Healthcare professionals' experiences with the use of antipsychotics in dementia.

Background: Antipsychotics are commonly administered to nursing home residents with dementia, despite the associated risk of severe adverse events. Objective: This study aimed to explore healthcare professionals' experiences in caring for nursing home residents with dementia, with a focus on rationales behind the use of antipsychotics. Method: Twelve semi-structured interviews with healthcare professionals' from Danish nursing homes were conducted and analyzed using the method Systematic Text Condensation. Results: Nonpharmacological interventions were reported as the primary approach to care and the first-choice treatment for behavioral and psychological symptoms of dementia (BPSD). Use of antipsychotics was considered to serve as a last resort, reserved for residents with severe symptoms. However, most informants preferred a more limited use. The study identified four main barriers to reduce the use of antipsychotics: "Scarcity of resources", "Perceiving antipsychotic use to provide relieve", "Reluctance towards deprescribing" and "Limited access to medical counseling", and three potential enablers: "Updating knowledge and nonpharmacological competencies", "Management support and clear procedures" and "Regularity in interdisciplinary collaboration". Conclusion: The treatment and care were reported as primarily following guidelines in BPSD. Several barriers were perceived to challenge the healthcare professionals' preference of limited use of antipsychotics. To further reduce the use, this study highlights the importance of understanding the adverse effects caused by limited resources, enhancing employee knowledge and competencies and ensuring regular interprofessional collaboration for assessing and reassessing the need to use antipsychotics.

Developing quality measures for non-pharmacological prevention and rehabilitation in primary health care for chronic conditions: a consensus study.

Poor health-related behaviours are root causes of a large number of chronic conditions; however, this study is the first to develop guideline-based quality measures targeting health-related behaviours through generic non-pharmacological secondary prevention and rehabilitation in municipal primary health care for persons with chronic conditions. From January 2020 to September 2021, a consensus study was conducted in accordance with the current scientific recommendations for developing guideline-based quality measures. A clinical expert panel (n = 11) was established and included a patient representative, health care professionals, researchers, and key specialists. The process for developing quality measures was led by methodologists and encompassed a modified Research and Development/University of California at Los Angeles (RAND/UCLA) study to evaluate consensus in the expert panel. The consensus recommendations were directed to a steering group including the Danish Ministry of Health, the Danish Regions, and the Local Government Denmark. The expert panel rated 102 clinical practice recommendations. Consensus was demonstrated on 13 quality measures assessing whether the patients are offered participation in and adhere to: self-management, smoking cessation, physical exercise training, nutritional efforts, and preventive consultation on excessive alcohol consumption; whether the patients participate in a closing meeting, whether they are offered follow-up, and whether reasons for dropout are documented. The identified quality measures constitute a framework for assessing the quality of non-pharmacological prevention and rehabilitation in municipal primary health care for persons with chronic conditions. The next steps focus on field testing of the quality measures to refine measure criteria and assess implementation. A close link between clinical practice, the evidence and practice recommendations, the data infrastructure, economic considerations, and national priorities was a key to the consensus process.

Protocol for DEprescribing and Care to reduce Antipsychotics in Dementia (DECADE)-A hybrid effectiveness-implementation pilot study.

INTRODUCTION: Behavioural and psychological symptoms of dementia (BPSD) should only rarely and briefly be treated with antipsychotics. Despite recommendations to the contrary, the use of antipsychotics in nursing home residents with dementia is widespread and followed by serious adverse effects. Intervention studies on methods to reduce the use of antipsychotics in persons with dementia are few and needed. The aim of this protocol is to describe the rationale and content of the intervention DEprescribing and Care to reduce Antipsychotics in DEmentia (DECADE)-a hybrid effectiveness-implementation pilot study. MATERIALS AND METHODS: This is a protocol of a prospective hybrid effectiveness-implementation pilot study. The primary aim of DECADE is to reduce the use of antipsychotic drugs by 50% in 50% of nursing home residents with dementia while maintaining or improving BPSD. The intervention is implemented in six nursing homes including approximately 190 residents with dementia and consists of Academic Detailing, medication review, education of nursing home staff, and care plans. The evaluation of feasibility and potential effectiveness is an overall assessment of all clinical and process outcomes. Logistic regression analyses will be used to investigate factors characterizing situations with prescription of antipsychotics. BPSD is analysed with a before- and after design using self-controlled case series methods and the use of antipsychotics is analysed as interrupted time series. DISCUSSION: This protocol describes a study that will provide an indication of DECADE effectiveness and a model for upscaling and further evaluation in a controlled design.

