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Aim: To identify indicators sensitive to the practice of primary healthcare nurse practitioners (PHCNPs)., Materials and Methods: A review of systematic reviews was undertaken to identify indicators sensitive to PHCNP practice. Published and grey literature was searched from January 1, 2010 to December 2, 2022. Titles/abstracts (n = 4251) and full texts (n = 365) were screened independently by two reviewers, with a third acting as a tie-breaker. Reference lists of relevant publications were reviewed. Risk of bias was examined independently by two reviewers using AMSTAR-2. Data were extracted by one reviewer and verified by a second reviewer to describe study characteristics, indicators, and results. Indicators were recoded into categories. Findings were summarized using narrative synthesis., Results: Forty-four systematic reviews were retained including 271 indicators that were recoded into 26 indicator categories at the patient, provider and health system levels. Nineteen reviews were assessed to be at low risk of bias. Patient indicator categories included activities of daily living, adaptation to health conditions, clinical conditions, diagnosis, education-patient, mortality, patient adherence, quality of life, satisfaction, and signs and symptoms. Provider indicator categories included adherence to best practice-providers, education-providers, illness prevention, interprofessional team functioning, and prescribing. Health system indicator categories included access to care, consultations, costs, emergency room visits, healthcare service delivery, hospitalizations, length of stay, patient safety, quality of care, scope of practice, and wait times., Discussion: Equal to improved care for almost all indicators was found consistently for the PHCNP group. Very few indicators favoured the control group. No indicator was identified for high/low fidelity simulation, cultural safety and cultural sensitivity with people in vulnerable situations or Indigenous Peoples., Conclusion: This review of systematic reviews identified patient, provider and health system indicators sensitive to PHCNP practice. The findings help clarify how PHCNPs contribute to care outcomes., Prospero Registration Number: CRD42020198182., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kilpatrick et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Oral antineoplastic drugs (OADs) play an increasing role in the treatment of cancer. Patients must have a high degree of understanding and autonomy to manage the numerous adverse effects at home. In Quebec, recommendations have been made for oncology pharmacists to systematically counsel all patients who are starting an OAD., Objective: To measure the impact of education provided by oncology pharmacists on patient activation., Methods: In this prospective, single-centre, observational cohort study, patients starting an OAD received education from oncology pharmacists, who used the 2020 updated version of information sheets from the Groupe d'étude en oncologie du Québec (GEOQ, www.geoq.info). The Patient Activation Measure (PAM-13) questionnaire was used to measure patients' activation before and after the intervention., Results: Of the 43 patients recruited in the intention-to-treat analysis, 41 were included in the modified intention-to-treat analysis. The mean difference between PAM-13 scores before and after the intervention was 2.30 (standard deviation [SD] 11.85) ( p = 0.22) in the intention-to-treat analysis and 3.63 (SD 10.33) ( p = 0.032) in the modified intention-to-treat analysis; these differences were less than the 5 points required for a result to be considered clinically meaningful. None of the effect-modifying variables for which data were collected had a significant impact on the degree of activation; however, a weak negative correlation was observed between the level of health literacy and the change in PAM-13 score., Conclusions: The study did not show a clinically meaningful change in patient activation following pharmacist-provided education, according to the updated GEOQ information sheets. Further studies are needed to evaluate these data in a larger population and to determine whether the impact of education persists beyond the first treatment cycle., Competing Interests: Competing interests: Karine Almanric has received speaker’s fees from Amgen Canada, and Ariane Cantin has received payment to attend a professional association meeting from her employer. No other competing interests were declared., (2023 Canadian Society of Hospital Pharmacists. All content in the Canadian Journal of Hospital Pharmacy is copyrighted by the Canadian Society of Hospital Pharmacy. In submitting their manuscripts, the authors transfer, assign, and otherwise convey all copyright ownership to CSHP.)

