Service quality in outpatient teaching hospital pharmacies based on the SERVQUAL model: An assessment in the south of Iran.

OBJECTIVES: The present study assessed the quality of services in the outpatient teaching hospital pharmacies affiliated to Shiraz University of Medical Sciences, Iran, in 2019 according to the SERVQUAL model to identify areas for improvement. METHODS: The research was cross-sectional, descriptive and analytical. Patients referred to the outpatient teaching hospital pharmacies affiliated to Shiraz University of Medical Sciences formed the study population. The sample size was 300 people chosen through the stratified sampling method proportional to the size as well as the convenience sampling method. The modified SERVQUAL questionnaire developed by Mohammadi et al. (in Eftekhar Ardabili H, Akbari Haghighi F, Mahmoudi M, Poorreza A. Evaluation of service quality based on the patients' expectations and perceptions in Zanjan hospitals. J Sch Public Health Inst Public Health Res. 2003;2:71-84) was used for data collection. Data analysis was performed by SPSS 24.0 using statistical tests of paired t-test, independent t-test and ANOVA. A P-value of <0.05 showed statistical significance. Moreover, EXCEL 2013 was used to draw the graphs. KEY FINDINGS: The results showed that the participants had higher expectations regarding the quality of pharmacy services in all six dimensions compared to their perceptions (negative gaps) and the difference was statistically significant (P <0.05). The largest gap was in the 'access' dimension (G = -0.44 ± 1.15) and the smallest one was in the 'reliability' dimension (G = -0.21 ± 1.30). Also, the mean of overall quality gap, among the patients' demographic characteristics, had a significant relationship only with having supplementary health insurance coverage (P = 0.03). CONCLUSIONS: It seems that hospital managers and technical managers of pharmacies should make several interventions in the field of staff empowerment and training empathy and teamwork skills. Also, strengthening the system of receiving quick and easy feedback from patients and paying attention to the voice of customers can pave the way for hospital managers and technical managers of pharmacies to enhance the service quality with subsequence reduction of the existing gaps.

Effects of the selective GPER1 agonist G1 on bone growth.

Estrogens may affect bone growth locally or systemically via the known estrogen receptors ESR1, ESR2 and G protein-coupled estrogen receptor 1 (GPER1). Mouse and human growth plate chondrocytes have been demonstrated to express GPER1 and ablation of this receptor increased bone length in mice. Therefore, GPER1 is an attractive target for therapeutic modulation of bone growth, which has never been explored. To investigate the effects of activated GPER1 on the growth plate, we locally exposed mouse metatarsal bones to different concentrations of the selective GPER1 agonist G1 for 14 days ex vivo. The results showed that none of the concentrations of G1 had any direct effect on metatarsal bone growth when compared to control. To evaluate if GPER1 stimulation may systemically modulate bone growth, ovariectomized C57BL/6 mice were treated with G1 or ß-estradiol (E2). Similarly, G1 did not influence tibia and femur growth in treated mice. As expected, E2 treatment suppressed bone growth in vivo. We conclude that ligand stimulation of GPER1 does not influence bone growth in mice.

Tamoxifen induces permanent growth arrest through selective induction of apoptosis in growth plate chondrocytes in cultured rat metatarsal bones.

Estrogen affects skeletal growth and promotes growth plate fusion in humans. High doses of estrogen have been used to limit growth in girls with predicted extreme tall stature; a treatment which has been associated with severe side effects. Selective estrogen receptor modulators (SERMs) could potentially be used as an alternative treatment. We chose to study the effects of Tamoxifen (Tam), a first generation SERM that has been used in the treatment of pubertal gynecomastia or McCune-Albright syndrome. Cultured fetal rat metatarsal bones were used to study the effects of Tam on longitudinal bone growth. In sectioned bones, chondrocyte apoptosis and proliferation were analyzed by TUNEL assay and BrdU incorporation, respectively. We also used a human chondrocytic cell line, HSC-2/8, to study the effects of Tam on apoptosis (FACS analysis and Cell Death detection ELISA) and caspase activation (caspase substrate cleavage and Western immunoblotting). Tam caused a dose-dependent growth retardation of cultured metatarsal bones. No catch-up growth was observed after Tam was removed from the culture medium. Detailed analysis of sectioned growth plate cartilage revealed increased apoptosis of chondrocytes within the resting and hypertrophic zones. HCS-2/8 cells also underwent apoptosis upon Tam treatment. Tam-induced apoptosis was caspase-dependent and completely abrogated by either caspase-8 or -9 inhibitors. A substrate assay revealed that caspase-8 is first activated followed by caspase-9 and -3. Finally, FasL secretion was stimulated by Tam and blocking of either FasL or Fas decreased Tam-induced apoptosis in chondrocytes. We here describe a novel mechanism of tamoxifen-induced apoptosis in chondrocytes, involving the activation of caspases and the FasL/Fas pathway, which diminishes the potential for bone growth.

