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Biomedical subjects

J A Johnson

Publications and source records attributed to J A Johnson.

At least 109 records · Page 6Linked to original sources

A bacteriophage encoding a pathogenicity island, a type-IV pilus and a phage receptor in cholera bacteria.

The virulence properties of many pathogenic bacteria are due to proteins encoded by large gene clusters called pathogenicity islands, which are found in a variety of human pathogens including Escherichia coli, Salmonella, Shigella, Yersinia, Helicobacter pylori, Vibrio cholerae, and animal and plant pathogens such as Dichelobacter nodosus and Pseudomonas syringae. Although the presence of pathogenicity islands is a prerequisite for many bacterial diseases, little is known about their origins or mechanism of transfer into the bacterium. The bacterial agent of epidemic cholera, Vibrio cholerae, contains a bacteriophage known as cholera-toxin phage (CTXphi), which encodes the cholera toxin, and a large pathogenicity island called the VPI (for V. cholerae pathogenicity island) which itself encodes a toxin-coregulated pilus that functions as a colonization factor and as a CTXphi receptor. We have now identified the VPI pathogenicity island as the genome of another filamentous bacteriophage, VPIphi. We show that VPIphi is transferred between V. cholerae strains and provide evidence that the TcpA subunit of the toxin-coregulated type IV pilus is in fact a coat protein of VPIphi. Our results are the first description of a phage that encodes a receptor for another phage and of a virus-virus interaction that is necessary for bacterial pathogenicity.

Bacterial Outer Membrane Proteins↗

Activation of antioxidant/electrophile-responsive elements in IMR-32 human neuroblastoma cells.

The present investigation demonstrates distinct patterns of activation for antioxidant/electrophile-responsive elements (ARE/EpREs) in cells of neuronal versus hepatic origin suggesting the possibility of cell-/tissue-specific signaling pathways and/or transcription factors required for ARE/EpRE activation. The ARE/EpRE is a cis-acting regulatory element found in 5'-flanking regions of numerous genes including NAD(P)H:quinone oxidoreductase (QR) and glutathione S-transferases. Insomuch as ARE/EpRE activation has been studied primarily in hepatoma cell lines there is little information on how these responsive elements and corresponding genes are regulated in brain. ARE/EpRE-reporter constructs were transiently transfected into IMR-32 human neuroblastoma cells. Activation of ARE/EpRE sequences by tert-butylhydroquinone (tBHQ), a redox-cycling compound, in IMR-32 cells (20- to 30-fold) is dramatically different from the minimal response seen in HepG2 human hepatoma cells (2- to 3-fold). beta-napthoflavone, an ARE/EpRE inducer in HepG2 cells, as well as the oxidants hydrogen peroxide and tert-butyl hydroperoxide did not induce the ARE/EpRE in IMR-32 cells. In addition, we show that the core sequence containing a complete 5' palindrome is necessary for maximal activation of the ARE/EpRE in IMR-32 cells. Mutations within this palindromic sequence decrease basal level expression and block induction by tBHQ but not phorbol 12-myristate 13-acetate. Furthermore, activation of the hQR-ARE/EpRE by tBHQ correlates with induction of endogenous QR activity in IMR-32 neuroblastoma cells (15-fold). Thus, elucidating the mechanism of ARE/EpRE activation in this human neuroblastoma cell line may identify unknown transcription factors or signal transduction cascades regulating ARE/EpRE-driven gene expression.

Antioxidants↗

Cadmium-mediated activation of the metal response element in human neuroblastoma cells lacking functional metal response element-binding transcription factor-1.

Metal response element-binding transcription factor-1 (MTF-1) binds specifically to metal response elements (MREs) and transactivates metallothionein (MT) gene expression in response to zinc and cadmium. This investigation contrasts the mechanism of mouse MT gene (mMT-I) promoter activation by cadmium and zinc in IMR-32 human neuroblastoma cells to determine whether MTF-1 binding to the MRE is necessary for activation by these metals. Cadmium activated a mMT-1 promoter (-150 base pairs) luciferase reporter 20-25-fold through a MRE-dependent mechanism. In contrast, zinc had little effect on the mMT-1 luciferase reporter. IMR-32 cells lacked MRE binding activity, and treatment with zinc in vitro or in vivo did not generate a MTF-1. MRE complex, suggesting that IMR-32 cells lack functional MTF-1. Overexpression of mMTF-1 regenerated a zinc-mediated induction of the MRE without affecting cadmium activation. Because no other transition metals tested activated the MRE, this effect appeared to be cadmium-specific. These data demonstrate that in IMR-32 human neuroblastoma cells, zinc and cadmium can use independent mechanisms for activation of the mMT-I promoter and cadmium-mediated MRE activation is independent of MTF-1 and zinc.

