Impact of kidney transplantation on sleep apnea severity: A prospective polysomnographic study.

Fluid overload has been associated with a high prevalence of sleep apnea (SA) in patients with end-stage kidney disease (ESKD). In this prospective study, we hypothesized that improvement in kidney function and hydration status after kidney transplantation (Tx) may result in an improvement in SA severity. A total of 196 patients on the kidney Tx waiting list were screened for SA using home nocturnal polysomnography (PSG) to measure the apnea-hypopnea index (AHI) and underwent bioimpedance to assess body composition. Of 88 participants (44.9%) with SA (AHI ≥ 15/h), 42 were reassessed 6 months post-Tx and were compared with 27 control patients. There was a significant, but small, post-Tx improvement in AHI (from 44.2 ± 24.3 to 34.7 ± 20.9/h, P = .02) that significantly correlated with a reduction in fluid overload (from 1.8 ± 2.0 to 1.2 ± 1.2 L, P = .02) and body water (from 54.9% to 51.6%, P = .003). A post-Tx increase in body fat mass (from 26% to 30%, P = .003) possibly blunted the beneficial impact of kidney Tx on SA. All parameters remained unchanged in the control group. In conclusion, SA is a frequent condition in ESKD patients and partially improved by kidney Tx. We suggest that SA should be systematically assessed before and after kidney Tx. ClinicalTrials.gov Identifier: NCT02020642.

Long-Term Mechanical Ventilation: Recommendations of the Swiss Society of Pulmonology.

Long-term mechanical ventilation is a well-established treatment for chronic hypercapnic respiratory failure (CHRF). It is aimed at improving CHRF-related symptoms, health-related quality of life, survival, and decreasing hospital admissions. In Switzerland, long-term mechanical ventilation has been increasingly used since the 1980s in hospital and home care settings. Over the years, its application has considerably expanded with accumulating evidence of beneficial effects in a broad range of conditions associated with CHRF. Most frequent indications for long-term mechanical ventilation are chronic obstructive pulmonary disease, obesity hypoventilation syndrome, neuromuscular and chest wall diseases. In the current consensus document, the Special Interest Group of the Swiss Society of Pulmonology reviews the most recent scientific literature on long-term mechanical ventilation and provides recommendations adapted to the particular setting of the Swiss healthcare system with a focus on the practice of non-invasive and invasive home ventilation in adults.

Ultrashort echo time imaging of the lungs under high-frequency noninvasive ventilation: A new approach to lung imaging.

BACKGROUND: Although ultrashort echo time (UTE) sequences allow excellent assessment of lung parenchyma, image quality remains lower than that of computed tomography (CT). PURPOSE: To investigate a high-frequency noninvasive ventilation (HF-NIV) technique allowing a stabilized inspiration and to compare image quality with current dedicated MR sequences. STUDY TYPE: Prospective. POPULATION: Ten healthy volunteers. FIELD STRENGTH/SEQUENCE: 3D radial UTE sequence at 1.5T. ASSESSMENT: UTE-HF-NIV sequence was compared with UTE-free-breathing (UTE-FB), reconstructed at end expiration (UTE-Exp) and average (UTE-Avg), and breath-hold VIBE sequences. The distance from lung apex to the dome of the right hemidiaphragm was measured. Visual assessment of the visibility and sharpness of normal anatomical structures was carried out. Dedicated software also quantitatively evaluated vessel-lung and right lung-liver interface sharpness. Apparent signal ratio (Sr) and contrast ratios (Cr) were quantitatively evaluated. STATISTICAL TESTS: Wilcoxon signed rank test for visual scores, paired t-test for continuous variables, significance at P < 0.05. RESULTS: The distance between apex and the right hemidiaphragmatic dome was significantly larger (P < 0.001) with UTE-HF-NIV compared with UTE-FB and VIBE acquisitions. Vessel and airway visibility had identical median visual scores with all UTE methods. Median visual scores for sharpness of vessels and airways were significantly higher (P < 0.001) with HF-NIV (vessels = 3; airways = 2) than in UTE-FB (vessels = 2; airways = 1) and VIBE (vessels = 1; airways = 1). Software-based vessel sharpness evaluation resulted in larger values in 8/10 volunteers with UTE-HF-NIV (67.3 ± 9.8) compared with UTE-Avg (62.3 ± 12.6) but the average difference was not significant (P = 0.28). The sharpness of the lung-liver interface was significantly higher (P < 0.001) with HF-NIV (17.3 ± 5.3) compared with UTE-Avg (14.1 ± 3.9). Significantly higher values (P < 0.01) of Sr and Cr were observed with UTE-HF-NIV compared with UTE-FB and VIBE. DATA CONCLUSION: HF-NIV allowing acquisition at full inspiration significantly improves image quality for lung imaging. This could offer the option to alternate some follow-up CT studies by using this technique. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;50:1789-1797.

