exposure is based on issued prescriptions; thus, patient adherence to their prescribed regimen is unknown and persistency an approximation. To increase the likelihood that selected patients were adhering to a basal–bolus treatment regimen prior to addition/switch to BIAsp 30, a minimum of two basal and two bolus prescriptions were required in the 12 months pre-index. However, this led to the inclusion of a relatively small number of patients. Other limitations include potential misclassification errors, lack of a reference group, and absence of data on dose and number of administered injections, which limits the generalizability of the results reported here. There is also potential for survivor treatment selection bias in included patients. The low rate of hypoglycaemic events leads us to believe that these are underreported and unreliable for comparison. The results of this study are aligned with previously published data for BIAsp 30 and suggest that, despite severe comorbidity, BIAsp 30 can be a relevant alternative to basal–bolus insulin regimens for people with T2D. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, agree to be accountable for all aspects of the work and have approved the final manuscript as submitted. Uffe Christian Braae and Anders Boeck Jensen contributed to the study design and Uffe Christian Braae to writing the study protocol. The statistical analysis was performed by Anders Boeck Jensen. All authors were involved in interpretation of the data and provided input to the manuscript at each stage. Medical writing and editorial support for the development of this manuscript, under the direction of the authors, were provided by Jane Blackburn, PhD, Edward Potts, MSc, Beverly La Ferla, MRes and Helen Marshall, BA, of Ashfield MedComms, an Inizio company, and funded by Novo Nordisk A/S, which also had a role in the review of the manuscript for scientific accuracy. Lotte Husemoen, of Novo Nordisk, Søborg, Denmark, provided substantial input during the study design phase and in interpretation of the study results. The study was sponsored by Novo Nordisk A/S. Professor Melanie Davies has acted as consultant, advisory board member and speaker for Boehringer Ingelheim, Lilly, Novo Nordisk and Sanofi, an advisory board member and speaker for AstraZeneca, an advisory board member for Pfizer, Medtronic and ShouTi Pharma Inc, and speaker for Novartis, Sanofi and Amgen. She has received grants in support of investigator and investigator-initiated trials from AstraZeneca, Sanofi-Aventis, Eli Lilly, Boehringer Ingelheim, Janssen and Novo Nordisk. Amra Ciric Alibegovic, Uffe Christian Braae and Pranav Kelkar are employed by, and hold shares in, Novo Nordisk A/S. Anders Boeck Jensen is employed by Novo Nordisk. The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/dom.15278. This study is based in part on data from the Clinical Practice Research Datalink (CPRD) obtained under licence from the UK Medicines and Healthcare products Regulatory Agency. The data are provided by patients, and collected by the UK National Health Service, as part of their care and support. The interpretation and conclusions contained in this study are those of the authors alone. Researchers should contact the CPRD's Independent Scientific Advisory Committee (ISAC) to obtain access to CPRD data. Supplementary Figure S1. Study design. Supplementary Figure S2. Flow of patients through data extraction. Supplementary Figure S3. HbA1c sensitivity analyses. Supplementary Table S1. Patient demographic and clinical characteristics at index. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Aims: Combining insulin with a glucagon-like peptide-1 receptor agonist (GLP-1RA) to treat type 2 diabetes (T2D) is common. While many studies have investigated concomitant therapy with basal insulin+GLP-1RA, few have reported on premixed insulin+GLP-1RA. We aimed to address this gap using data from the Clinical Practice Research Datalink Aurum database in England.Methods: This retrospective cohort study with propensity score matching assessed glycaemic levels and other clinical outcomes in people with T2D, comparing biphasic insulin aspart 30/70 (BIAsp 30) + GLP-1RA with basal insulin (insulin detemir/glargine U100) + GLP-1RA (from 2006 to 2021).Results: In total, 4770 eligible people were identified; 1511 had a BIAsp 30 + GLP-1RA regimen and were propensity score-matched to an equal number receiving basal+GLP-1RA. There was no significant difference in glycated haemoglobin (HbA1c) reduction between cohorts at 6 months (p = 0.15), with a decrease of -1.07 (95% CI: -1.16; -0.98) %-points (-11.7 mmol/mol [95% CI: -12.7; -10.7]) in the BIAsp 30 + GLP-1RA cohort, versus -0.97 (95% CI: -1.07; -0.88) %-points (-10.6 mmol/mol [95% CI: -11.7; -9.6]) in the basal+GLP-1RA cohort. Body mass index (BMI) decreased by -0.35 kg/m2 (95% CI: -0.52;-0.18) at 6 months with BIAsp 30 + GLP-1RA, versus -0.72 kg/m2 (95% CI: -0.90;-0.54) with basal+GLP-1RA (p = 0.003). BMI was influenced by the initiation sequence of GLP-1RA in relation to insulin (p < 0.0001). Hypoglycaemia rates were low and not significantly different between cohorts.Conclusions: Combining BIAsp 30 + GLP-1RA provides glycaemic control with no significant difference to that of propensity score-matched people receiving basal insulin+GLP-1RA, with no increase in hypoglycaemia risk or weight gain.