Base Sequence↗

Coordinate regulation of NAD(P)H:quinone oxidoreductase and glutathione-S-transferases in primary cultures of rat neurons and glia: role of the antioxidant/electrophile responsive element.

NAD(P)H:quinone oxidoreductase (QR) and glutathione-S-transferases (GSTs) are among the enzymes believed to protect an organism against oxidative stress. To test if redox-cycling compounds regulate the expression of these enzymes in cells of neural origin, primary cultures of rat cerebellar neurons and glia were treated with tert-butylhydroquinone (tBHQ) and hydroquinone (HQ). Basal levels of endogenous QR and GST activity were significantly greater in glia than neurons; and QR, GSTP1, and A3 were increased in glial but not neuronal cultures by treatment with tBHQ and HQ. A possible role for protein kinase C (PKC) in the tBHQ-mediated increase in QR and GST was evaluated by activating PKC with phorbol 12-myristate 13-acetate or inhibiting PKC with bisindolylmaleimide I. PKC was not involved in maintaining basal expression or mediating the increased expression of GST or QR by tBHQ. Transcriptional activation of QR and rGSTP1 by tBHQ could be mediated through a common responsive element present in the 5'-flanking region of both genes, the antioxidant/electrophile responsive element (ARE/EpRE). Transient transfection of the glial cultures with rGSTP1- or rQR1-ARE/EpRE-luciferase reporter constructs demonstrated that tBHQ transcriptionally activates the ARE/EpRE. Thus, the increased expression of genes regulated by the ARE/EpRE in cells of the central nervous system may provide protection against oxidative stress.

Animals↗

Does use of intravascular ultrasound accelerate arteriopathy in heart transplant recipients?

BACKGROUND: Intravascular ultrasound (IVUS) is a sensitive method for assessing allograft vasculopathy in heart transplant recipients, but it is not known whether this instrumentation traumatizes the transplanted arteries and affects progression of arteriopathy. METHODS AND RESULTS: Yearly coronary angiograms were obtained in 86 patients who underwent heart transplantation between January 1991 and May 1995. Patients were divided into 3 groups: (1) no IVUS performed after transplantation (group 1, n = 47); (2) IVUS of the left anterior descending artery (LAD) performed only at year 1 (group 2, n = 13); and (3) IVUS of the LAD performed at both baseline (within 2 months after transplantation) and year 1 after transplantation (group 3, n = 26). Coronary angiography measurements of lumen diameter were performed at 5 segments along the length of the LAD and left circumflex artery (LCX) from baseline through the second-year studies except in group 2, which did not receive a baseline angiogram; IVUS measurements were obtained at 10 cross sections from each artery. At baseline, there was no significant difference in vessel diameter for either the LAD or the LCX artery between the IVUS (group 3) and no IVUS (group 1) groups. Within each group, the lumen of both the LAD and LCX narrowed from baseline to year 1 (group 1: 3.3 +/- 0.6 mm to 2.8 +/- 0.5 mm in LAD, P =.001; 3. 3 +/- 0.6 mm to 3.0 +/- 0.5 mm in LCX, P =.006; group 3: 3.5 +/- 0.7 mm to 3.1 +/- 0.6 mm in LAD, P =.01; 3.1 +/- 0.6 mm to 2.8 +/- 0.5 mm in LCX, P = 0.07), but there were no significant differences between the instrumented artery (LAD) and control artery (LCX) or further changes observed at year 2. There were also no significant differences in the percent reductions at year 1 and year 2 between arteries or between groups. By IVUS, from baseline to year 1 in group 3, the plaque cross-sectional area (CSA) increased (1.6 +/- 1. 9 to 2.3 +/- 1.7 mm(2), P <.0001), the lumen CSA decreased (12.7 +/- 3.7 to 11.7 +/- 3.3 mm(2), P =.04), and the maximum lumen diameter decreased (4.2 +/- 0.6 to 4.0 +/- 0.6 mm, P =.04). CONCLUSIONS: The use of IVUS is not associated with acceleration of arteriopathy in heart transplantation recipients. Luminal narrowing occurs predominantly during the first year after transplantation. There was no significant change in lumen dimensions during the second year.

