Lifetime Of Patient Research Articles

Epidemiology of basal and cutaneous squamous cell carcinoma in the U.K. 2013-15: a cohort study.

SummaryBackgroundBasal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), together known as keratinocyte cancers (KCs), are the commonest cancer in white ethnic populations. Recent improvements to registry data collection in England has allowed more accurate analysis of the epidemiology of BCC and cSCC and for the first time we are able to provide an accurate (representative) tumour burden for KC in the U.K.ObjectivesTo estimate the incidence of BCC and cSCC in the U.K.MethodsA cohort of patients with KCs between 2013 and 2015 were identified using linkage to diagnostic codes derived from pathology reports collected into the national cancer registry. Data from England's cancer registry were combined with data from Scotland, Northern Ireland and Wales. European age‐standardized incidence rates (EASRs) of the first BCC and cSCC per patient per annum (PPPA) were calculated.ResultsIn the U.K, the EASR of the first BCC and cSCC PPPA in 2013–15 were 285 and 77 per 100 000 person years, respectively (211 120 KCs total in 2015). The mean annual percentage increase was 5% between 2013 and 2015 for both BCC and cSCC. By counting the first KC PPPA, we include an additional 51% KCs compared with the previous reporting technique which counts only the first BCC and cSCC in a patient's lifetime, yet it represents a probable underestimation of 5–11% of the true tumour count.ConclusionsBased on an improved methodology, a more representative incidence of KC is presented, which is essential to healthcare planning and will lead to improved understanding of the epidemiology of KC. What's already known about this topic? Keratinocyte cancers (KCs) are the most common cancers affecting white ethnic populations.The incidence of basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) is increasing worldwide including the U.K., most commonly in elderly male Caucasian patients.These cancers are traditionally substantially underreported and frequently excluded from national cancer statistics. What does this study add? Using improved data collection methods in England and validated tumour‐reporting techniques, we report the most accurate BCC and cSCC incidence data for the U.K. ever published.Identifying the first BCC and cSCC per patient per annum, the incidence of BCC and cSCC in the U.K. (excluding Wales) was 285 and 77 per 100 000 person years, respectively, between 2013 and 2015, with more than 210 000 KCs in the U.K. in 2015.

Invasive Fungal Infection.

The incidence of invasive fungal infection is approximately 6 cases per 100 000 persons per year. It is estimated that only half of such infections are detected during the patient's lifetime, making this one of the more common overlooked causes of death in intensive-care patients. The low detection rate is due in part to the complexity of the diagnostic work-up, in which the clinical, radiological, and microbiological findings must be considered. Fungi with resistance to antimycotic drugs have been found to be on the rise around the world. This review is based on pertinent publications retrieved from a selective search in PubMed, with special attention to guidelines on the diagnosis and treatment of invasive fungal infections caused by Candida spp., Aspergillus spp., Mucorales, and Fusarium spp. The clinical risk factors for invasive fungal infection include, among others, congenital immune deficiency, protracted (>10 days) marked granulocytopenia (<0.5 x 109/L), allogeneic stem-cell transplantation, and treatment with immunosuppressive drugs or corticosteroids. High-risk groups include patients in intensive care and those with structural pulmonary disease and/or compli- cated influenza. The first line of treatment, supported by the findings of randomized clinical trials, consists of echinocandins for in- fections with Candida spp. (candidemia response rates: 75.6% for anidulafungin vs. 60.2% for fluconazole) and azole antimycotic drugs for infections with Aspergillus spp. (response rates: 52.8% for voriconazole vs. 31.6% for conventional amphotericin B). The recommended first-line treatment also depends on the local epidemiology. This challenge should be met by interdisciplinary collaboration. Therapeutic decision-making should also take account of the often severe undesired effects of antimycotic drugs (including impairment of hepatic and/or renal function) and the numerous interactions that some of them have with other drugs. Invasive fungal infections are often overlooked in routine hospital care. They should be incorporated into antimicro- bial stewardship programs as an essential component. There is also a pressing need for the development of new classes of antimycotic drug.