[Arterial hypertension and obstructive sleep apnea syndrome: state of knowledge]. / Hypertension artérielle et syndrome des apnées obstructives du sommeil†: état des connaissances.

Obstructive sleep apnea syndrome (OSAS) and arterial hypertension (HT) are two frequent, often concomitant diseases, who are both associated with an increased cardiovascular risk. In the last years, an association between these two entities has been established. The purpose of this article is to review the current knowledge about the link between HT and OSAS, the pathophysiological mechanisms involved in the common genesis of the two conditions and the characteristics suggesting an underlying OSAS in a hypertensive subject. We will also update readers about the current screening of OSAS in which primary care physicians are directly involved, and review the pros and cons of different treatment options for HT in OSAS.

Le syndrome des apnées obstructives du sommeil (SAOS) et l'hypertension artérielle (HTA) sont deux pathologies fréquentes, souvent concomitantes, qui sont toutes deux associées à un risque cardiovasculaire augmenté. Le but de cet article est de revoir l'état actuel des connaissances sur l'association entre HTA et SAOS, en se basant sur les mécanismes physiopathologiques impliqués dans la genèse commune aux deux conditions. L'article passe en revue les caractéristiques qui devraient faire suspecter un SAOS chez un sujet hypertendu et fait le point sur la démarche de dépistage du SAOS par le médecin traitant et sur les différentes options thérapeutiques à disposition pour le traitement de l'HTA associée au SAOS.

[Toxocariasis, a neglected disease in Switzerland ?] / Toxocarose : une maladie négligée en Suisse ?

Toxocariasis is a zoonotic disease that occurs when humans are infected by the parasites Toxocara canis or Toxocara cati. Toxocariasis is highly prevalent in tropical areas, but can also be found in industrialized countries, particularly in rural areas. Clinical presentation can range from asymptomatic infection to more severe disease. Diagnosis of toxocariasis is based on suggestive clinical findings, eosinophilia and a positive serological testing. Albendazole represents the first-line treatment, associated with corticosteroids in case of severe disease. Here we describe three clinical cases of toxocariasis in order to illustrate the clinical presentation, diagnosis and treatment of this unrecognized disease.

La toxocarose est une zoonose liée à l'infection de l'homme par Toxocara canis et Toxocara cati. Sa prévalence est élevée dans les zones tropicales, mais également dans les pays industrialisés, notamment dans les zones rurales. La plupart des formes sont asymptomatiques, se révélant par la présence d'une éosinophilie. Une dissémination, syndrome de larva migrans viscérale, et une atteinte oculaire, syndrome de larva migrans oculaire, sont les deux principaux syndromes. Le diagnostic de la toxocarose repose sur la présence d'une symptomatologie compatible, d'une éosinophilie et d'une sérologie positive. Le traitement de choix est l'albendazole, associé aux corticostéroïdes en cas d'atteinte sévère. Nous présentons trois cas de toxocarose, afin d'illustrer la présentation, le diagnostic et la prise en charge de cette infection méconnue.

Association between obesity and glomerular hyperfiltration: the confounding effect of smoking and sodium and protein intakes.

