Interrater reliability of a tool to assess omission of prescription and inappropriate prescriptions in paediatrics.

Background Potentially inappropriate medication (PIM) and potential prescription omission (PPO) are common issues in pharmacotherapy in vulnerable populations. A first tool to assess PIM's and PPO's targeting pediatric populations: POPI «Pediatrics Omission of Prescriptions and Inappropriate Prescriptions¼ was created in 2014. Objective This study aimed to evaluate inter-rater reliability between healthcare professionals who apply POPI. Setting: Mother and child emergency ward of a university hospital. Method Twenty cases with or without PIM or PPO were identified in a previous retrospective PIM-PPO prevalence study on 15,973 patients. One doctor and one pharmacist, who participated in the creation of POPI tool, identified PIM and PPO ("gold standard response"). These cases were reviewed independently by eleven clinicians (generalists, pediatricians, pharmacists, residents), with no previous experience of this tool. Interrater agreement was calculated by using the Kappa agreement test. Main outcome measure: Inter-clinician agreement. Results A high level of agreement of PIM and PPO detection was recorded (PIM: median = 0.80; PPO: median = 0.71). Conclusion POPI demonstrated a good interrater reliability. This validation by many clinicians proves that POPI is a reliable tool. Other multicenter and prospective studies should be conducted to evaluate economical and clinical impacts of POPI.

Contouring workload in adjuvant breast cancer radiotherapy.

PURPOSE: To measure the impact of contouring on worktime in the adjuvant radiation treatment of breast cancer, and to identify factors that might affect the measurements. MATERIAL AND METHODS: The dates and times of contouring clinical target volumes and organs at risk were recorded by a senior and by two junior radiation oncologists. Outcome measurements were contour times and the time from start to approval. The factors evaluated were patient age, type of surgery, radiation targets and setup, operator, planning station, part of the day and day of the week on which the contouring started. The Welch test was used to comparatively assess the measurements. RESULTS: Two hundred and three cases were included in the analysis. The mean contour time per patient was 34minutes for a mean of 4.72 structures, with a mean of 7.1minutes per structure. The clinical target volume and organs at risk times did not differ significantly. The mean time from start to approval per patient was 29.4hours. Factors significantly associated with longer contour times were breast-conserving surgery (P=0.026), prone setup (P=0.002), junior operator (P<0.0001), Pinnacle planning station (P=0.026), contouring start in the morning (P=0.001), and contouring start by the end of the week (P<0.0001). Factors significantly associated with time from start to approval were age (P=0.038), junior operator (P<0.0001), planning station (P=0.016), and contouring start by the end of the week (P=0.004). CONCLUSION: Contouring is a time-consuming process. Each delineated structure influences worktime, and many factors may be targeted for optimization of the workflow. These preliminary data will serve as basis for future prospective studies to determine how to establish a cost-effective solution.

[Consensus validation of a tool to identify inappropriate prescribing in pediatrics (POPI)]. / Validation par consensus d'un outil d'identification de prescriptions inappropriées en pédiatrie (POPI).

OBJECTIVE: Medication errors including inappropriate prescriptions and drug omissions are one of the causes of adverse drug events in children. Our aim was to develop a preliminary screening tool to detect omissions and inappropriate prescriptions in pediatrics based on French and international guidelines. MATERIEL AND METHODS: Disease classification was based on the prevalence rate of pathology and hospital statistics. The criteria were obtained by reviewing many French and international references. The Delphi consensus technique was used to establish the content validity of POPI. The level of agreement and the proposals of healthcare professionals was noted on a nine-point Likert scale. RESULTS: The criteria were categorized according to the main physiological systems (gastroenterology, respiratory infections, pain, neurology, dermatology, and miscellaneous). They were distributed to 16 French pediatric panelists (eight pharmacists, eight pediatricians who were hospital-based [50%] or working in the community [50%]). After two rounds of the Delphi process, 101 of 108 criteria were chosen with strong consensus (76 inappropriate prescriptions and 25 omissions). CONCLUSIONS: POPI is the first screening tool to detect inappropriate prescriptions and omissions in pediatrics. It is now necessary to conduct a prospective study to determine inter-rater reliability and the tool's detection capacity.

