Evaluation of Prescribing and Administering As-Needed Pain Medications Based on Pain Severity Scores.

Pain is a common symptom reported by patients admitted to hospitals in both medical and surgical units. Due to the subjective and multidimensional nature of pain, it should be assessed regularly to ensure patient pain control. Suboptimal prescribing of opioids and other pain medications contribute to the inadequate treatment of pain. To combat the wide variability and response to pain medications, many providers prescribe as-needed range orders of pain medications to cover each pain severity. These range orders enable necessary and safe adjustments in dose based on individual responses to treatment. Currently, there are no studies analyzing the prescribing of pain medications based on pain severity, leaving a gap in literature in inpatient pain management. The purpose of this retrospective cohort study was to evaluate the appropriateness of prescribing as-needed pain medications based on the patient's pain severity scores throughout their hospital stay at a 125-bed community hospital in Northeast Ohio on the general medicine floor. Secondarily, this study also evaluated the administration of pain medications by nursing staff based on patient-reported pain severity scores. Statistical analyses including Chi-square tests, t-tests, Fisher's Exact tests and descriptive statistics were utilized to determine the significance of the data collected. This study found that there was a statistically significant difference between appropriately (47.4%) and inappropriately (52.6%) prescribed pain medications (P<0.001). There was also a statistically significant difference between appropriately (40.5%) and inappropriately (59.5%) administered pain medications (P<0.001). Pharmacists hope to improve pain management practices by providing education to both providers and nurses to prevent poor patient outcomes and uncontrolled pain.

Effectiveness of dietary inorganic nitrate for lowering blood pressure in hypertensive adults: a systematic review.

OBJECTIVE: The objective of this review was to evaluate the effectiveness of inorganic nitrate on blood pressure in hypertensive adults. INTRODUCTION: Hypertension is associated with increased risk of morbidity and mortality in adults. Inorganic nitrate could be beneficial for lowering blood pressure and reducing cardiovascular disease risks. Evidence related to the treatment of hypertension through sources of inorganic nitrate has been presented. INCLUSION CRITERIA: The review considered studies on adults aged 18 years and over, with blood pressure greater than 120/80 mmHg, undergoing interventions focusing on the effects of inorganic nitrate on blood pressure. Studies that included inorganic nitrate intake via dietary modification, in the form of a dietary supplement, and/or by the consumption of beetroot juice were considered. The comparator was no intervention of inorganic nitrate; different dosage, frequency, duration of inorganic nitrate; and other interventions that are administered to reduce and manage blood pressure. The primary outcomes were systolic and diastolic blood pressure effects. Experimental, quasi-experimental, analytical observational and pilot study designs were considered for inclusion. METHODS: Databases were searched for published and unpublished studies, available in English, from January 2013 to January 2018. Critical appraisal was conducted using standardized instruments from the Joanna Briggs Institute (JBI) and the methodological quality of included studies was considered to be moderate. Data were extracted using the JBI data extraction instrument. Data were presented in a narrative form due to the heterogeneity of included studies. RESULTS: Twelve papers were included in the systematic review with a total of 321 participants. Ten were randomized controlled trials and two were quasi-experimental studies. All participants had baseline blood pressures greater than 120/80 mmHg. Some studies included participants with comorbidities such as diabetes or heart failure with preserved ejection fraction. Inorganic nitrate was administered multiple ways throughout the studies including the following: beetroot juice, beetroot gel, nitric oxide lozenge, high nitrate diet, and raw and cooked beet juice. Doses and treatment intervals varied. Some studies included exercise as part of the intervention protocol.Meta-analysis was not conducted due to heterogeneity that existed within the studies. Blood pressure was measured in multiple settings by manual, digital or ambulatory means. The noted outcome patterns were as follows: no change in systolic blood pressure and diastolic blood pressure, decrease in systolic blood pressure and diastolic blood pressure, or decrease in systolic blood pressure with no change in diastolic blood pressure. Possible reasons for the diverse findings include the following: age, comorbidities, use of antihypertensives by participants; source and dose of nitrate; and intervention and follow-up time frames. CONCLUSIONS: There is insufficient evidence to support or refute the use of inorganic nitrate for any effect on blood pressure at this time. Therefore, there is no concrete base for the development of practice guidelines until stronger evidence becomes available. The gaps in the literature along with the study limitations identified necessitate the need for more research on inorganic nitrate and how it relates to blood pressure.