Insulin degludec (degludec) has proven benefits in type 2 diabetes (T2D), in terms of improved glycaemic control, low risk of hypoglycaemia, and flexibility in dosing time. This prospective non-interventional UPDATES study aimed to investigate whether results obtained from randomised clinical trials and other real-world studies with degludec are generalisable to patients with T2D in routine clinical practice in Saudi Arabia. Eligible adults (n = 561) with T2D received degludec for 26–34 weeks, at physicians’ discretion and in accordance with local routine clinical practice. The primary endpoint was mean change in HbA1c from baseline to end of study (EOS). Secondary endpoints included mean change from baseline to EOS in fasting plasma glucose (FPG), daily insulin dose and rate of hypoglycaemia. At baseline, mean age, HbA1c and FPG were 55.7 years, 9.4
Consumer purchase data (CPD) can be a powerful tool in the investigation of foodborne outbreaks through analyses of electronic records of food that individuals buy. The objective of this study was to develop a common framework for use of CPD in foodborne outbreak investigations using the expertise of European public health professionals from 11 European countries. We also aimed to describe barriers and limitations preventing CPD utilization. CPD are mainly gathered from supermarket loyalty programmes, smaller consortia, and independent supermarkets. Privacy legislation governing CPD was perceived as the most crucial barrier for CPD usage, but still resolvable. The main practical challenges were obtaining consumer consent for CPD usage, the associated workload, data access, format, and analysis. Harmonising methods and reporting across countries, standardised consent forms and electronic consent methods were identified as solutions. This guideline was developed to support outbreak investigators in overcoming barriers in using CPD, thereby increasing public health professionals' application and value of this powerful investigation tool. In addition, we hope this framework will lead to more public health institutions, in collaboration with food safety authorities, making use of CPD in outbreak investigations in the future.
The cestode Taenia solium is responsible for a considerable cross-sectoral health and economic burden due to human neurocysticercosis and porcine cysticercosis.The 2012 World Health Organization (WHO) roadmap for neglected tropical diseases called for the development of a validated strategy for control of T. solium; however, such a strategy is not yet available.In 2019, WHO launched a global consultation aimed at refining the post-2020 targets for control of T. solium for a new roadmap for neglected tropical diseases.In response, two groups working on taeniasis and cysticercosis mathematical models (cystiSim and EPICYST models), together with a range of other stakeholders organized a workshop to provide technical input to the WHO consultation and develop a research plan to support efforts to achieve the post-2020 targets.The workshop led to the formation of a collaboration, CystiTeam, which aims to tackle the population biology, transmission dynamics, epidemiology and control of T. solium through mathematical modelling approaches.In this paper, we outline developments in T. solium control and in particular the use of modelling to help achieve post-2020 targets for control of T. solium.We discuss the steps involved in improving confidence in the predictive capacities of existing mathematical and computational models on T. solium transmission, including model comparison, refinement, calibration and validation.Expanding the CystiTeam partnership to other research groups and stakeholders, particularly those operating in different geographical and endemic areas, will enhance the prospects of improving the applicability of T. solium transmission models to inform taeniasis and cysticercosis control strategies.