Impact of intensity-modulated and image-guided radiotherapy on elderly patients undergoing chemoradiation for locally advanced head and neck cancer.

PURPOSE: In this work, the treatment tolerance of elderly patients (≥70 years) undergoing intensity-modulated radiotherapy (IMRT) and image-guided radiotherapy (IGRT) and chemotherapy for locally advanced head and neck cancer was assessed. PATIENTS AND METHODS: A retrospective review of 112 patients undergoing concurrent chemoradiation for locally advanced head and neck cancer was performed. Treatment toxicity, protocol violations, long-term complications, and survival were compared between 85 younger patients (< 70 years) and 27 older patients (≥ 70 years). RESULTS: Grade 3-4 treatment toxicity was observed in 88.2% and 88.8% for younger and older patients, respectively. Mean weight loss and treatment break were 5.9 and 3.9 kg (p = 0.03) and 7.3 and 7.8 days (p = 0.8) for younger and older patients, respectively. Seven patients (8.2%) did not complete treatment in the younger group compared to 1 patient (3.7%) in the older group (p = 0.6). No significant differences in protocol violations and survival were found between the two groups. CONCLUSION: Compared to younger patients, elderly patients with locally advanced head and neck cancer tolerated chemoradiation with IMRT and IGRT well, and should not be denied curative treatment based solely on age.

Human papillomavirus-associated oropharyngeal cancer: a new clinical entity.

The incidence of oropharyngeal cancers is rising worldwide in both nonsmokers and nondrinkers. Epidemiology studies suggest a strong association between human papillomavirus (HPV) 16 infection, changing sexual behavior and cancer development. Despite initial presentation with locally advanced disease and poorly differentiated histology, HPV-associated oropharyngeal carcinoma is associated with a good prognosis because its response to chemotherapy and radiation. Clinicians should be aware of the risk of oropharyngeal cancer in young people to avoid unnecessary delay in diagnosis and treatment. A history of oral sex should be elicited in young patients with enlarged neck nodes and/or tonsillar masses.

Technical aspects of the integration of three-dimensional treatment planning dose parameters (GEC-ESTRO Working Group) into pre-implant planning for LDR gynecological interstitial brachytherapy.

This study investigates the technical feasibility of pre-implant image-based treatment planning for LDR GYN interstitial brachytherapy(IB) based on the GEC-ESTRO guidelines. Initially, a virtual plan is generated based on the prescription dose and GEC-ESTRO defined OAR dose constraints with a pre-implant CT. After the actual implant, a regular diagnostic CT was obtained and fused with our pre-implant scan/initial treatment plan in our planning software. The Flexi-needle position changes, and treatment plan modifications were made if needed. Dose values were normalized to equivalent doses in 2 Gy fractions (LQED 2 Gy) derived from the linear-quadratic model with alpha/beta of 3 for late responding tissues and alpha/beta of 10 for early responding tissues. D(90) to the CTV, which was gross tumor (GTV) at the time of brachytherapy with a margin to count for microscopic disease, was 84.7 +/- 4.9% of the prescribed dose. The OAR doses were evaluated by D(2cc) (EBRT+IB). Mean D(2cc) values (LQED(2Gy)) for the rectum, bladder, sigmoid, and small bowel were the following: 63.7 +/- 8.4 Gy, 61.2 +/- 6.9 Gy, 48.0 +/- 3.5 Gy, and 49.9 +/- 4.2 Gy. This study confirms the feasibility of applying the GEC-ESTRO recommended dose parameters in pre-implant CT-based treatment planning in GYN IB. In the process, this pre-implant technique also demonstrates a good approximation of the target volume dose coverage, and doses to the OARs.

Analysis of factors influencing aspiration risk following chemoradiation for oropharyngeal cancer.