Germline Elongator mutations in Sonic Hedgehog medulloblastoma.

Cancer genomics has revealed many genes and core molecular processes that contribute to human malignancies, but the genetic and molecular bases of many rare cancers remains unclear. Genetic predisposition accounts for 5 to 10% of cancer diagnoses in children1,2, and genetic events that cooperate with known somatic driver events are poorly understood. Pathogenic germline variants in established cancer predisposition genes have been recently identified in 5% of patients with the malignant brain tumour medulloblastoma3. Here, by analysing all protein-coding genes, we identify and replicate rare germline loss-of-function variants across ELP1 in 14% of paediatric patients with the medulloblastoma subgroup Sonic Hedgehog (MBSHH). ELP1 was the most common medulloblastoma predisposition gene and increased the prevalence of genetic predisposition to 40% among paediatric patients with MBSHH. Parent-offspring and pedigree analyses identified two families with a history of paediatric medulloblastoma. ELP1-associated medulloblastomas were restricted to the molecular SHHα subtype4 and characterized by universal biallelic inactivation of ELP1 owing to somatic loss of chromosome arm 9q. Most ELP1-associated medulloblastomas also exhibited somatic alterations in PTCH1, which suggests that germline ELP1 loss-of-function variants predispose individuals to tumour development in combination with constitutive activation of SHH signalling. ELP1 is the largest subunit of the evolutionarily conserved Elongator complex, which catalyses translational elongation through tRNA modifications at the wobble (U34) position5,6. Tumours from patients with ELP1-associated MBSHH were characterized by a destabilized Elongator complex, loss of Elongator-dependent tRNA modifications, codon-dependent translational reprogramming, and induction of the unfolded protein response, consistent with loss of protein homeostasis due to Elongator deficiency in model systems7-9. Thus, genetic predisposition to proteome instability may be a determinant in the pathogenesis of paediatric brain cancers. These results support investigation of the role of protein homeostasis in other cancer types and potential for therapeutic interference.

EPI-CT: design, challenges and epidemiological methods of an international study on cancer risk after paediatric and young adult CT.

Computed tomography (CT) has great clinical utility and its usage has increased dramatically over the years. Concerns have been raised, however, about health impacts of ionising radiation exposure from CTs, particularly in children, who have a higher risk for some radiation induced diseases. Direct estimation of the health impact of these exposures is needed, but the conduct of epidemiological studies of paediatric CT populations poses a number of challenges which, if not addressed, could invalidate the results. The aim of the present paper is to review the main challenges of a study on the health impact of paediatric CTs and how the protocol of the European collaborative study EPI-CT, coordinated by the International Agency for Research on Cancer (IARC), is designed to address them. The study, based on a common protocol, is being conducted in Belgium, Denmark, France, Germany, the Netherlands, Norway, Spain, Sweden and the United Kingdom and it has recruited over one million patients suitable for long-term prospective follow-up. Cohort accrual relies on records of participating hospital radiology departments. Basic demographic information and technical data on the CT procedure needed to estimate organ doses are being abstracted and passive follow-up is being conducted by linkage to population-based cancer and mortality registries. The main issues which may affect the validity of study results include missing doses from other radiological procedures, missing CTs, confounding by CT indication and socioeconomic status and dose reconstruction. Sub-studies are underway to evaluate their potential impact. By focusing on the issues which challenge the validity of risk estimates from CT exposures, EPI-CT will be able to address limitations of previous CT studies, thus providing reliable estimates of risk of solid tumours and leukaemia from paediatric CT exposures and scientific bases for the optimisation of paediatric CT protocols and patient protection.

[Treatment of hypercalcaemia].