Effectiveness of dietary inorganic nitrate in lowering blood pressure in hypertensive adults: a systematic review protocol.

REVIEW QUESTION: The question of this review is: what is the effect of dietary inorganic nitrate on blood pressure in adults with blood pressure >120/80mmHg?

Injection of recombinant human type VII collagen corrects the disease phenotype in a murine model of dystrophic epidermolysis bullosa.

Patients with recessive dystrophic epidermolysis bullosa (RDEB) have incurable skin fragility, blistering, and scarring due to mutations in the gene that encodes for type VII collagen (C7) that mediates dermal-epidermal adherence in human skin. We showed previously that intradermal injection of recombinant C7 into transplanted human DEB skin equivalents stably restored C7 expression at the basement membrane zone (BMZ) and reversed the RDEB disease features. In this study, we evaluated the feasibility of protein therapy in a C7 null mouse (Col7a1(-/-)) which recapitulates the features of human RDEB. We intradermally injected purified human C7 into DEB mice and found that the injected human C7 stably incorporated into the mouse BMZ, formed anchoring fibrils, and corrected the DEB murine phenotype, as demonstrated by decreased skin fragility, reduced new blister formation, and markedly prolonged survival. After 4 weeks, treated DEB mice developed circulating anti-human C7 antibodies. Most surprisingly, these anti-C7 antibodies neither bound directly to the mouse's BMZ nor prevented the incorporation of newly injected human C7 into the BMZ. Anti-C7 antibody production was prevented by treating the mice with an anti-CD40L monoclonal antibody, MR1. We conclude that protein therapy may be feasible for the treatment of human patients with RDEB.

Autoimmunity to type VII collagen: epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is an acquired, mechanobullous disease characterized by autoimmunity to type VII collagen. Type VII collagen makes anchoring fibrils, structures that connect the epidermis and its underlying basement membrane zone to the papillary dermis. EBA patients exhibit skin fragility, blisters, scars and milia formation reminiscent of genetic dystrophic epidermolysis bullosa (DEB). DEB patients have diminutive or absent anchoring fibrils due to a genetic defect in the gene encoding type VII collagen. EBA patients have a decrease in normally functioning anchoring fibrils secondary to an abnormality in their immune system in which they produce 'pathogenic' IgG anti-type VII collagen antibodies. The pathogenicity of these autoantibodies has been demonstrated by passive transfer animal models, in which anti-type VII collagen antibodies injected into a mouse produced an EBA-like blistering disease in the animal. EBA has several distinct clinical presentations. It can present with features similar to DEB, bullous pemphigoid, cicatricial pemphigoid, Brunsting-Perry pemphigoid or IgA bullous dermatosis. Treatment for EBA is unsatisfactory, however, some therapeutic success has been reported with colchicine, dapsone, photophoresis, infliximab and intravenous immunoglobulin.

Autoimmunity to type VII collagen: epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is an acquired, autoimmune, mechanobullous disease with clinical features reminiscent of genetic dystrophic epidermolysis bullosa (DEB). EBA patients have skin fragility, blisters, scars, and milia formation. DEB is due to a genetic defect in the gene-encoding type VII collagen, which makes anchoring fibrils, structures that attach the epidermis and its underlying basement membrane zone onto the papillary dermis. DEB patients have a decrease in normally functioning anchoring fibrils. EBA patients have the same problem, but their decrease in normally functioning anchoring fibrils is because of an abnormality in their immune system in which they produce anti-type VII collagen antibodies that attack their anchoring fibrils. These IgG anti-type VII collagen antibodies are "pathogenic" because when injected into a mouse, the mouse develops an EBA-like blistering disease. EBA has several distinct clinical presentations. It can present with features similar to DEB. It can also present with features reminiscent of bullous pemphigoid, cicatricial pemphigoid, Brunsting-Perry pemphigoid, or IgA bullous dermatosis. Treatment for EBA is unsatisfactory. Some therapeutic success has been reported with colchichine, dapsone, photopheresis, infliximab, and IVIG.

