Paramutation at the maize pl1 locus is associated with RdDM activity at distal tandem repeats.

Exceptions to Mendelian inheritance often highlight novel chromosomal behaviors. The maize Pl1-Rhoades allele conferring plant pigmentation can display inheritance patterns deviating from Mendelian expectations in a behavior known as paramutation. However, the chromosome features mediating such exceptions remain unknown. Here we show that small RNA production reflecting RNA polymerase IV function within a distal downstream set of five tandem repeats is coincident with meiotically-heritable repression of the Pl1-Rhoades transcription unit. A related pl1 haplotype with three, but not one with two, repeat units also displays the trans-homolog silencing typifying paramutations. 4C interactions, CHD3a-dependent small RNA profiles, nuclease sensitivity, and polyadenylated RNA levels highlight a repeat subregion having regulatory potential. Our comparative and mutant analyses show that transcriptional repression of Pl1-Rhoades correlates with 24-nucleotide RNA production and cytosine methylation at this subregion indicating the action of a specific DNA-dependent RNA polymerase complex. These findings support a working model in which pl1 paramutation depends on trans-chromosomal RNA-directed DNA methylation operating at a discrete cis-linked and copy-number-dependent transcriptional regulatory element.

Durable benefit after treatment of obstructive benign prostatic hyperplasia with a novel drug-device combination product: 2-year outcomes from the EVEREST-I study.

PURPOSE: To evaluate the safety and efficacy of the Optilume BPH Catheter System for the treatment of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). METHODS: This open-label, single-arm study enrolled eighty subjects with LUTS secondary to BPH who were treated with the Optilume BPH Catheter System. Symptoms were recorded utilizing the International Prostate Symptom Score (IPSS) and Benign Prostatic Hyperplasia Impact Index (BPH-II). Functional improvement was measured utilizing peak urinary flow rate (Qmax) and post-void residual urine volume (PVR). Adverse events were systematically captured and reported at each follow-up visit. RESULTS: Subjects treated with the Optilume BPH Catheter System experienced a significant improvement in LUTS from baseline through 2 years of follow-up, as measured by IPSS (22.3 vs 8.2, p < 0.001) and BPH-II (6.9 vs 2.3, p < 0.001). Functional improvement was also significant, with Qmax improving from an average of 10.9 mL/s at baseline to 17.2 mL/s at the 2-year follow-up and PVR improving from 63.1 to 45.0 mL. Treatment-related adverse events were typically minor, with none occurring between 1- and 2-year post-treatment. CONCLUSIONS: The Optilume BPH Catheter System is a unique minimally invasive surgical therapy that combines mechanical and pharmaceutical aspects for the treatment of BPH. The functional and symptomatic improvements seen after treatment are significant and have been sustained through 2 years in this early feasibility study. REGISTRATION: NCT03423979, registered February 6, 2018.

OnabotulinumtoxinA improves oral aperture in patients with scleroderma: A small clinical trial.

BACKGROUND: Reduced oral aperture (ROA), resulting from systemic sclerosis (SSc), is a debilitating condition with limited treatment options. Improvement in oral function has been reported with perioral administration of botulinum toxin type A. OBJECTIVE: To prospectively evaluate the efficacy of onabotulinumtoxinA (onabotA) injection in improving oral opening and quality of life in SSc patients with ROA. METHODS: Seventeen women with SSc and ROA were treated with 16 units of onabotA in 8 different sites around the cutaneous lips. Measurements of maximum mouth opening were taken before treatment, at 2 weeks posttreatment, and at 3 months posttreatment. Function and quality of life were also assessed via surveys. RESULTS: Interincisor and interlabial distances were significantly increased 2 weeks after treatment with onabotA (P < .001) but not 3 months after. Subjective improvement in quality of life was noted. LIMITATIONS: This single-institution study enrolled 17 patients and did not have a placebo control group. CONCLUSION: OnabotA appears to have a strong short-term symptomatic benefit in patients with ROA due to SSc, with possible benefit to quality of life.