It is important to identify the cause of hypercalcaemia to give the best possible treatment. The primary treatment is to remove the underlying cause and rehydration. When the parathyroid hormone (PTH) level is elevated the most common causes are primary hyperparathyroidism and thiazides. The treatment is operation and discontinuation of the medicine. Cinacalcet can be used to lower the serum calcium level preoperatively. When the PTH level is low the most common causes are dehydration, malignant disease and treatment with calcium. The hypercalcaemia in malignant disease can be treated with prednisone, bisphosphonates and denosumab.

Mechanical heart valve cavitation in patients with bileaflet valves.

Today, the quality of mechanical heart valves is quite high, and implantation has become a routine clinical procedure with a low operative mortality (< 5%). However, patients still face the risks of blood cell damage, thromboembolic events, and material failure of the prosthetic device. One mechanism found to be a possible contributor to these adverse effects is cavitation. In vitro, cavitation has been directly demonstrated by visualization and indirectly in vivo by registering of high frequency pressure fluctuations (HFPF). Tilting disc valves are thought of having higher cavitation potential than bileaflet valves due to higher closing velocities. However, the thromboembolic potential seems to be the same. Further studies are therefore needed to investigate the cavitation potential of bileaflet valves in vivo. The post processing of HFPF have shown difficulties when applied on bileaflet vavles due to asynchronous closure of the two leaflets. The aim of this study was therefore to isolate the pressure signature from each leaflet closure and perform cavitation analyses on each component. Six patients were included in the study (St. Jude Medical (n=3) and CarboMedics (n=3); all aortic bileaflet mechanical heart valves). HFPFs were recorded intraoperatively through a hydrophone at the aortic root. The pressure signature relating to the first and second leaflet closure was isolated and cavitation parameters were calculated (RMS after 50 kHz highpass filtering and signal energy). Data were averaged over 30 heart cycles. For all patients both the RMS value and signal energy of the second leaflet closure were higher than for the first leaflet closure. This indicates that the second leaflet closure is most prone to cause cavitation. Therefore, quantifying cavitation based on the HFPF related to the second leaflet closure may suggest that the cavitation potential for bileaflet valves in vivo may be higher than previous studies have suggested.

Brain tumors in children and adolescents and exposure to animals and farm life: a multicenter case-control study (CEFALO).

OBJECTIVES: The etiology of brain tumors in children and adolescents is largely unknown, and very few environmental risk factors have been identified. The aim of this study was to examine the relationship between pre- or postnatal animal contacts or farm exposures and the risk of childhood brain tumors (CBTs), since infectious agents may pose a risk factor and a proposed mechanism is transferral of infectious agents from animals to humans. METHODS: The case-control study conducted in Denmark, Norway, Sweden, and Switzerland included brain tumor cases diagnosed from 2004 to 2008 aged 7-19 years at diagnosis. Three hundred and fifty-two cases (83 % participation rate) were matched to 646 population-based controls (71 % participation rate). Conditional logistic regression was used to estimate odds ratios. RESULTS: Maternal farm residence during pregnancy was inversely related to all CBTs combined (adjusted odds ratio (aOR) = 0.40, 95 % confidence interval (CI) = 0.19-0.88), as was the child's farm residence but not statistically significantly so (aOR = 0.57, 95 % CI = 0.28-1.17). Exposure to animals was in general not related to CBT risk except postnatal contact with birds showing reduced aORs of all CBTs (0.67, 95 % CI = 0.46-0.97) and primitive neuroectodermal tumor (0.28, 95 % CI = 0.10-0.83). Sensitivity analyses focusing on early exposure of the child did not change the associations observed for the entire exposure period with the exception of exposure to goats and sheep which was associated with reduced risks of both all CBTs (aOR = 0.48, 95 % CI = 0.24-0.97) and astrocytomas (aOR = 0.29, 95 % CI = 0.10-0.87). CONCLUSION: Altogether, our data indicate an inverse association between the mother during pregnancy or the child living on a farm and CBT risk, which contrasts with the existing literature and merits further attention. With respect to exposure to animals, we did not observe any systematic pattern. This suggests that a potential protective effect of farm residence is mediated by some other factor than animal contact.

Predictors and overestimation of recalled mobile phone use among children and adolescents.

