Prediction of nipple involvement in breast cancer after neoadjuvant chemotherapy: Should we rely on breast MRI to preserve the nipple?

BACKGROUND: Indications for nipple sparing mastectomy (NSM) is extending to post-neoadjuvant chemotherapy (NAC) setting. Eligibility for NSM with an optimum tumor-nipple distance (TND) after NAC is unclear. We examined predictive factors for nipple tumor involvement in patients undergoing total mastectomy following NAC. METHODS: Clinical and pathological data from prospectively collected medical records of women with invasive breast carcinoma, who were undergone NAC and total mastectomy with sentinel lymph node biopsy and/or axillary lymph node dissection were analyzed. PreNAC and postNAC magnetic resonance imaging (MRI) views were examined and a cut-off TND value for predicting the negative nipple tumor status was determined. RESULTS: Among 180 women, the final mastectomy specimen analysis revealed that 12 (7%) had nipple involvement as invasive carcinoma. Patients with nipple involvement had more postNAC multifocal/multicentric tumors (p: 0.03), larger tumors on preNAC and postNAC images (p: 0.002 and p < 0.001), shorter median TNDs on preNAC and postNAC images (7 mm-IQR 1.5-14, p: 0.005 and 8.5 mm-IQR 3-15.5, p < 0.001, respectively), more nipple retraction on preNAC and postNAC images (p: 0.007 and p: 0.006) and more nipple areola complex skin thickening (> 2mm) on preNAC and postNAC images (p < 0.001 and p: 0.01). The best likelihood ratios (LR) belonged to the postNAC positivity of the < 20 mm TND, with a + LR of 3.40, and - LR of 0.11 for nipple involvement. PreNAC positivity of the < 20 mm TND also had a similar - LR of 0.14. CONCLUSION: A TND-cut-off  ≥ 2 cm on preNAC and postNAC MRI was shown to be highly predictive of negative nipple tumor involvement.

Sleeve gastrectomy-induced endocrine changes in the remnant stomachs of premenopausal and postmenopausal rats: role of the estrogen receptors.

BACKGROUND: Although alterations in the plasma levels of leptin, glucagon-like peptide-1, and gastrin were linked with bariatric surgery outcomes, gastric production of these peptides was not elucidated before. OBJECTIVE: The aim was to evaluate the impact of estrogen depletion and estrogen receptors (ERs) on sleeve gastrectomy (SG)-induced alterations in gastric hormone production, gastric mucosal integrity, and bone mass. SETTING: Physiology Research Lab at the University. METHODS: Female Sprague-Dawley rats underwent ovariectomy or sham operation (control), and 2 months later SG or sham SG was performed. Rats received either nonselective agonist 17 ß, ER-α agonist, ER-ß agonist, or vehicle for 3 weeks. Trunk blood and gastric tissues were collected for biochemical measurements, while histopathologic examination was performed in gastric and femur samples. RESULTS: In the presence of intact ovaries, SG-induced weight loss was accompanied by reductions in the gastric synthesis of leptin and gastrin, while gastric glucagon-like peptide-1 was additionally decreased when SG was performed at the postmenopausal state. SG elevated the depleted serum estradiol levels of menopause, implicating a beneficial effect, but the occurrence of severe gastric mucosal injury was triggered. On the other hand, using ER agonists upregulated gastrin-expressing cells, ameliorated gastric injury, and improved bone loss. CONCLUSIONS: SG, either at premenopausal or postmenopausal state, resulted in considerable loss in bone mass, along with reductions in the gastric levels of gastrin and leptin. Functional status of the ovaries needs to be taken into consideration when monitoring the outcomes of SG, and ER agonists could be of value in controlling SG-induced complications.

Response Assessment With Molecular Characterization of Circulating Tumor Cells and Plasma MicroRNA Profiling in Patients With Locally Advanced Breast Cancer During Neoadjuvant Chemotherapy.