Validation of Phase-Resolved Functional Lung (PREFUL) Magnetic Resonance Imaging Pulse Wave Transit Time Compared to Echocardiography in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Phase-resolved functional lung (PREFUL) magnetic resonance imaging (MRI) pulmonary pulse wave transit time (pPTT) is a contrast agent free, vascular imaging biomarker, but has not been validated in chronic obstructive pulmonary disease (COPD). PURPOSE: To validate PREFUL with echocardiographic pPTT as a reference standard and to compare arterial/venous pPTT mapping with spirometry and clinical parameters. STUDY TYPE: Prospective. POPULATION: Twenty-one patients (62% female) with COPD and 44 healthy participants (50% female). FIELD STRENGTH/SEQUENCE: 1.5 T; 2D-spoiled gradient-echo sequence. ASSESSMENT: Three coronal PREFUL MRI slices, echocardiography, and spirometry including forced expiratory volume in 1 second (FEV1, liter) and predicted defined as FEV1 in% divided by the population average FEV1%, were performed. Pulmonary pulse transit time from the main artery to the microvasculature (PREFUL pPTT), to the right upper lobe vein (PREFUL pPTTav , echo pPTTav ), from microvasculature to right upper lobe vein (PREFULvein ) and the ratio of PREFUL pPTT to PREFUL pPTTvein were calculated. Body mass index (BMI), Global Initiative for COPD (GOLD) stage 1-4, disease duration, and cigarette packs smoked per day multiplied by the smoked years (pack years) were computed. STATISTICAL TESTS: Shapiro-Wilk-test, paired-two-sided-t-tests, Bland-Altman-analysis, coefficient of variation, Pearson ρ were applied, pPTT data were compared between 21 subjects from the 44 healthy subjects who were age- and sex-matched to the COPD cohort, P < 0.05 was considered statistically significant. RESULTS: PREFUL pPTTav significantly correlated with echo pPTTav (ρ = 0.95) with 1.85 msec bias, 95% limits of agreement: 55.94 msec, -52.23 msec in all participants (P = 0.59). In the healthy participants, PREFUL and echo pPTTav significantly correlated with age (ρ = 0.81, ρ = 0.78), FEV1 (ρ = -0.47, ρ = -0.34) and BMI (ρ = 0.56, ρ = 0.51). In COPD patients, PREFUL pPTT significantly correlated with FEV1 predicted (ρ = -0.59), GOLD (ρ = 0.53), disease duration (ρ = 0.54), and pack years (ρ = 0.49). DATA CONCLUSION: Arteriovenous PTT measured by PREFUL MRI corresponds precisely to echocardiography and appears to be feasible even in severe COPD. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 2.

Repeatability of Phase-Resolved Functional Lung (PREFUL)-MRI Ventilation and Perfusion Parameters in Healthy Subjects and COPD Patients.

