Clinical Health States Research Articles

PCR143 European Quality of Life Five Dimension (EQ-5D) Utility Values for Clinical Health States in Fabry Disease (FD): Insights from Pegunigalsidase Alpha Clinical Trials

PCR143 European Quality of Life Five Dimension (EQ-5D) Utility Values for Clinical Health States in Fabry Disease (FD): Insights from Pegunigalsidase Alpha Clinical Trials

COMPARATIVE CLINICAL CHARACTERISTICS OF HEALTH STATUS IN CHILDREN RESIDING IN ENVIRONMENTALLY POLLUTED AREA EXPOSED TO CHEMICAL FACTORS

Introduction. Prolonged residence of children in polluted environments significantly impairs their health, primarily due to the presence of chemical reagents (sulphur compounds). These chemical reagents induce nonspecific, polysystemic syndromes that affect the gastrointestinal, urinary, and immune systems, thus warranting the formation of risk groups to facilitate individual assessment, prevention, and treatment. This study aims at investigating the health status of children residing in an area affected by environmental contamination from sulphur chemicals. Material and Methods. The study employed general clinical analyses, ultrasound scanning, and medical and statistical analysis to examine 88 children. The sample included 56 children residing in an environment that is highly polluted with sulphur compounds and 32 children in a control group living in a conditionally clean environment. The participants were assessed by medical specialists including paediatricians, gastroenterologists, nephrologists, neurologists, ophthalmologists, immunologists, pulmonologists and dentists. Objective medical examinations were conducted using instrumental methods, including ultrasound diagnostics of internal organs and the thyroid gland, as well as echocardiography and densitometry. The statistical processing of the findings obtained was carried out by using the "Statistica 5.0" application program package and the standard statistical analysis (Excel 2010). The reliability in the examined groups of children was calculated according to the Student's criterion and was considered significant at p<0.01.
 Results. Assessment of the clinical health status of 88 children was performed based on their primary medical records (form 112-o), complaints, medical history, diseases, age parameters, and laboratory indicators. The main group demonstrated statistically significant changes with a probability of p<0.01. Children aged 13 to 16 years were more prevalent in the first group (30.4% versus 15.6%) and experienced significantly higher complaint frequency (p<0.01) than the control group. This suggests non-specific manifestations of general intoxication and environmental maladaptation in children. Several detrimental factors were found to reduce the overall response of the children's bodies within the main group (р<0.01), which serve as a premorbid background. These factors include the frequency of ante- and postnatal conditions such as preeclampsia during the first and second half of pregnancy, early artificial feeding, frequent acute respiratory distress syndrome (ARDS) and atopic history of dermatitis. A spectrum of sickness was discovered during the analysis of the clinical health state of the main group with a probability of p<0.01. This includes chronic ailments of the gastroduodenal region (64.2% as opposed to 37.5%), biliary tract dyskinesia (32.1% - 18, 8%), dysmetabolic nephropathy (46.4% compared to 25.0%) and vegetative-vascular dystonia (46.4% and 15.6%). These findings indicate a decline in the body's immunological reactivity. Conclusions. The study reveals a significant decrease in the health status of children residing in an ecologically polluted environment with chemical sulfur compounds, compared to those dwelling in a clean environment (p<0.01). Chronic conditions affecting the gastroduodenal region, dysmetabolic nephropathy, vegetative-vascular dystonia, recurrent colds, chronic tonsillitis, and dental caries were detected in the main study group. These conditions significantly (p<0.01) imply the development of ecopathological syndromes, the creation of at-risk groups, and the need for preventive methods. Technical abbreviations will be explained when first used. Identified alterations in the clinical status of the assessed children with xenobiotic intoxication syndromes necessitate the establishment of at-risk groups, the pre-emptive avoidance and management of detected ecopathology.

PCR105 The Impact of Key Health State Transitions on Health-Related Quality of Life (HRQOL) in Duchenne Muscular Dystrophy (DMD): A Qualitative Study

The progression of DMD is characterized by loss of ambulation (LOA) and upper limb function, cardiorespiratory impairment, and early mortality. While much attention is focused on LOA, the impact of other aspects of progression on HRQoL is less clear. Understanding patient perspectives on these aspects is important to provide context to clinical health states in DMD, and link changes in DMD symptoms to patient experiences. The objective of this study was to obtain insights on how key health state transitions affect HRQoL among individuals with DMD.