BACKGROUND: Cells detaching from the primary tumor site are metastasis initiator cells, and the detection of CTC, known as liquid biopsy, is an important test of biomarkers of cancer progression. We investigated the molecular characterization of circulating tumor cells (CTCs), profiled the plasma microRNA (miR) content, and analyzed the relationship with the clinical outcomes by sampling the peripheral blood from patients with locally advanced breast cancer before and after neoadjuvant chemotherapy. PATIENTS AND METHODS: Markers of breast cancer, epithelial-mesenchymal transition (EMT), drug resistance, and stem cells were used for CTC isolation and characterization. Plasma miR profiles were obtained from selected patients with CTC positivity determined using next-generation sequencing. RESULTS: The proportion of CTC, EMT, and stem cell marker positivity was 16.7%, 8.3%, and 25% before and 18.2%, 15.2%, and 9.1% after treatment, respectively. A significant correlation was found between the pretreatment CTCs and ALDH1 positivity (P = .0245). These CTCs with stemness properties were observed in most hormone receptor-positive, human epidermal growth factor receptor 2-negative cases and were also present with a high incidence in cases of early metastasis. miR-146b-5p and miR-199a-5p, which are involved in metastasis, invasion, and EMT, were accompanied by CTC positivity, and miR-4646-3p was associated with the development of early metastasis. CONCLUSIONS: Molecular characterization of CTCs and miR profiling of serial samples from patients with locally advanced breast cancer during neoadjuvant chemotherapy appears to be a very useful in predicting cure and clinical course and might be a key to developing new targeted therapies.

Impact of older age on local treatment decisionss.

Managing elderly breast cancer patients brings challenges both to physicians and patients themselves. There are certain controversial issues regarding local treatment of early breast cancer in this population. Since elderly patients are more likely to have comorbidities and functional limitations, they are more prone to undertreatment. Although surgical treatment in elderly patients were reported to be safe, severity and number of comorbidities are shown to be related with increased complications, hence may lead to higher mortality and lower life quality. Therefore, frailty is one of the concerns which prevents elderly patients to receive standard-of-care local treatment. Nevertheless, breast cancers developing in elderly are more likely to be low grade and luminal type. Until now, primary endocrine treatment without surgical resection, omitting whole breast irradiation after partial mastectomy and avoiding sentinel lymph node biopsy, which are otherwise accepted as standard-of-care, were questionned in healthy, low-risk, elderly fit patients. Two main issues were suggested to be considered when assessing the impact of local treatment options in this patient group; the clinical significance of treatments' effects, and the patients' expectations. Due to their vulnerability, baseline geriatric assessment should be the initial step for management in elderly breast cancer patients. Even in those who are healthy and fit with long life-expectancy, de-escalation in management might be an option in low-risk patients after considering patients' individual expectations and limited clinical benefits of standard local treatment options.

Preventive medicine of von Hippel-Lindau disease-associated pancreatic neuroendocrine tumors.

Pancreatic neuroendocrine tumors (PanNETs) are rare in von Hippel-Lindau disease (VHL) but cause serious morbidity and mortality. Management guidelines for VHL-PanNETs continue to be based on limited evidence, and survival data to guide surgical management are lacking. We established the European-American-Asian-VHL-PanNET-Registry to assess data for risks for metastases, survival and long-term outcomes to provide best management recommendations. Of 2330 VHL patients, 273 had a total of 484 PanNETs. Median age at diagnosis of PanNET was 35 years (range 10-75). Fifty-five (20%) patients had metastatic PanNETs. Metastatic PanNETs were significantly larger (median size 5 vs 2 cm; P < 0.001) and tumor volume doubling time (TVDT) was faster (22 vs 126 months; P = 0.001). All metastatic tumors were ≥2.8 cm. Codons 161 and 167 were hotspots for VHL germline mutations with enhanced risk for metastatic PanNETs. Multivariate prediction modeling disclosed maximum tumor diameter and TVDT as significant predictors for metastatic disease (positive and negative predictive values of 51% and 100% for diameter cut-off ≥2.8 cm, 44% and 91% for TVDT cut-off of ≤24 months). In 117 of 273 patients, PanNETs >1.5 cm in diameter were operated. Ten-year survival was significantly longer in operated vs non-operated patients, in particular for PanNETs <2.8 cm vs ≥2.8 cm (94% vs 85% by 10 years; P = 0.020; 80% vs 50% at 10 years; P = 0.030). This study demonstrates that patients with PanNET approaching the cut-off diameter of 2.8 cm should be operated. Mutations in exon 3, especially of codons 161/167 are at enhanced risk for metastatic PanNETs. Survival is significantly longer in operated non-metastatic VHL-PanNETs.