The cartilage matrix protein subdomain of type VII collagen is pathogenic for epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is an acquired bullous disease of the skin characterized by IgG autoantibodies against type VII (anchoring fibril) collagen. We previously defined four immunodominant antigenic epitopes within the noncollagenous 1 (NC1) domain of type VII collagen. In this study, we produced an additional recombinant fusion protein from the NC1 domain corresponding to the N-terminal 227 amino acids (residues 1 to 227), which contains homology with cartilage matrix protein (CMP). Using enzyme-linked immunosorbent assay and immunoblot analysis, we tested sera from EBA patients (n = 32), bullous systemic lupus erythematosus patients (n = 3), bullous pemphigoid patients (n = 15), and normal humans (n = 12). Twenty-six of 32 EBA sera and two of three bullous systemic lupus erythematosus sera reacted with the CMP domain, whereas none of the control sera did. Affinity-purified anti-CMP EBA antibodies injected into hairless mice produced the clinical, histological, immunological, and ultrastructural features of EBA. F(ab')(2) fragments generated from anti-CMP EBA autoantibodies did not induce disease. Our studies provide the first evidence that EBA autoantibodies to the CMP subdomain of NC1 are pathogenic and induce blister formation. This is the first antigenic epitope on type VII collagen demonstrated to be a pathogenic target for EBA autoantibodies.

Intravenously injected human fibroblasts home to skin wounds, deliver type VII collagen, and promote wound healing.

Patients with dystrophic epidermolysis bullosa (DEB) have incurable skin fragility, blistering, and multiple skin wounds because of mutations in the gene that encodes for type VII collagen (C7), which holds together the epidermal and dermal layers of human skin. The intradermal injection of gene-corrected DEB fibroblasts, recombinant C7 protein, or lentiviral vectors expressing C7 is a potential therapy for DEB. Nevertheless, severe DEB causes widespread wounds and treatment would require multiple injections. An alternative strategy might be to inject genetically engineered cells into the patient's circulation that home to the skin wounds and deposit the transgene product. In this study, we demonstrated that intravenously (IV) injected, molecularly engineered DEB fibroblasts (overexpressing human C7) homed to murine skin wounds and continuously delivered C7 at the wound site, where it incorporated into the skin's basement membrane zone and formed anchoring fibril structures. Wounds made on murine or grafted human skin demonstrated accelerated healing when the animals were IV injected with gene-corrected DEB fibroblasts. Our data demonstrate that abundant C7 promotes wound healing. This is also the first evidence that IV injected, molecularly engineered skin fibroblasts can deliver C7 to skin wounds. This strategy could be useful for treating DEB patients.

Induction of epidermolysis bullosa acquisita in mice by passive transfer of autoantibodies from patients.

Epidermolysis bullosa acquisita (EBA) is an autoimmune sub-epidermal blistering disease characterized by autoantibodies to type VII (anchoring fibril) collagen. To date, however, direct evidence for a pathogenic role of human EBA autoantibodies has not been demonstrated. In this study, we affinity-purified anti-type VII collagen antibodies from EBA patients' sera and then injected them into adult hairless immunocompetent mice. Mice injected with EBA autoantibodies developed skin fragility, blisters, erosions, and nail loss on their paws - all features of EBA patients. By clinical, histological, immunological, and ultrastructural parameters, the induced lesions were reminiscent of human EBA. Histology showed bullous lesions with an epidermal-dermal separation. IgG and C3 deposits were observed at the epidermal-dermal junction. All mice had serum antibodies that labeled the dermal side of salt-split human skin like EBA sera. Direct immunogold electron microscopy specifically localized deposits of human IgG to anchoring fibrils. (Fab')(2) fragments generated from EBA autoantibodies did not induce disease. We conclude that EBA human patient autoantibodies cause sub-epidermal blisters and induce EBA skin lesions in mice. These passive transfer studies demonstrate that human EBA autoantibodies are pathogenic. This novel EBA mouse model can be used to further investigate EBA autoimmunity and to develop possible therapies.