BACKGROUND: Free-breathing phase-resolved functional lung (PREFUL)-MRI may be useful for treatment monitoring in chronic obstructive pulmonary disease (COPD) patients with dyspnea. PREFUL test-retest reliability is essential for clinical application. PURPOSE: To measure the repeatability of PREFUL-MRI ventilation (V) and perfusion (Q) parameters. STUDY TYPE: Retrospective and prospective. POPULATION: A total of 28 COPD patients and 57 healthy subjects. FIELD STRENGTH/SEQUENCE: 1.5T MRI/2D spoiled gradient echo imaging. ASSESSMENT: V and Q lung parameter maps based on three coronal slices were obtained at baseline and after 14 days (COPD patients) or after a short pause outside the scanner (healthy subjects). Regional ventilation (RVent) and imaging flow volume loops by cross-correlation (ccVent) were quantified. Q was normalized to the signal of the main pulmonary artery (QN ) and quantified (QQuant ). Pulmonary pulse wave transit time (pPTT), voxel-by-voxel (regional), and whole lung (global) ventilation defect percentage based on RVent (VDPRVent ) and ccVent (VDPccVent ), perfusion defect percentage (QDP), and ventilation/perfusion match based on RVent (VQMRVent ) and ccVent (VQMccVent ) were calculated. STATISTICAL TESTS: Regional V and Q were analyzed globally for each subject. Each parameter's median of scans 1 and 2 were assessed by Wilcoxon sign rank test. A parameter's repeatability was analyzed by Bland-Altman analyses, coefficients of variation, intraclass correlation coefficients (ICC), and power calculations. The regional voxel repeatability was examined by calculating the Sørensen-Dice coefficient. RESULTS: There was no bias and no significant differences between the first and second MRI for any parameters (P > 0.05). Coefficient of variation ranged from 2.26% (ccVent) to 19.31% (QDP), ICC from 0.93 (QDP) to 0.60 (pPTT), the smallest detectable difference was 0.002 ccVent. Regional comparison showed the highest overlap (84%) in VDPRVent in healthy voxels and the lowest (53%) in VDPccVent defect voxels. DATA CONCLUSION: V and Q PREFUL-MRI parameters were repeatable over two scan sessions in both healthy controls and COPD patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.

Bladder squamous cell carcinoma in a pregnant woman: case report and review of the literature.

BACKGROUND: Bladder tumors in pregnancy are extremely rare. No more than 50 cases have been published to date, including all histologic variants, and only three cases of bladder squamous cell carcinoma have been described. CASE PRESENTATION: We present a clinical case of a 31-year-old woman with bladder squamous cell carcinoma in the second trimester of pregnancy. After a C-section at 30 weeks, we performed radical cystectomy with extended bilateral lymphadenectomy, hysterectomy and right oophorectomy. The Studer neobladder technique was performed for urinary tract reconstruction. Definitive pathology showed invasive bladder squamous cell carcinoma, Grade 2, with microscopic infiltration of the perivesical fat, negative margins, and 3/28 lymph nodes with carcinoma (pT3aN2M0). The patient underwent 18 months of surveillance after radical cystectomy, without recurrence by PET-CT. CONCLUSIONS: Bladder cancer in pregnant women is extremely rare but must be considered in those with recurrent gross hematuria and/or recurrent urinary tract infection. To our knowledge, this case involves the longest recurrence-free survival of a pregnant woman with squamous cell bladder cancer published thus far.

Safety and Efficacy of Dermal Fillers in Patients With Connective Tissue Disease: A Review.

BACKGROUND: Dermal fillers such as hyaluronic acid, poly-l-lactic acid, and polymethyl-methacrylate are often used to treat cutaneous defects such as lipoatrophy. However, concern exists regarding their use in patients with a connective tissue disease (CTD) because of a theoretical risk of disease reactivation or exacerbation. Evidence regarding their use in patients with CTD also remains limited. OBJECTIVE: This review intends to summarize and evaluate the available literature regarding the use of dermal fillers in patients with CTD. MATERIALS AND METHODS: A literature search until May 2020 was conducted through PubMed, Ovid MEDLINE, and Ovid Embase to identify articles discussing the treatment of cutaneous defects secondary to CTD. Articles discussing the use of autologous fat transfer alone were excluded. RESULTS: Twenty-three articles were reviewed. The amount of available evidence varies between the type of CTD and type of filler with morphea having the most published evidence out of the CTDs discussed and hyaluronic acid having the most published evidence out of the fillers discussed. Most studies demonstrated positive results with no report of disease reactivation or exacerbation. CONCLUSION: Despite limited available evidence, dermal fillers seem to be safe as an adjunctive treatment for cutaneous defects in patients with CTD.

Review of the Current Medical and Surgical Treatment Options for Microstomia in Patients With Scleroderma.