Our aim was to identify risk factors for aspiration following concurrent chemoradiation for oropharyngeal cancer. 46 patients with locally advanced oropharyngeal carcinoma underwent concurrent chemoradiation at our institution. All patients underwent modified barium swallow to assess dysphagia severity and to determine the need for continued tube feedings after treatment. Dysphagia severity was graded as 1-7. There were 5 Grade 2, 11 Grade 3, 5 Grade 4, 5 Grade 5, 10 Grade 6 and 10 Grade 7 scores. 25 patients (54%) developed aspiration (5 trace, 20 severe). The aspiration rate for T1-T2 and T3-T4 tumours was 31% and 67%, respectively (p = 0.03). There was no statistical difference in the aspiration rate between the base of the tongue and tonsillar carcinoma (p = 0.23). Despite anatomical organ preservation, most patients with locally advanced oropharyngeal carcinoma had moderate to severe dysphagia after chemoradiation. Patients with large tumours had a significant risk of developing aspiration following treatment.

Safety and effectiveness of vascular endoprosthesis for malignant superior vena cava syndrome.

BACKGROUND: Superior vena cava syndrome management has been traditionally radiation therapy, chemotherapy or chemoradiation, depending on the underlying malignancy involved and individual clinicopathological features of the case. Recent emergence of endovascular stents offer the opportunity for immediate relief of the venous stenosis. This review examines findings from the published series which used endovascular prosthesis for this syndrome with regards to efficacy and safety. METHODS: Literature search identified studies using endovascular stents as initial therapy or for recurrence of malignant superior vena cava syndrome. Effectiveness and toxicity from stent placement was assessed. RESULTS: Endovascular stent placement provides immediate haemodynamic relief of venous compression either before or after definitive therapy in the majority of cancer patients. Severe bleedings, cardiopulmonary complications and stent migrations remain significant problems for patient management. CONCLUSIONS: Endovascular prosthesis is an effective modality for malignant superior vena cava syndrome with acceptable morbidity. Prospective studies should be performed to determine the optimal anticoagulation regimen.

Analysis of the factors influencing dysphagia severity upon diagnosis of head and neck cancer.

Our aim was to assess the influence of age, co-morbidity factors and tumour characteristics on dysphagia severity in the diagnosis of head and neck cancer. Modified barium swallow (MBS) examinations were performed in patients at diagnosis of head and neck cancer. Dysphagia was graded on a scale of 1 to 7 of increasing severity. Between 2000 and 2006, 236 patients with dysphagia underwent MBS at diagnosis of their head and neck cancer. 82 patients were scored as Grade 1, 88 as Grade 2, 29 as Grade 3, 15 as Grade 4, 9 as Grade 5, 5 as Grade 6, and 8 as Grade 7. Grade 3-7 dysphagia occurred in 20% and 31% of patients with T1-T2 and T3-T4 tumours, respectively (p = 0.004). Corresponding values for N0-N1 and N2-N3 tumours were 20% and 39%, respectively (p = 0.002). The percentage of patients with Grade 3-7 dysphagia was 5%, 29%, 33% and 52% for oral cavity, laryngeal, oropharyngeal and hypopharyngeal tumours, respectively, (p = 0.002). Age and co-morbidity factors (e.g. diabetes, hypertension, coronary artery disease, peripheral vascular diseases and arthritis) did not appear to have an impact on swallowing in this limited retrospective study. Patients with locally advanced stages (T3-T4, N2-N3) are at risk of severe dysphagia. Patients with oral cavity tumours appear to be less at risk of dysphagia than those with tumours in different anatomic locations. The role of age and co-morbidity factors should be investigated in future prospective studies.

A novel antigenic variant of Canine parvovirus from a Vietnamese dog.

