The cost-effectiveness of physician assistants/associates: A systematic review of international evidence.

BACKGROUND: The global utilization of the physician assistant/associate (PA) is growing. Their increasing presence is in response to the rising demands of demographic changes, new developments in healthcare, and physician shortages. While PAs are present on four continents, the evidence of whether their employment contributes to more efficient healthcare has not been assessed in the aggregate. We undertook a systematic review of the literature on PA cost-effectiveness as compared to physicians. Cost-effectiveness was operationalized as quality, accessibility, and the cost of care. METHODS AND FINDINGS: Literature to June 2021 was searched across five biomedical databases and filtered for eligibility. Publications that met the inclusion criteria were categorized by date, country, design, and results by three researchers independently. All studies were screened with the Risk of Bias in Non-randomised Studies-of Interventions (ROBIN-I) tool. The literature search produced 4,855 titles, and after applying criteria, 39 studies met inclusion (34 North America, 4 Europe, 1 Africa). Ten studies had a prospective design, and 29 were retrospective. Four studies were assessed as biased in results reporting. While most studies included a small number of PAs, five studies were national in origin and assessed the employment of a few hundred PAs and their care of thousands of patients. In 34 studies, the PA was employed as a substitute for traditional physician services, and in five studies, the PA was employed in a complementary role. The quality of care delivered by a PA was comparable to a physician's care in 15 studies, and in 18 studies, the quality of care exceeded that of a physician. In total, 29 studies showed that both labor and resource costs were lower when the PA delivered the care than when the physician delivered the care. CONCLUSIONS: Most of the studies were of good methodological quality, and the results point in the same direction; PAs delivered the same or better care outcomes as physicians with the same or less cost of care. Sometimes this efficiency was due to their reduced labor cost and sometimes because they were more effective as producers of care and activity.

Physician Assistants and Nurse Practitioners in Primary Care Plus: A Systematic Review.

INTRODUCTION: Shifting specialist care from the hospital to primary care/community care (also called primary care plus) is proposed as one option to reduce the increasing healthcare costs, improve quality of care and accessibility. The aim of this systematic review was to get insight in primary care plus provided by physician assistants or nurse practitioners. METHODS: Scientific databases and reference list were searched. Hits were screened on title/abstract and full text. Studies published between 1990-2018 with any study design were included. Risk of bias assessment was performed using QualSyst tool. RESULTS: Search resulted in 5.848 hits, 15 studies were included. Studies investigated nurse practitioners only. Primary care plus was at least equally effective as hospital care (patient-related outcomes). The number of admission/referral rates was significantly reduced in favor of primary care plus. Barriers to implement primary care plus included obtaining equipment, structural funding, direct access to patient-data. Facilitators included multidisciplinary collaboration, medical specialist support, protocols. CONCLUSIONS AND DISCUSSION: Quality of care within primary care plus delivered by nurse practitioners appears to be guaranteed, at patient-level and professional-level, with better access to healthcare and fewer referrals to hospital. Most studies were of restricted methodological quality. Findings should be interpreted with caution.

[Physician assistant for the somatic care in the mental health care]. / Physician assistant voor de somatische zorg binnen de ggz.

.

Liposome-encapsulated dexamethasone attenuates ventilator-induced lung inflammation.

BACKGROUND AND PURPOSE: Systemic glucocorticoid therapy may effectively attenuate lung inflammation but also induce severe side-effects. Delivery of glucocorticoids by liposomes could therefore be beneficial. We investigated if liposome-encapsulated dexamethasone inhibited ventilator-induced lung inflammation. Furthermore, we evaluated whether targeting of cellular Fcγ-receptors (FcγRs) by conjugating immunoglobulin G (IgG) to liposomes, would improve the efficacy of dexamethasone-liposomes in attenuating granulocyte infiltration, one of the hallmarks of lung inflammation. EXPERIMENTAL APPROACH: Mice were anaesthetized, tracheotomized and mechanically ventilated for 5 h with either 'low' tidal volumes ∼7.5 mL·kg(-1) (LV(T) ) or 'high' tidal volumes ∼15 mL·kg(-1) (HV(T) ). At initiation of ventilation, we intravenously administered dexamethasone encapsulated in liposomes (Dex-liposomes), dexamethasone encapsulated in IgG-modified liposomes (IgG-Dex-liposomes) or free dexamethasone. Non-ventilated mice served as controls. KEY RESULTS: Dex-liposomes attenuated granulocyte infiltration and IL-6 mRNA expression after LV(T) -ventilation, but not after HV(T) -ventilation. Dex-liposomes also down-regulated mRNA expression of IL-1ß and KC, but not of CCL2 (MCP-1) in lungs of LV(T) and HV(T) -ventilated mice. Importantly, IgG-Dex-liposomes inhibited granulocyte influx caused by either LV(T) or HV(T) -ventilation. IgG-Dex-liposomes diminished IL-1ß and KC mRNA expression in both ventilation groups, and IL-6 and CCL2 mRNA expression in the LV(T) -ventilated group. Free dexamethasone prevented granulocyte influx and inflammatory mediator expression induced by LV(T) or HV(T) -ventilation. CONCLUSIONS AND IMPLICATIONS: FcγR-targeted IgG-Dex-liposomes are pharmacologically more effective than Dex-liposomes particularly in inhibiting pulmonary granulocyte infiltration. IgG-Dex-liposomes inhibited most parameters of ventilator-induced lung inflammation as effectively as free dexamethasone, with the advantage that liposome-encapsulated dexamethasone will be released locally in the lung thereby preventing systemic side-effects.