BACKGROUND: Most patients with scleroderma suffer from microstomia, which can have debilitating consequences on their quality of life. Unfortunately, treatment options remain limited. No specific guidelines exist; hence, microstomia remains a challenge to treat in this patient population. OBJECTIVE: This review aims to evaluate the different medical and surgical treatment modalities currently available for microstomia in patients with scleroderma and make recommendations for future research. MATERIALS AND METHODS: A search of PubMed, Ovid MEDLINE, and Ovid Embase was conducted to identify articles discussing the treatment of microstomia in scleroderma. Twenty articles discussing surgical therapy and one article discussing medical therapy were reviewed. RESULTS: Mostly because of a scarcity of high-level evidence, no individual therapy has documented long-term efficacy. Some treatments demonstrate positive results and warrant further research. CONCLUSION: Given the variability of results, specific recommendations for the treatment of microstomia in patients with scleroderma are difficult to establish. A multifaceted approach that includes surgical and medical therapy is likely the best option to improve oral aperture in this patient population. Surgical treatments such as neurotoxins, autologous fat grafting, and ultraviolet A1 phototherapy may hold the most potential for improvement.

Utilization of Marine Waste to Obtain ß-Chitin Nanofibers and Films from Giant Humboldt Squid Dosidicus gigas.

ß-chitin was isolated from marine waste, giant Humboldt squid Dosidicus gigas, and further converted to nanofibers by use of a collider machine under acidic conditions (pH 3). The FTIR, TGA, and NMR analysis confirmed the efficient extraction of ß-chitin. The SEM, TEM, and XRD characterization results verified that ß-chitin crystalline structure were maintained after mechanical treatment. The mean particle size of ß-chitin nanofibers was in the range between 10 and 15 nm, according to the TEM analysis. In addition, the ß-chitin nanofibers were converted into films by the simple solvent-casting and drying process at 60 °C. The obtained films had high lightness, which was evidenced by the CIELAB color test. Moreover, the films showed the medium swelling degree (250-290%) in aqueous solutions of different pH and good mechanical resistance in the range between 4 and 17 MPa, depending on film thickness. The results obtained in this work show that marine waste can be efficiently converted to biomaterial by use of mild extractive conditions and simple mechanical treatment, offering great potential for the future development of sustainable multifunctional materials for various industrial applications such as food packaging, agriculture, and/or wound dressing.

Design, Synthesis, and In Silico Multitarget Pharmacological Simulations of Acid Bioisosteres with a Validated In Vivo Antihyperglycemic Effect.

Substituted phenylacetic (1-3), phenylpropanoic (4-6), and benzylidenethiazolidine-2,4-dione (7-9) derivatives were designed according to a multitarget unified pharmacophore pattern that has shown robust antidiabetic activity. This bioactivity is due to the simultaneous polypharmacological stimulation of receptors PPARα, PPARγ, and GPR40 and the enzyme inhibition of aldose reductase (AR) and protein tyrosine phosphatase 1B (PTP-1B). The nine compounds share the same four pharmacophore elements: an acid moiety, an aromatic ring, a bulky hydrophobic group, and a flexible linker between the latter two elements. Addition and substitution reactions were performed to obtain molecules at moderated yields. In silico pharmacological consensus analysis (PHACA) was conducted to determine their possible modes of action, protein affinities, toxicological activities, and drug-like properties. The results were combined with in vivo assays to evaluate the ability of these compounds to decrease glucose levels in diabetic mice at a 100 mg/kg single dose. Compounds 6 (a phenylpropanoic acid derivative) and 9 (a benzylidenethiazolidine-2,4-dione derivative) ameliorated the hyperglycemic peak in a statically significant manner in a mouse model of type 2 diabetes. Finally, molecular dynamics simulations were executed on the top performing compounds to shed light on their mechanism of action. The simulations showed the flexible nature of the binding pocket of AR, and showed that both compounds remained bound during the simulation time, although not sharing the same binding mode. In conclusion, we designed nine acid bioisosteres with robust in vivo antihyperglycemic activity that were predicted to have favorable pharmacokinetic and toxicological profiles. Together, these findings provide evidence that supports the molecular design we employed, where the unified pharmacophores possess a strong antidiabetic action due to their multitarget activation.

