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.

Feed intake patterns nor growth rates of pigs are affected by dietary resistant starch, despite marked differences in digestion.

Current feed evaluation systems often assume that fermented starch (i.e. resistant starch (RS)) yields less energy than digested starch. However, growth rates of pigs fed low and high RS diets are often the same when feed is available ad libitum. This may be explained by its effect on digestive processes changing feeding behavior, and consequently energy utilization. This study aims to investigate the effect of RS on nutrient digestion and digesta passage rate in pigs, in combination with its effect on feeding behavior and growth performance under ad libitum conditions. In experiment 1, 20 male pigs (40 ± 2.82 kg) were fed diets containing either 50% waxy maize starch (low in RS (LRS)) or high-amylose maize starch (high in RS (HRS)), and soluble and insoluble indigestible markers. After 14 days of adaptation to the diets, pigs were fed hourly to reach steady state (6 h), dissected, and digesta were collected from eight segments. From the collected samples, nutrient digestion and passage rate of the solid and liquid digesta fraction were determined. In experiment 2, 288 pigs (80 ± 0.48 kg; sex ratio per pen 1 : 1; boar : gilt) were housed in groups of 6. Pigs were ad libitum-fed one of the experimental diets, and slaughtered at approximately 115 kg. Feed intake, growth and carcass parameters were measured. Ileal starch digestibility was greater for LRS-fed than for HRS-fed pigs (98.0% v. 74.0%; P < 0.001), where the additional undigested starch in HRS-fed pigs was fermented in the large intestine. No effects of RS on digesta passage rate of the solid or liquid digesta fraction and on feeding behavior were observed. Growth rate and feed intake did not differ between diets, whereas feed efficiency of HRS-fed pigs was 1%-unit higher than that of LRS-fed pigs (P = 0.041). The efficiency of feed used for carcass gain did not differ between diets indicating that the difference in feed efficiency was determined by the non-carcass fraction. Despite a 30% greater RS intake (of total starch) with HRS than with LRS, carcass gain and feed efficiency used for carcass gain were unaffected. RS did not affect digesta passage rate nor feeding behavior suggesting that the difference in energy intake between fermented and digested starch is compensated for post-absorptively. Our results indicate that the net energy value of fermented starch currently used in pig feed evaluation systems is underestimated and should be reconsidered.

[Symptomatic hyponatremia in a 43-year-old woman after a skiing accident with head injuries]. / Symptomatische Hyponatriämie bei einer 43-Jährigen nach Skiunfall mit Kopftrauma.

This article reports the case of a 43-year-old woman who presented to the emergency room with headache and paresthesia after a fall on the head while skiing. She had clinical signs of volume depletion and blood test showed severe hyponatremia. Cerebral imaging was unremarkable. The diagnosis of cerebral salt-wasting syndrome (CSWS) was made, which is defined by the presence of extracellular volume depletion due to a tubular defect in renal sodium transport in patients with normal adrenal and thyroid function. The disease is mostly secondary to a neurological disease or head trauma. The patient rapidly improved after volume therapy and treatment with mineralocorticoids. The differentiation of CSWS from the syndrome of inappropriate antidiuretic hormone (SIADH) secretion can be challenging but the distinction is important because treatment options are very different.

Development and content of the biopsychosocial primary care intervention 'Back on Track' for a subgroup of people with chronic low back pain.

Biopsychosocial interventions provided in multidisciplinary settings are promising for improving functional disability levels in patients with chronic low back pain (CLBP). These multidisciplinary biopsychosocial interventions mainly focus on cognitive-behavioural approaches that aim to change negative cognitions, emotions, behaviour, work and social factors. As some patients with CLBP treated in primary care settings also experience psychosocial factors that influence their level of disability, these patients may benefit from the provision of a biopsychosocial intervention in primary care. This paper will provide a detailed description of the development and content of the biopsychosocial primary care intervention 'Back on Track' for this specific subgroup of patients. The Back on Track intervention was developed based on available scientific evidence and clinical experience from multidisciplinary pain rehabilitation programmes, and its effectiveness is currently being tested. CLINICAL TRIAL REGISTRATION NUMBER: NCT02220543.

Characterization of monoclonal antibodies physically adsorbed onto polystyrene latex particles.

The physicochemical and immunochemical properties of monoclonal antibodies (MAbs), adsorbed onto polystyrene latex particles, have been investigated. Both native and pH 2 pretreated MAbs were compared before and after immobilization. It was found that the antigen binding capacity of the immobilized, acidic pretreated MAbs was significantly higher than for the immobilized, native IgG molecules. This enhanced antigen binding capacity appeared to be due to an improved molecular orientation following adsorption of the monomeric, pH 2 treated IgG fraction. Additionally, experiments using F(ab')2 fragments demonstrated that the Fc portion of the MAb molecule is of major importance for achieving the enhanced binding capacity. Binding studies showed that the (apparent) affinity of native and pH 2 pretreated MAbs were similar; the K(a) values of the immobilized MAbs were higher than those of MAbs in solution.