The effects of protein ingestion on GH concentrations in visceral obesity.

Growth hormone (GH), a hormone originating from the anterior pituitary gland, is an important regulator of metabolism and body composition. Low GH secretion is associated with features of the metabolic syndrome, in particular increased visceral body fat and decreased lean body mass. It has been shown that GH release can be promoted by ingestion of protein, in particular gelatin protein. The question remains; is the GH-promoting effect of gelatin protein also present in a population with blunted GH response, such as visceral obesity? 8 lean women (age: 23+/-3 years, BMI: 21.6+/-2.0 kg/m (2)) and 8 visceral obese women (age: 28+/-7 years, BMI: 33.8+/-5.5 kg/m (2)) were compared with regard to their 5-h GH response after oral ingestion of gelatin protein (0.6 g protein per kg bodyweight), placebo (water), or injection of growth hormone releasing hormone (GHRH) (1 mu/kg body weight), in a randomized crossover design. GH response after placebo, gelatin protein, or GHRH was higher in lean subjects than in visceral obese subjects (p<0.05). Ingestion of gelatin protein increased GH response compared with placebo in both visceral obese (182.1+/-81.6 microg/l.5 h vs. 28.4+/-29.8 microg/l.5 h) and lean (631.7+/-144.2 microg/l.5 h vs. 241.0+/-196.8 microg/l.5 h) subjects (p<0.05). GH response after ingestion of gelatin protein in visceral obese did not differ from that in lean, placebo-treated subjects (p=0.45). GH concentrations after GHRH injection correlated significantly with GH concentrations after gelatin ingestion (AUC; r=0.71, p<0.01, Peak; r=0.81, p<0.01). Further research is needed to investigate if gelatin protein is able to improve metabolic abnormalities in hyposomatotropism in the long term or to investigate the relevance of protein as diagnostic tool in hyposomatotropism.

The effects of dietary protein on the somatotropic axis: a comparison of soy, gelatin, alpha-lactalbumin and milk.

BACKGROUND/OBJECTIVES: Growth hormone (GH) is an important regulator of growth and body composition. It has been shown that GH release can be promoted by administration of various amino acids (AAs), such as arginine and lysine, that are present in soy protein. We previously showed that oral ingestion of soy protein stimulates the GH release, it is not known however to which extent other proteins stimulate the GH secretion. SUBJECTS/METHODS: Ingestion of soy protein (soy), gelatin protein (gelatin), alpha-lactalbumin protein (alpha-lactalbumin) and milk protein (milk) were compared on their GH-stimulating capacity. After oral ingestion of protein (0.6 g protein per kg bodyweight), blood was sampled every 20 min for 5 h to analyze GH, AA, insulin and glucose concentrations. The study was performed in eight healthy women (aged 19-26 years; body mass index 19-26 kg/m(2)) in a randomized, single blind, placebo-controlled crossover design. RESULTS: GH responses were more increased after ingestion of gelatine (8.2+/-1.1 microg/l) compared with ingestion of soy, alpha-lactalbumin and milk (5.0+/-0.8, 4.5+/-0.6 and 6.4+/-1.0 microg/l, respectively) (P<0.05). After ingestion of each protein, GH responses were higher compared with placebo ingestion (P<0.05). Simultaneously ingestion of gelatin resulted in the highest serum-arginine concentrations (ARG) compared with after ingestion of the other proteins (P<0.05). Insulin as well as glucose concentrations were not different after ingestion of the various proteins (P<0.05). CONCLUSIONS: The GH-promoting activity of protein depends on the protein source, in that, gelatin protein is the most potent GH stimulator. Arginine may be the responsible AA in the GH-promoting effect of gelatin, although each protein may have its own specific AA-spectrum involved in the stimulation of the somatotropic axis.