Adult↗

Transmission of live laparoscopic surgery over the Internet2.

BACKGROUND: Video broadcasting of surgical procedures is an important tool for education, training, and consultation. Current video conferencing systems are expensive and time-consuming and require preplanning. Real-time Internet video is known for its poor quality and relies on the equipment and the speed of the connection. The Internet2, a new high-speed (up to 2,048 Mbps), large bandwidth data network presently connects more than 100 universities and corporations. We have successfully used the Internet2 to broadcast the first real-time, high-quality audio/video program from a live laparoscopic operation to distant points. METHODS: Video output of the laparoscopic camera and audio from a wireless microphone were broadcast to distant sites using a proprietary, PC-based implementation of H.320 video conferencing over a TCP/IP network connected to the Internet2. The receiving sites participated in two-way, real-time video and audio communications and graded the quality of the signal they received. RESULTS: On August 25, 1998, a laparoscopic Nissen fundoplication was transmitted to Internet2 stations in Colorado, Pennsylvania, and to an Internet station in New York. On September 28 and 29, 1998, we broadcast laparoscopic operations throughout both days to the Internet2 Fall Conference in San Francisco, California. Most recently, on February 24, 1999, we transmitted a laparoscopic Heller myotomy to the Abilene Network Launch Event in Washington, DC. CONCLUSIONS: The Internet2 is currently able to provide the bandwidth needed for a turn-key video conferencing system with high-resolution, real-time transmission. The system could be used for a variety of teaching and educational programs for experienced surgeons, residents, and medical students.

General Surgery↗

Impact of genetic polymorphisms of the beta2-adrenergic receptor on albuterol bronchodilator pharmacodynamics.

OBJECTIVE: To determine whether genetic polymorphisms of the beta2-adrenergic receptor gene affect the relationship between albuterol (INN, salbutamol) plasma concentrations and the forced expiratory volume in 1 second (FEV1) in subjects with moderate asthma. METHODS: Sixteen clinically stable patients with moderate asthma who participated in a pharmacokinetic-pharmacodynamic study of albuterol volunteered to provide a blood sample for determination of beta2-adrenergic receptor genotype. FEV1 and plasma concentrations of albuterol were determined at various times after administration of an oral solution that contained 8 mg albuterol. Patients withheld inhaled beta2-agonist and corticosteroid therapy 12 and 24 hours, respectively, before the study. beta2-Adrenergic receptor genotype was determined by polymerase chain reaction with allele-specific oligonucleotide hybridization. RESULTS: Albuterol-evoked FEV1 was higher and the response was more rapid in Arg16 homozygotes compared with the cohort of carriers of the Gly16 variant: Maximal percentage increase in FEV1 (%deltaFEV1), 18% versus 4.9% (P < .03); area under FEV1 albuterol concentration curve, 194%.mL/ng versus 30%.mL/ng (P < .05); initial slope (dE/dC), 1.43%.mL/ng versus 0.55%.mL/ng (P < .003). CONCLUSIONS: The beta2-adrenergic receptor gene polymorphism is a major determinant of bronchodilator response to albuterol. Future pharmacodynamic studies of beta2-agonists should include determination of 02-adrenergic receptor genotype.

Adrenergic beta-Agonists↗

Malignant tumors of Stensen's duct.

A rare case of squamous cell carcinoma arising in Stensen's duct is reported. The literature concerning malignant neoplasia originating in this site is reviewed, with attention given to the histopathologic diversity of neoplasms occurring in the duct, criteria for determination of origin in the duct, and outcomes of therapy.

Aged↗

Supplemental pinning improves the stability of external fixation in distal radius fractures during simulated finger and forearm motion.