Current Challenges and Emergent Technologies for Manufacturing Artificial Right Ventricle to Pulmonary Artery (RV-PA) Cardiac Conduits.

Despite advances in modern surgery, congenital heart disease remains a medical challenge and major cause of infant mortality. Valved conduits are routinely used to surgically correct blood flow in hearts with congenital malformations by connecting the right ventricle to the pulmonary artery (RV-PA). This review explores the current range of RV-PA conduits and describes their strengths and disadvantages. Homografts and xenografts are currently the primary treatment modalities, however both graft types have limited biocompatibility and durability, and present a disease transmission risk. Structural deterioration of a replaced valve can lead to pulmonary valve stenosis and/or regurgitation. Moreover, as current RV-PA conduits are of a fixed size, multiple subsequent operations are required to upsize a valved conduit over a patient's lifetime. We assess emerging biomaterials and tissue engineering techniques with a view to replicating the features of native tissues, including matching the durability and elasticity required for normal fluid flow dynamics. The benefits and limitations of incorporating cellular elements within the biomaterial are also discussed. Present review demonstrates that an alignment of medical and engineering disciplines will be ultimately required to produce a biocompatible and high-functioning artificial conduit.

Cost-effectiveness of early cancer surveillance for patients with Li-Fraumeni syndrome.

Patients with germline TP53 pathogenic variants (Li-Fraumeni syndrome [LFS]) are at extremely high lifetime risk of developing cancer. Recent data suggest that tumor surveillance for patients with LFS may improve survival through early cancer detection. The objective of this study was to assess the cost-effectiveness of a cancer surveillance strategy for patients with LFS compared with those whose tumors present clinically. A Markov decision analytic model was developed from a third-party payer perspective to estimate cost-effectiveness of routine cancer surveillance over a patient's lifetime. The model consisted of four possible health states: no cancer, cancer, post-cancer survivorship, and death. Model outcomes were costs (2015 United States Dollars [USD]), effectiveness (life years [LY] gained), and incremental cost-effectiveness ratio (ICER; change in cost/LY gained). One-way sensitivity analyses and probabilistic sensitivity analyses examined parameter uncertainty. The model showed a mean cost of $46496 and $117102 and yielded 23 and 27 LY for the nonsurveillance and surveillance strategies, respectively. The ICER for early cancer surveillance versus no surveillance was $17125 per additional LY gained. At the commonly accepted willingness to pay threshold of $100000/life-year gained, surveillance had a 98% probability of being the most cost-effective strategy for early cancer detection in this high-risk population. Presymptomatic cancer surveillance is cost-effective for patients with germline pathogenic variants in TP53. Lack of insurance coverage or reimbursement in this population may have significant consequences and leads to undetected cancers presenting in later stages of disease with worse clinical outcomes.

Assessment of Disease Progression in Patients with Repaired Tetralogy of Fallot Using Cardiac Magnetic Resonance Imaging

Background: Tetralogy of Fallot (ToF) is the commonest cyanotic congenital heart disease with a long term survival of over 85%, making adult survivors an ever growing population. Late pulmonary outflow tract and pulmonary valve post-operative complications are frequent, leading to risk of right ventricular (RV) failure and arrhythmias related sudden death. Timing of pulmonary valve intervention remains challenging, with early intervention being balanced against the risk with the number of interventions over a patient's life time. Imaging frequency for correct timing of intervention is unclear, largely based around estimation of rate of RV dilatation. Aim: To perform a systematic review of the use of cardiac magnetic resonance imaging (CMR) to predict disease progression (RV dilatation, dysfunction, or adverse clinical event) in patients with repaired tetralogy of Fallot (rToF), and use the information to determine the optimal interval for follow-up CMR. Methods: PubMed searched from inception until 30th April 2018 for relevant articles. Results: 25 studies identified. Right and left ventricular volumes and function have proven significance in predicting timing for intervention. Severity of pulmonary valve regurgitation has also been shown to predict progression of RV dilatation, with pulmonary valve regurgitant volume appearing more predictive than regurgitant fraction. Optimal frequency of clinical and imaging review in adult patients with rToF remains uncertain. Conclusion: The optimal timing of repeat cardiac imaging in rToF remains controversial, with a three year schedule for repeat CMR appearing reasonable in asymptomatic patients. Large prospective studies will provide important information to guide clinical decision in this area.