Respiratory inductive plethysmography accuracy at varying PEEP levels and degrees of acute lung injury.

BACKGROUND AND OBJECTIVE: This study was performed to assess the accuracy of respiratory inductive plethysmographic (RIP) estimated lung volume changes at varying positive end-expiratory pressures (PEEP) during different degrees of acute respiratory failure. METHODS: Measurements of inspiratory tidal volume were validated in eight piglets during constant volume ventilation at incremental and decremental PEEP levels and with increasing severity of pulmonary injury. RIP accuracy was assessed with calibration from the healthy state, from the disease state as the measurement error was assessed, and at various PEEP levels. RESULTS: Best results (bias 3%, precision 7%) were obtained in healthy animals. RIP accuracy decreased with progressing degrees of acute respiratory failure and was PEEP dependent, unless RIP was calibrated again. When calibration was performed in the disease state as the measurement error was assessed, bias was reduced but precision did not improve (bias -2%, precision 9%). CONCLUSIONS: RIP accuracy is within the accuracy range found in monitoring devices currently in clinical use. Most reliable results with RIP are obtained when measurements are preceded by calibration in pulmonary conditions that are comparable to the measurement period. When RIP calibration is not possible, fixed weighting of the RIP signals with species and subject size adequate factors is an alternative. Measurement errors should be taken into account with interpretation of small volume changes.

Mechanical ventilation of healthy rats suppresses peripheral immune function.

This study was designed to investigate the possible effect of injurious mechanical ventilation on peripheral immune function of healthy rats. Three ventilation strategies were compared: 1) low peak inspiratory pressure (PIP)/positive end-expiratory pressure (PEEP); 2) high PIP/PEEP; and 3) high PIP/zero PEEP (ZEEP). As a reference group, healthy, nonventilated, sham-operated, anaesthetised rats were used. After 4 h, rats were sacrificed and macrophage inflammatory protein (MIP)-2 levels in lung and plasma were determined. Peripheral immune function was determined by measurement of splenic natural killer (NK) activity, mitogen-induced splenocyte proliferation and in vitro cytokine production. All immune measurements in the low PIP/PEEP group did not differ from the immune measurements in the reference group. High PIP strategies, irrespective of applied PEEP, enhanced MIP-2 levels in lung and plasma. NK cell activity, mitogen-induced splenocyte proliferation and MIP-2 and interleukin (IL)-10 production significantly decreased after high PIP/PEEP ventilation. In the high PIP/ZEEP-ventilated group, the decrease in splenocyte proliferation, MIP-2 and IL-10 production and NK cell activity was more pronounced and interferon-gamma production was also significantly lower than in the low PIP/PEEP group. These data show that high positive inspiratory pressure ventilation induces an inflammatory response in the lung, whereas at the same time the peripheral immune response is downregulated. Ventilator-induced peripheral immune suppression may contribute to poor outcome in acute respiratory distress syndrome patients.

A system for integrated measurement of ventilator settings, lung volume change and blood gases during high-frequency oscillatory ventilation.

To describe and validate a system for integrated measurement of ventilator settings and dependent physiological variables during high-frequency oscillatory ventilation (HFOV). A custom interface was built for data acquisition. Lung volume change was determined by respirator inductive plethysmography (RIP), modified to sampling rates of 140 Hz. Blood gas analysis was obtained using a continuous intra-arterial blood gas monitoring system. FIO2 was measured by means of an electrochemical sensor. Pressure at the airway opening and trachea (microtip transducer) were sampled. The data acquired were sent to a laptop computer for analysis, display and storage. The system was tested during a lung recruitment procedure in an animal model of respiratory distress. Linearity of the RIP was checked by gas volume injection using a supersyringe. The system operated successfully. Agreement between RIP-measured volume with injected volume was excellent; bias was 5 ml; limits of agreement were 1-9 ml. Graphs were obtained, showing the relationship between imposed mean airway pressure and lung volume change, and oxygenation. The integration of ventilator settings and dependent physiological variables may provide useful information for clinical, instructional and research application.

Dexamethasone for treatment of patients mechanically ventilated for lower respiratory tract infection caused by respiratory syncytial virus.