External fixation is commonly used in the treatment of distal radius fractures. In this in vitro study, we investigated changes in fracture stability when using supplemental radial styloid pinning in combination with external fixation. Eight previously frozen cadaveric upper extremities were mounted in a computer-controlled wrist-loading apparatus. This device was used to generate finger and forearm motions through loading relevant tendons. An unstable extra-articular distal radius fracture was simulated by removing a dorsal wedge from the distal radius metaphysis. An electromagnetic tracking system measured fragment motion following randomized application of a Hoffman external fixator, a Hoffman external fixator with 2 supplemental radial styloid pins, and a dorsal 3.5-mm AO plate. Regardless of the fixation technique used in this unstable fracture model, fragment motion occurred when postoperative finger and forearm motions were simulated. The addition of radial styloid pins to a construct stabilized by an external fixator significantly improved fragment stability, approaching that achieved with the dorsal AO plate.

Biomechanical Phenomena↗

Sickle cell telemedicine and standard clinical encounters: a comparison of patient satisfaction.

OBJECTIVES: To determine patient satisfaction with telemedicine encounters among adults with sickle cell disease and compare their scores with SCD patients who have standard medical encounters (as controls). METHODS: Adults patients were recruited from a list of participants in sickle cell telemedicine clinics and prospectively at the time of clinic encounter. Patients were assigned to telemedicine or standard encounter groups. Demographic and pertinent clinical data were obtained for all subjects, and the Client Satisfaction Questionnaire (CSQ-8) was administered. Patients were also asked for open-ended comments regarding their satisfaction with the service. Their responses were recorded verbatim. RESULTS: Patients with telemedicine (n = 60) and standard encounters (n = 60) were comparable in gender, genotype, education, employment, and mean number of sickle cell disease-related complications. Patients in the telemedicine group were younger (p< 0.005), more likely to have Medicaid insurance (p = 0.009), and more likely be taking hydroxyurea (p = 0.003) than patients in the control encounter group. Mean CSQ scores for the telemedicine group were high (total: 28.82+/-3.06), and there was no difference for any item between encounter groups (p = 0.389). Patients in the standard encounter group were more likely to provide positive open-ended comments regarding the encounter (95% vs. 70%; p = 0.001). Negative comments were generally in the area of confidentiality. CONCLUSIONS: While some patients expressed concern about confidentiality with telemedicine, the benefits of improved access and continuity of care were recognized, and overall satisfaction with telemedicine was high. These findings support the use of telemedicine as an acceptable health care delivery option for rural, underserved populations with sickle cell disease.

Adult↗

IFN-tau exhibits potent suppression of human papillomavirus E6/E7 oncoprotein expression.

The effects of interferon-tau (IFN-tau) on tumor suppressor factors and virus oncoprotein expression were compared with two other type I IFN in human papillomavirus (HPV-16)-transformed cells. Nontumorigenic human keratinocytes, HuKc/HPV-16d-2C (d-2C), treated with recombinant human IFN-alpha2a (Roferon), a human recombinant alpha IFN hybrid, alpha B/D (IFN-alphaB/D), or ovine IFN-tau were evaluated for their effects on the levels of E6 and E7 expression. IFN-tau was comparable to IFN-alpha2a in decreasing intracellular levels of E6 and E7, and IFN-alphaB/D was more effective than IFN-a2a in suppressing E7 levels. All three IFN were capable of increasing the cellular concentration of wild-type p53 tumor suppressor with the magnitude IFN-tau > IFN-alpha2a > IFN-alphaB/D. Increases in p53 concentrations correlated with the observed decreases in E6 mRNA and protein levels. The antiviral effects observed in this study reveal that IFN-tau has potent antipapillomavirus activity. Sequences/structures unique to IFN-tau could allow for alternative IFN/receptor interactions and may explain the differences in biologic function.

Antiviral Agents↗

Selective inhibition of human papillomavirus-induced cell proliferation by (S)-1-[3-hydroxy-2-(phosphonylmethoxy)propyl]cytosine.