Regional Clinical and Biochemical Differences among Patients with Primary Hyperparathyroidism.

BACKGROUND: Environmental habitat may play a role in clinical disparities of primary hyperparathyroidism (pHPT) patients. AIMS: To compare preoperative clinical symptoms and associated conditions and surgical findings in patients with pHPT, living in different geographical regions from the Black Sea, Mediterranean and Anatolia regions. STUDY DESIGN: Retrospective, clinical-based multi-centric study of 694 patients with pHPT. METHODS: Patients from 23 centers and 8 different geographical regions were included. Data related to baseline demographics, clinical, pathologic and treatment characteristics of 8 regions were collected and included age, gender, residential data, symptoms, history of fracture, existence of brown tumor, serum total Ca and p levels, serum parathormone (PTH) levels, serum 25-OH vitamin D levels, bone mineral density, size of the resected abnormal parathyroid gland(s), histology, as well as the presence of ectopia, presence of dual adenoma, and multiple endocrine neoplasia (MEN)- or familial-related disease. RESULTS: The median age was 54. Asymptomatic patient rate was 25%. The median PTH level was 232 pg/mL and serum total Ca was 11.4 mg/dL. Eighty-seven percent of patients had an adenoma and 90% of these had a single adenoma. Hyperplasia was detected in 79 patients and cancer in 9 patients. The median adenoma size was 16 mm. Significant parameters differing between regions were preoperative symptoms, serum Ca and p levels, and adenoma size. All patients from South-East Anatolia were symptomatic, while the lowest p values were reported from East Anatolia and the largest adenoma size, as well as highest Ca levels, were from Bulgaria. CONCLUSION: Habitat conditions vary between geographical regions. This affects the clinicopathological features of patients with pHPT.

Diagnostic Value of Diffusion-weighted Imaging and Apparent Diffusion Coefficient Values in the Differentiation of Breast Lesions, Histpathologic Subgroups and Correlation with Prognostic Factors using 3.0 Tesla MR.

OBJECTIVE: The aim of this study was to evaluate the effect of the apparent diffusion coefficient (ADC) and diffusion-weighted imaging in differentiating benign from malignant breast lesions, histopathologic subtypes of breast tumors, and to find a correlation with prognostic factors using 3T MR. MATERIALS AND METHODS: A total of 165 patients aged between 16 and 78 years with 181 histopathologically-verifed breast lesions were enrolled in this study. A 3T MR system and bilateral phased array breast coil was used. Diffusion-weighted imaging was performed with spin echo "echo planar" with "b" values: 50, 400, and 800 seconds/mm2. ADC values were calculated for normal fibroglandular tissue and breast lesions. ADC values of independent groups were compared using Student's t-test. ROC analysis was used to find a threshold ADC value in the differentiation of lesions. RESULTS: The mean ADC values were 1.35±0.16 × 10-3 mm2/s for normal fibroglandular tissue, 1.41±0.24 × 10-3 mm2/s for benign breast lesions and 0.83±0.19 × 10-3 mm2/s for malignant breast lesions. The AUC with ROC analysis was 0.945 and the threshold for ADC was 1.08 × 10-3 mm2/s with a sensitivity and specificity of 92% and 92%, respectively. The threshold value for ADC ratio was 0.9 with 96% sensitivity and 89% specificity. The mean ADC of malignant breast lesions was statistically lower for benign lesions (p<0.01). We found no correlation between the mean ADC values and ER-PR receptor, Her2, and Ki-67 values. CONCLUSION: Diffusion-weighted imaging has high diagnostic value with high sensitivity and specificity in differentiating malignant and benign breast lesions.