Economic assessment of dexrazoxane in prophylaxis of cardiotoxicity in children undergoing chemotherapy with anthracyclines

Cancer in individuals 0 to 19 years of age is considered rare when compared to incidence in older age brackets, and is estimated at 2% to 3% of all malignant tumors recorded in Brazil. The use of anthracyclines is frequently associated with cardiotoxicity, and these drugs are part of approximately 60% of treatment protocols in pediatric oncology. Among the existing strategies for the prevention of cardiotoxicity, dexrazoxane obtained favorable results based on intermediate outcomes (biochemical markers and echocardiographic parameters). This study was based on a cost-effectiveness assessment comparing the use of dexrazoxane in different populations, besides an assessment of the budget impact from the technology's potential incorporation. The patient's lifetime was used as the timeline, and the analysis was performed from the perspective of the Brazilian Unified National Health System (SUS). A budget impact analysis was also performed for each technology. After a literature search, a Markov model was developed, capable of comparing the use of dexrazoxane in six profiles of patients at risk of developing cardiotoxicity. Use of the drug in children under 5 years of age proved to be the most cost-effective alternative (incremental cost effectiveness ratio - ICER of BRL 6,156.96), followed by use in all patients (ICER of BRL 58,968.70). If the price decreased to less than BRL 250.00 per vial, the alternative of using the drug in all children would become the most cost-effective. The budget impact at 5 years was BRL 30,622,404.81 for use only in children under 5 years of age. Using the technology in all the children could produce an incremental impact of BRL 94,352,898.77.

The Cost-Effectiveness of Bimodal Stimulation Compared to Unilateral and Bilateral Cochlear Implant Use in Adults with Bilateral Severe to Profound Deafness.

An increasing number of severe-profoundly deaf adult unilateral cochlear implant (CI) users receive bimodal stimulation; that is, they use a conventional acoustic hearing aid (HA) in their nonimplanted ear. The combination of electric and contralateral acoustic hearing provides additional benefits to hearing and also to general health-related quality of life compared with unilateral CI use. Bilateral CI is a treatment alternative to both unilateral CI and bimodal stimulation in some healthcare systems. The objective of this study was to conduct an economic evaluation of bimodal stimulation compared with other management options for adults with bilateral severe to profound deafness. The economic evaluation took the form of a cost-utility analysis and compared bimodal stimulation (CI+HA) to two treatment alternatives: unilateral and bilateral CI. The analysis used a public healthcare system perspective based on data from the United Kingdom and the United States. Costs and health benefits were identified for both alternatives and estimated across a patient's lifetime using Markov state transition models. Utilities were based on Health Utilities Index estimates, and health outcomes were expressed in Quality Adjusted Life Years (QALYs). The results were presented using the Incremental Cost-Effectiveness Ratio and the Net Monetary Benefit approach to determine the cost-effectiveness of bimodal stimulation. Probabilistic sensitivity analyses explored the degree of overall uncertainty using Monte Carlo simulation. Deterministic sensitivity analyses and analysis of covariance identified parameters to which the model was most sensitive; that is, whose values had a strong influence on the intervention that was determined to be most cost-effective. A value of information analysis was performed to determine the potential value to be gained from additional research on bimodal stimulation. The base case model showed that bimodal stimulation was the most cost-effective treatment option with a decision certainty of 72 and 67% in the United Kingdom and United States, respectively. Despite producing more QALYs than either unilateral CI or bimodal stimulation, bilateral CI was found not to be cost-effective because it was associated with excessive costs. Compared with unilateral CI, the increased costs of bimodal stimulation were outweighed by the gain in quality of life. Bimodal stimulation was found to cost an extra £174 per person in the United Kingdom ($937 in the US) and yielded an additional 0.114 QALYs compared with unilateral CI, resulting in an Incremental Cost-Effectiveness Ratio of £1521 per QALY gained in the United Kingdom ($8192/QALY in the United States). The most influential variable was the utility gained from the simultaneous use of both devices (CI+HA) compared with Unilateral CI. The value of further research was £4,383,922 at £20,000/QALY ($86,955,460 at $50,000/QALY in the United States). This study provides evidence of the most cost-effective treatment alternative for adults with bilateral severe to profound deafness from publicly funded healthcare perspectives of the United Kingdom and United States. Bimodal stimulation was found to be more cost-effective than unilateral and bilateral CI across a wide range of willingness-to-pay thresholds. If there is scope for future research, conducting interventional designs to obtain utilities for bimodal stimulation compared with unilateral CI would reduce decision uncertainty considerably.