PURPOSE: Glomerular hyperfiltration has been suggested as a possible mechanism linking obesity and chronic kidney disease (CKD), independently of classical risk factors. We explored the association of overweight and obesity with glomerular hyperfiltration in a large sample of the Swiss adult population, accounting for several confounders including dietary factors. METHODS: Data from a 2010 to 2012 cross-sectional population-based survey in Switzerland were used. Creatinine clearance (CrCl) was determined from 24-h urine collection; CrCl > 140 ml/min was used to define glomerular hyperfiltration. Participants were categorized into lean (<25 kg/m(2)), overweight (25-29.9 kg/m(2)) and obese (≥30 kg/m(2)) according to body mass index (BMI). RESULTS: A total of 1339 participants were included in the analysis [median (IQR) age 49.4 (34.3-63.5) years, 48.9 % men]. The prevalences of overweight and obesity were 32.2 and 14.2 %, respectively. Median CrCl was 102[84-121] ml/min in lean, 110 [87-136] ml/min in overweight and 124 [97-150] ml/min in obese participants (p < 0.001). The prevalence of glomerular hyperfiltration increased across BMI categories (10.4, 20.8 and 34.7 %, respectively; p < 0.001). This positive association remained significant after adjusting for age, sex, hypertension, diabetes, smoking and dietary factors (sodium and protein intakes): odds ratio [95 %CI] 2.39 [1.52-3.76] (p < 0.001) for overweight versus lean and 4.10[2.31-7.27] (p < 0.001) for obesity versus lean. CONCLUSIONS: BMI categories and glomerular hyperfiltration are positively associated, independently of other known CKD risk factors and dietary confounders, suggesting that glomerular hyperfiltration may represent an early renal phenotype in obesity. Our observations confirm the significant association of glomerular hyperfiltration with sodium and protein intakes and identify sodium intake as an important modifying factor of the association between hyperfiltration and obesity.

Nocturnal hypoventilation in neuromuscular disease: prevalence according to different definitions issued from the literature.

PURPOSE: Restrictive respiratory failure is a major cause of morbidity and mortality in neuromuscular diseases (NMD). Home mechanical ventilation (HMV) is used to treat hypoventilation, identified by daytime hypercapnia or nocturnal desaturation. Recently, transcutaneous measure of CO2 (TcCO2) has been increasingly used to detect hypoventilation, using different cut-offs. We aimed to compare the prevalence of hypoventilation in an unselected adult NMD population according to different definitions issued from the literature. METHODS: All consecutive nocturnal capno-oximetries performed between 2010 and 2014 in unventilated adult NMD patients were analysed retrospectively. Concomitant blood gas analysis and lung function data were collected. Patients on oxygen therapy were excluded. Hypoventilation was defined according to eight criteria, based on daytime PaCO2, daytime base excess, nocturnal SpO2 or TcCO2. RESULTS: Data from 232 patients were analysed (mean age 43.1 ± 15.4 years; 50.0 % women; vital capacity 59.2 ± 24.2 % of predicted). The hypoventilation prevalence was 10.3 to 61.2 %, depending on the used definition. The different definitions showed 49.1 to 94.8 % concordance (Cohen's kappa for agreement 0.115 to 0.763). Overall agreement between the eight definitions was poor (Light's kappa 0.267), and agreement between definitions based on nocturnal SpO2 and those based on TcCO2 was even lower (Light's kappa 0.204). CONCLUSIONS: We found large differences in hypoventilation prevalence according to the used definition. This has practical consequences, as HMV indication relies upon hypoventilation detection. We believe that capno-oximetry should be included in the diagnostic tools used to detect hypoventilation but this requires an update of consensus guidelines to agree upon the best definition.

Accuracy of tidal volume delivered by home mechanical ventilation during mouthpiece ventilation: A bench evaluation.

The aim of our study was to evaluate efficacy and reliability of currently available ventilators for mouthpiece ventilation (MPV). Five life-support home ventilators were assessed in a bench test using different settings simulating the specificities of MPV, such as intermittent circuit disconnection and presence of continuous leaks. The intermittent disconnection of the circuit caused relevant swings in the delivered tidal volume ( VT), showing a VT overshoot during the disconnection periods and a VT decrease when the interface was reconnected to the test lung. The five ventilators showed substantial differences in the number of respiratory cycles necessary to reach a stable VT in the volume-controlled setting, ranging from 1.3 ± 0.6 to 7.3 ± 1.2 cycles. These differences were less accentuated in the volume-assisted setting (MPV-dedicated mode, when available). Our data show large differences in the capacity of the different ventilators to deal with the rapidly changing respiratory load features that characterize MPV, which can be further accentuated according to the used ventilator setting. The dedicated MPV modes allow improvement in the performance of ventilators only in some defined situations. This has practical consequences for the choice of the ventilator to be used for MPV in a specific patient.

