Effectiveness of nurse-led services for people with chronic disease in achieving an outcome of continuity of care at the primary-secondary healthcare interface: A quantitative systematic review.

BACKGROUND: Globally, chronic disease is a leading cause of illness, disability and death and an important driver of health system utilization and spending. Continuity of care is a significant component of quality healthcare. However, an association between nurse-led services, interventions, patient outcomes and continuity of care at the primary and secondary interface as an outcome, has not been established for people with chronic disease. OBJECTIVE: To identify the effectiveness of nurse-led services for people with chronic disease in achieving an outcome of continuity of care at the primary-secondary healthcare interface. DESIGN: Quantitative systematic review. DATA SOURCES: Systematic searches of Medline, Cochrane, Embase, Emcare, JBI and Scopus databases were conducted of studies published between 1946 and May 2019 using the search terms "nurse", "continuity of care" and "chronic disease". REVIEW METHODS: Quality of the included studies was assessed using the Cochrane risk of bias tool for randomized controlled trials and Joanna Briggs Institute quality appraisal checklists. A second reviewer screened 10% of full text articles and all articles in critical appraisal. Studies were excluded from the review if they were of poor methodological quality or the description of the effect of the nurse-led service was inadequately reported. RESULTS: Fourteen studies were included in the review (n=4,090 participants). All studies incorporated recognized continuity of care interventions. The nurse-led services were associated with fewer hospitalizations, reduced by 2-8.9% and re-admissions reduced by 14.8-51% (n=886). Reporting of positive patient experiences and improvement in symptoms and lifestyle was also evident. An association of nurse-led services with improved continuity of care between primary and secondary health services as an outcome per se could not be concluded. CONCLUSION: Nurse-led services for adults provide coordinated interventions that support continuity of care for people with chronic disease in both the primary and secondary healthcare settings that are associated with reduced hospitalizations or readmissions and patient satisfaction. However, the limited use of validated continuity of care outcome measurement tools precluded establishing correlations between interventions, patient outcomes and continuity of care as a specific outcome.

Medication use and potentially high-risk prescribing in older patients hospitalized for diabetes: a missed opportunity to improve care?

AIMS: To examine the appropriateness of medicine use and potentially high-risk prescribing before and after hospitalization for diabetes. METHODS: A retrospective cohort study of patients hospitalized for diabetes was conducted using administrative data from the Australian Government Department of Veterans' Affairs for the period between 1 January 2012 and 31 December 2012. The appropriateness of medicine use and potentially high-risk prescribing, including hyper-polypharmacy and associated treatment conflicts, were examined for the 120-day periods before and after hospitalization. RESULTS: A total of 876 patients were hospitalized for a diabetes-related complication. Of these, 25% were not dispensed an antidiabetic medicine 4 months before hospitalization and 25% had not had their HbA1c levels measured in the preceding 6 months. The use of antidiabetic medicines increased to 85% after hospitalization, with a 25.6% relative increase (95% CI 10.9-42.1) in the proportion of those dispensed insulin. The prevalence of high-risk prescribing before hospital admission was high; 70% had > 10 medicines dispensed, a third had at least one treatment conflict and half were dispensed a potentially inappropriate medicine. The use of long-acting sulphonylureas and corticosteroids had relative decreases of 46.0% (95% CI 17.0-64.9) and 29.9% (95% CI 8.8-46.0), respectively. Few changes in other high-risk prescribing patterns were observed after discharge. CONCLUSIONS: This study has identified poor medication-related care and, in particular, high-risk-prescribing in people subsequently hospitalized for diabetes. While diabetes medicine use improved after hospitalization, there was little change in potentially inappropriate medicine use, which suggests that an opportunity to improve medication use in this older vulnerable population has been missed.

Effect of a general practitioner management plan on health outcomes and hospitalisations in older patients with diabetes.