Clinical and economic outcomes associated with treatment sequences in patients with BRAF-mutant advanced melanoma.

The cost-effectiveness of treatment sequences in BRAF-mutant advanced melanoma. A discrete event simulation model was developed to estimate total costs and health outcomes over a patient's lifetime (30 years). Efficacy was based on the CheckMate 067/069 trials and a matching-adjusted-indirect comparison between immuno-oncology and targeted therapies. Safety, cost (in US dollars; US third-party payer perspective) and health-related quality-of-life inputs were based on published literature. Estimated survival gain was higher for sequences initiating with anti-PD-1 + anti-CTLA-4 than for anti-PD-1 monotherapy or BRAF+MEK inhibitors. The incremental cost-effectiveness ratio per QALY gained for first-line anti-PD-1 + anti-CTLA-4 was US$54,273 versus first-line anti-PD-1 and $79,124 versus first-line BRAF+MEK inhibitors. Initiating treatment with anti-PD-1 + anti-CTLA-4 was more cost-effective than initiation with anti-PD-1 monotherapy or BRAF+MEK inhibitors.

Haab striae: Optical coherence tomographic analysis

To study Haab striae in adults with primary congenital glaucoma and describe them by anterior segment optical coherence tomography, as well as analyze their evolution over the patient's lifetime. Three patients with primary congenital glaucoma were recruited, aged between 17 and 48 years old, with incidentally noted Haab striae on glaucoma consultation. They were studied by: slit lamp; anterior segment optical coherence tomography, Heidelberg Engineering Inc., Germany, (with anterior segment module) and Cirrus HD-OCT, Carl Zeiss Meditec, Dublin, California, USA (with 3D reconstruction); and specular biomicroscopy. The results obtained were contrasted with other studies performed in children. Rounded excrescences protruding towards the anterior chamber were found, as well as dense, irregular tissue between them. In addition, endothelial abnormalities (polymegathism and polymorphism) were found. These findings fit the evolution of those obtained in pediatric studies and remain stable in adult life. Through noninvasive methods such as optical coherence tomography and specular biomicroscopy, it is possible to make the diagnosis and follow up these patients. The findings suggest posterior corneal topographic changes; additional studies on this subject may be necessary.

Biologically guided implant therapy: A diagnostic and therapeutic strategy of conservation and preservation based on periodontal staging and grading.

Biologically guided implant therapy is based on the new periodontitis classification system recently released by the American Academy of Periodontology and the European Federation of Periodontology that uses staging and grading for the diagnosis of periodontitis. This paper proposes that periodontitis staging and grading should be used in dental implant therapy as a means to ensure maximum conservation of teeth and maximum preservation of alveolar bone. These biologic principles should guide the treatment planning process and supersede a mechanically based, restoratively driven rationale that should be secondary to the biologic principles of conservation and preservation but part of the collaborative treatment planning process. And treatment alternatives throughout the patient's lifetime should be provided for in case of prosthesis loss due to peri-implantitis. The use of grading will help with recognition of systemic aspects that can have a negative impact.