A Markov Decision Process Framework for Optimal Cancer Chemotherapy Dose Selection

Chemotherapy is arguably the most effective treatment for treating cancer. However, it triggers toxic effects on patients due to its interaction with normal cells. In this paper, we propose a finite-horizon Markov decision process framework for optimal chemotherapy dose selection during cancer treatment. In contrast to many other research works, our model accommodates all possible patient’s clinical health states that could be considered during treatment. We study the use of our model by applying it on Wilms tumor. We explore three different cases of varying transition probabilities and rewards. Our numerical results agree with clinical intuition and demonstrate the potential applicability of our model.

The Use of Telemedicine in The Development of Professionalism in Areas of Obstetrics and Gynecology in Indonesia

The utilization of medical information sent from one site to another via electronic communications to improve a patient's clinical health state is known as telemedicine. Indonesia is made up of several islands, and not every location has the same level of medical care. Therefore, telemedicine has considerable potential as an alternative in medical practice moreover in Obstetrics and Gynecology area, which need some routine and comparative approaches. In obstetrics and gynecology, telemedicine has been used for prenatal care, obstetric psychiatry, and monitoring chronic disease during pregnancy. Telemedicine brings many advantages and disadvantages to both patients and health professionals. Telemedicine can provide the basis for decision-making, encouraging patients, and promoting self-help once patients have gained such understanding. Therefore, the development of telemedicine in Indonesia.

Outcome and predictors of remission in bipolar-I patients experiencing manic episode and treated with oral antipsychotics and/or mood stabilizers

This observational study aimed to identify internal (clinical-demographic, temperamental characteristics) and external (childhood trauma, psychosocial characteristics) factors potentially predicting remission at 12 weeks in bipolar-I patients experiencing manic episode and requiring to start or switch treatment with oral antipsychotics and/or mood stabilizers. The following scales were administered: the Young Mania Rating Scale (YMRS), the Montgomery-Asberg Depression Rating Scale (MADRS), the Functioning Assessment Short Test (FAST), and the Clinical Global Impression for Bipolar Disorders (CGI-BP). A logistic regression analysis was carried out to test the effect of the explored factors on remission rate (YMRS score ≤12), functionality, and clinical outcomes at week 12. Overall, 243 patients were enrolled and 197 (81.1%) completed the follow-up. Remission at week 12 was achieved in 200 (82.3%) patients. Marked improvements from baseline were observed in MADRS, FAST, CGI-BP mania, and bipolar illness scores. None of the factors was associated with remission, or showed strong correlations with the improvements in clinical health state. In our sample, after 12 weeks of initiation or change of oral therapy for mania in bipolar-I patients, treatment was associated with rapid improvements in symptoms and functioning in most patients. Factors predictive of remission and clinical improvements in manic symptoms were not identified.

Early health economic modelling of single-stage cartilage repair. Guiding implementation of technologies in regenerative medicine.

Both the complexity of clinically applied tissue engineering techniques for articular cartilage repair - such as autologous chondrocyte implantation (ACI) - plus increasing healthcare costs, and market competition, are forcing a shift in focus from two-stage to single-stage interventions that are more cost-effective. Early health economic models are expected to provide essential insight in the parameters driving the cost-effectiveness of new interventions before they are introduced into clinical practice. The present study estimated the likely incremental cost-effectiveness ratio (ICER) of a new investigator-driven single-stage procedure (IMPACT) compared with both microfracture and ACI, and identified those parameters that affect the cost-effectiveness. A decision tree with clinical health states was constructed. The ICER was calculated by dividing the incremental societal costs by the incremental Quality Adjusted Life Years (QALYs). Costs were determined from a societal perspective. A headroom analysis was performed to determine the maximum price of IMPACT compared with both ACI and microfracture, assuming a societal willingness to pay (WTP) of €30 000/QALY. One-way sensitivity analysis was performed to identify those parameters that drive the cost-effectiveness. The societal costs of IMPACT, ACI and microfracture were found to be €11 797, €29 741 and €6081, respectively. An 8% increase in all utilities after IMPACT changes the ICER of IMPACT vs. microfracture from €147 513/QALY to €28 588/QALY. Compared with ACI, IMPACT is less costly, which is largely attributable to the cell expansion procedure that has been rendered redundant. While microfracture can be considered the most cost-effective treatment option for smaller defects, a single-stage tissue engineering procedure can replace ACI to improve the cost-effectiveness for treating larger defects, especially if clinical non-inferiority can be achieved. Copyright © 2016 John Wiley & Sons, Ltd.

Is Meta-Analysis for Utility Values Appropriate Given the Potential Impact Different Elicitation Methods Have on Values?