Background: This study aims to identify the most frequently cited articles published in the Journal of Arthroplasty ( JOA ) and to analyze the trends in the content and contributors of the literature within the journal., Methods: The 100 most cited articles published in the JOA were accessed using the Scopus database. The number of citations, year of publication, level of evidence (LOE), article type, country of origin, and contributing institution were each recorded for each article., Results: The United States (63%) was the most prolific publishing nation. The 1990s (30%) and 2000s (47%) were the most productive decades. The most common article category was clinical outcomes (33%), followed by technical note (16%) and biomechanics (14%). The plurality of the top 100 articles were well-designed case-control or cohort studies of LOE II (46%) followed by LOE V (32%) and LOE I (11%)., Conclusions: Using citation analysis, the most influential articles in the JOA were comprehensively and objectively analyzed. The most popular fields of research involved clinical outcomes (33%) and technical note (16%), both of which increase an article's likelihood of being highly cited. Knowledge of the most influential articles in the JOA allows for appreciation of current and potential future areas of literature regarding diagnosis, management, and outcome of a patient undergoing arthroplasty., (© 2022 The Authors.)

Competing Interests: Conflits d’intérêts: Aucune déclaration.

Introduction: Primary healthcare nurse practitioners (PHCNPs) practice in a wide range of clinical settings and with diverse patient populations. Several systematic reviews have examined outcomes of PHCNP roles. However, there is a lack of consistency in the definitions used for the PHCNP role across the reviews. The identification of indicators sensitive to PHCNP practice from the perspective of patients, providers and the healthcare system will allow researchers, clinicians and decision-makers to understand how these providers contribute to outcomes of care., Methods and Analysis: A review of systematic reviews is proposed to describe the current state of knowledge about indicators sensitive to PHCNP practice using recognised role definitions. Outcomes of interest include any outcome indicator measuring the effectiveness of PHCNPs. We will limit our search to 2010 onwards to capture the most up-to-date trends. The following electronic databases will be searched: Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library Database of Systematic Reviews and Controlled Trials Register, Database of Abstracts of Reviews of Effects, EMBASE, Global Health, Health Economics Evaluation Database, Health Evidence, HealthStar, Health Systems Evidence, Joanna Briggs Institute, Medline, PDQ-Evidence, PubMed and Web of Science. The search strategies will be reviewed by an academic librarian. Reference lists of all relevant publications will be reviewed. Grey literature will be searched from 2010 onwards, and will include: CADTH Information Services, CADTH's Grey Matters tool, OpenGrey, Organisation for Economic Co-operation and Development, ProQuest Dissertation and Theses and WHO. The PROSPERO International Prospective Register of Systematic Reviews will be searched to identify registered review protocols. The review protocol was developed using Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols recommendations. A narrative synthesis will be used to summarise study findings., Ethics and Dissemination: No ethical approval is required for the study. The data used in the study will be abstracted from published systematic reviews. Dissemination strategies will include peer-reviewed publication, conference presentations and presentations to key stakeholders., Prospero Registration Number: CRD42020198182., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Mycophenolate mofetil (MMF), an immunosuppressant drug used in organ transplantation to prevent rejection, is being used increasingly in association with cyclosporine and tacrolimus. Mycophenolic acid (MPA) is primarily metabolized in the liver to its 7-O-glucuronide (MPAG) derivative. The concentrations of MPAG in serum are many times the concentrations of MPA. Although MPAG has not shown immunosuppressant activity, it was postulated that it could displace MPA from its binding sites on albumin and hence increase the biologic effects of MPA. This effect could be important for patients with acute renal failure; under this condition, MPAG was shown to accumulate. The goal of this study was to document the MPAG/MPA concentration ratio in 100 renal transplant patients under a mixed immunosuppressive therapy. Further, the study addressed the question of whether MPAG can displace MPA in vivo from bound albumin in a representative renal transplant patient population under immunosuppressive therapy. Levels of MPAG and MPA were measured by high-performance liquid chromatography. The distribution of the ratios was not parametric as it tailed toward elevated values. After a square root transformation of the data, parametric analysis was possible. The average MPAG/MPA ratio was 15.0 +/- 2.2 for men versus 7.7 +/- 0.9 for women. Men treated with MMF and tacrolimus showed a lower ratio than patients treated with MMF and cyclosporine, confirming that tacrolimus inhibits glucuronidation of MPA. Further, it was determined that at physiologic concentrations, MPAG does not increase the amount of free MPA. Because MPAG can favor the elimination of MPA, it can be concluded that gender differences and cotreatment with tacrolimus must be taken into consideration when MMF is being administered.