Objectives: The aim of this study was to make a comprehensive economic assessment of the costs of hospital-acquired C. difficile infections (CDI). Methods: We carried out a retrospective matched cohort study utilizing Danish registry data with national coverage to identify CDI cases and matched reference patients without CDI (controls) for economic burden assessment in Denmark covering 2011–2014. Health care costs and public transfer costs were obtained from national registries, and calculated for 1 year prior to, and 2 years after index admission using descriptive statistics and regression analysis. Results: The study included 12,768 CDI patients and 23,272 matched controls. The total health care cost was significantly larger for CDI cases than controls throughout all periods. During the index admission period, cost was €12,867 per CDI case compared to €4,522 (p < 0.001) for controls, which increased to an average of €31,388 and €19,512 (p < 0.001) in Year 1 for the two groups, respectively. Excess costs were found both among infections with onset in hospitals and in the community. Diagnosis compatible with complications increased costs to on average >€91,000 per case. The regression analysis showed that CDI adds a substantial economic burden, but only explains about 1/3 of the crude difference observed in the matched analysis. Discussion: The major economic impact of hospital-acquired CDI with complications underlines the importance of preventing complications in these patients. Our study provides an informed estimate of the potential economic gain per patient by successful intervention, which is likely to be relatively comparable across countries.
A field trial was conducted in Tanzania to determine the effectiveness of TSOL18 vaccine used concurrently with oxfendazole (OFZ), and of OFZ alone, on T. solium cysticercosis determined by organ and half carcase dissection of slaughter age pigs. This study followed a quasi-experimental group design. Suitable trial sites were randomly allocated to either treatment group T1 (OFZ treatment alone [30mg/kg, Paranthic 10%]) or T2 (TSOL18 [1ml, Cysvax] plus OFZ). Three 4-monthly treatments were administered to eligible pigs. A random selection of pigs were necropsied at baseline and at endline, 2-3.5 months after the final treatment. Additionally, untreated pigs from T1 and T2 areas were necropsied at endline to provide contemporaneous comparisons with T1 and T2 pigs. Baseline prevalence of viable T. solium cysticerci for T1 was 25.5% (Exact 95% CI: 13.9, 40.3; n = 12/47), and for T2 was 12.0% (CI: 6.4, 20.0; n = 12/100). At endline, prevalence was 2.8% for T1 (CI: 0.1, 14.5, n = 1/36) and 0% for T2 (CI: 0, 4.7, n = 0/77). Among untreated pigs, three had viable cysticerci, one from T1 area (12.5%, CI: 0.3, 52.7; n = 1/8) and two from T2 area (5.7%, CI: 0.7, 19.2, n = 2/35). Fisher's exact test showed significant changes in prevalence from baseline to endline in both groups (T1: p = 0.005, T2: p = 0.001). Firth's penalized Maximum Likelihood method suggested the changes were not significant relative to their controls (T1: p = 0.245, T2: p = 0.076). These findings showed a significant reduction in the prevalence of viable cysticerci from baseline to endline after both interventions. However, the changes could not be definitively attributed to the interventions due, in part, to small numbers of control pigs. Concurrent administration of the TSOL18 and OFZ cleared infection among assessed pigs whereas infection remained after treatment with OFZ only. Further studies including larger sample sizes would be required for more definitive conclusions. A One Health approach is recommended for rapid and sustainable impact.