Monitoring of the production of monoclonal antibodies by hybridomas. Part I: Long-term cultivation in hollow fibre bioreactors using serum-free medium.

The long-term cultivation of hybridoma cells in hollow fibre bioreactors using serum-free medium, was monitored with respect to quantitative and qualitative aspects of the produced mAbs, cell viability, LDH and proteolytic activity. During the culture periods of hybridoma cells producing mAb OT-1C and 3A, the mAb concentration showed a decreasing trend with a concomitant increase of IgG fragments. The major IgG fragments did not bind the antigen and the molecular weights were significantly different from the corresponding IgG heavy and light chains. In addition, a good correlation was found between cell lysis, the presence of acid protease(s) and IgG fragments. The physicochemical and immunochemical properties of the "intact" mAbs (such as molecular weights, IEF patterns and affinity) did not change significantly during the culture period.

Monitoring of the production of monoclonal antibodies by hybridomas. Part II: Characterization and purification of acid proteases present in cell culture supernatant.

An acid proteolytic activity has been found in cell culture supernatants from long-term cultivations of hybridoma cells in hollow fibre bioreactors using serum free medium. The proteolytic activity has now been further characterized and the main results were: (1) the proteolytic activity showed a maximum around pH 3 and declined essentially to zero at pH 8; (2) the activity was specifically inhibited by pepstatin A; (3) the acid proteases consisted of two sets of closely spaced bands with apparent molecular weights of 40-45K and 90-105K, respectively; (4) the protease bands (40-45K and 90-105K) were reactive with anti-human cathepsin D; (5) the IEP values of the acid proteases ranged from pH 4.55-6.5. Furthermore, IgG incubation with the acid proteases isolated from hybridoma cells yielded fragments similar to those found in serum-free hollow fibre cell culture supernatants. These results indicated that the IgG fragments are the result of degradation by cathepsin D like proteases released after cell death or cell lysis.

Affinity of monoclonal antibodies. Interpretation of the positive cooperative nature of anti-hCG/hCG interactions.

The interaction of some individual MAbs and human chorionic gonadotrophin (hCG) showed apparent positive cooperativity as observed by equilibrium binding studies. This form of cooperative interaction has now been further characterized. The main results were: (1) the apparent positive cooperativity was strongly dependent upon concentration and temperature; (2) the cooperativity was strongly reduced by using peptic F(ab')2 fragments of IgG and became undetectable when the MAb was replaced by the corresponding Fab fragment; (3) the molecular weight of the complex changed from 226 kDa to 450 kDa upon increasing the hCG/MAb ratio. From these and additional results it is hypothesized that the apparent positive cooperativity results from self (Fc-Fc) associations mediated or facilitated by prior antigen binding.

Application of a sol particle immunoassay to the determination of affinity constants of monoclonal antibodies.

The affinity constants (Ka) of monoclonal antibodies (MAb) for binding to their corresponding antigens (Ag), unlabelled and in buffered solution were determined by the following procedure: 1. Incubation of MAb (fixed concentration) with Ag (concentration dilution series). 2. Rapid bound/free separation by adding immobilized second antibody, followed by centrifugation. 3. Determination of free Ag in the supernatant using a gold sol particle agglutination immunoassay (SPIA) in a microtitration plate format. 4. Calculations and interpretation were based on Scatchard and Sips plots. Ka values found by this procedure were found to be similar to those obtained by a radio-immunoassay (RIA) procedure. The present method avoids possible artefacts in Ka values introduced by the procedure or chemical modification due to labelling of MAb or Ag. It enables rapid, simultaneous screening of a considerable number of different MAbs under non-specialized (i.e. RIA) laboratory conditions.

Inorganic pyrophosphate synthesis during methanogenesis from methylcoenzyme M by cell-free extracts of Methanobacterium thermoautotrophicum (strain delta H).

Cell-free extracts of Methanobacterium thermoautotrophicum (strain delta H) were found to contain high concentrations of inorganic pyrophosphate (up to 40 mM). The compound was accumulated by the organism despite high activity of inorganic pyrophosphatase which was found to be present in the cell extracts (1-2 mumol min-1 mg protein-1). This activity was strongly inhibited at [PPi] greater than 1.0 mM. It was demonstrated that PPi synthesis occurred during methylcoenzyme M reduction under hydrogen atmosphere: in the first stage of the reaction for each mole of methane formed one mole of PPi was produced. Inhibition of the methylcoenzyme M reduction by 2-bromoethanesulfonic acid or by high concentrations (greater than 3 microM) of tetrachlorosalicylanilide also inhibited PPi synthesis. In contrast, low concentrations (1.3 microM) of tetrachlorosalicylanilide only inhibited PPi synthesis to the same extent as the methylcoenzyme M reduction was affected. In a later stage of the methylcoenzyme M reduction, PPi synthesis dropped and a second, as yet unidentified, unstable compound was formed. Synthesis of this compound also paralleled methane formation in a stoichiometric way and was affected by the inhibiting substances in a similar way as PPi synthesis.