Nine isolates of Canine parvovirus (CPV) were obtained from Vietnamese dogs and cats. One canine isolate showed a unique antigenic property which indicates a novel antigenic variant of CPV-2b when examined with hemagglutination inhibition tests using our monoclonal antibodies, 21C3 and 19D7, which were recently developed. This isolate had an amino acid substitution of residue 426, Asp to Glu, and the same substitution has recently been found in CPV from Italian dogs. This study first showed that such substitution caused an antigenic difference demonstrable by monoclonal antibodies and that a similar evolution may have occurred in CPV in Vietnam.

The risk of venous thromboembolic disease in patients with monoclonal gammopathy of undetermined significance.

BACKGROUND: Recent evidence indicates that patients with multiple myeloma receiving combination chemotherapy containing thalidomide are at a significantly high risk for venous thromboembolic disease (VTD). However, information on the occurrence of VTD in a related disorder, benign monoclonal gammopathy of undetermined significance (MGUS), is limited. PATIENTS AND METHODS: We prospectively investigated patients with MGUS for the occurrence of VTD. The diagnosis of MGUS was based on well known criteria for the disorder. The variables examined were sex, age, race, presence of underlying conditions, level and type of immunoglobulin [serum monoclonal (M)-protein] platelet counts and level of fibrinogen. RESULTS: Of a total of 310 patients with MGUS, 19 (6.1%) developed VTD after a median follow-up of 44 months (range 12-67 months). In a univariate analysis, age >/=65 years (P=0.01), M-protein >/=16 g/l (P=0.001) and progression to plasma cell or lymphoproliferative disorders (28 of 310 patients; P=0.001) were significant risk factors for VTD. In multivariate analysis, M-spike >/=16 g/l [risk ratio (RR)=6.3; 95% confidence interval (CI) 2.25-17.6; P=0.001] and future development of plasma cell or lymphoproliferative disorder (RR = 4.2; 95% CI 1.64-10.7; P=0.003) were variables strongly associated with the occurrence of VTD. A total of 46 patients (14.8%) died during the follow-up period of the study. CONCLUSION: This study demonstrates that patients with MGUS are at increased risk for VTD. Although a clear reason for the pre-thrombotic state in these patients is not currently evident, few risk factors were identified in the group of patients examined.

Dysphagia following chemoradiation for locally advanced head and neck cancer.

BACKGROUND: To assess the prevalence, severity and morbidity of dysphagia following concurrent chemoradiation for head and neck cancer. PATIENTS AND METHODS: Patients who underwent chemotherapy and radiation for head and neck malignancies were evaluated for their ability to resume oral feeding following treatment. Modified barium swallow (MBS) studies were performed if the patients complained of dysphagia or if there was clinical suspicion of aspiration. The severity of dysphagia was graded on a scale of 1-7. If significant abnormalities were found, swallowing studies were repeated until resolution of dysphagia. RESULTS: Between March 1999 and May 2002, 55 patients with locally advanced head and neck cancer underwent concurrent chemotherapy and radiation. Aspiration pneumonia was observed in eight patients, three during treatment and five following treatment. Five patients died from pneumonia. Two patients developed respiratory failure requiring intubation as a complication of pneumonia. At a median follow-up of 17 months (range 6-48 months), 25 patients (45%) developed severe dysphagia requiring prolonged tube feedings for more than 3 months (22 patients) or repeated dilatations (three patients). Among 33 patients who underwent MBS following treatment, 12 patients (36%) had silent aspiration (grade 6-7 dysphagia). Thirteen patients (39%) developed grade 4-5 dysphagia which required prolonged enteral nutritional support to supplement their oral intake. Most patients had severe weight loss (0-21 kg) during treatment, likely due in part to mucositis in the orodigestive tube. CONCLUSIONS: Dysphagia is a common, debilitating and potentially life-threatening sequela of concurrent chemoradiation for head and neck malignancy. Physicians should be aware that the clinical manifestations of aspiration may be unreliable and insidious, because of the depressed cough reflex. Modified and traditional barium swallows should be performed following treatment to assess the safety of oral feeding and the structural integrity of the pharynx and esophagus. Patients with severe dysphagia may benefit from rehabilitation. Tube feeding should be continued for those with aspiration.

