Long-Term Stability of Lorazepam in Sodium Chloride 0.9% Stored at Different Temperatures in Different Containers.

Background and Objective: Infusion containing lorazepam is used by geriatric department to limit anxiety disorders in the elderly. Currently, these infusions are prepared according to demand by the nursing staff, but the preparation in advance in a centralized service could improve quality of preparation and time management. The aim of this study was to investigate the long-term stability of this infusion in polypropylene syringes stored at 5 ± 3°C. Then, results obtained were compared with stability data of lorazepam in syringes stored at room temperature, glass bottles at 5 ± 3°C, and glass bottles at room temperature. Method: Eight syringes and 6 bottles of infusion were prepared by diluting 1 mL lorazepam 4 mg in 23 mL of NaCl 0.9% under aseptic conditions. Five syringes and 3 bottles were stored at 5 ± 3°C and 3 syringes and 3 bottles were stored at room temperature for 30 days. During the storage period, particle appearance or color change were periodically checked by visual and microscope inspection. Turbidity was assessed by measurements of optical density (OD) at 3 wavelengths (350 nm, 410 nm, 550 nm). The stability of pH was also evaluated. The lorazepam concentrations were measured at each time point by high-performance liquid chromatography with ultraviolet detector at 220 nm. Results: Solutions were physically unstable in syringes at 5 ± 3°C after 4 days: crystals and a drop of OD at 350 nm were observed. However, pH was stable. After 2 days, solutions were considered as chemically unstable because a loss of lorazepam concentration higher than 10% was noticed: the lower 1-sided confidence limit at 95% was below 90% of the initial concentration. To assess temperature and polypropylene influence, results were compared with those obtained for syringes at room temperature and bottles at 5 ± 3°C and room temperature. Precipitation, drop of OD at 350 nm, and chemical instability were observed in all conditions. Conclusion: Solutions of lorazepam were unstable after 2 days in syringes at 5 ± 3°C. Preparation in advance appears, therefore, not possible for the clinical use. Storage conditions (temperature and form) do not improve the stability.

Assessment of eosinophilic airway inflammation as a contribution to the diagnosis of occupational asthma.

BACKGROUND: Ascertaining the presence of asthma through the assessment of nonspecific bronchial hyperresponsiveness (NSBH) is a key step in the diagnosis of occupational asthma (OA). We aimed at investigating whether indices of airway inflammation including fractional exhaled nitric oxide (FeNO) and sputum eosinophils would be useful adjuncts to the measurement of NSBH in diagnosing OA defined as a positive specific inhalation challenge (SIC). METHODS: The study included 240 consecutive subjects with a suspicion of OA who completed a SIC, of whom 133 showed a positive response. The sensitivity, specificity, and predictive values of NSBH, and FeNO, as well as sputum eosinophil counts assessed at baseline of the SIC were determined. RESULTS: A concentration of histamine inducing a 20% decline in FEV1 (PC20 ) ≤16 mg/mL showed a sensitivity of 87% and a specificity of 36%. A FeNO level ≥25 ppb and a sputum eosinophil count ≥2% provided lower sensitivity rates (47% and 39%, respectively) than the PC20 value. Eight of the 17 subjects without baseline NSBH despite a positive SIC showed a sputum eosinophil count ≥2%, a FeNO level ≥25 ppb, or both outcomes. Combining either a PC20 value ≤16 mg/mL or a FeNO ≥25 ppb increased the sensitivity to 91%. Using either a PC20 ≤16 mg/mL or a sputum eosinophil count ≥1% increased the sensitivity to 94%. CONCLUSION: Adding the assessment of FeNO level and sputum eosinophils to NSBH improves the identification of subjects who may have OA and require further objective testing before excluding the possibility of OA.

Long-term stability of dexamethasone and alizapride or ondansetron in sodium chloride 0.9% polyolefin bag at 5±3°C.