Percutaneous tricuspid valve implantation in failing bioprosthesis.

Severe tricuspid valve (TV) dysfunction in patients with congenital heart disease (CHD) is usually treated by open heart surgery in relatively young patients. If a valve plasty is not possible, a biological valve is implanted with a limited durability. Due to valve degeneration repeated valve exchanges are necessary in these patients. To expand the lifetime of a bioprosthesis in tricuspid position percutaneous TV implantation (PTVI) was introduced recently. PTVI is a promising new catheter interventional technology. The current review summarizes the indication for PTVI, describes the procedure itself and gives an outlook on medium to long-term results of this catheter intervention. PTVI in patients with severe TV dysfunction is less invasive, safe and effective, if performed by an experienced operator, and may help to reduce the total number of open-heart surgeries during a patient's life time. However, further studies with larger patient numbers and longer follow-up are needed.

A Muscle Synergy-Inspired Control Design to Coordinate Functional Electrical Stimulation and a Powered Exoskeleton: Artificial Generation of Synergies to Reduce Input Dimensionality

Mobility disorders caused by spinal cord injury (SCI), stroke, or progressive neurological diseases such as multiple sclerosis and amyotrophic lateral sclerosis, lead to a deterioration in quality of life. Resulting sequelae, such as pressure ulcers, depression, and urinary infections, require constant medical care throughout a patient's lifetime. Evidence has shown that, following an injury or a disease, individuals who use rehabilitative interventions to restore walking and standing functions experience fewer secondary medical complications than do wheelchair users [1]. Two such rehabilitative interventions include functional electrical stimulation (FES) and powered exoskeletons. These technologies have the potential to mitigate secondary health complications, lower medical expenses, and achieve independent ambulation in individuals following an SCI.

“in the Patients' Hands”- a Structured Survey of Patient Voices to Prioritise Research Questions in Rare Inherited Anaemias: The James Lind Alliance Priority Setting Partnership