BACKGROUND: Little is known about the impact of a general practitioner management plan (GPMP) on health outcomes of patients with diabetes. AIM: To examine the impact of a GPMP on the risk of hospitalisation for diabetes. METHODS: A retrospective study using administrative data from the Australian Government Department of Veterans' Affairs was conducted (1 July 2006 to 30 June 2014) of diabetes patients either exposed or unexposed to a GPMP. The primary end-point was the risk of first hospitalisation for a diabetes-related complication and was assessed using Cox proportional hazard regression models with death as a competing risk. Secondary end-points included rates of receiving guideline care for diabetes, with differences assessed using Poisson regression analyses. RESULTS: A total of 16 214 patients with diabetes were included; 8091 had a GPMP, and 8123 did not. After 1 year, 545 (6.7%) patients with a GPMP and 634 (7.8%) of patients without a GPMP were hospitalised for a diabetes complication. There was a 22% reduction in the risk of being hospitalised for a diabetes complication (adjusted hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.87, P < 0.0001) for those who received a GPMP by comparison to those who did not. Increased rates of diabetes guideline care, HbA1c claims (adjusted HR 1.29, 95% CI 1.25-1.33) and microalbuminura claims (adjusted HR 1.65, 95% CI 1.58-1.72) were observed after a GPMP. CONCLUSION: Provision of a GPMP in older patients with diabetes resulted in improved health outcomes, delaying the risk of hospitalisation at 12 months for diabetes complications. GPMP should be included as part of routine primary care for older patients with diabetes.

Antithrombotic use following transient ischaemic attack or ischaemic stroke among older Australians with atrial fibrillation.

Hospital audits may underestimate anticoagulant use among acute ischaemic stroke patients with atrial fibrillation (AF), as treatment may commence after discharge. To account for this, antithrombotic use in the 4 months after hospitalisation for transient ischaemic attack or ischaemic stroke among AF patients was assessed using claims data. Results suggest that treatment may be commenced soon after discharge and should be considered when assessing prevalence of use.

General practitioner management plans delaying time to next potentially preventable hospitalisation for patients with heart failure.

BACKGROUND: Several studies have shown that the Australian Medicare-funded chronic disease management programme can lead to improvements in care processes. No study has examined the impact on long-term health outcomes. AIMS: This retrospective cohort study assessed the association between provision of a general practitioner management plan and time to next potentially preventable hospitalisation for older patients with heart failure. METHODS: We used the Australian Government Department of Veterans' Affairs (DVA) claims database and compared patients exposed to a general practitioner management plan with those who did not receive the service. Kaplan-Meier analysis and Cox proportional hazards models were used to compare time until next potentially preventable hospitalisation for heart failure between the exposed and unexposed groups. RESULTS: There were 1993 patients exposed to a general practitioner management plan and 3986 unexposed patients. Adjusted results showed a 23% reduction in the rate of potentially preventable hospitalisation for heart failure at any time (adjusted hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.92; P = 0.0051) among those with a general practitioner management plan compared with the unexposed patients. Within one year, 8.6% of the exposed group compared with 10.7% of the unexposed group had a potentially preventable hospitalisation for heart failure. CONCLUSIONS: A general practitioner management plan is associated with delayed time to next potentially preventable hospitalisation for heart failure.

Comorbid chronic diseases, discordant impact on mortality in older people: a 14-year longitudinal population study.