Background The cestode Taenia solium causes the neglected (zoonotic) tropical disease cysticercosis, a leading cause of preventable epilepsy in endemic low and middle-income countries. Transmission models can inform current scaling-up of control efforts by helping to identify, validate and optimise control and elimination strategies as proposed by the World Health Organization (WHO). Methodology/Principal findings A systematic literature search was conducted using the PRISMA approach to identify and compare existing T. solium transmission models, and related Taeniidae infection transmission models. In total, 28 modelling papers were identified, of which four modelled T. solium exclusively. Different modelling approaches for T. solium included deterministic, Reed-Frost, individual-based, decision-tree, and conceptual frameworks. Simulated interventions across models agreed on the importance of coverage for impactful effectiveness to be achieved. Other Taeniidae infection transmission models comprised force-of-infection (FoI), population-based (mainly Echinococcus granulosus) and individual-based (mainly E. multilocularis) modelling approaches. Spatial structure has also been incorporated (E. multilocularis and Taenia ovis) in recognition of spatial aggregation of parasite eggs in the environment and movement of wild animal host populations. Conclusions/Significance Gaps identified from examining the wider Taeniidae family models highlighted the potential role of FoI modelling to inform model parameterisation, as well as the need for spatial modelling and suitable structuring of interventions as key areas for future T. solium model development. We conclude that working with field partners to address data gaps and conducting cross-model validation with baseline and longitudinal data will be critical to building consensus-led and epidemiological setting-appropriate intervention strategies to help fulfil the WHO targets.
Background Taenia solium taeniosis/cysticercosis is a public health and agricultural problem, especially in low-income countries, and has been ranked the top foodborne parasitic hazard globally. In 2012, the World Health Organization published a roadmap that called for a validated strategy for T. solium control and elimination by 2015. This goal has not been met, and validated evidence of effective control or elimination in endemic countries is still incomplete. Measuring and evaluating success of control programmes remains difficult, as locally acceptable targets have not been defined as part of the 2012 roadmap nor from other sources, and the performance of tools to measure effect are limited. Discussion We believe that an international agreement supported by the tripartite World Health Organization, Food and Agriculture Organization of the United Nations, and World Organisation for Animal Health is needed to facilitate endemic countries in publicising SMART (Specific, Measurable, Achievable/attainable, Relevant, Time-bound) country-level control target goals. These goals should be achievable through locally acceptable adoption of options from within a standardised ‘intervention tool-kit’, and progress towards these goals should be monitored using standardised and consistent diagnostics. Several intervention tools are available which can contribute to control of T. solium , but the combination of these - the most effective control algorithm - still needs to be identified. In order to mount control efforts and ensure political commitment, stakeholder engagement and funding, we argue that a stepwise approach, as developed for Rabies control, is necessary if control efforts are to be successful and sustainable. Conclusions The stepwise approach can provide the framework for the development of realistic control goals of endemic areas, the implementation of intervention algorithms, and the standardised monitoring of the evaluation of the progress towards obtaining the control target goals and eventually elimination.
BackgroundTaenia solium is a zoonotic tapeworm widely distributed across sub-Saharan Africa. Specific health education is regarded as a central element in controlling T. solium. In 2014, an electronic health education tool called ‘The Vicious Worm’, which was concerned with prevention of T. solium was introduced to health and agricultural professionals in Mbeya, Tanzania, an endemic setting.Introduction to ´The Vicious Worm’ of 1.5 hours significantly improved the participants’ knowledge. This study revisited the same study subjects one year later to assess persistence of knowledge regarding T. solium taeniosis/cysticercosis and to assess if the health education had changed work practices for the participants and the public.MethodsThe study was conducted in Tanzania between June and August 2015, with a fixed population of health and agricultural professionals recruited from a previous study testing ‘The Vicious Worm’. The study used a test, a questionnaire survey, as well as semi-structured group and individual interviews.ResultsThe 79 study subjects, all health or agricultural professionals, had within one year relocated from Mbeya to 16 of 21 administrative regions of Tanzania. Sixty-four agreed to participate in the test and 48 to an interview. The test showed significant improvement in knowledge regarding T. solium taeniosis/cysticercosis, compared with the baseline knowledge level of the participants. Interview data found that the participants had used ‘The Vicious Worm’ as an educational tool and applied the knowledge from the program to implement new practices consisting of by-laws and practical workshops on building latrines, pig pens and hand washing stations in their communities.ConclusionIntroduction to ‘The Vicious Worm’ led to changed practices and persistence in knowledge regarding T. solium. Incorporating health education as a specific health intervention tool should be encouraged and implemented at national or programmatic level.