INTRODUCTION: The aim of the study was to investigate the long-term stability of dexamethasone 10mg associated with alizapride 100mg or ondansetron 8mg in 100mL of 0.9% sodium chloride solution stored at 5±3°C. METHOD: Solutions of 0.9% sodium chloride 100mL in polyolefin bags (n=5) containing approximately dexamethasone (DEX) 10mg associated with alizapride (ALI) 100mg or ondansetron (OND) 8mg were prepared under aseptic conditions and stored about 30 days at 5±3°C. ALI, DEX and OND concentrations were measured by high-performance liquid chromatography (HPLC). Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCL 5M and NaOH 5M before and after heating at 100°C was also performed. Solutions were considered stable if the 95% one-sided lower confidence limit of the concentration remains superior to 90% of the initial concentration or 95% of the initial concentration when any signs of physical instability exist as recently recommend. RESULTS: The calibration was linear over the following range from 20 to 1.25mg/100mL for DEX, from 200 to 12.5mg/100mL for ALI and from 20 to 1.25mg/100mL for OND with a calculated correlation coefficient (r2) of 0.998, 0.999 and 0.999, respectively. The inter- and intra-assay precision was below 10% for both mixtures. All formulations were physically stable during the storage. The lower confidence limit of the concentration for these solutions remains superior to 90% of the initial concentration at this date as recommended by the Food and Drug Administration (FDA) until 30 days. CONCLUSION: The HPLC method is specific and reproducible and can easily be adopted for monitoring the quality control in the production of DEX-ALI and DEX-OND bags. Solutions of DEX-ALI and DEX-OND were physically and chemically stable for 30 days in polyolefin bags stored at 5±3°C and could therefore be prepared in advance.

The role of allergen components for the diagnosis of latex-induced occupational asthma.

BACKGROUND: Recombinant Hevea brasiliensis (rHev b) natural rubber latex (NRL) allergen components have been developed to assess the patients' allergen sensitization profile and to improve the diagnosis of NRL allergy. OBJECTIVE: To examine whether the determination of specific IgE (sIgE) reactivity to a panel of recombinant allergen components would be helpful for diagnosing NRL-induced occupational asthma (OA) in predicting the outcome of a specific inhalation test. METHODS: sIgE levels to NRL extract and 12 recombinant NRL allergen components were assessed in 82 subjects with OA ascertained by a positive specific inhalation challenge (SIC) with NRL gloves and in 25 symptomatic subjects with a negative challenge. RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of a NRL-sIgE level ≥0.35 kUA /l as compared to the result of SICs were 94%, 48%, 86%, and 71%, respectively. The positive predictive value increased above 95% when increasing the cutoff value to 5.41 kUA /l. Subjects with a positive SIC showed a significantly higher rate of sIgE reactivity to rHev b 5, 6.01, 6.02, and 11 than those with a negative SIC. A sIgE sum score against rHev b 5 plus 6.01/6.02 ≥ 1.46 kUA /l provided a positive predictive value >95% with a higher sensitivity (79%) and diagnostic efficiency (Youden index: 0.67) as compared with a NRL-sIgE ≥5.41 kUA /l (49% and 0.41, respectively). CONCLUSION: In suspected OA, high levels of sIgE against rHev b 5 combined with rHev b 6.01 or 6.02 are the most efficient predictors of a bronchial response to NRL.

Long-term stability of ketamine hydrochloride 50mg/ml injection in 3ml syringes.

INTRODUCTION: Ketamine hydrochloride (Ketalar(®)) injection is often used as a general anesthetic agent. It is particularly suited to short-term interventions. It can also be used as an inducer of anesthesia before the administration of other anesthetic agents. The aim of this study was to evaluate the stability of ketamine hydrochloride in 3ml polypropylene syringes after storage for up to 180days at room temperature. METHOD: Syringes containing ketamine hydrochloride (50mg/ml) were prepared and stored at room temperature (25°C) for 180days. The concentrations were measured by validated ultra-performance liquid chromatography-diode array detection at 0, 7, 14, 28, 60, 84, 112, 140 and 180days. A degradation test was performed to evaluate the specificity of the analysis. At each time point, the pH, color and visible particles of each solution were also assessed. RESULTS: Degradation tests proved no interfering peaks with ketamine. All solutions were physically stable during the storage. The lower confidence limit of the concentration for these solutions remains superior to 90% of the initial concentration at this date as recommended by the Food and Drug Administration (FDA) until 180days (100%±2%). CONCLUSION: Solutions of ketamine (50mg/ml) were chemically stable for 180days in polypropylene syringes with storage at room temperature and could be prepared in advance by a centralized intravenous admixture service.