New anthropometry-based age- and sex-specific reference values for urinary 24-hour creatinine excretion based on the adult Swiss population.

BACKGROUND: Urinary creatinine excretion is used as a marker of completeness of timed urine collections, which are a keystone of several metabolic evaluations in clinical investigations and epidemiological surveys. METHODS: We used data from two independent Swiss cross-sectional population-based studies with standardised 24-hour urinary collection and measured anthropometric variables. Only data from adults of European descent, with estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2 and reported completeness of the urinary collection were retained. A linear regression model was developed to predict centiles of the 24-hour urinary creatinine excretion in 1,137 participants from the Swiss Survey on Salt and validated in 994 participants from the Swiss Kidney Project on Genes in Hypertension. RESULTS: The mean urinary creatinine excretion was 193 ± 41 µmol/kg/24 hours in men and 151 ± 38 µmol/kg/24 hours in women in the Swiss Survey on Salt. The values were inversely correlated with age and body mass index (BMI). CONCLUSIONS: We propose a validated prediction equation for 24-hour urinary creatinine excretion in the general European population, based on readily available variables such as age, sex and BMI, and a few derived normograms to ease its clinical application. This should help healthcare providers to interpret the completeness of a 24-hour urine collection in daily clinical practice and in epidemiological population studies.

Prevalence of obesity and overweight and associated nutritional factors in a population-based Swiss sample: an opportunity to analyze the impact of three different European cultural roots.

PURPOSE: Obesity represents a growing public health concern worldwide. The latest data in Switzerland rely on self-reported body mass index (BMI), leading to underestimation of prevalence. We reassessed the prevalence of obesity and overweight in a sample of the Swiss population using measured BMI and waist circumference (WC) and explored the association with nutritional factors and living in different linguistic-cultural regions. METHODS: Data of 1,505 participants of a cross-sectional population-based survey in the three linguistic regions of Switzerland were analyzed. BMI and WC were measured, and a 24-h urine collection was performed to evaluate dietary sodium, potassium and protein intake. RESULTS: The prevalence of overweight, obesity and abdominal obesity was 32.2, 14.2 and 33.6%, respectively. Significant differences were observed in the regional distribution, with a lower prevalence in the Italian-speaking population. Low educational level, current smoking, scarce physical activity and being migrant were associated with an higher prevalence of obesity. Sodium, potassium and protein intake increased significantly across BMI categories. CONCLUSIONS: Obesity and overweight affect almost half of the Swiss adolescents and adults, and the prevalence appears to increase. Using BMI and WC to define obesity led to different prevalences. Differences were furthermore observed across Swiss linguistic-cultural regions, despite a common socio-economic and governmental framework. We found a positive association between obesity and salt intake, with a potential deleterious synergistic effect on cardiovascular risk.

Obstructive sleep apnea in the hemodialysis population: are clinicians putting existing scientific evidence into practice?

Introduction: Hemodialysis (HD) populations have a high prevalence of Obstructive Sleep Apnea (OSA), which was specifically linked with fluid overload. HD fluid management targeting a low dry weight was shown to reduce OSA severity, opening to novel therapeutic options. We assessed nephrologists' awareness of OSA diagnosis in HD patients and whether they integrate the current knowledge into their fluid management strategy. Material and methods: We performed a multicenter, cross-sectional study between July 2022 and July 2023, screening all HD patients of four HD units, and included those with confirmed OSA. We collected anthropometric parameters and fluid status from electronic dossiers. Predialysis fluid overload was measured by multifrequency bioelectrical impedance (BCM®). Nephrologists were asked to identify patients with known OSA, without consulting medical dossiers. The fluid management of patients identified as "OSA positive" was compared to that of patients misclassified as "OSA negative". Results: Among 193 HD patients, 23.0% (n=45) had confirmed OSA. The mean age was 76.0 ± 7.5 years, 82.2% were men. Only 60% were correctly identified as "OSA positive" by nephrologists; 14.7% of patients on CPAP were identified. BMI was the only factor associated with correct OSA identification. The predialysis fluid overload tended to be greater in "OSA positive" patients than in the "OSA negative" patients (2.2 ± 1.4 kg vs 1.5 ± 1.3 kg; p=0.08), but there was no difference in postdialysis achievement of dry weight between the groups (residual overweight 0.2 ± 1.0 kg and 0.1 ± 0.7 kg; p= 0.672). Conclusions: Our study suggests that the application of scientific evidence to the management of OSA in dialysis patients is not systematic. However, nephrologists have attempted to strictly achieve dry weight in all patients, regardless of OSA status. Sensibilization of nephrologists on the clinical and diagnostic peculiarities of OSA in HD patients may improve OSA diagnosis and therapeutic care.