A growing body of literature addresses possible health effects of mobile phone use in children and adolescents by relying on the study participants' retrospective reconstruction of mobile phone use. In this study, we used data from the international case-control study CEFALO to compare self-reported with objectively operator-recorded mobile phone use. The aim of the study was to assess predictors of level of mobile phone use as well as factors that are associated with overestimating own mobile phone use. For cumulative number and duration of calls as well as for time since first subscription we calculated the ratio of self-reported to operator-recorded mobile phone use. We used multiple linear regression models to assess possible predictors of the average number and duration of calls per day and logistic regression models to assess possible predictors of overestimation. The cumulative number and duration of calls as well as the time since first subscription of mobile phones were overestimated on average by the study participants. Likelihood to overestimate number and duration of calls was not significantly different for controls compared to cases (OR=1.1, 95%-CI: 0.5 to 2.5 and OR=1.9, 95%-CI: 0.85 to 4.3, respectively). However, likelihood to overestimate was associated with other health related factors such as age and sex. As a consequence, such factors act as confounders in studies relying solely on self-reported mobile phone use and have to be considered in the analysis.

Thalidomide in 42 patients with prurigo nodularis Hyde.

The aim of this study was to describe the use of thalidomide in the treatment of prurigo nodularis Hyde (PNH) refractory to other treatments or in cases where other treatments cannot be used due to side effects. 77 medical records were retrospectively reviewed for the following data: sex, age, age at the beginning of thalidomide treatment, dermatological diagnosis, duration of the skin disease, previous treatments, indications for treatment with thalidomide, effect of treatment, duration of treatment with thalidomide, reasons for cessation of thalidomide treatment, and side effects. 54 patients had PNH. All patients were refractory to standard therapy or had side effects to treatment. 42 patients were treated with thalidomide and the majority of patients experienced clinical improvement. The most common reason for discontinuation of therapy was side effects, the most frequent being peripheral neuropathy and sedation. Thalidomide effectively treats PNH refractory to standard medications. However, physicians must be aware of possible side effects, especially peripheral neuropathy.

Mobile phone use and brain tumors in children and adolescents: a multicenter case-control study.

BACKGROUND: It has been hypothesized that children and adolescents might be more vulnerable to possible health effects from mobile phone exposure than adults. We investigated whether mobile phone use is associated with brain tumor risk among children and adolescents. METHODS: CEFALO is a multicenter case-control study conducted in Denmark, Sweden, Norway, and Switzerland that includes all children and adolescents aged 7-19 years who were diagnosed with a brain tumor between 2004 and 2008. We conducted interviews, in person, with 352 case patients (participation rate: 83%) and 646 control subjects (participation rate: 71%) and their parents. Control subjects were randomly selected from population registries and matched by age, sex, and geographical region. We asked about mobile phone use and included mobile phone operator records when available. Odds ratios (ORs) for brain tumor risk and 95% confidence intervals (CIs) were calculated using conditional logistic regression models. RESULTS: Regular users of mobile phones were not statistically significantly more likely to have been diagnosed with brain tumors compared with nonusers (OR = 1.36; 95% CI = 0.92 to 2.02). Children who started to use mobile phones at least 5 years ago were not at increased risk compared with those who had never regularly used mobile phones (OR = 1.26, 95% CI = 0.70 to 2.28). In a subset of study participants for whom operator recorded data were available, brain tumor risk was related to the time elapsed since the mobile phone subscription was started but not to amount of use. No increased risk of brain tumors was observed for brain areas receiving the highest amount of exposure. CONCLUSION: The absence of an exposure-response relationship either in terms of the amount of mobile phone use or by localization of the brain tumor argues against a causal association.

Impact of random and systematic recall errors and selection bias in case--control studies on mobile phone use and brain tumors in adolescents (CEFALO study).

Whether the use of mobile phones is a risk factor for brain tumors in adolescents is currently being studied. Case--control studies investigating this possible relationship are prone to recall error and selection bias. We assessed the potential impact of random and systematic recall error and selection bias on odds ratios (ORs) by performing simulations based on real data from an ongoing case--control study of mobile phones and brain tumor risk in children and adolescents (CEFALO study). Simulations were conducted for two mobile phone exposure categories: regular and heavy use. Our choice of levels of recall error was guided by a validation study that compared objective network operator data with the self-reported amount of mobile phone use in CEFALO. In our validation study, cases overestimated their number of calls by 9% on average and controls by 34%. Cases also overestimated their duration of calls by 52% on average and controls by 163%. The participation rates in CEFALO were 83% for cases and 71% for controls. In a variety of scenarios, the combined impact of recall error and selection bias on the estimated ORs was complex. These simulations are useful for the interpretation of previous case-control studies on brain tumor and mobile phone use in adults as well as for the interpretation of future studies on adolescents.