A growing number of published articles report estimates from meta-analysis or meta-regression on health state utility values (HSUVs), with a view to providing input into decision-analytic models. Pooling HSUVs is problematic because of the fact that different valuation methods and different preference-based measures (PBMs) can generate different values on exactly the same clinical health state. Existing meta-analyses of HSUVs are characterised by high levels of heterogeneity, and meta-regressions have identified significant (and substantial) impacts arising from the elicitation method used. The use of meta-regression with few utility values and inclusion criteria that extend beyond the required utility value has not helped. There is the potential to explore greater use of mapping between different PBMs and valuation methods prior to data synthesis, which could support greater use of pooling values. Researchers wishing to populate decision-analytic models have a responsibility to incorporate all high-quality evidence available. In relation to HSUVs, greater understanding of the differences between different methods and greater consistency of methodology is required before this can be achieved.

Subsyndromal delirium -- experience in psychiatry -- expectations for postoperative management

The phenomenon of delirium is well known since over 100 years. The anesthesiology has recognized that early detection and therapy results in significant improvement of postoperative clinical state of health of the patients. In the following article it will be discussed that it could be profitable to make a further step: threatening the subsyndromal delirium. Because there are only few experiences in anesthesiology, this thesis will be substantiated by datas from psychiatry.

Oral immunosuppressive medication for growing pigs in transplantation studies

Immunosuppressive (IS) medication is needed to avoid graft rejection in porcine transplantation models. An ideal IS therapy should have no side-effects, but increased susceptibility to infections, disturbed intestinal microflora and toxic effects on organs and tissues are commonly reported. The aim of the present study was to design an IS protocol with tacrolimus and mycophenolic acid to be used for maintenance therapy in the post-transplant period. An eligible whole blood trough value for tacrolimus was 5-15 μg/L. Conventional specific pathogen-free pigs were fitted with an indwelling catheter under general anaesthesia, and after the acclimatization period three groups were formed: group A (n= 4) received 0.15 mg/kg body weight (BW) twice daily tacrolimus and 500 mg twice daily mycophenolic acid; group B (n= 4) received 0.3 mg/kg BW twice daily tacrolimus and 500 mg twice daily mycophenolic acid; group C (n= 2) did not receive any medication. Daily clinical examinations and analyses of blood concentrations of tacrolimus and glucose were performed. Total and differential white blood cell counts, enzyme activities, bilirubin and electrolyte concentrations were measured every fourth day. At the end of the experiment, the pigs were killed with an overdose of pentobarbital intravenously and a necropsy was performed immediately. All animals seemed to tolerate the IS treatment well. No alterations in their clinical state of health were observed throughout the study and daily weight gain was similar for the three groups. The necropsy did not reveal any pathological findings related to medication. The study showed that 0.25 mg/kg BW twice daily tacrolimus and 500 mg twice daily mycophenolic acid would be an appropriate maintenance dosage for conventional pigs.

Effects of streptozotocin-induced diabetes in domestic pigs with focus on the amino acid metabolism

Streptozotocin (STZ) given intravenously destroys pancreatic beta cells and is widely used in animal models to mimic type 1 diabetes. The effects of STZ on the clinical state of health and metabolism were studied in six high health certified domestic pigs weighing 19+/-1.3 kg at the start of the experiment. A single STZ dose of 150 mg/kg of body weight successfully induced hyperglycaemia and alterations in amino acid metabolism. Within 9 h after STZ administration, the blood glucose values fell from 5.4-7.5 mmol/L to 0.8-2.2 mmol/L. Hypoglycaemia was treated with 0.5 g glucose/kg body weight. In all pigs, hyperglycaemia was produced 24 h after STZ treatment, and 3 days after STZ injection, the glucose concentration was >25 mmol/L. Mean C-peptide concentration was 0.25+/-0.16 microg/L since 2 days after STZ injection until the end of the study. The serum concentration of the branched-chain amino acids (BCAA) increased four-fold, and alanine and taurine decreased by approximately 70% and 50%, respectively, after STZ treatment. All but one pig remained brisk and the physical examination was normal except for a retarded growth rate and a reduction of the skeletal muscle. At the end of the study, the pigs were moderately emaciated. Postmortem examination confirmed muscle wasting and a reduction of abdominal and subcutaneous fat. In conclusion, STZ-induced diabetes in pigs fulfils the requirements for a good animal model for type 1 diabetes with respect to clinical signs of the disease and alterations in the carbohydrate and amino acid metabolism.