Concurrent interferon-alpha and radiation for head and neck melanoma.

Melanoma cells are resistant to radiation in part due to their capacity to repair sublethal damage. A large fraction dose is therefore often utilized. However, if the tumour is located close to critical structures with modest tolerance, high fraction doses increase the risk for late complications compared with standard fractionation, but using the latter alone risks the desired outcome. Concurrent systemic biotherapy with standard radiation fractions may therefore represent an acceptable compromise. The outcome of concurrent systemic interferon-alpha (IFNalpha) and radiation in three patients with head and neck melanoma was evaluated. Standard radiation fractions were used because of the radiosensitizing properties of IFNalpha. Acute toxicity was significant and required treatment interruptions. However, all side effects subsided following treatment. All three patients achieved local control at follow-up periods of 24, 18 and 19 months, respectively. One patient developed widespread distant metastases. The combination of IFNalpha with radiation is considered feasible in terms of outcome and should be investigated with a larger cohort of patients. Toxicity is significant, and the addition of radioprotectors could be desirable.

Analysis of factors related to the occurrence of chronic disseminated candidiasis in patients with acute leukemia in a non-bone marrow transplant setting: a follow-up study.

BACKGROUND: Chronic disseminated candidiasis (CDC) is a serious complication of treatment in patients with acute leukemia. Although some general risk factors are known to predispose to systemic fungal infections, few studies have addressed the relevance of certain clinical and laboratory features in patients with CDC. PATIENTS AND METHODS: To define a subset of patients at high risk for CDC, the authors evaluated the demographics and clinical and laboratory characteristics of 423 patients with acute leukemia. Patients who had bone marrow transplant before the diagnosis of CDC were excluded from the analysis. The diagnosis of CDC was based on blood cultures, liver biopsy, and imaging studies. The authors conducted 2 separate regression analyses on 3 subsets of patients: patients without documented candidiasis (n = 374), patients with CDC (n = 23), and patients with candidemia (n = 26). RESULTS: According to multivariate analysis, younger age (P = 0.009; odds ratio [OR], 1.96; 95% confidence interval [CI], 1.72-2.99), duration of neutropenia of 15 days or longer (P = 0.0003; OR, 11.7; 95% CI, 3.04-45.1), and use of prophylactic quinolone antibiotics (P = 0.039; OR, 3.85; 95% CI, 1.11-13.4) emerged as independent factors related to the development of CDC in patients with acute leukemia. The presence of severe mucositis, colonization with Candida, and administration of high-dose ara-C were statistically significant parameters in univariate analysis only (P = 0.0001, P = 0.003, and P = 0.058, respectively). CONCLUSIONS: On the basis of the results of this investigation, it is possible to define a subset of patients with acute leukemia at very high risk for CDC. Because of the morbidity and mortality of this infection, a targeted prophylactic approach may be more effective and less costly than the random administration of antifungal agents.

Disseminated intravascular coagulation in solid tumors: clinical and pathologic study.

Disseminated intravascular coagulation (DIC) is a well known hemostatic complication of solid tumors. We evaluated the occurrence of DIC in 1117 patients with solid tumors. Of these patients, 76 (6.8%) were diagnosed with DIC. There were a total of 145 bleeding and clotting episodes reported in the 76 patients. Thrombocytopenia, hypofibrinogemia, elevated D-dimer and fibrinogen degradation products were the most common coagulation abnormalities encountered in patients with DIC. In multivariate analysis, older age (p = .0001), male gender (p = .009), advanced malignancies (p = .027), breast cancer (p = .038) and the presence of necrosis in the tumor specimen (p = .004), emerged as independent factors significantly related to the occurrence of DIC in patients with solid tumors. Of the 76 patients, 25 (33%) achieved response to treatment of DIC as defined in the study. Patients with early stage and advanced malignancies who developed DIC had inferior survival when compared with their counterparts without DIC (p = .039 and p = .005, respectively). Taken together, this study indicates that certain clinical and laboratory features are more common in patients with solid tumors who developed DIC. The occurrence of DIC appears to have an independent effect on survival of patients with cancer. Cooperative studies are encouraged to better address the usefulness and optimal prophylactic heparin regimen in patients at risk for DIC.