Factors associated with a continuous regular analgesic use - a population-based study of more than 45,000 Danish women and men 18-45 years of age.

PURPOSE: Widespread use of and serious adverse effects associated with use of analgesics accentuates the need to consider factors related to analgesic use. The objective of this study was to describe continuous regular analgesics use and examine factors associated with a continuous regular analgesic use. METHODS: The study was based on data from two surveys and included a random sample of women and men aged 18-45 years from the general Danish population. Information on analgesics use, self-rated health, demographic and lifestyle factors was collected using a self-administered questionnaire. A total of 28,000 women and 33 000 men were invited to participate and 22,199 women (response-rate 81.4%) and 23,080 men (response-rate 71.0%), respectively, were included in the study. Data were analyzed using multivariate logistic regression. RESULTS: We found that 27% of the women and 18% of the men reported a regular monthly use of at least seven analgesic tablets during the last year (continuous regular analgesics use). Besides poor self-rated health we found in both sexes that increasing age, poor self-rated fitness, and smoking were related to a continuous regular analgesics use. Nulliparity, low level of education, overweight/obesity, binge drinking, and abstinence were associated with a continuous regular analgesics use for women, while underweight and marital/cohabiting status were associated with a continuous regular analgesics use only for men. CONCLUSIONS: Regular monthly analgesic use during the last year was generally prevalent. Besides self-rated health, several socio-demographic and lifestyle factors were associated with a continuous regular analgesic use, although with some gender differences.

Effect of fish oil (n-3 polyunsaturated fatty acids) on plasma lipids, lipoproteins and inflammatory markers in HIV-infected patients treated with antiretroviral therapy: a randomized, double-blind, placebo-controlled study.

Patients on antiretroviral therapy are reported to have an increased risk of cardiovascular disease. We aimed to investigate the effect of n-3 polyunsaturated fatty acids (n-3 PUFAs) on plasma lipids, lipoproteins and inflammatory markers in HIV-infected patients treated with antiretroviral therapy. We randomized 51 patients in a placebo-controlled, double-blind trial to receive either 2 capsules of Omacor twice daily or 2 capsules of placebo. Compliance was measured by determining levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in neutrophils. Plasma triglycerides were reduced in the n-3 PUFA group by 0.14 mmol/l after 12 weeks of treatment (n=26), while plasma triglycerides increased by 0.36 mmol/l in the control group (n=25). The difference between groups was significant, p=0.03. No significant effect of treatment was found for total cholesterol, high-density lipoprotein (HDL) or low-density lipoprotein (LDL) cholesterol or apolipoproteins. There was a significant increase in leukotriene B5 (LTB5) and LTB5/LTB4 ratio in the n-3 PUFA group compared to the control group. Baseline values for intercellular adhesion molecule-1 (ICAM), vascular cell adhesion molecule-1 (VCAM) and highly sensitive C-reactive protein (hsCRP) were comparable at baseline, and the intervention did not change these parameters significantly. The present study showed that treatment with n-3 PUFA slightly decreased plasma triglycerides and induced anti-inflammatory effects by increasing formation of anti-inflammatory LTB5.

Cancer incidence among patients with alcohol use disorders--long-term follow-up.