BACKGROUND: A study was undertaken to evaluate the efficacy of dexamethasone in patients mechanically ventilated for lower respiratory infection caused by respiratory syncytial virus (RSV-LRTI). METHODS: In a multicentre randomised controlled trial patients were randomised to receive either intravenous dexamethasone (0.15 mg/kg 6 hourly for 48 hours) or placebo. End points were the duration of mechanical ventilation, length of stay (LOS) in the pediatric intensive care unit (PICU) and in hospital, and the duration of supplemental oxygen administration. RESULTS: Thirty seven patients received dexamethasone and 45 received placebo. There was no significant difference in any of the end points between the two groups. In a post hoc analysis patients were stratified into those with mild gas exchange anomalies (PaO(2)/FiO(2) >200 mm Hg and/or mean airway pressure 10 cm H(2)O, pneumonia group). In the 39 patients with bronchiolitis the duration of mechanical ventilation was 4.3 days shorter in the dexamethasone group than in the placebo group (4.9 v 9.2 days, 95% CI -7.8 to -0.8, p=0.02) and the duration of supplemental oxygen was 3.6 days shorter (7.7 v 11.3 days, 95% CI -8.0 to -0.1, p=0.048). No differences in end points were found in the pneumonia group. CONCLUSIONS: Dexamethasone had no beneficial effect in patients mechanically ventilated for RSV-LRTI but was found to have a beneficial effect in patients with bronchiolitis.

[Fulminating pneumococcal septicemia in a 2 year old child with sickle cell anemia]. / Fulminant verlopende pneumokokkensepsis bij een 2-jarig kind met sikkelcelanemie.

A 2-year-old boy known with homozygous sickle cell anaemia became acutely ill at home. Despite intensive care, he died a few hours later due to pneumococcal septicaemia. In young children with homozygous sickle cell anaemia, spleen function is already severely impaired in childhood due to haemolysis and frequent vaso-occlusive episodes. These children therefore have an elevated susceptibility to severe invasive infections with encapsulated bacteria. Vaccination against pneumococci at-2 years of age, re-vaccination every 3-5 years, and antibiotic prophylaxis until 5 years of age, and thereafter with possible infections, are therefore necessary.

[Tetanus in a young unvaccinated girl after a fall in the street]. / Tetanus bij een jong ongevaccineerd meisje na een val op straat.

A 4-year-old girl developed tetanus after she had fallen on the street a week before. She had never been vaccinated and despite pressure from the family practitioner, the parents refused to allow her to be given human anti-tetanus immunoglobulin as a matter of principle after the wound had been stitched. Seven days later she was admitted to hospital with trismus and risus sardonicus. Upon initial treatment with human anti-tetanus immunoglobulin and penicillin, and subsequently metronidazole, her clinical condition deteriorated with opisthotonus and life-threatening respiratory insufficiency, upon which she was moved to the intensive-care department where she was intubated and mechanically ventilated for two weeks. Finally she made a complete clinical recovery. Thanks to the extensive national vaccination program, tetanus has become a rare disease in the Netherlands. However, the very serious course and possible fatal outcome warrant a keen attitude and adequate treatment.

Once-daily versus multiple-daily gentamicin in infants and children.

In this prospective randomized trial, the efficacy and safety of once-daily administration of gentamicin were compared with multiple-daily administration in infants and children. In addition, pharmacokinetic variables were calculated. Gentamicin therapy was started at a dose of 5 mg/kg per day under individual dose or dosage interval adjustments to achieve target levels. Fifty-two infants and children aged 1 month (postterm) to 16 years were enrolled. The duration of fever from the start of therapy, the percentage decline of C-reactive protein (CRP) on day 3 of treatment, and the clinical outcome were used as efficacy parameters. Nephrotoxicity was evaluated using creatinine serum levels. Basic characteristics in both groups were comparable. A good clinical response was observed in both groups. Fever may have resolved faster with multiple-daily administration, but this was not statistically significant. The percentage of decline of CRP was also comparable in both groups. Nephrotoxicity occurred in six patients, three per group. Many patients were too ill or too young to perform hearing tests, but no clinical signs of ototoxicity were observed. Mean doses of 6.8 mg/kg per day (multiple-daily administration) and 7.3 mg/kg per day (once-daily administration) were necessary to meet the target gentamicin levels. Triple-daily doses had to be reduced to a twice-daily regimen in 17 of 26 children. Dose and dosage interval adaptations can be performed by Bayesian forecasting using a one-compartment model with one set of K(e) and V(d) parameters. The authors consider both regimens equally effective, with a comparable incidence of nephrotoxicity. A starting dose of 6.5 mg/kg once daily is advised.

Reduction of oscillatory pressure along the endotracheal tube is indicative for maximal respiratory compliance during high-frequency oscillatory ventilation: a mathematical model study.