Integrating Pharmacomechanical Treatments for Pulmonary Embolism Management within a Hub-and-Spoke System in the Swiss Ticino Region.

The Swiss Ticino regional pulmonary embolism response team (PERT) features direct access to various pharmacomechanical PE management options within a hub/spoke system, by integrating evidence, guidelines' recommendations and personal experiences. This system involves a collaborative management of patients among the hospitals distributed throughout the region, which refer selected intermediate-high or high PE patients to a second-level hub center, located in Lugano at Cardiocentro Ticino, belonging to the Ente Ospedaliero Cantonale (EOC). The hub provides 24/7 catheterization laboratory activation for catheter-based intervention (CBI), surgical embolectomy and/or a mechanical support system such as extracorporeal membrane oxygenation (ECMO). The hub hosts PE patients after percutaneous or surgical intervention in two intensive care units, one specialized in cardiovascular anesthesiology, to be preferred for patients without relevant comorbidities or with hemodynamic instability and one specialized in post-surgical care, to be preferred for PE patients after trauma or surgery or with relevant comorbidities, such as cancer. From April 2022 to December 2023, a total of 65 patients were referred to the hub for CBI, including ultrasound-assisted catheter-directed thrombolysis (USAT) or large-bore aspiration intervention. No patient received ECMO or underwent surgical embolectomy.

Reticulocyte dynamic and hemoglobin variability in hemodialysis patients treated with Darbepoetin alfa and C.E.R.A.: a randomized controlled trial.

BACKGROUND: In a simulation based on a pharmacokinetic model we demonstrated that increasing the erythropoiesis stimulating agents (ESAs) half-life or shortening their administration interval decreases hemoglobin variability. The benefit of reducing the administration interval was however lessened by the variability induced by more frequent dosage adjustments. The purpose of this study was to analyze the reticulocyte and hemoglobin kinetics and variability under different ESAs and administration intervals in a collective of chronic hemodialysis patients. METHODS: The study was designed as an open-label, randomized, four-period cross-over investigation, including 30 patients under chronic hemodialysis at the regional hospital of Locarno (Switzerland) in February 2010 and lasting 2 years. Four subcutaneous treatment strategies (C.E.R.A. every 4 weeks Q4W and every 2 weeks Q2W, Darbepoetin alfa Q4W and Q2W) were compared with each other. The mean square successive difference of hemoglobin, reticulocyte count and ESAs dose was used to quantify variability. We distinguished a short- and a long-term variability based respectively on the weekly and monthly successive difference. RESULTS: No difference was found in the mean values of biological parameters (hemoglobin, reticulocytes, and ferritin) between the 4 strategies. ESAs type did not affect hemoglobin and reticulocyte variability, but C.E.R.A induced a more sustained reticulocytes response over time and increased the risk of hemoglobin overshooting (OR 2.7, p = 0.01). Shortening the administration interval lessened the amplitude of reticulocyte count fluctuations but resulted in more frequent ESAs dose adjustments and in amplified reticulocyte and hemoglobin variability. Q2W administration interval was however more favorable in terms of ESAs dose, allowing a 38% C.E.R.A. dose reduction, and no increase of Darbepoetin alfa. CONCLUSIONS: The reticulocyte dynamic was a more sensitive marker of time instability of the hemoglobin response under ESAs therapy. The ESAs administration interval had a greater impact on hemoglobin variability than the ESAs type. The more protracted reticulocyte response induced by C.E.R.A. could explain both, the observed higher risk of overshoot and the significant increase in efficacy when shortening its administration interval. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01666301.

Resuming Swallowing and Oral Feeding in Tracheostomized COVID-19 Patients: Experience of a Swiss COVID-Center and Narrative Literature Review.