Kidney transplantation is a well recognized form of treatment for end-stage renal failure patients. Transplanted patients can hope for a prolonged and productive life. Many factors are responsible for the improvement of kidney transplantation over the last years. Despite its progress and success, many limitations still exist: shortage of kidney, humoral hypersensitivity or recipients, side effects of immunosuppressive medication and chronic rejection. Will the induction of specific tolerance to xenograft, with the help of transgenic biology, be the solution of tomorrow?

Rapamycin (RAPA) is a strong immunosuppressant and is able to prevent allograft rejection in animal models. We have demonstrated that RAPA could strongly inhibit in vitro immunoglobulin (Ig) production by human lymphocytes. The present study investigated the long-term in vivo effect of RAPA on humoral and cellular immune responses, and the effect of RAPA on accelerated rejection. It was shown that RAPA strongly inhibited antigen (Ag) specific antibody (AB) production (i.e. cytotoxic Ab to donor lymphocytes and Ab to tetanus toxoid) during the period of drug administration. The accelerated rejection of cardiac allografts in presensitized animals was alleviated by RAPA administration. These results suggest the potential application of RAPA in treatment of presensitized candidates for organ transplantation. A little more than two months after the drug withdrawal, the rats were basically competent in Ab response to further Ag challenges. When tested 4 months after the RAPA-treatment, the rats showed uncompromised cardiac allograft rejection, and the cellular immune response in vitro according to mixed lymphocyte reaction (MLR) and mitogen-stimulated proliferation were not hampered. Such results suggest that the immune system can return to normal status without sequelae after discontinuation of RAPA.

Rapamycin (RAPA) is a new immunosuppressant which is 50-fold to 100-fold more potent than cyclosporin A (CyA) in inhibiting cellular immune responses and allograft rejection in animal models of organ transplantation. The drug's effect on in vitro IgE synthesis by interleukin (IL)4-stimulated human peripheral blood mononuclear cells was examined and compared with CyA's effect in this study. RAPA was found to be about 100-fold more potent than CyA in inhibiting IgE synthesis. Its inhibitory effect on IgE production was significant if it was added to the culture before Day 6 of a 14-day culture. The suppression was accompanied by the inhibitory effect on cell proliferation and on IgE-binding factor (IgE-BF) production. IL2 was able to partially reverse CyA- but not RAPA-induced inhibition of IgE production. Commercial B cell growth factor (cBCGF) was not able to reverse either RAPA- or CyA-induced suppression of IgE synthesis. The strong inhibitory effect of RAPA in IgE synthesis may be useful in certain clinical applications where overproduction of pathogenic IgE is a key issue. RAPA can also be used as a tool to dissect the regulation of IgE production.

Human immunodeficiency virus (HIV)-infected multinucleated giant cells previously were detected only in the central nervous system of HIV-positive patients. Reported here are the first cases in which such infected cells were observed outside the central nervous system, in the oropharyngeal lymphoid tissues. Tonsils and adenoids were removed individually from two asymptomatic homosexual men. Follicular hyperplasia and many interfollicular multinucleated giant cells most often in contact with or in close proximity of the mucous membrane were seen. The latter were positive for lysozyme, alpha-1 anti-chymotrypsin, OKM1, and S-100 protein in accordance with a histiocytic origin. In situ hybridization with an HIV envelope-specific RNA probe demonstrated the presence of viral RNA in these multinucleated giant cells. These findings support the role of peripheral histiocytes as a primary virus reservoir early in the disease. They also underline the potential role of oropharyngeal tissue as a primary target in some cases.

Simultaneous harvesting of the liver and whole pancreas is usually not performed because it is believed that the shared vascular supply of both organs is incompatible with safe grafting. A careful review of the vascular anatomy, however, shows that simultaneous removal of the two organs is feasible, and a technique is described by which the liver is revascularized in the recipient through the celiac axis or the common hepatic artery and the pancreas is revascularized through the superior mesenteric and splenic arteries. When the vascular supply is abnormal, reconstruction of the vascular tree of one or both organs may be needed. The results of this technique used on 10 recipients are analysed.