OBJECTIVES: To determine the impact of comorbid chronic diseases on mortality in older people. DESIGN: Prospective cohort study (1992-2006). Associations between numbers of chronic diseases or mutually exclusive comorbid chronic diseases on mortality over 14 years, by Cox proportional hazards model adjusting for sociodemographic variables or Kaplan-Meier analyses, respectively. SETTING: Population based, Australia. PARTICIPANTS: 2087 randomly selected participants aged ≥65 years old, living in the community or institutions. MAIN RESULTS: Participants with 3-4 or ≥5 diseases had a 25% (95% CI 1.05 to 1.5, p=0.01) and 80% (95% CI 1.5 to 2.2, p<0.0001) increased risk of mortality, respectively, by comparison with no chronic disease, after adjusting for age, sex and residential status. When cardiovascular disease (CVD), mental health problem or diabetes were comorbid with arthritis, there was a trend towards increased survival (range 8.2-9.5 years) by comparison with CVD, mental health problem or diabetes alone (survival 5.8-6.9 years). This increase in survival with arthritis as a comorbidity was negated when CVD and mental health problems or CVD and diabetes were present in disease combinations together. CONCLUSION: Older people with ≥3 chronic diseases have increased risk of mortality, but discordant effects on survival depend on specific disease combinations. These results raise the hypothesis that patients who have an increased likelihood of opportunity for care from their physician are more likely to have comorbid diseases detected and managed.

Roles of cyclooxygenase (COX)-1 and COX-2 in prostanoid production by human endothelial cells: selective up-regulation of prostacyclin synthesis by COX-2.

The two cyclooxygenase (COX) isoforms, COX-1 and COX-2, both metabolize arachidonic acid to PGH(2), the common substrate for thromboxane A(2) (TXA(2)), prostacyclin (PGI(2)), and PGE(2) synthesis. We characterized the synthesis of these prostanoids in HUVECs in relation to COX-1 and COX-2 activity. Untreated HUVEC expressed only COX-1, whereas addition of IL-1beta caused induction of COX-2. TXA(2) was the predominant COX-1-derived product, and TXA(2) synthesis changed little with up-regulation of COX-2 by IL-1beta (2-fold increase). By contrast, COX-2 up-regulation was associated with large increases in the synthesis of PGI(2) and PGE(2) (54- and 84-fold increases, respectively). Addition of the selective COX-2 inhibitor, NS-398, almost completely abolished PGI(2) and PGE(2) synthesis, but had little effect on TXA(2) synthesis. The up-regulation of COX-2 by IL-1beta was accompanied by specific up-regulation of PGI synthase and PGE synthase, but not TX synthase. An examination of the substrate concentration dependencies showed that the pathway of TXA(2) synthesis was saturated at a 20-fold lower arachidonic acid concentration than that for PGI(2) and PGE(2) synthesis. In conclusion, endothelial prostanoid synthesis appears to be differentially regulated by the induction of COX-2. The apparent PGI(2) and PGE(2) linkage with COX-2 activity may be explained by a temporal increase in total COX activity, together with selective up-regulation of PGI synthase and PGE synthase, and different kinetic characteristics of the terminal synthases. These findings have particular importance with regard to the potential for cardiovascular consequences of COX-2 inhibition.

Up-regulation of endothelial cyclooxygenase-2 and prostanoid synthesis by platelets. Role of thromboxane A2.

Platelet-vascular endothelial cell interactions are central to the maintenance of vascular homeostasis. Thromboxane A2 (TXA2) and prostacyclin (prostaglandin (PG)I2) are the major products of cyclooxygenase (COX) metabolism by platelets and the vascular endothelium, respectively. Here we report the effects of platelet-endothelial interactions on human umbilical vein endothelial cells (HUVECs) COX-2 expression and prostanoid synthesis. Co-incubation of platelets with HUVECs resulted in a dose-dependent induction in COX-2 expression. This was accompanied by a relatively small increase in thromboxane B2 synthesis (2 ng) by comparison to the production of 6-keto-PGF1alpha and PGE2, which increased by approximately 14 and 12 ng, respectively. Abrogation of platelet-HUVEC interactions excluded direct cell-cell contact as a required event. Preincubation of HUVECs with SQ29548, a TXA2 receptor antagonist, dose-dependently inhibited platelet-induced COX-2 expression and prostanoid synthesis. Similarly, if platelet TXA2 synthesis was inhibited no induction of COX-2 was observed. Furthermore, a TXA2 analog, carbocyclic TXA2, induced HUVEC COX-2 expression and the synthesis of 6-keto-PGF1alpha and PGE2. This was also associated with an increase in the expression and activity of PGI synthase and PGE synthase but not TX synthase. Platelet co-incubation (or TXA2) also selectively activated the p44/42 mitogen-activated protein kinase pathway to regulate HUVEC COX-2 expression. Thus it seems that platelet-derived TXA2 can act in a paracrine manner to up-regulate endothelial COX-2 expression and PGI2 synthesis. These observations are of particular importance given the recent observations regarding selective COX-2 inhibitors and the suppression of PGI2 synthesis.