Patients with rare inherited anaemias (RIAs) may take years to receive a precise diagnosis. Lack of equitable access to the few centres of specialist expertise means not all patients will receive the same standard of care. Few treatments have been developed, in part from lack of research. The research agenda is traditionally set by scientists, the medical profession, funding bodies and pharmaceutical companies. The voice of patients and carers is rarely considered in deciding which questions will be addressed in studies. Involving patients in setting the research agenda is likely to improve the validity and quality of research, but the practicalities of surveying patient voices objectively are not straightforward. Using a well-established, structured format for collecting patient-driven priorities, we carried out a James Lind Alliance (JLA) Priority Setting Partnership (PSP) in RIA. This has been used internationally to produce patient-driven research priorities in >60 disorders, eg blood transfusion and donation.The aim of the study was to determine what people with RIAs, their carers and health professionals believe to be the most important areas for future research using a 3-step sequential survey approach. The steering group (SG) comprised adult and paediatric haematologists, nurses, patients, representatives from patient organisations, and a JLA facilitator, reflecting representation from medical and lay stakeholders. The SG chose to focus this piece of work on disorders which are individually rare or very rare to provide the first ever opportunity for a collective voice: Diamond-Blackfan Anaemia, Congenital Dyserythropoietic Anaemia, Congenital Sideroblastic Anaemia, red cell membrane and enzyme disorders, and transfusion-dependent unexplained RIAs. The SG devised the first survey (PSP Survey 1) comprising open questions to address the diagnosis, treatment, and management of these conditions. Survey 1 was distributed UK-wide to adult and paediatric haematologists, patient organisations and support groups and on social media. The British Society of Haematology distributed to all members. Haematologists were invited to send the survey to their patients.88 people responded to PSP Survey 1, listing questions they would most like answered. Of these, 23% were patients, 27% relatives/friends, 44% health/social care professionals, 6% other. A total of 314 valid questions were submitted, then filtered by grouping similar/overlapping questions, removing those answered in the literature, leaving 48 unanswered questions to be taken forward in PSP Survey 2. 120 respondents ranked each question on a Likert scale, indicating the degree of personal importance. Individual scores were totalled to provide a shortlist of 25 questions for Stage 3, a one-day multidisciplinary workshop with 30 people representing the breadth of stakeholders recruited via patient and clinician groups and through social media. The Stage 3 PSP workshop identified the ‘Top 10‘ questions by crossover multidisciplinary mini-working groups reaching a consensus using shared understanding between patients and professionals:Would a national formal network of clinicians with expertise and /or a national multidisciplinary team meeting improve care for patients with (RIA)?Can the diagnostic pathways be improved to provide faster and more accurate diagnoses in a cost effective manner?Could an understanding of the cellular and molecular processes in red blood cell production lead to new treatments?Could the need for iron chelation be reduced? Could current approaches and monitoring be improved?How do existing drugs for RIA work? Could this understanding lead to new treatments and new ways of delivering treatments?How can the fatigue of severe anaemia be managed (apart from blood transfusions)?Would a register of all RIA patients in the UK (including data and samples) improve care?How is quality of life affected by RIA and its treatment? How could this be improved for patients?What factors indicate that a person with a RIA needs a transfusion, and what is the best regime to maintain safety and quality of life?How can high quality care be sustained throughout a patient's lifetime (e.g. from child to adult and into old age)?Engagement by funding bodies to prioritise funding for projects addressing these patient-selected priorities is now key to ensure the success of this initiative. DisclosuresNo relevant conflicts of interest to declare.

Bipolar Disorders: Antipsychotic Drug Therapy of Aripiprazole an Open Label Study

Patients with bipolar disorder are exceptionally challenging to manage because of the dynamic, chronic, and fluctuating nature of their disease. Typically, the symptoms of bipolar disorder first appear in adolescence or early adulthood, and are repeated over the patient's lifetime, expressed as unpredictable recurrences of hypomanic/manic or depressive episodes. The lifetime prevalence of bipolar disorder in adults is reported to be approximately 4%, and its management was estimated to cost the US healthcare system in 2009 $150 billion in combined direct and indirect costs.

Sequential treatment approaches in the management of BRAF wild-type advanced melanoma: a cost-effectiveness analysis.

To evaluate the cost-effectiveness of treatment sequences with checkpoint inhibitors in patients with BRAF wild-type melanoma. Using a discrete event simulation model, cost and health outcomes were estimated. Pooled data from CheckMate 067/069 trials were used to calculate survival outcomes including treatment-free interval extrapolated over a patient's lifetime. Costs accounted for treatment, administration, toxicity, and disease management. First-line anti-PD-1+ anti-CTLA-4 initiating sequences had the highest estimated mean survival gain (7.6-7.7 years), driven by a longer estimated mean treatment-free interval (5.3 years). Incremental costs per incremental quality-adjusted life year gained for anti-PD-1 + anti-CTLA-4 followed by chemotherapy were US$30,955 versus anti-PD-1 initiating sequences, within the willingness-to-pay threshold. Anti-PD-1+ anti-CTLA-4 initiating sequences for BRAF wild-type melanoma are cost-effective versus anti-PD-1.

Association Between Race and Ethnicity and Hip Fracture Outcomes in a Universally Insured Population.