Radiofrequency ablation of benign symptomatic thyroid nodules: prospective safety and efficacy study.

BACKGROUND: Radiofrequency ablation (RFA) is a relatively novel procedure in the management of benign nodular goiter. This study was conducted to evaluate the safety and efficacy of ultrasound (US)-guided percutaneous RFA for benign symptomatic thyroid nodules as an alternative to surgery. METHODS: The study involved patients for whom a fine needle aspiration biopsy had proved a diagnosis of benign nodular goiter and had nodule-related symptoms such as dysphagia, cosmetic problems, sensation of foreign body in the neck, hyperthyroidism due to autonomous nodules or fear of malignancy. Percutaneous RFA was performed as an outpatient procedure under local anesthesia. The primary outcome was an evaluation of the changes in symptom scores (0-10) for pain, dysphagia and foreign body sensation at the 1st, 3rd, and 6th months after the RFA procedure. Secondary outcomes were assessing volume changes in nodules, complication rates, and changes in thyroid function status. RESULTS: A total of 33 patients (24% female, 76% male) and a total of 65 nodules were included into the study. More than one nodule was treated in 63.6% of the patients. We found a statistically significant improvement from baseline to values at the 1st, 3rd, and 6th months, respectively, as follows: pain scores (2.9 ± 2.7, 2.3 ± 2.01, 1.8 ± 1.7, and 1.5 ± 1.2, p 0.005), dysphagia scores (3.9 ± 2.7, 2.6 ± 1.9; 1.7 ± 1.6, and 1.1 ± 0.3, p 0.032), and foreign body sensation scores 3.6 ± 3, 2.5 ± 2.2; 1.6 ± 1.5, and 1.1 ± 0.4, p 0.002).The mean pre-treatment nodule volume was 7.3 ± 8.3 mL. There was a statistically significant size reduction in the nodules at the 1st, 3rd, and 6th months after RFA (3.5 ± 3.8, 2.7 ± 3.4, and 1.2 ± 1.7 mL, p 0.002). The volume reduction was found to be 74% at 6th months following the RFA (p 0.005). 8 patients had autonomously functioning nodules in the pre-treatment period, 50% (n: 4) became euthyroid at the 6th month after RFA. There were no complaints other than pain (12%). CONCLUSION: RFA can be an alternative treatment modality in the management of benign symptomatic thyroid nodules. The results showed that it is a safe and effective procedure.

Five-Year Disease-Free Follow-Up of a Borderline Breast Phyllodes Tumor in a 15-year-old Patient.

Phyllodes tumors are large breast tumors representing only 1% of breast neoplasms and are rarely seen in young women. Histologically, phyllodes tumors are classified as benign, borderline, or malignant based on the characteristics of the stroma. Although wide local excision is recommended for the treatment modality, the reoccurrence rate after surgical excision varies between 36% and 65%, with recurrence more likely in those with the tumor at the margins of excision. Our aim was to report -a case in a 15-year-old girl with a 115-mm borderline phyllodes tumor in her left breast mimicking a juvenile fibroadenoma. We presented a 5-year disease-free follow-up after wide local excision with negative margins.

Should we consider topical silver nitrate irrigation as a definitive nonsurgical treatment for perianal fistula?

BACKGROUND: Surgery is currently the sole treatment modality for anal fistulas. However, surgery is associated with complications such as permanent incontinence, which reduces quality of life. OBJECTIVE: To determine the rate of complete clinical healing of anal fistulas after irrigation of the fistula tract with silver nitrate solution as a nonsurgical treatment. DESIGN: Prospective single arm study. SETTING: Tertiary university hospital PATIENTS: : Adult patients with symptomatic perianal fistula presenting between June 2012 and January 2013. INTERVENTION: Irrigation of the fistula tract with 1% silver nitrate solution. Irrigation was repeated every 2 weeks when necessary. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of complete clinical healing. RESULTS: Fifty-six consecutive patients with anal fistula were analyzed. Of those, 29 (52%) had complete clinical healing without recurrence for a median of 10 months. The median number of irrigations needed for complete clinical healing was 4 (1-10). The level of satisfaction was excellent in patients with complete clinical healing. The frequency of complaints was the only independent factor that had an impact on healing; patients with intermittent discharge had a significantly higher rate of complete clinical healing (67%) than those with continuous discharge (40%). There were no notable complications. LIMITATIONS: Short follow-up, small sample size, and no comparisons. CONCLUSION: This study demonstrates that the application of silver nitrate solution often produces a favorable outcome in the treatment of anal fistula. This method may be considered as a first-line treatment for the disease because it is simple, performed on an outpatient basis, minimally invasive, and lacks the complications encountered with current conventional surgical modalities.