Toxicity of High-Dose Chlorambucil in Wistar Rats

The aim of this study was to determine the maximum tolerated dose and the haematological and non-haematological toxicity of chlorambucil in male Wistar rats. Chlorambucil (pulverized pills or pure substance) was dissolved in ethanol and administered orally at a dose ranging from 0.15 to 50 mg/kg/day for 5 days. Evaluations of experimental rats included general clinical state of health, body weight, haematological indicators (red blood cell count, white blood cell count, platelet count, differential leukocyte count, packed cell volume and haemoglobin concentration), biochemical plasma indicators (urea, creatinine, ALP, ALT, AST, Na, K, Cl), immunophenotype of leukocytes (CD3, CD8 and CD4 markers), as well as histopathology. Doses of chlorambucil from 0.15 to 0.75 mg/kg/day had no effect on the general clinical state of health as well as on other laboratory variables. Doses of 2–12 mg/kg/day were well tolerated, but mild myelotoxicity (leukopaenia) and elevated activities of liver transaminases were found. Doses of 20 to 50 mg/kg/day were myelotoxic (p < 0.01) with prevailing lymphopaenia but only minimum effects on red blood cells and platelets. Histology revealed pneumotoxicity, nephrotoxicity and damage to the gastrointestinal tract. Doses of 40 and 50 mg/kg/day resulted in acute lethal effects in 50% and 75% of individuals, respectively. Results of this study are intended for use in the testing of chlorambucil in combination with other drugs as a conditioning for bone marrow transplantation.

The Use of Disease-Specific Outcome Measures in Cost-Utility Analysis

The Functional Assessment of Cancer Therapy-Lung (FACT-L) is a validated, sensitive and reliable patient questionnaire that evaluates and quantifies quality of life (QOL) across several domains, including lung cancer-related symptoms. The FACT-L was not designed for use in economic evaluation and does not incorporate preferences into its scoring system. To derive a set of Dutch preference weights for FACT-L health states that can be used to convert FACT-L into a single value that can be used in cost-utility analyses. A representative sample of the Dutch population (n = 1076) directly valued an orthogonal set of eight FACT-L health states on a 100-point rating scale with the anchor points 'worst imaginable health state' and 'best imaginable health state'. Eleven FACT-L items were selected to describe the FACT-L health states that were directly valued. Regression analysis was used to interpolate values for all other possible health states. Scores were transformed into values on a scale where 0 indicated dead and 1 indicated full health. The estimated values for FACT-L health states ranged from 0.08 to 0.93. The estimated value sets were applied to FACT-L data of lung cancer patients participating in a clinical study. Significant differences in the mean value and mean gain of 0.12 and 0.07, respectively, were found between patients in remission and patients with progressive disease at 4 weeks' follow-up. Our results reaffirmed that the methodology used here is a feasible option to convert data collected with a disease-specific outcome measure into preferences. We concluded that the sensitivity of the derived set of societal preferences to capture differences and changes in clinical health states is an indication of its construct validity.

Effects of a 2-week treatment with pulsed monochromatic light in healthy pigs: a clinical and morphological study.

Pulsed monochromatic light (PML) is now used clinically for pain relief and wound healing in both human and veterinary practice. The purpose of this study was to evaluated the clinical and pathological effects of PML irradiation in an animal model, using healthy specific pathogen-free pigs. After 2 weeks of habituation, one group of animals (n=9) underwent treatment with pulsating monochromatic infrared and red light while the control group (n=9) was left untreated. PML was given five times a week during a 2-week period, and at each treatment the total radiant exposure was 6.3 J/cm2. At the completion of the study, all pigs were subjected to complete necropsy. None of the animals showed any clinical signs of disease during the study period. The measured hematological and clinico-chemical variables all showed values within the reference range and the daily weight gain was high in both the treatment and control groups (825 and 923 g/day, respectively). The pathological examination revealed no morphological differences between treated and non-treated animals. In healthy pigs, no adverse effects of low-energy photon therapy on the clinical state of health or on the morphology of different tissues were observed.

Quality-adjusted time without symptoms or toxicity analysis of interferon maintenance in multiple myeloma.