Prior studies have documented racial and ethnic disparities in hip fracture treatment and outcome, and unequal access is commonly cited as a potential mediator. We sought to assess whether disparities in hip fracture outcome persist within a universally insured population of patients enrolled in a managed health-care system. A U.S. integrated health systems registry was used to identify patients who underwent treatment for a hip fracture when they were ≥60 years of age from 2009 to 2014. Patient demographics, procedure details, and outcomes were obtained from the registry. Differences in outcome according to race/ethnicity were analyzed using multivariable regression analysis with adjustment for socioeconomic status and other potential confounders. Of 17,790 patients, 79.4% were white, 3.9% were black, 9.4% were Hispanic, and 7.4% were Asian. Compared with white patients, black patients had a similar 1-year mortality rate (odds ratio [OR] = 0.93, 95% confidence interval [CI] = 0.79 to 1.09, p = 0.37), Hispanic patients had a lower rate (OR = 0.85, 95% = CI = 0.75 to 0.96, p = 0.01), and Asian patients also had a lower rate (OR = 0.65, 95% CI = 0.56 to 0.76, p < 0.001). There were no differences in terms of surgical delay, 90-day emergency department visits, or reoperations during the patient's lifetime (p > 0.05) between the groups. Compared with white patients, black and Hispanic patients had fewer 90-day postoperative complications (p = 0.04 and p = 0.01, respectively); 90-day unplanned readmissions were less common among Asian patients (p = 0.03) but more common among black patients (p = 0.01). In this study of hip fractures treated in an integrated managed care system, minority patients were found to have postoperative mortality rates that were similar to, or lower than, those of white patients. These findings may be related to the equal access and/or standardized protocols associated with treatment in this managed care system. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Cost-effectiveness of a quality improvement bundle for emergency laparotomy.

BackgroundThe recent Emergency Laparotomy Pathway Quality Improvement Care (ELPQuiC) study showed that the use of a specific care bundle reduced mortality in patients undergoing emergency laparotomy. However, the costs of implementation of the ELPQuiC bundle remain unknown. The aim of this study was to assess the in‐hospital and societal costs of implementing the ELPQuiC bundle.MethodsThe ELPQuiC study employed a before–after approach using quality improvement methodology. To assess the costs and cost‐effectiveness of the bundle, two models were constructed: a short‐term model to assess in‐hospital costs and a long‐term model (societal decision tree) to evaluate the patient's lifetime costs (in euros).ResultsUsing health economic modelling and data collected from the ELPQuiC study, estimated costs for initial implementation of the ELPQuiC bundle were €30 026·11 (range 1794·64–40 784·06) per hospital. In‐hospital costs per patient were estimated at €14 817·24 for standard (non‐care bundle) treatment versus €15 971·24 for the ELPQuiC bundle treatment. Taking a societal perspective, lifetime costs of the patient in the standard group were €23 058·87, compared with €19 102·37 for patients receiving the ELPQuiC bundle. The increased life expectancy of 4 months for patients treated with the ELPQuiC bundle was associated with cost savings of €11 410·38 per quality‐adjusted life‐year saved.ConclusionImplementation of the ELPQuiC bundle is associated with lower mortality and higher in‐hospital costs but reduced societal costs.

Abnormalities in Skeletal Muscle Myogenesis, Growth, and Regeneration in Myotonic Dystrophy.