AIMS: The aim of this study was to compare the cancer morbidity in a large cohort of patients with alcohol use disorders in the general Danish population. METHODS: We included 15,258 men and 3552 women free of cancer when attending the Copenhagen Outpatient Clinic for Alcoholics in the period from 1954 to 1992. The cancer incidence until 1999 of the patients and the general Danish population was obtained through linkage with the Danish Cancer Registry. The incidence rates were standardized (SIR) according to sex, age and calendar time. RESULTS: A total of 2145 men developed cancer compared to 1140.8 expected cases (SIR = 1.9; 95% confidence interval (CI) 1.8-2.0), while 601 women developed cancer compared to 239.1 expected cases (SIR = 2.5; 95% CI 2.3-2.7). Highly significant and strongly elevated incidence rates were found for cancer of the tongue, mouth, pharynx, oesophagus, liver, larynx and lung. A higher incidence rate was seen for renal cancer for both men (1.4; 1.1-1.8) and women (2.1; 1.0-3.8). The incidence of breast cancer in women was non-significantly elevated, but significantly elevated incidence rate was found for cervical cancer (1.8; 1.2-2.6). We did not observe increased incidence of colon, rectal or urinary bladder cancer. CONCLUSIONS: In conclusion, this study confirms the well-established association between high alcohol intake and cancer of the upper digestive tract and liver. In addition, the results indicate a significantly elevated occurrence of renal cancer, but not of breast cancer and colorectal cancer, in patients with alcohol use disorders.

Quantitative evaluation of a novel sensor for measuring muscular tissue flow and gases.

Information about muscular tissue flow is important for diagnosing, treating and monitoring patients with tissue ischemia. For this purpose an objective method which is reproducible and continuous is needed. In co-operation with the company Unisense A/S, we have developed a sensor for instantaneous and continuous monitoring of muscle tissue flow in vivo. The method is based on a flexible microsensor which emits and measures minute amounts of inert tracer gases. The objective was to evaluate the capability of the microsensor to measure varying degrees of tissue flow changes and compare these measurements with the 133Xenon Washout Technique for measuring local perfusion rates in skeletal muscle. The Unisense microsensor was tested in the gracilis muscle of six anaesthetized pigs subjected to varying degrees of muscle ischemia. We found that both tissue flow and pO2 declined in synchrony with reduced blood flow to the lower extremities. All the data from the Unisense microsensor show the same trend as the Xenon data and thus confirms that the microsensor can measure changes in tissue flow.

[Surfactant treatment of newborn infants receiving continuous positive airway pressure treatment]. / Surfaktantbehandling af nyfødte børn i continuous positive airway pressure-behandling.

INTRODUCTION: The purpose of this study was to examine the efficiency of a single dose of fast-acting exogenous surfactant (Curosurf) given to premature babies with progressive respiratory insufficiency. Curosurf was given as early rescue therapy during a brief intubation (INSURE method: INtubation-SURfactant-Extubation) during treatment with nasal Continuous Positive Airway Pressure (CPAP). MATERIALS AND METHODS: Retrospective study of 115 premature infants with respiratory distress syndrome born and treated at Odense University Hospital during the years 1999 to 2004. The criterion for surfactant treatment was a decrease in the arterial/alveolar oxygen tension ratio (or corresponding values for the fraction of inspired oxygen) below 0.36 in infants with gestational age (GA) < 30 weeks and 0.22 in more mature infants. RESULTS: The primary end point was survival during the first week of life without mechanical ventilation. This end point was reached by 51% of the infants with GA < 30 weeks. However, the effect proved to be GA-dependent, increasing from 22% in infants with a GA of 24-25 weeks to 86% in week 29. Seventy percent survived to be discharged. In infants with GA > 29 weeks the effect was 87%, and all survived. CONCLUSION: The effect of surfactant therapy administered per the INSURE method is GA-dependent, and the method works best after GA week 25. The question is whether earlier therapy will increase its efficiency or the method has reached its limit.

Intraoperative and postoperative evaluation of cavitation in mechanical heart valve patients.

BACKGROUND: Cavitation has been claimed partly responsible for the increased risk of thromboembolic complications, hemolysis, and fatal valve failure seen in mechanical heart valve patients. In vivo studies have investigated cavitation using high-pass filtering of the high-frequency pressure fluctuations with the root mean square values as an assessment of intensities. In vitro studies have shown that this well-known method may not be ideal owing to loss of data as a consequence of filtering, and because it requires a priori knowledge of the valve resonance pattern. Therefore, a new method has been developed, which decomposes the signal into nondeterministic (cavitation) and deterministic (valve resonance) signal components, and hence decreases data loss. This study aimed to evaluate cavitation in patients with mechanical, biological, and native heart valves both intraoperatively and postoperatively using the new method. METHODS: High-frequency pressure fluctuations were measured by a hydrophone intraoperatively and postoperatively in 14 patients with mechanical valves, 10 patients with normal aortic valves, and 5 patients with bioprosthesis. The total signal energy was evaluated as nondeterministic and deterministic energies. RESULTS: Nondeterministic energies were verified both intraoperatively and postoperatively in all patients who had a mechanical valve; this finding confirms the cavitation potential of mechanical valves. None of the data recorded in patients with bioprosthetic or native valves contained nondeterministic energy. CONCLUSIONS: The study confirms the presence of cavitation in mechanical heart valve patients using the nondeterministic energy of high-frequency pressure fluctuations as a quantitative measure of cavitation both intraoperatively and postoperatively.