Microwave freeze-thaw technique of injectable drugs. A review from 1980 to 2014.

OBJECTIVE: Microwave freeze-thaw treatment (MFTT) of injectable drugs can support the development of centralized intravenous admixtures services (CIVAS). The aim of the review is to collect information and results about this method. METHODS: A systematic review of the scientific literature about injectable drug stability studies was performed. The data are presented in a table and describe name of the drug, producer, final concentration, temperature and time of freezing storage, type of microwave oven, thawing power, method of dosage and results after treatment or final long-term storage at 5±3 °C. RESULTS: From 1980 to 2014, 59 drugs were studied by MFTT and the results were presented in 49 publications. Forty papers were presented by 8 teams (2 to 18 by team). The temperatures of freezing storage vary from -70 °C to -10 °C, the time storage from 4 hours to 12 months, the thaw from low to full power. Dosages are mainly made by high performance liquid chromatography. Most of the 59 drugs are stable during and after treatment. Only 3 teams have tested the long-term stability after MFTT, the first for ganciclovir after 7 days, the second for ceftizoxime after 30 days and the third for 19 drugs after 11 to 70 days. CONCLUSIONS: This review can help CIVAS to take in charge the productions of ready-to-use injectable drugs.

Long-term stability of acyclovir in 0.9% NaCl infusion polyolefin bags at 5±3°C after freeze-thaw treatment: a generic product versus the brand name.

INTRODUCTION: The aim of the study was to investigate the long-term stability of acyclovir 5 mg/mL (a generic product versus the brand name) in NaCl 0.9% after storage at 5±3°C and to evaluate the influence of initial freezing and microwave thawing on this stability. METHODS: Five bags of Acyclovir® Hospira 5 mg/mL (A) and five bags of Zovirax® GSK 5 mg/mL (B) were prepared under aseptic conditions and stored 3 months at -20°C, then thawed and stored 30 days at 4°C. Five bags of Acyclovir® 5 mg/mL (C) and five bags of Zovirax® 5 mg/mL (D) were also prepared under aseptic conditions and stored 30 days at 5±3°C. Optic density measurement at different wavelengths, pH measurement and optic microscope observations were performed periodically during the storage. A forced degradation test with HCl 12 M and NaOH 5 M before and after heating at 100°C was also performed. The concentrations were measured by HPLC-PDA. RESULTS: The only one forced degradation test that yielded chromatograms with degradation products peak was the test with the acid solution heated at 100°C without interference with the native product. No significant change in pH values or optic densities were seen during the study for both products. No crystals were seen with the optic microscope during the study. Acyclovir® and Zovirax® solutions were stable for at least 21 days according to the FDA recommendations. Moreover, there was no statistical difference between regression lines of those two products and two storage conditions. CONCLUSION: Under the conditions of this study, Acyclovir® 5 mg/mL in 100 mL of NaCl 0.9% infusion remains stable at least for 21 days at 5±3°C with or without freezing at -20°C during the three previous months. There is no statistical difference between the brand name and a generic product. Acyclovir may be prepared in advanced by a centralized intravenous additive service, frozen in polyolefin bags and microwave thawed before storage under refrigeration until 21 days.

[The long-term chemical stability of injectable drugs reconstituted in Hospital Pharmacy]. / Stabilité chimique à long terme de médications injectables reconstituées en Pharmacie Hospitaliére.