Resveratrol treatment delays growth plate fusion and improves bone growth in female rabbits.

Trans-resveratrol (RES), naturally produced by many plants, has a structure similar to synthetic estrogen diethylstilbestrol, but any effect on bone growth has not yet been clarified. Pre-pubertal ovary-intact New Zealand white rabbits received daily oral administration of either vehicle (control) or RES (200 mg/kg) until growth plate fusion occurred. Bone growth and growth plate size were longitudinally monitored by X-ray imaging, while at the endpoint, bone length was assessed by a digital caliper. In addition, pubertal ovariectomized (OVX) rabbits were treated with vehicle, RES or estradiol cypionate (positive control) for 7 or 10 weeks and fetal rat metatarsal bones were cultured in vitro with RES (0.03 µM-50 µM) and followed for up to 19 days. In ovary-intact rabbits, sixteen-week treatment with RES increased tibiae and vertebrae bone growth and subsequently improved final length. In OVX rabbits, RES delayed fusion of the distal tibia, distal femur and proximal tibia epiphyses and femur length and vertebral bone growth increased when compared with controls. Histomorphometrical analysis showed that RES-treated OVX rabbits had a wider distal femur growth plate, enlarged resting zone, increased number/size of hypertrophic chondrocytes, increased height of the hypertrophic zone, and suppressed chondrocyte expression of VEGF and laminin. In cultured fetal rat metatarsal bones, RES stimulated growth at 0.3 µM while at higher concentrations (10 µM and 50 µM) growth was inhibited. We conclude that RES has the potential to improve longitudinal bone growth. The effect was associated with a delay of growth plate fusion resulting in increased final length. These effects were accompanied by a profound suppression of VEGF and laminin expression suggesting that impairment of growth plate vascularization might be an underlying mechanism.

Pro-inflammatory cytokines produced by growth plate chondrocytes may act locally to modulate longitudinal bone growth.

INTRODUCTION: Interleukin-1ß (IL-1ß) and tumour necrosis factor-α (TNF-α), both cytokines upregulated during chronic inflammation, are known to suppress bone growth. So far no role of these cytokines in modulation of normal bone growth has been established. METHODOLOGY: Applying RT-PCR and immunohistochemistry, expression of IL-1ß and TNF-α was studied in cultured fetal (E20) rat metatarsal bones. Anakinra (500 µg/ml; IL-1 receptor antagonist) and/or etanercept (500 µg/ml; soluble TNF-α receptor) were used to block cytokine actions. RESULTS: The local expression of IL-1ß and TNF-α was confirmed in the rat metatarsal growth plate. When cultured for 12 days and compared to control, the length of bones exposed to anakinra, etanercept, or anakinra plus etanercept increased by 7.7 ± 2.0 (p < 0.05), 11.7 ± 2.8 (p < 0.01) and 20.3 ± 1.9% (p < 0.001), respectively, while the height of the hypertrophic growth plate zone (collagen X staining) increased by 11.0 ± 6.7, 17.4 ± 7.1 and 43.1 ± 5.0% (p < 0.01), respectively. Moreover, etanercept increased chondrocyte proliferation (BrdU incorporation). CONCLUSION: Our findings that IL-1ß and TNF-α are produced by growth plate chondrocytes and that their antagonists improve growth of cultured metatarsal bones suggest that these cytokines play a physiological role in the normal regulation of longitudinal bone growth.

Estrogen signaling in growth plate cartilage.

It is well known that sex steroids, in particular estrogens, play an important role in longitudinal bone growth during puberty. High doses of estrogen therapy can reduce the final height of an individual, but such treatment is also associated with severe side effects. At the same time, attenuation of estrogen production by aromatase inhibitors increases adult final height, inhibiting bone turnover, which influences bone architecture and may increase the risk for vertebrae fractures. SERMs, which display either estrogenic and/or antiestrogenic effects, bind to ERs with different affinities and subsequently recruit co-modulators of transcription in a tissue-specific manner.

The biologics anakinra and etanercept prevent cytokine-induced growth retardation in cultured fetal rat metatarsal bones.