The present study was undertaken to evaluate whether the acid-base status influences the rate of acetate metabolism in patients chronically hemodialyzed against acetate. Ten patients (5 "intolerant" and 5 "tolerant" to acetate) received in a randomized order and for three consecutive dialyses each of the six following infusions in the venous line of the dialyzer: NaHCO3 (22, 44 or 88 mEq/h), NaCl (22 or 44 mEq/h) or Dextrose 5% in water (30 mmol/h). Plasma acetate was measured at the end of the dialysis. Bicarbonate infusions increased significantly blood pH and plasma bicarbonate but did not change the plasma acetate concentration at the end of dialysis. We conclude that the rate of acetate metabolism is not modified by changes in the acid-base status within the range usually observed in hemodialyzed patients. A significant hypoxemia per dialysis was noted only in AT patients with lower plasma acetate and rapid acetate metabolism. We conclude that acetate metabolism (and not plasma acetate concentration) plays a significant role in dialysis-induced hypoxemia.

A preparation of cyclosporine (CsA) in liposomes was tested in the rat to evaluate its effectiveness in reducing CsA nephrotoxicity. The drug was injected intravenously in unilaterally nephrectomized Lewis rats at a daily dose of 25 mg/kg for 14 days, either in a cremophore solution (eight rats) or in a preparation of liposomes (eight rats). Another group of four animals received the cremophore solution alone. Overall, rats treated with the CsA-liposome preparation had reduced toxicity, exhibiting better survival rates and less weight loss than those treated with the CsA-cremophore. Incorporating CsA into liposomes induced a statistically significant (p less than 0.05) reduction in the otherwise progressive increase of serum creatinine during week 2 of the experiment. Following administration of CsA-liposome preparation, epithelial cells of the proximal renal tubules appeared morphologically normal, without evidence of vacuolization, which is characteristic of CsA nephrotoxicity and was seen in the CsA-cremophore group. Although the exact mechanism is not clearly understood, it is likely that the tissue distribution of CsA, when incorporated into liposomes, is modified in favour of the reticuloendothelial cells, thereby sparing highly sensitive, but non-target organs such as the kidneys.

Because the elimination of gentamicin, a potent aminoglycoside antibiotic, is dependent almost entirely on renal excretion, renal functional impairment drastically changes the pharmacokinetics of this drug. As a first step in the study of the effects of renal insufficiency and the anephric state on the pharmacokinetic parameters of gentamicin, serum and urine levels of this drug were studied after a single intravenous bolus dose during hemodialysis in patients suffering from chronic renal failure. The data were fitted to the two-compartment open model and the appropriate kinetic parameters were calculated with the COMPT computer program modified by Pfeffer. The rate constant of metabolism was estimated from plasma and dialysis rate constants of elimination. The rate of renal excretion was shown to be very weak in patients who were not anuric. The use of the mathematical equations of the two-compartment open model demonstrated that, after a single dose of gentamicin, the percentage of decrease of serum concentration with time does not represent, because of tissue binding retention, the percentage of drug eliminated from the body. It was shown that pharmacokinetic parameters represent a useful tool in the optimization of gentamicin therapy.

The capacity of chronically hemodialyzed patients to metabolize acetate during conventional hemodialysis was evaluated using a retrospective study in 219 patients dialyzed for up to ten years under similar dialysis conditions. For each patient, and using all available data, a regression line relating the changes of plasma total CO2 during dialysis as a function of the pre-dialysis value was calculated. The intercept of this function indicates the plasma concentration where the losses of bicarbonate in the dialysate is matched by the generation of bicarbonate arising from the metabolism of acetate. This value therefore represents an individual index of the capacity of each patient to metabolize acetate. A value for this index smaller than 18.0 mM was considered abnormal. It was shown that around 10% of chronically hemodialyzed patients are clearly unable to metabolize acetate optimally. This defect is not related to the duration of dialysis, body weight or quality of hemodialysis treatments but is strongly related to sex, 19 of the 22 "acetate intolerant" patients being women. In a prospective study, all the 60 patients of the same population undergoing active dialysis were studied, and this index identified 12 abnormal (11 women, 1 man) patients and 48 normal patients. Plasma acetate measured at the end their dialysis treatments were significantly higher in abnormal than in normal patients. It is concluded: that this index is useful to identify the patients unable to metabolize acetate optimally; that only around 10% of hemodialyzed patients present a severe problem when dialyzed against acetate and should be dialyzed against bicarbonate; that dialysis against acetate does not fully correct the metabolic acidosis even in "normal" patients.