[«Missing time¼: Experiences of demand management doctors in Chilean primary health care]. / «Falta tiempo¼: experiencias de médicos gestores de la demanda en la atención primaria de salud chilena.

OBJECTIVE: Characterize the current situation of the demand manager physician (DMP) in primary health care (PHC), from the perceptions of those who fulfill this role, their medical peers and the directors of the family health centers (CESFAMs). DESIGN: Qualitative cross-sectional study with a grounded theory approach. SITE: Four CESFAMs from the South East Metropolitan Health Service in Santiago, Chile. PARTICIPANTS: Demand manager physician, general practitioners and directors of CESFAM. METHOD: A semi-structured interview and discussion group were used as data collection technique. Open, axial, and selective coding was carried out with the support of the NVivo12 software. RESULTS: In practice, DMP performs more functions than those defined for the position by the Ministry of Health, generating the feeling of lack of time to carry out their work, what represents their main barrier at work and reflects the absence of institutional support they receive from their employees. Among these invisible functions are: providing feedback to the medical team, leading clinical meetings, and generating reference protocols. For the good performance of the DMP it is necessary to have technical skills and be recognized by their peers. It was estimated that the family doctor is the most suitable professional for the position. The work of the DMP is limited by institutional factors such as waiting lists, lack of specialists, and poor coordination between levels of care. CONCLUSIONS: Standardizing the functions of the DMP is a necessary element for its consolidation and achieving the objectives of maintaining continuity of care in the population.

Scented lotions may cause scaring and premature fading of tattoos.

Although tattoo artists provide tattoo aftercare instructions to their clients, recommendations are often not cost-effective or supported by evidence. A 22-year-old man developed a pruritic red rash over his healing tattoo one week after receiving the tattoo. Although multiple queries were negative, the patient did note use of a scented lotion before the eruption. We determined that allergic contact dermatitis from the scented lotion caused scarring and premature fading of the new tattoo. Tattoo artists should recommend avoidance of scented lotions and instruct clients to care for their new tattoo like a wound in their aftercare instructions.

Histopathologic vasculitis from the periulcer edge: A retrospective cohort study.

BACKGROUND: Histopathologic vasculitis is often reported in periulcer specimens, but the frequency and clinical significance of this finding have not been evaluated. OBJECTIVE: We evaluated the sensitivity, specificity, negative predictive value, and positive predictive value of histopathologic vasculitis from the periulcer edge for detecting ulcers due to cutaneous vasculitis. METHODS: We performed a retrospective chart review of patients with leg ulcers at a tertiary hospital between 2009 and 2016. Histopathologic slides were evaluated by 2 dermatopathologists who were blinded to the etiology of ulcer. Focal vasculitis was defined as involvement of fewer than 3 vessels. RESULTS: Vasculitis at the periulcer edge was seen in 51.6% of the specimens (32 of 62). Of the specimens with histopathologic vasculitis, focal vasculitis was seen in the majority of specimens (71.9% [23 of 32]), whereas diffuse vasculitis was observed in 28.1% (9 of 32). Periulcer vasculitis yielded a high sensitivity (100% [95% confidence interval, 29%-100%]). Furthermore, the specificity was low (50.9% [95% confidence interval, 38.1%-63.6%]) for detecting vasculitis-induced ulcers. LIMITATIONS: Small number of vasculitis-induced ulcers. CONCLUSION: Focal vasculitis from the periulcer edge is a nonspecific finding and provides little diagnostic value in determining the etiology of lower leg ulcers. Emphasis should be placed on the combination of clinical history and examination, histology, and laboratory findings when diagnosing ulcers.