Prognosis for papillary serous carcinoma of the endometrium after surgical staging.

BACKGROUND: To investigate the pattern of failure and the prognosis following pathological staging for uterine papillary serous carcinoma (UPSC). PATIENTS AND METHODS: A retrospective review was conducted of 22 patients with UPSC, treated between 1989 and 1998 at a single institution. All patients were surgically staged. Two patients with advanced disease received chemotherapy only. Two patients with early-stage disease were followed without further treatment. Eighteen patients received postoperative irradiation; eight patients received whole abdominal irradiation (WART), and the remaining 10 patients, pelvic irradiation (PRT). In addition, seven of these patients received vaginal cuff irradiation with low-dose-rate or high-dose-rate brachytherapy. Toxicity, pattern of failure, and survival were evaluated and compared to the literature. RESULTS: Seven patients (32%) developed distant metastases, three out of seven (42%) after WART. Four out of seven patients who had distant metastases died from disease progression during subsequent chemotherapy. All patients with distant metastases had locally advanced-stage disease at presentation (six stage III, one stage IV). Four patients with pelvic recurrences developed concurrent (2) and subsequent (2) distant metastases. Three patients had isolated distant metastases. No patient with early stage-disease (stage I and II) died from disease progression. CONCLUSION: Pathological staging should be performed for all patients with UPSC to determine the prognosis as well as to tailor the treatment. The role of abdominal irradiation in the treatment of UPSC is yet to be determined; however, such an approach may not be necessary for the control of disease for patients with early-stage (I and II) disease. Patients with locally advanced-stage (stage III) disease are at risk of local regional failures and distant metastases despite WART. Therefore, the benefit of WART for advanced-stage disease is also questionable. Paclitaxel-based chemotherapy is currently being investigated in this setting.

Interferon-alpha combined with radiotherapy in the treatment of unresectable melanoma.

A case of recurrent and twice resected sinonasal melanoma is presented. The large recurrent tumor was found to regress by a concurrent combination of 6660 cGy photon radiation and subcutaneous interferon-alpha injections given for a period of 8 weeks. Possible mechanisms of potentiation between interferon and radiation are discussed. The unexpected result in this case report raises interesting questions about this treatment combination.

Treatment of refractory T-cell malignancies using gemcitabine.

We have treated 10 patients with relapsed or refractory T-cell malignancies using gemcitabine. The drug was administered intravenously over 30 min at a dose of 1200 mg/m2 on d 1, 8 and 15 of each 28-d cycle. The mean age of the patients was 62 years and the mean number of administered cycles was three. Of the 10 patients, two achieved a complete response and four a partial response, for an overall response rate of 60% (95% confidence interval 20--35%). The toxicity of chemotherapy was mild and manageable in all patients. These encouraging results warrant further investigation of gemcitabine either as a single agent or in combination regimens as early salvage treatment for patients with refractory T-cell haematological neoplasms.

Sulfa drug screening in yeast: fifteen sulfa drugs compete with p-aminobenzoate in Saccharomyces cerevisiae.

Sulfa drugs have been used as antimicrobials for decades but resistance is now a problem. For major eukaryotic pathogens, including Plasmodium and Pneumocystis, sulfa drug testing is difficult or impossible. We have shown that the eukaryote yeast can be used as a model for the study of sulfa drugs within certain parameters. Fifteen sulfa drugs inhibited yeast growth in a manner indicating competition with p-aminobenzoate (pABA). Such competition resulted from direct addition of pABA or through increased expression of the pABA synthase gene (ABZ1). The model system predicts that overexpression of the pABA synthase gene can lead to drug resistance.