In-vivo prediction of cavitation near a Medtronic Hall valve.

BACKGROUND AND AIM OF THE STUDY: Quantification of cavitation near mechanical heart valves in vivo is currently based on measurements of high-frequency pressure fluctuations (HFPF). Until now, mechanical resonance components have been removed using a high-pass filter. However, isolating cavitation and resonance signal components by separating the deterministic and non-deterministic parts of the HFPF signal has recently been proposed as a new method. It was hypothesized that the non-deterministic signal energy, Enon-det, of the HFPF signal correlates with previous parameters indicating cavitation in vivo, specifically the root mean square pressure after appropriate high-pass filtering (P(RMS)) and the rate of change in transvalvular pressure with respect to time (dP/dt). METHODS: Medtronic Hall 29 mm mitral valves were implanted in five pigs (body weight 80 kg). The hemodynamic condition was varied by infusion of dobutamine and blood volume regulation to achieve a wide range of dP/dt (100 to 4,700 mmHg/s). According to previous studies, P(RMS) was deduced using the HP-filtering cut-off frequency of 50 kHz for this particular valve. The transvalvular dP/dt was derived as the average slope 5 ms prior to valve closure. RESULTS: Power relationships were found between Enon-det and P(RMS) (P(RMS) = 1.27 x Enon-det0.49), and between Enon-det and dP/dt. The correlation between Enon-det and P(RMS) was very strong (r = 0.98), whereas the correlation between Enon-det and dP/dt was notably weaker (r = 0.68). CONCLUSION: Enon-det was an excellent predictor of P(RMS), obtained after appropriate filtering. The present data suggested that the signal energy above 50 kHz was almost completely non-deterministic. It can therefore be proposed that Enon-det is a more direct and easily accessible parameter than those previously suggested for the purpose of cavitation quantification. This parameter is able to quantify the pressure fluctuations thought to occur from cavitation in vivo, and may be applicable for non-invasive recordings.

Indication of cavitation in mechanical heart valve patients.

BACKGROUND AND AIM OF THE STUDY: Cavitation may cause erosion of prosthetic heart valve material. The phenomenon has been extensively studied in vitro, and an association between the presence of cavitation bubbles and high-frequency pressure fluctuations (HFPF) has been established. In-vivo studies examining this phenomenon are scarce; hence, the study aim was to compare HFPF in patients with native, bioprosthetic or mechanical aortic valves, using both invasive and non-invasive measuring techniques. METHODS: Measurements were carried out in 16 patients implanted with a St. Jude Medical aortic valve; two control groups comprised 10 patients with normal aortic valves after coronary artery bypass surgery, and five patients implanted with a Carpentier-Edwards pericardial aortic bioprosthesis. HFPF were measured intraoperatively using a hydrophone placed near the aortic annulus, and postoperatively using the same hydrophone mounted in a specially designed water-filled sound chamber. The frequency spectrum was evaluated using Fast Fourier transformation, and the root mean square (RMS) value of the pressure signals was calculated in the frequency range 50-150 kHz. RESULTS: HFPF with intensities significantly above the noise floor were registered using both methods in the vicinity of mechanical heart valves. The RMS values of the HFPF for all three patient groups measured intra- and postoperatively disclosed a significant difference between the mechanical valves and the two control groups, indicating that there is no cavitation in the vicinity of the biological or the native valves. CONCLUSION: HFPF are present in the vicinity of mechanical aortic valves and can be measured in patients, both invasively and non-invasively. This indication of cavitation was not observed in patients with either native or bioprosthetic aortic valves.