During the COVID-19 pandemic, percutaneous tracheostomy proved to be an effective option in the management of patients with prolonged periods of intubation. In fact, among other things, it allowed early discharge from ICUs and contributed to reducing overcrowding in intensive care settings, a central and critical point in the COVID pandemic. As a direct consequence, the management and the weaning of frail, tracheostomized and ventilated patients was diverted to sub-intensive or normal hospitalization wards. One central challenge in this setting is the resumption of swallowing and oral feeding, which require interdisciplinary management involving a phoniatrician, ENT, pneumologist, and speech therapist. With this article, we aim to share the experience of a Swiss COVID-19 Center and to draw up a narrative review on the issues concerning the management of the tracheostomy cannula during swallowing resumption, integrating the most recent evidence from the literature with the clinical experiences of the professionals directly involved in the management of tracheostomized COVID-19 patients. In view of the heterogeneity of COVID-19 patients, we believe that the procedures described in the article are applicable to a larger population of patients undergoing tracheostomy weaning.

[Late-onset asthma]. / Asthme a début tardif.

Late-onset asthma is a common disease, with characteristics that differentiate it from childhood asthma persisting in adults, including a heterogeneity of underlying mechanism, a correlation with occupational exposure and the tendency to chronicize. Inadequate perception of the disease importance and difficulties in diagnosis, due to the association to COPD, the broad differential diagnosis spectrum and an atypical clinical manifestation, make this disease entity underdiagnosed and under-treated, with consequences for morbidity and mortality. The treatment of adults with asthma follows the usual guidelines, but must take into account an occasional poor therapeutic response and the risk of side effects in polymorbid patients.

Nutritional status, swallowing disorders, and respiratory prognosis in adult Duchenne muscular dystrophy patients.

Malnutrition and swallowing disorders are common in Duchenne muscular dystrophy (DMD) patients. We assessed, in adult DMD with home mechanical ventilation (HMV) and cough assist device, its prevalence and the relationships with respiratory muscle strength and long-term respiratory prognosis. We reviewed the patients (n = 117, age 18-39 years [median 24]), followed in a reference center, from 2006 to 2015, to obtain clinical baseline, nutritional status, vital capacity (VC), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP). The median body mass index (BMI) was low (15.6 kg/m²). Included patients had severe restrictive respiratory function with a median VC of 10.5% [7-17] of the predicted value. All patients were on HMV. Prevalence of malnutrition, swallowing disorders, and gastrostomy were respectively 62%, 34%, and 11%. BMI and serum albumin level were significantly associated with MIP, MEP, and VC. The 1-year/5-years cumulative incidences of respiratory events (pulmonary sepsis and acute respiratory distress) were, respectively, 20.7%/44.5%. Using univariate analysis, predictive factors for respiratory events were swallowing disorders (p = .001), transthyretinemia (p = .034), MIP (p = .039), and MEP (p = .03) but not BMI or albuminemia. Using multivariate analysis, only swallowing disorders remained significantly associated with respiratory events (OR = 4.2, IC 95% 1.31-12.2, p = .01). In conclusion, this study highlights the interrelationships between nutritional intake, swallowing function, airway clearance, and respiratory function in adult DMD. A multidisciplinary approach focusing on these previous factors is essential to optimize DMD patient health.

Mouthpiece ventilation in neuromuscular disorders: Narrative review of technical issues important for clinical success.

In neuromuscular disorders (NMDs), nocturnal non-invasive ventilation (NIV) via a nasal mask is offered when hypercapnic respiratory failure occurs. With disease progression, nocturnal NIV needs to be extended into the daytime. Mouthpiece ventilation (MPV) is an option for daytime NIV. MPV represents a difficult task for home ventilators due to rapidly changing load conditions resulting from intermittent connections and disconnections from MPV circuit. The 252nd ENMC International Expert Workshop, held March 6th to 8th 2020 in Amsterdam, reported general guidelines for management of daytime MPV in NMDs. This report could not present all the detail regarding the technical issues important for clinical success of MPV. Based on the expert workshop discussions and the evidence from existing studies, the current narrative review aims to identify the technical issues of MPV and offers guidance via a decisional algorithm and educational figures providing relevant information that is important for successful implementation of MPV.