Myotonic dystrophy type 1 (DM1) and 2 (DM2) are autosomal dominant degenerative neuromuscular disorders characterized by progressive skeletal muscle weakness, atrophy, and myotonia with progeroid features. Although both DM1 and DM2 are characterized by skeletal muscle dysfunction and also share other clinical features, the diseases differ in the muscle groups that are affected. In DM1, distal muscles are mainly affected, whereas in DM2 problems are mostly found in proximal muscles. In addition, manifestation in DM1 is generally more severe, with possible congenital or childhood-onset of disease and prominent CNS involvement. DM1 and DM2 are caused by expansion of (CTG•CAG)n and (CCTG•CAGG)n repeats in the 3′ non-coding region of DMPK and in intron 1 of CNBP, respectively, and in overlapping antisense genes. This critical review will focus on the pleiotropic problems that occur during development, growth, regeneration, and aging of skeletal muscle in patients who inherited these expansions. The current best-accepted idea is that most muscle symptoms can be explained by pathomechanistic effects of repeat expansion on RNA-mediated pathways. However, aberrations in DNA replication and transcription of the DM loci or in protein translation and proteome homeostasis could also affect the control of proliferation and differentiation of muscle progenitor cells or the maintenance and physiological integrity of muscle fibers during a patient’s lifetime. Here, we will discuss these molecular and cellular processes and summarize current knowledge about the role of embryonic and adult muscle-resident stem cells in growth, homeostasis, regeneration, and premature aging of healthy and diseased muscle tissue. Of particular interest is that also progenitor cells from extramuscular sources, such as pericytes and mesoangioblasts, can participate in myogenic differentiation. We will examine the potential of all these types of cells in the application of regenerative medicine for muscular dystrophies and evaluate new possibilities for their use in future therapy of DM.

Cost-Effectiveness of Self-Expandable Transcatheter Aortic Valves in Intermediate-Risk Patients

A recent clinical trial showed that self-expandable transcatheter aortic valve replacement (TAVR) was non-inferior to surgical aortic valve replacement (SAVR). However, the cost-effectiveness of self-expandable TAVR in the intermediate-risk population remains unknown. A cost-utility analysis from the Canadian health care system payer's perspective was undertaken to compare self-expandable TAVR with SAVR. A fully probabilistic Markov model over the patient's lifetime was constructed to estimate differences in costs (2016 Canadian dollars) and effectiveness (quality-adjusted life-years [QALYs]), discounted at 1.5% per annum. Incremental cost-effectiveness ratios (ICERs) were calculated. Efficacy inputs were obtained from the Surgical Replacement and Transcatheter Aortic Valve Implantation trial, and costs were primarily obtained from the Canadian Institute of Health Information. Probabilistic analysis (PA) and one-way deterministic sensitivity analyses were conducted around key point estimates to address uncertainty. In the base case analysis, with discounting, the total lifetime costs (mean ± standard deviation) in the TAVR and SAVR arms were $44,299 ± $7,260 and $32,994 ± $13,434, respectively, whereas total effectiveness values were 6.42 ± 1.33 QALYs and 6.28 ± 1.32 QALYs, respectively. This yielded an incremental cost of $11,305 and incremental effectiveness of 0.15 QALYs when TAVR was compared with SAVR for an ICER of $76,736/QALY. In the PA, there was moderate uncertainty, with 52.8% and 57.2% of simulations less than willingness-to-pay thresholds of $50,000 and $100,000, respectively. In the sensitivity analysis, when the cost of TAVR valve system was priced at $17,397 (base case $22,000 Canadian dollars), TAVR was found to be cost-effective at a willingness-to-pay threshold of $50,000/QALY. Self-expandable TAVR was found to be cost-effective; however, there was moderate uncertainty, reflecting the non-inferiority nature of the data.

Ventriculoperitoneal shunt complications: A review

Abstract Ventriculoperitoneal shunt (VPS) placement is one of the most commonly performed neurosurgical procedures and is necessary to treat most forms of hydrocephalus. Unfortunately, complications related to VPS placement are common, and multiple shunt revisions are almost expected throughout a patient's lifetime. Shunt malfunction may be attributed to multiple causes, including obstruction, infection, pseudocyst formation and bowel perforation. VPS obstruction, which is most often occurs in the proximal catheter, is the most common cause of VPS malfunction. Hardware infection is the second most common cause of VPS malfunction, and this is a complication is most often observed in infants, with premature infants being the most susceptible. Despite continuous attempts to reduce the incidence of VPS complications, such as improved sterile techniques, antibiotic impregnated catheters, and programmable valves, VPS malfunction remains a major problem, which often leads to multiple and costly hospital admissions. In the present review, the most common complications of VPS are discussed, including presentation and appropriate management.