(S)-1-[3-Hydroxy-2-(phosphonylmethoxy)propyl]cytosine (HPMPC) is a nucleoside phosphonate analog which in its active diphosphorylated form is known to inhibit herpesvirus DNA polymerase. In this study, we have demonstrated that, in a dose-dependent manner, this compound irreversibly suppressed proliferation of cells infected with human papillomavirus (HPV), which does not possess a viral DNA polymerase. To elucidate the mechanism of cell growth inhibition, cell cycle indicator-regulator expression, thymidine incorporation, transcript levels of apoptosis factors, and anabolic products of HPMPC following drug treatment were evaluated. HPMPC treatment reduced WAF1 (p21) levels independent of those of p53, while proliferating cell nuclear antigen increased. However, in comparison to controls, HPMPC-treated cells displayed a decrease in thymidine incorporation, indicating an inhibition of host DNA polymerase activity. In normal primary keratinocytes, HPMPC predominantly accumulated in the form of the choline adduct HPMPCp-choline. However, in HPV type 16-transformed keratinocytes, HPMPCpp was the most abundant anabolic product, with little HPMPCp-choline having formed. The data imply that an unrecognized viral factor is modulating the conversion of nucleotides, including HPMPC, to the triphosphorylated form.

Antiviral Agents↗

Cloning and sequencing of the genes downstream of the wbf gene cluster of Vibrio cholerae serogroup O139 and analysis of the junction genes in other serogroups.

The DNA sequence of the O-antigen biosynthesis cluster (wbf) of a recently emergent pathogen, Vibrio cholerae serogroup O139, has been determined. Here we report the sequence of the genes downstream of the O139 wbfX gene and analysis of the genes flanking the wbf gene cluster in other serogroups. The gene downstream of wbfX, designated rjg (right junction gene), is predicted to be not required for O-antigen biosynthesis but appears to be a hot spot for DNA rearrangements. Several variants of the rjg gene (three different insertions and a deletion) have been found in other serogroups. DNA dot blot analysis of 106 V. cholerae strains showed the presence of the left and right junction genes, gmhD and rjg, respectively, in all strains. Further, these genes mapped to a single I-CeuI fragment in all 21 strains analyzed by pulsed-field gel electrophoresis, indicating a close linkage. The insertion sequence element IS1358, found in both O1 and O139 wb* regions, is present in 61% of the strains tested; interestingly, where present, it is predominantly linked to the wb* region. These results indicated a cassette-like organization of the wb* region, with the conserved genes (gmhD and rjg) flanking the divergent, serogroup-specific wb* genes and IS1358. A similar organization of the wb* region in other serogroups raises the possibility of the emergence of new pathogens by homologous recombination via the junction genes.

Amino Acid Sequence↗

Evidence of avian leukosis virus subgroup E and endogenous avian virus in measles and mumps vaccines derived from chicken cells: investigation of transmission to vaccine recipients.

Reverse transcriptase (RT) activity has been detected recently in all chicken cell-derived measles and mumps vaccines. A study of a vaccine manufactured in Europe indicated that the RT is associated with particles containing endogenous avian retrovirus (EAV-0) RNA and originates from the chicken embryonic fibroblasts (CEF) used as a substrate for propagation of the vaccine. We investigated the origin of RT in measles and mumps vaccines from a U.S. manufacturer and confirm the presence of RT and EAV RNA. Additionally, we provide new evidence for the presence of avian leukosis virus (ALV) in both CEF supernatants and vaccines. ALV pol sequences were first identified in particle-associated RNA by amplification with degenerate retroviral pol primers. ALV RNA sequences from both the gag and env regions were also detected. Analysis of hypervariable region 2 of env revealed a subgroup E sequence, an endogenous-type ALV. Both CEF- and vaccine-derived RT activity could be blocked by antibodies to ALV RT. Release of ALV-like virus particles from uninoculated CEF was also documented by electron microscopy. Nonetheless, infectivity studies on susceptible 15B1 chicken cells gave no evidence of infectious ALV, which is consistent with the phenotypes of the ev loci identified in the CEF. PCR analysis of ALV and EAV proviral sequences in peripheral blood mononuclear cells from 33 children after measles and mumps vaccination yielded negative results. Our data indicate that the sources of RT activity in all RT-positive measles and mumps vaccines may not be similar and depend on the particular endogenous retroviral loci present in the chicken cell substrate used. The present data do not support transmission of either ALV or EAV to recipients of the U.S.-made vaccine and provide reassurance for current immunization policies.

Animals↗

Replicability of SF-36 summary scores by the SF-12 in stroke patients.