Outcomes of adrenal-sparing surgery or total adrenalectomy in phaeochromocytoma associated with multiple endocrine neoplasia type 2: an international retrospective population-based study.

BACKGROUND: The prevention of medullary thyroid cancer in patients with multiple endocrine neoplasia type 2 syndrome has demonstrated the ability of molecular diagnosis and prophylactic surgery to improve patient outcomes. However, the other major neoplasia associated with multiple endocrine neoplasia type 2, phaeochromocytoma, is not as well characterised in terms of occurrence and treatment outcomes. In this study, we aimed to systematically characterise the outcomes of management of phaeochromocytoma associated with multiple endocrine neoplasia type 2. METHODS: This multinational observational retrospective population-based study compiled data on patients with multiple endocrine neoplasia type 2 from 30 academic medical centres across Europe, the Americas, and Asia. Patients were included if they were carriers of germline pathogenic mutations of the RET gene, or were first-degree relatives with histologically proven medullary thyroid cancer and phaeochromocytoma. We gathered clinical information about patients'RET genotype, type of treatment for phaeochromocytoma (ie, unilateral or bilateral operations as adrenalectomy or adrenal-sparing surgery, and as open or endoscopic operations), and postoperative outcomes (adrenal function, malignancy, and death). The type of surgery was decided by each investigator and the timing of surgery was patient driven. The primary aim of our analysis was to compare disease-free survival after either adrenal-sparing surgery or adrenalectomy. FINDINGS: 1210 patients with multiple endocrine neoplasia type 2 were included in our database, 563 of whom had phaeochromocytoma. Treatment was adrenalectomy in 438 (79%) of 552 operated patients, and adrenal-sparing surgery in 114 (21%). Phaeochromocytoma recurrence occurred in four (3%) of 153 of the operated glands after adrenal-sparing surgery after 6-13 years, compared with 11 (2%) of 717 glands operated by adrenalectomy (p=0.57). Postoperative adrenal insufficiency or steroid dependency developed in 292 (86%) of 339 patients with bilateral phaeochromocytoma who underwent surgery. However, 47 (57%) of 82 patients with bilateral phaeochromocytoma who underwent adrenal-sparing surgery did not become steroid dependent. INTERPRETATION: The treatment of multiple endocrine neoplasia type 2-related phaeochromocytoma continues to rely on adrenalectomies with their associated Addisonian-like complications and consequent lifelong dependency on steroids. Adrenal-sparing surgery, a highly successful treatment option in experienced centres, should be the surgical approach of choice to reduce these complications.

Gallstones and Concomitant Gastric Helicobacter pylori Infection.

Background. The association of gallstones with Helicobacter pylori has been investigated but not clearly demonstrated. In this study, the presence of H. pylori in the gallbladder mucosa of patients with symptomatic gallstones was investigated. Method. Ninety-four consecutive patients with symptomatic gallstone disease were enrolled for the study. Gastroscopy and gastric H. pylori urease test were done before cholecystectomy to all patients who accepted. After cholecystectomy, the gallbladder tissue was investigated in terms of H. pylori by urease test, Giemsa, and immunohistochemical stain. Results. Overall 35 patients (37%) gallbladder mucosa tested positive for H. pylori with any of the three tests. Correlation of the three tests Giemsa, IHC, and rapid urease test was significant (r s : 0590, P > 0.001). Rapid urease test was positive in the gastric mucosa in 47 (58.7%) patients, and it was positive in the gallbladder mucosa in 21 patients (22%). In 15 patients both gastric and gallbladder tested positive with the urease test. There was significant correlation of rapid urease test in both of gallbladder and gastric mucosa (P = 0.0001). Conclusion. Study demonstrates the presence of H. pylori in the gallbladders of 37% of patients with symptomatic gallstones.