We hypothesized that during high-frequency oscillatory ventilation (HFOV), a reduction of peak-to-peak oscillatory pressure along the endotracheal tube is maximal when respiratory system compliance is maximal. We made a mathematical model of the endotracheal tube and the respiratory system of a neonate suffering from idiopathic respiratory distress syndrome (IRDS). The model consisted of linear viscous and inertive elements, a non-linear endotracheal tube resistance, and a non-linear compliance allowing for alveolar recruitment and overdistention. Respiratory compliance was maximal at the transition between maximal recruitment and minimal overdistention. A new variable, the oscillatory pressure ratio (OPR), was defined as the ratio between peak-to-peak oscillatory pressures at the distal end and the proximal opening of the endotracheal tube, respectively. The respiratory variables of four patients were fed into the model, and the relationship between respiratory system compliance and OPR was determined. OPR decreased as compliance increased, except for very low compliances below where 0.08 mL. cm H2O(-1), and OPR increased with increasing compliance. The relationship between mean airway pressure P(aw) and OPR revealed that the minimal OPR (range, 0.37-0.78) and maximal respiratory compliance coincided at the same P(aw). However, the relationship did depend on oscillation frequency, applied oscillatory pressure, and endotracheal tube resistance, parameters that may change during clinical application of HFOV. When 81 permutations of nominal and extreme respiratory variables were used in the model, the minimum OPR (0.60 +/- 0.23) and maximum compliance coincided in all cases. These model experiments support our hypothesis. The results indicate that the OPR may be a useful index to optimize lung expansion, where lung recruitment is maximal and overdistention minimal. In vivo tests will be needed to reveal the feasibility and reliability of such an index for biomedical and clinical application.

Status asthmaticus treated by high-frequency oscillatory ventilation.

We present a 2.5-year-old girl in severe asthma crisis who clinically deteriorated on conventional mechanical ventilation, but was successfully ventilated with high-frequency oscillatory ventilation (HFOV). Although HFOV is accepted as a technique for managing pediatric respiratory failure, its use in obstructive airway disease is generally thought to be contraindicated because of the risk of dynamic air-trapping. However, we suggest that obstructive airway disease can safely be managed with HFOV, provided certain conditions are met. These include the application of sufficiently high mean airway pressures to open and stent the airways ("an open airway strategy"), lower frequencies to overcome the greater attenuation of the oscillatory waves in the narrowed airways, permissive hypercapnia to enable reducing pressure swings as much as possible, longer expiratory times, and muscle paralysis to avoid spontaneous breathing.

Pediatric risk of mortality (PRISM) score in meningococcal disease.

UNLABELLED: To assess the pediatric risk of mortality (PRISM) score as a prognostic scoring system in severe meningococcal disease, the files of 53 consecutive patients admitted to a tertiary pediatric intensive care with a clinical diagnosis of meningococcal disease and positive cultures from blood and/or cerebrospinal fluid were analysed. PRISM-score-based expected mortality was compared with observed mortality. Expected mortality in the whole study population was 29% while observed mortality was 19% (P<0.05). The highest expected and observed mortality was found in septicaemic patients without (documented) meningitis, while meningitis patients without septicaemia had the lowest mortality. All patients with a mortality risk below 18.3% (n = 29) survived whereas all those with a mortality risk of 65% or higher (n = 7) died. Of the 17 patients with a mortality risk between 18.3% and 63.9%, 14 survived and 3 died. The area under the receiver-operating characteristic (ROC) curve was 0.94, which is at least comparable with the best-performing meningococcal-disease-specific scoring systems. CONCLUSION: The PRISM score is a useful generic measure of severity of illness in meningococcal disease and can be used to determine the effectiveness of different treatment strategies.

Monocyte interleukin-12 production is inversely related to duration of respiratory failure in respiratory syncytial virus bronchiolitis.

The correlation of clinical and immunological parameters with the duration of respiratory failure was investigated to identify factors determining the clinical outcome of respiratory syncytial virus (RSV) bronchiolitis necessitating mechanical ventilation. At initiation of mechanical ventilation in 30 patients with RSV, production of interleukin (IL)-12 and IL-10 was measured in 48-h peripheral blood cell cultures that were stimulated with lipopolysaccharide and interferon-gamma. The ventilation index (VI)-an indicator of respiratory dysfunction that includes partial pressure of arterial CO2, peak airway pressure, and respiratory rate-correlated with the duration of mechanical ventilation (r=.47; P=.013). Age was not associated with the duration of mechanical ventilation. A highly significant inverse correlation was found between the duration of mechanical ventilation and the production of IL-12 at admission (r=-.62; P<.001). This correlation was independent of VI. No correlation was found between IL-10 production and the duration of mechanical ventilation. It is hypothesized that low monocyte IL-12 response during initial RSV infection adversely affects clinical outcome of patients with severe RSV bronchiolitis.