In a randomized trial conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), interferon alpha-2b (IFN) maintenance therapy (2 mU/m2 subcutaneously three times per week) after successful induction with melphalan and prednisone was found to prolong time to progression in patients with multiple myeloma. A favorable effect on survival was also present, but this difference was of borderline significance. However, IFN toxicity was a concern. To evaluate the trade-off between the clinical benefits of IFN and the associated toxicity, we applied the method of quality-adjusted time without symptoms or toxicity (Q-TWiST). Three clinical health states were defined in this analysis: time with toxicity (TOX), time without disease relapse or toxicity (TWiST), and time following disease relapse (REL). Toxicity information for IFN had been collected using patient-completed diaries so the actual duration of each adverse event could be determined. The health states TOX and REL were weighted using utility scores to account for a possible decrement in quality of life, a weighted sum of the health state durations is used as a measure of quality-adjusted time. The health state durations were calculated at 72 months median follow-up. Patients in the IFN group gained an average of 9.8 months without disease relapse (P = .001) and 5.8 months of overall survival (P = .074) versus the control group. However, the IFN group suffered an average of 4.1 months of moderate or worse toxicity (P < .001). The clinical benefits of IFN outweigh the negative effects associated with treatment toxicity for a wide range of plausible utilities.

Comparing Treatments Using Quality-Adjusted Survival: The Q-TWiST Method

Abstract The quality of life of patients is an important component of evaluation of therapies. We present an overview of a statistical method called Q-TWiST (Quality-Adjusted Time Without Symptoms and Toxicity) which incorporates quality-of-life considerations into treatment comparisons. Multivariate censored survival data are used to partition the overall survival time into periods of time spent in a set of progressive clinical health states which may differ in quality of life. Mean health state durations, restricted to the follow-up limits of the clinical trial, are derived from the data and combined with value weights to estimate quality-adjusted survival. The methodology emphasizes treatment comparisons based on threshold utility analyses that highlight trade-offs between different health state durations; it is not intended to provide a unique result combining quality and quantity of life. We also describe three recent extensions of the methodology: covariates can be included using proportional hazard...

Treatment of Testicular Seminoma in Patients with HIV Infection

The problem of adequate management of testicular germ cell tumors in patients with AIDS is increasingly important, as reflected by the increasing number of reports on the unclear pathogenetic association of the two conditions. Two HIV-positive patients (32 and 39 years old) at CDC stages II and IIb with pure seminoma have been treated. Both patients initially underwent semicastration. One patient (tumor stage IIa) then had retroperitoneal radiotherapy, and the other (tumor stage IIc) four cycles of carboplatin therapy. They have had no relapse after 35 and 14 months, respectively, and there has been no progression in the HIV infection stage. Stage-oriented treatment for testicular germ-cell tumors can, in principle, be applied in patients with HIV infection. Radiotherapy and chemotherapy do not necessarily lead to a deterioration in the clinical state of health of the immune status of HIV-infected patients and carboplatin monotherapy is an effective treatment with few side effects in patients with metastatic seminoma.

Congenital nemaline myopathy: A clinical follow-up study of twelve patients

A clinical follow-up of 12 patients with congenital nemaline myopathy (CNM) is reported. The aims of the study were to characterise the disease further, to investigate the prognosis of CNM and the factors influencing it, to find guidelines for treatment and, through neuropsychological tests, electroencephalography and computed tomography of the head, to determine whether the central nervous system is affected. The following distribution of muscular weakness was constantly found: the weakest muscles were the facial muscles, the flexors of the neck and trunk, the dorsiflexors of the feet and the extensors of the toes. The distal limb muscles and the limb-girdle muscles were clearly weaker than the proximal limb muscles. No signs of involvement of the central nervous system were detected, and IQs showed a skew towards higher levels. The clinical state of health had deteriorated in 10 of the 12 patients and improved in 2. In addition to the grade of disease activity, prognosis seemed to be influenced mainly by the development of scoliosis and by the restricted respiratory capacity. Since no specific therapy is available for this disease, recommendations for the management of CNM include active rehabilitation and vigorous treatment of respiratory infections. Physiotherapy should focus especially on the maintenance of cardiorespiratory capacity and the prevention and treatment of scoliosis. Long periods of immobilisation should be avoided.

The effects of patient characteristics and beliefs on responses to behavioral interventions for control of chronic diseases

Tests of behavioral interventions seldom examine changes in health beliefs and behaviors thought to be prerequisites of improved outcome health states and they do not attempt to specify how patient characteristics or pretest measures influence responses to the intervention. In this study an experimental nursing intervention, its impact on hypertensive patients' beliefs about their disease, efficacy of medications and diet, as well as blood pressure and weight are described. Among patients from the experimental group, the ability of selected pretest variables to predict clinical outcomes and changes in clinical health states was evaluated. The intervention was successful in lowering diastolic blood pressure and altering certain beliefs held by the patients. The pretest characteristics were not successful in explaining hypertensive patients' responses to the intervention. Explanations for this are pursued through remarks from the content analysis of the intervention protocol. From these observations, the original health belief model was revised. The discussion concludes with a set of research questions that may prove promising for future research.