Efficacy of prophylactic antibiotic administration for breast cancer surgery in overweight or obese patients: a randomized controlled trial.

OBJECTIVE: To assess the impact of prophylactic antibiotics on the prevention of surgical site infection (SSI) and the cost-effectiveness of this prophylaxis for breast cancer surgery in overweight or obese women. BACKGROUND DATA: SSI is higher than expected after breast surgery. Obesity was found to be one of the risk factors. METHODS: The trial was designed as a phase IV randomized, controlled, parallel-group efficacy trial. It was conducted at a tertiary university hospital. Overweight or obese women with clinically early-stage breast cancer who had been assigned to undergo surgery were eligible. Patients were randomly allocated to either a prophylaxis or a control group by using a computer-generated list. The prophylaxis group received 1 g ampicillin-sulbactam intravenously at anesthesia. The control group received no intervention. Patients and observers were blinded to the assignments. The primary outcome was the comparison of SSI incidences of the 2 groups. Patients were monitored for 30 days. RESULTS: A total of 369 patients were included in final analysis, out of which 187 were allocated for prophylaxis and 182 were randomly assigned to the control group. Analysis was done according to the intention-to-treat principle. Prophylaxis significantly reduced the SSI rate (4.8%) in the prophylaxis group when compared with that in the control group [13.7%; relative risk (RR) 0.35; 95% CI: 0.17-0.73]. No adverse reaction was observed. The mean SSI-related cost (20.26 USD) was found to be significantly higher in the control group when compared with that (8.48 USD) in the prophylaxis group. CONCLUSION: Antibiotic prophylaxis significantly decreased SSI incidence after elective surgery and was shown to be cost-effective in obese breast cancer patients. ClinicalTrials.gov Identifier: NCT00356148.

Transumbilical multiple-port laparoscopic cholecystectomy using standard laparoscopic instruments.

INTRODUCTION: As a complement to standard laparoscopy, single incision laparoscopic cholecystectomy (SILS) is gaining popularity. We report our technique and our initial experience with transumbilical multi-port laparoscopic cholecystectomy (TUMP-LC) without an access device, with standard laparoscopic instruments, and report the clinical outcomes. MATERIAL AND METHODS: Twenty-five (23 F: 2 M) consecutive patients with symptomatic cholelithiasis were included. The surgical outcomes such as length of stay, complications and perioperative morbidity were analyzed. For evaluation of surgical stress preoperative and postoperative C-reactive protein (CRP) values at 6 h and 24 h were measured. Postoperative pain was evaluated using a standard 10-point visual analogue scale (VAS). RESULTS: The mean duration of the surgery was 44.56 minutes (range, 18-110). Additional trocars were needed in two (8%) cases. Mean pain scores post-operatively at 4 h, 12 h and 24 h were 4 ± 1.19, 3.64 ± 1.03 and 2.24 ± 0.96, respectively (p < 0.0001). Plasma CRP values increased at 6 h and started to decrease at 24 h (p < 0.0001). None of the cases were converted to open surgery and no major complications occurred. DISCUSSION: TUMP-LC using standard laparoscopic instrumentation without an access device is an effective alternative to standard four-incision laparoscopic cholecystectomy. Our technique maintains the principles of the conventional procedure and the instrumentation, but also improves the access.

Patient knowledge about drugs prescribed at primary healthcare facilities.