BACKGROUND AND PURPOSE: The replicability of the physical and mental component summary scores of the Short Form (SF)-36 has been established using the SF-12 in selected patient populations but has yet to be assessed in stroke patients. If the summary scores of the SF-12 are highly correlated with those of the SF-36, the benefits of using a shorter health-status measure may be realized without substantial loss of information or precision. Both self-reported and proxy assessments were evaluated for replicability. METHODS: Intraclass correlation coefficients (ICCs) and linear regression were used to assess the ability of the SF-12 physical component summary (PCS-12) scores to predict PCS-36 scores and the SF-12 mental component summary (MCS-12) scores to predict MCS-36 scores. Multivariate regression was used to explore the relationship between SF-12 and SF-36 scores. RESULTS: The MCS-12 and PCS-12 scores were strongly correlated with the corresponding SF-36 summary scores for surveys completed by proxy or self-report (ICCs ranged from 0.954 to 0.973). Regression analysis of the proxy assessments indicated that patient age was an important effect modifier in the relationship between MCS-12 and MCS-36 scores. CONCLUSIONS: The SF-12 reproduced SF-36 summary scores without substantial loss of information in stroke patients. Accordingly, the SF-12 can be used at the summary score level as a substitute for the SF-36 in stroke survivors capable of self-report. However, the mental health summary scores of proxy assessments are influenced by patient age, thereby limiting the replicability of the SF-36 by the SF-12 under these conditions.

Aged↗

Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP): a randomized trial design of the effect of a community pharmacist intervention program on serum cholesterol risk.

OBJECTIVE: To determine the efficacy of a program of intervention by pharmacists on lipid risk management in patients at high risk for cardiovascular events. METHODS: Randomized, multicenter (44 sites in Alberta and Saskatchewan) study of community pharmacist intervention versus usual care in 1000 patients. Patients are those at high risk of vascular events (existing atherosclerotic vascular disease, or diabetes with > or = 1 other risk factor). After obtaining consent, the pharmacist calls the Project Office to randomize. Patients allocated to intervention receive a brochure and education about cardiovascular risk factors. Pharmacists also complete a physician contact form, which lists the patient's risk factors, medications, and any recommendations. A point-of-care cholesterol test is performed, the result is discussed with the patient, and it is entered on the contact form. If appropriate, the patient is asked to see his or her primary care physician for further assessment and/or treatment, and the form is faxed to the physician. Patients are followed up at two, four, eight, 12, and 16 weeks. During follow-up visits, pharmacists provide educational reinforcement and check for primary end point occurrence. Patients allocated to usual care receive the brochure only, with minimal follow-up. The primary end point is a composite of measurement of a complete lipid panel by the physician, or addition or modification of lipid-lowering drug therapy. Substudies will evaluate economics (third-party payer and pharmacy manager perspective), patient satisfaction, and quality of life. CONCLUSIONS: SCRIP (Study of Cardiovascular Risk Intervention by Pharmacists) is a unique ongoing trial that is evaluating a community pharmacist intervention designed to optimize cholesterol risk management in patients at high risk for cardiovascular events.

Aged↗

The impact of pharmacist interventions on health-related quality of life.

OBJECTIVE: To describe and evaluate pharmacy practice-based studies that include health-related quality of life (HRQL) as an outcome measure in assessments of pharmacist interventions and to recommend approaches for incorporating HRQL as a patient outcome in pharmacy practice-based intervention studies. METHODS: Citations were identified in MEDLINE, Healthstar, EMBASE, and International Pharmaceutical Abstracts from January 1988 to February 1999 using terms for health-related quality of life and pharmacist interventions. Abstracts were screened by two reviewers and articles that reported a pharmacist intervention performed with HRQL as an outcome measure were included. RESULTS: Of 689 citations identified by the literature search terms, 11 met the inclusion criteria. Nine studies contained a disease-specific focus. The SF-36, or its variations, was the only generic instrument used, and seven studies described using a disease-specific instrument. Pharmacist interventions inconsistently demonstrated positive effects on patient HRQL. DISCUSSION: Possible reasons for not detecting significant differences in HRQL include length of study period, insufficient sample size and power, selection bias, labeling effects, the type of measure applied, and lack of actual influence of pharmaceutical services on HRQL. Strategies to strengthen the design and methodologic approach, such as the reporting of effect size, are recommended. CONCLUSIONS: In order to demonstrate the positive effect of pharmaceutical services on patient health, pharmacy practice researchers should continue incorporating HRQL outcome measures, complemented by clinical, economic, and other humanistic outcome indicators.

Community Pharmacy Services↗