Eicosanoid production by human monocytes: does COX-2 contribute to a self-limiting inflammatory response?

The eicosanoids, prostaglandin E2 (PGE2) and thromboxane A2 (TXA2), are involved in inflammatory events. TXA2 has potentially pro-inflammatory actions and PGE2 has actions which can be considered both pro- and antiinflammatory. Therefore, it is potentially significant that production of TXA2 and PGE2 by stimulated monocytes have very different time courses. TXA2 synthesis is immediate and dependent on cyclooxygenase Type 1 (COX-1) activity whereas PGE2 synthesis is delayed and dependent on COX-2 activity. These apparent COX-isotype dependencies of TXA2 and PGE2 synthesis can be explained by differences in the affinities of TXA synthase and PGE synthase for the common substrate, PGH2. The findings have implications for the use of NSAIDs and selective COX-2 inhibitors whose actions can increase the monocyte TXA2/PGE2 ratio.

Differential regulation of prostaglandin E2 and thromboxane A2 production in human monocytes: implications for the use of cyclooxygenase inhibitors.

There is an autocrine relationship between eicosanoid and cytokine synthesis, with the ratio of prostaglandin E2 (PGE2)/thromboxane A2 (TXA2) being one of the determinants of the level of cytokine synthesis. In monocytes, cyclooxygenase type 1 (COX-1) activity appears to favor TXA2 production and COX-2 activity appears to favor PGE2 production. This has led to speculation regarding possible linkage of COX isozymes with PGE and TXA synthase. We have studied the kinetics of PGE2 and TXA2 synthesis under conditions that rely on COX-1 or -2 activity. With small amounts of endogenously generated prostaglandin H2 (PGH2), TXA2 synthesis was greater than PGE2. With greater amounts of endogenously generated PGH2, PGE2 synthesis was greater than TXA2. Also, TXA synthase was saturated at lower substrate concentrations than PGE synthase. This pattern was observed irrespective of whether PGH2 was produced by COX-1 or COX-2 or whether it was added directly. Furthermore, the inhibition of eicosanoid production by the action of nonsteroidal anti-inflammatory drugs or by the prevention of COX-2 induction with the p38 mitogen-activated protein kinase inhibitor SKF86002 was greater for PGE2 than for TXA2. It is proposed that different kinetics of PGE synthase and TXA synthase account for the patterns of production of these eicosanoids in monocytes under a variety of experimental conditions. These properties provide an alternative explanation to notional linkage or compartmentalization of COX-1 or -2 with the respective terminal synthases and that therapeutically induced changes in eicosanoid ratios toward predominance of TXA2 may have unwanted effects in long-term anti-inflammatory and anti-arthritic therapy.

Assay of cyclooxygenase-1 and 2 in human monocytes.