BACKGROUND/AIMS: Chronic inflammation during childhood often leads to impaired bone growth and reduced adult height. Proinflammatory cytokines interleukin (IL)-1ß and tumor necrosis factor (TNF)-α synergistically impair bone growth in vitro. We hypothesized that biologic agents may rescue bones from cytokine-induced growth impairment and that insulin growth factor (IGF)-I may potentiate such an effect. METHODOLOGY: Metatarsal bones from fetal Sprague-Dawley rats (19-20 days p.c.) were treated with IL-1ß plus TNF-α, or the combination of these cytokines with anakinra (IL-1 receptor antagonist), etanercept (TNF-inhibitor) and/or IGF-I. The bones were measured and growth expressed as percent increase in bone length over the 7-day culture period. RESULTS: When exposed to IL-1ß plus TNF-α (10 + 10 ng/ml), bone growth was markedly suppressed (6.6 ± 1.4 vs. 50.6 ± 2.5% in control bones; p < 0.001). The growth of cytokine exposed bones (IL-1ß plus TNF-α) was dose-dependently rescued by anakinra (0.05-500 µg/ml) or etanercept (0.5-500 µg/ml); at the highest concentrations, growth was similar as in control bones never exposed to cytokines. Also when combining IGF-I (100 ng/ml) and relatively low concentrations of anakinra (0.05 µg/ml) or etanercept (5 µg/ml), growth was rescued in an additive way. CONCLUSION: Etanercept and anakinra efficiently and dose-dependently prevent cytokine-induced bone growth impairment, and combination with IGF-I further improves bone growth.

Genetic regulation of the growth plate.

The epiphyseal growth plate consists of a layer of cartilage present only during the growth period and vanishes soon after puberty in long bones. It is divided to three well-defined zones, from epiphyses; resting, proliferative, and hypertrophic zones. Chondrocyte proliferation and differentiation and subsequent bone formation in this cartilage are controlled by various endocrine, autocrine, and paracrine factors which finally results into elimination of the cartilaginous tissue and promotion of the epiphyseal fusion. As chondrocytes differentiate from round, quiescent, and single structure to flatten and proliferative and then large and terminally differentiated, they experience changes in their gene expression pattern which allow them to transform from cartilaginous tissue to bone. This review summarizes the literature in this area and shortly describes different factors that affect growth plate cartilage both at the local and systemic levels. This may eventually help us to develop new treatment strategies of different growth disorders.

Catch-up growth after dexamethasone withdrawal occurs in cultured postnatal rat metatarsal bones.

Children exposed to systemic glucocorticoids often exhibit growth retardation and after the cessation of therapy catch-up growth occurs in many, but not all patients. The developmental regulation and underlying cellular mechanisms of catch-up growth are not fully understood. To clarify this issue, we established an in vitro model of catch-up growth. Here we present a protocol for the long-term culture (up to 160 days) of fetal (E20) as well as postnatal (P8) rat metatarsal bones which allowed us to characterize ex vivo the phenomenon of catch-up growth without any influence by systemic factors. The relevance of the model was confirmed by the demonstration that the growth of fetal and postnatal bones were stimulated by IGF1 (100 ng/ml) and inhibited by dexamethasone (Dexa; 1 microM). We found that the capacity to undergo catch-up growth was restricted to postnatal bones. Catch-up growth occurred after postnatal bones had been exposed to Dexa for 7 or 12 days but not after a more prolonged exposure (19 days). Incomplete catch-up growth resulted in compromised bone length when assessed at the end of the 4-month period of culture. While exposure to Dexa was associated with decreased chondrocyte proliferation and differentiation, catch-up growth was only associated with increased cell proliferation. We conclude that the phenomenon of catch-up growth after Dexa treatment is intrinsic to the growth plate and primarily mediated by an upregulation of chondrocyte proliferation.

Tamoxifen impairs both longitudinal and cortical bone growth in young male rats.

Tamoxifen (Tam) has been used experimentally to treat boys with gynecomastia and girls with McCune-Albright syndrome. This drug was recently shown to inhibit the growth of cultured fetal rat metatarsal bones and thus might also affect bone growth in vivo. Four-week-old Sprague-Dawley rats were gavaged daily with vehicle alone (peanut oil), Tam (40 mg/kg/d; 1 or 4 wk), or estradiol (40 microg/kg/d; 4 wk). Five of the 10 rats in each group were killed after 4 wk and the other five after 14 wk of recovery. Bone growth was followed by repeat DXA scans, whereas other bone parameters and spine length were evaluated by pQCT and X-ray at the time of death. Four-week Tam treatment significantly decreased body weight, nose-anus distance, spinal and tibial bone lengths, trabecular BMD, cortical periosteal circumference, and bone strength and also reduced serum IGF-I levels (424 +/- 54 versus 606 +/- 53 ng/ml in control; p < 0.05). Analysis of the tibial growth plate of treated rats showed elevated chondrocyte proliferation (BrdU) and apoptosis (TUNEL), as well as decreases in the number of hypertrophic chondrocytes and in the size of terminal hypertrophic chondrocytes. Despite a complete catch-up of body weight after 14 wk of recovery, the tibia was still shorter (p < 0.001) and its cortical region was smaller. We conclude that, when administered at a clinically relevant dose, Tam causes persistent retardation of longitudinal and cortical radial bone growth in young male rats. Our findings suggest that this inhibition results from local effects on the growth plate cartilage and systemic suppression of IGF-I production. Based on these rat data, we believe that Tam, if given to growing individuals, might compromise cortical bone growth, bone strength, and adult height.