OBJECTIVE: Providing adequate information to the patients about their drugs is an essential principle of rational pharmacotherapy. This study investigates the knowledge of general practice patients about their drugs, since the level of knowledge of the patient about the medication is highly associated with the outcome of the therapy. METHODS: A total of 1618 patients who applied to primary healthcare centers in Istanbul and accepted to participate in the study were asked about the name(s) and effect(s) of the drug(s) on their prescriptions. Factors that might influence the background knowledge and perception of patients such as sociodemographic characteristics, drug-use habits and practitioners' attitudes were also questioned. Information provided by the patients was compared with the prescriptions. RESULTS: Only 10.9% of the respondents could recall the names of their drug(s) correctly. Level of education, and gender, had a positive impact on recalling drug names. Patients, who received a refill prescription, with a chronic disease, and who had self-medication before applying to the health center reported more accurate information. Less than half of the practitioners had informed their patients about the drug effects; and 7% of the patients have been requested to repeat the instructions and warnings about his/her medication(s). The patients to name their drugs correctly also knew the drug effects twice as much the patients who could not recall their drug(s)' name. The drugs which were correctly named were the ones used in chronic diseases. CONCLUSION: It appears that patients, particularly who are poorly educated, males, and who received a first prescription know little about their prescribed drugs. These results suggest that patients' education about drugs is an important issue regarding rational drug use which deserves urgent improvement.

Prescribing habits of general practitioners in the treatment of childhood respiratory-tract infections.

OBJECTIVE: In the present study, prescribing behavior of general practitioners (GPs) was investigated in the example of childhood upper and lower respiratory-tract infections (URTIs and LRTIs). STUDY DESIGN: A face-to-face interview was performed with 352 parents admitted to seven primary health care centers for their children diagnosed with URTI or LRTI. Prescriptions ( n=331) written by 25 GPs working at these centers were analyzed regarding legibility, format and suitability of drug choice. RESULTS: Almost 60% of parents had self-medicated their children prior to admitting to the doctor. Of the patients, 29 (8.2%) were not examined by the physicians, but were directly prescribed medicine. The physicians did not tell the diagnosis to 25.3% of the patients, did not inform 41.2% of them about the drugs and did not caution 95.7% about the side effects. Further, the physicians did not inform 42.6% of the patients about drug use instructions, did not inform 83.5% about the warnings and did not inform 81.2% about non-drug treatment. Approximately 5% of the individuals remembered the name of the drugs. Only 26.3% of the prescriptions were easily readable, and only five scripts (1.5%) contained all necessary information. The majority of the patients were given antibiotics, penicillin+beta lactamase inhibitors being the first. Paracetamol was the most frequently prescribed analgesic/antipyretic for both indications, followed by nimesulide and ibuprofen. CONCLUSIONS: The present study revealed inappropriate drug use in the treatment of respiratory-tract infections in children at the primary health care level in a district of Istanbul, Turkey. Furthermore, it has been shown that GPs practicing at primary health care centers should be trained to give adequate information about the disease and the treatment to the patients/parents to achieve good compliance and optimal drug therapy for children.

Impact of a short postgraduate course in rational pharmacotherapy for general practitioners.

AIMS: The impact of a short postgraduate course on rational pharmacotherapy planning behaviour of general practitioners (GP) was investigated via a face-to-face interview with 25 GPs working at health centres in Istanbul. METHODS: GPs were randomly allocated to control and intervention groups. Intervention group attended a 3-day-training program preceded and followed by a written exam to plan treatment for simulated cases with a selected indication. The participants' therapeutic competence was also tested at the post-test for an unexposed indication to show the transfer effect of the course. In addition, patients treated by these GP's were interviewed and the prescriptions were analysed regarding rational use of drugs (RUD) principles at the baseline, 2 weeks and 4 months after the course. RESULTS: At the baseline there was not any significant difference between the control and intervention groups in terms of irrational prescribing habits. The questionnaires revealed that the GPs were not applying RUD rules in making their treatment plans and they were not educating their patients efficiently. Training produced a significant improvement in prescribing habits of the intervention group, which was preserved for 4 months after the course. However, very low scores of the pretest indicate the urgent necessity for solutions. CONCLUSIONS: Training medical doctors on RUD not only at the under- but also at the postgraduate level deserves attention and should be considered by all sides of the problem including academia, health authorities and medical associations.