Localization and age distribution of telangiectases in children and adolescents with hereditary hemorrhagic telangiectasia: A retrospective cohort study.

BACKGROUND: The location of telangiectases in hereditary hemorrhagic telangiectasia (HHT), as set forth in the consensus diagnostic (Curaçao) criteria, is based primarily on adults. OBJECTIVE: Document the locations and numbers of telangiectases in a cohort of pediatric patients with HHT. METHODS: A retrospective chart review using a standardized data collection form for site and number of telangiectases was performed for pediatric patients with HHT (age, 0-18 years) from 2005 to 2016. RESULTS: Of 90 pediatric patients with HHT, 71% had one or more telangiectases. Of all the telangiectases counted (N = 319), cutaneous telangiectases were more common (73%) than oral telangiectases (27%). The hands were the most frequent site, accounting for 33% of all telangiectases. Adolescents were more likely than children to have cutaneous telangiectases (85% vs 50% [Q = 0.005]). The most frequent sites in children younger than 10 years were the hands excluding the fingers (27%), fingers (25%), and face (23%). Only 23% of subjects (21 of 90) presented with multiple (≥3) telangiectases at locations considered characteristic for the current consensus diagnosis guidelines (lips, oral cavity, and fingers). LIMITATIONS: Ascertainment bias based on recruitment. CONCLUSIONS: In this pediatric population, telangiectases at sites not included as "characteristic" by the Curaçao diagnostic criteria were common. The Curaçao criteria in regard to both number and location of telangiectases may be inadequate in the pediatric HHT population.

Hispanic Tattoo Artists Could Provide Skin Cancer Prevention via Aftercare Instructions and Social Media

BACKGROUND: The incidence of melanoma and non-melanoma skin cancer in the Hispanic population has increased. Hispanics are more likely to present with advance-staged melanoma and worse overall prognosis. Thus, public health campaigns are necessary to target the underrepresented Hispanic population. OBJECTIVE: To explore Hispanic tattoo artists' skin cancer knowledge, sun safety recommendations, and their willingness to implement primary and secondary skin cancer prevention in their daily work routines. METHODS: We conducted an in-depth semi-structured interview study with ten Hispanic tattoo artists. Interviews were conducted at multiple tattoo studios in Salt Lake City, Utah.Data was coded by a third-party. Thematic analysis identified recurrent sub-themes from the transcript. RESULTS: Majority of Hispanic tattoo artists had a high percentage of Hispanic clientele (mean: 51%, range: 25-93%) and repeat customers (mean: 73%, range: 50-90%). All tattoo artists had suboptimal skin cancer knowledge. Most Hispanic tattoo artists provide inadequate sun protective information in their aftercare instructions including a specific Sun Protection Factor, sunscreen reapplication, and protective clothing. However, all tattoo artists were willing to provide sun protective information on their social media profiles and undergo primary and secondary skin cancer prevention training. CONCLUSION: Hispanic tattoo artists could serve as public health allies and influence early detection of skin cancers in the Hispanic population by implementing preventative skin cancer behaviors in their daily work routines and providing comprehensive sun safety information through aftercare instructions and social media. J Drugs Dermatol. 2019;18(12):1237-1243.

Long-term survivors of childhood bone and soft tissue sarcomas are at risk of hospitalization.