OBJECTIVE AND DESIGN: There is frequently poor correlation between in vitro methods for calculated cyclooxygenase (COX)-1/COX-2 selectivities of inflammatory agents. Therefore, we have examined the use of a single stimulus in a single cell type containing both COX isoforms, for determining the selectivities of COX-inhibitory agents. METHODS: Fresh human monocytes were stimulated with arachidonic acid (AA; 10 microM) for 15 min and prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) production were used as a measure of COX-1 activity. To measure COX-2 activity, cells were transiently pre-treated with aspirin to irreversibly inhibit constitutive COX-1, treated with lipopolysaccharide (LPS) to induce COX-2 and then stimulated with AA. RESULTS: Eicosanoid production in resting monocytes was predominantly COX-1 derived since it was not inhibited by NS-398 and also, COX-2 was not detectable. In LPS treated monocytes pre-treated transiently with aspirin, neither the level of induced COX-2 nor the activity was affected. Using the mean of the results for PGE2 and TXB2 inhibition, the COX-1/COX-2 ratios of the IC50 values for aspirin and NS-398 are < 0.1 and > 130, respectively. CONCLUSIONS: This study has provided a system for investigating inhibition of COX isotypes without the potentially confounding effects of using different cell types with different stimuli for each isotype as seen in other published systems. Dose responses to aspirin and NS-398 which are COX- and COX-2 selective inhibitors respectively, confirmed the utility of this system.

Regulation of tumor necrosis factor-alpha and IL-1 beta synthesis by thromboxane A2 in nonadherent human monocytes.

Synthesis of TNF-alpha and IL-1beta, by monocytes/macrophages can be partially regulated by the eicosanoid, PGE2. We report here that inhibition of both PGE2 and thromboxane A2 (TXA2) synthesis by a prostaglandin H synthase inhibitor, NS-398, had no effect on the synthesis of either TNF-alpha or IL-1beta, even though the addition of PGE2 to these treated cells dose-dependently inhibited TNF-alpha and IL-1beta synthesis. Because TXA2 is a major eicosanoid product of stimulated human monocytes, we examined its influence on cytokine production. Inhibition of thromboxane synthase by carboxyheptyl imidazole (CI) resulted in inhibition of TNF-alpha (61 +/- 4.3%; n = 8; p < 0.001) and IL-1beta (54 +/- 4.2%; n = 8; p < 0.001) synthesis by serum-treated zymosan-stimulated nonadherent human monocytes. This effect was observed when cytokine production was measured by ELISA or bioactivity assays. Furthermore, the addition of a TXA2 agonist, carbocyclic TXA2, to CI-treated monocytes dose-dependently restored the levels of TNF-alpha and IL-1beta synthesis to those found with serum-treated zymosan stimulation alone. Inhibition of TXA2 activity by the thromboxane receptor antagonists, pinane TXA2 or SQ 29,548, also inhibited the production of TNF-alpha (67 +/- 2.4% and 65 +/- 2.7%, respectively; n = 8; p < 0.001) and IL-1beta (59 +/- 3.3% and 70 +/- 1.2%, respectively; n = 8; p < 0.001). Treatment with CI resulted in a partial decrease in TNF-alpha mRNA levels (60 +/- 12.0%; n = 4), but had little or no effect on IL-1beta mRNA levels. These novel observations implicate TXA2 as an important paracrine or autocrine facilitator of TNF-alpha and IL-1beta production in stimulated human monocytes and suggest that levels of TNF-alpha and IL-1beta synthesis are determined in part by the balance between TXA2 and PGE2 production in human monocytes.

The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil.

The effect of a flaxseed oil-based diet on tumor necrosis factor alpha (TNF alpha) and interleukin 1 beta (IL-1 beta) synthesis was examined in healthy volunteers. Use of flaxseed oil in domestic food preparation for 4 wk inhibited TNF alpha and IL-1 beta production by approximately 30%. Fish-oil supplementation (9 g/d) continued for a further 4 wk; TNF alpha and IL-1 beta synthesis were inhibited by 74% and 80%, respectively. There was a significant inverse exponential relation between TNF alpha or IL-1 beta synthesis and mononuclear cell content of eicosapentaenoic acid (EPA), an n--3 fatty acid derived from ingested EPA (fish oil) or metabolism of ingested alpha-linolenic acid (flaxseed oil). Cytokine production decreased as cellular EPA increased to approximately 1% of total fatty acids. Further increases in EPA content did not result in further decreases in cytokine production. The results indicate that vegetable oils rich in n--3 fatty acids inhibit TNF alpha and IL-1 beta synthesis.