BACKGROUND: Childhood cancer survivors can have a high burden of chronic conditions related to cancer treatment, some of which are debilitating or potentially life-threatening. Much remains to be learned about late effects in bone and soft tissue sarcoma survivors. PROCEDURES: The Utah Cancer Registry was used to identify survivors of bone (N = 71) and soft tissue sarcomas (N = 98) who were diagnosed at ages 0-20 years between 1973 and 2007 and were alive at least 5 years after diagnosis. We selected an age-sex-matched comparison cohort (N = 934). Hospitalizations from 1996 to 2012 were extracted from the Utah Department of Health statewide inpatient hospitalization discharge records. Cox, Poisson, and Gamma regressions were used to evaluate the risk of hospitalization, rate of admission, and length of stay for survivors versus the comparison cohort. Primary ICD-9 codes defined the most common reasons for hospitalizations. RESULTS: The hazard ratio (HR) of any hospitalization was higher for survivors in reference to the comparison cohort (HR = 2.12, 95% confidence interval [CI] 1.51-2.97). Survivors experienced more hospital admissions (rate ratio [RR] = 4.58, 95% CI 3.92-5.35) and longer length of stay (RR = 1.28, 95% CI 1.12-1.46) compared with the comparison cohort. Survivors treated with any chemotherapy were at three-fold higher risk (HR = 3.37, 95% CI 1.94-5.83) of hospitalization compared with survivors who received surgery and/or radiation alone. Among hospitalized survivors, the most common reason was injury for bone tumor (26.8%) and neoplasm for soft tissue sarcoma (12.2%). CONCLUSION: Childhood survivors of bone tumor and soft tissue sarcoma face ongoing risk of hospitalization for years after diagnosis.

Development and validation of the knowledge and attitudes regarding antibiotics and resistance (KAAR-11) questionnaire for primary care physicians.

OBJECTIVES: The aim of this study was to develop a novel, self-administered questionnaire to identify primary-care physicians' knowledge and attitudes regarding antibiotics and resistance (KAAR). METHODS: The study population comprised primary care physicians. The study was conducted in five phases. Phase I consisted of a systematic review and qualitative focus-group study (n = 33 physicians), in which items were formulated so as to be measured on a continuous, visual analogue scale (VAS); in Phase II, content validation and face validity were evaluated by a panel of experts, which reformulated, added and deleted items; Phase III consisted of a pilot study on a population possessing similar characteristics (n = 15); in Phase IV, we analysed reliability by means of a test-retest study (n = 91) and calculated the intraclass correlation coefficients (ICCs); and in Phase V, we assessed construct validity by applying the known-groups technique, measuring the differences between contrasting groups of physicians formed according to antibiotic prescription quality indicators (group 1, n = 156 versus group 2, n = 191). RESULTS: Following Phases I and II, the questionnaire contained 16 knowledge and attitude items. Participants in the pilot study (Phase III) reported no difficulty. The test-retest study (Phase IV) showed that 11 of the 16 initial knowledge and attitude items yielded an ICC > 0.5, while analysis of known-groups validity (Phase V) showed that 13 of the 16 initial items which assessed knowledge and attitudes discriminated between physicians with good and bad indicators of antibiotics prescription. CONCLUSION: The final 11 item KAAR questionnaire appears to be valid, reliable and responsive.

Determinants of antibiotic dispensing without a medical prescription: a cross-sectional study in the north of Spain.

OBJECTIVES: Antibiotic resistance is a major public health concern and is greatly exacerbated by inappropriate antibiotic use at a community level. The aim of this study was to ascertain which attitudes of community pharmacists were related to inappropriate antibiotic dispensing. METHODS: We conducted a cross-sectional study of community pharmacists in a region situated in northern Spain (n = 393). Personal interviews were conducted using a self-administered questionnaire. The degree of agreement with each item of knowledge and attitude was measured using an unnumbered, horizontal visual analogue scale, with replies being scored from 0 (total disagreement) to 10 (total agreement). The data were analysed using logistic regression. RESULTS: Of the total of 286 pharmacists (72.8%) who completed the questionnaire, 185 (64.7%) acknowledged having undertaken dispensing of antibiotics without a medical prescription (DAwMP). Attitudes such as patient complacency, external responsibility, indifference and insufficient knowledge were shown to be related to DAwMP. In contrast, no association was found with any of the pharmacists' personal or professional traits. CONCLUSIONS: This study confirms that, albeit unlawful, DAwMP is a common practice in Spanish pharmacies. DAwMP was seen to be usually associated with some of the attitudes evaluated.