BACKGROUND: Other injectable preparations than parenteral nutrition admixture and injectable cytotoxic drugs could be prepared by Centralised IntraVenous Admixture Service (CIVAS) if the Long-term stability of the drugs is known. However, this information is not always available. PURPOSE: To develop a program of chemical drug stability analysis in collaboration between Hospital Pharmacy, Medical Laboratory and Scientific Support Unit to determine the long-term stability of largely used injectable anti-infectious and non-anti-infectious drugs. MATERIAL AND METHODS: After a setup of the High Performance Liquid Chromatography (HPLCI method, 28 drugs were reconstituted in laminar air flow hood, 17 of them stored directly at 5 +/- 3 degrees C and 19 stored in the freezer at -20 degrees C, thawed by microwave following a standardised procedure and stored at 5 +/- 3 degrees C before use. Concentration stability was evaluated by regression analysis. RESULTS: For each drug, long-term stability has varied from 11 days to 180 days. The freeze-thaw treatment by microwave may enhance the stability (from 30 to 120 days) and allow batch-scale production of intravenous drugs, less expensive in term of manpower and sterile device than a drug reconstitution at the ward. The results were published by 55 posters in international congress and by 36 publications in national and international pharmaceutical journals. CONCLUSIONS: Our findings contribute to enhance the scale of drugs that may be take on by a CIVAS.

Characterization of ß-cell plasticity mechanisms induced in mice by a transient source of exogenous insulin.

ß-Cell plasticity governs the adjustment of ß-cell mass and function to ensure normoglycemia. The study of how ß-cell mass is controlled and the identification of alternative sources of ß-cells are active fields of research. ß-Cell plasticity has been implicated in numerous physiological and pathological conditions. We developed a mice model in which we induced major ß-cell mass atrophy by implanting insulin pellets (IPI) for 7 or 10 days. The implants were then removed (IPR) to observe the timing and characteristics of ß-cell regeneration in parallel to changes in glycemia. Following IPR, the endocrine mass was reduced by 60% at day 7 and by 75% at day 10, and transient hyperglycemia was observed, which resolved within 1 wk. Five days after IPR, enhanced ß-cell proliferation and an increased frequency of small islets were observed in 7-day IPI mice. ß-Cell mass was fully restored after an additional 2 days. For the 10-day IPI group, ß-cell and endocrine mass were no longer significantly different from those of the control group at 2 wk post-IPR. Furthermore, real-time quantitative PCR analysis of endocrine structures isolated by laser capture microdissection indicated sequentially enhanced expression of the pancreatic transcription factors ß(2)/NeuroD and Pdx-1 post-IPR. Thus, our data suggest this mouse model of ß-cell plasticity not only relies on replication but also involves enhanced cell differentiation plasticity.

Insights into fast-track colon surgery: a plea for a tailored program.

BACKGROUND: This retrospective study compared the fast-track colon surgery program to conventional perioperative care and assessed factors that influence postoperative length of stay. DESIGN: This retrospective study included 124 fast-track and 119 conventional care colon surgical patients. Exclusion criteria were primary rectal disease, stoma, American Society of Anesthesiologists score IV, and Association Française de Chirurgie index 3 or 4. Laparoscopy was the preferred approach. Variables influencing length of stay were analyzed by multivariate linear and logistic regression. RESULTS: Overall mortality and complication rates were not significantly different between groups (fast-track vs. controls 0 vs. 0.8 %, 30.6 vs. 38.6 % respectively). As expected, median length of stay was significantly reduced in fast-track patients (3 vs. 6 days, p < 0.001), but emergency readmission rate was higher (16.9 vs. 7.6 %, p = 0.026), although rehospitalization rates were similar (8 vs. 4.2 %, not significant). Independent risk factors of increased length of stay were identified as age >69 years (p = 0.001), laparotomy (p = 0.011), and conventional perioperative care (p < 0.001). CONCLUSIONS: The introduction of a fast-track program reduced postoperative length of stay without increasing complication rate. This study proposes a modulation of the program according to patient age and surgical approach.

Altemeier's procedure for rectal prolapse: analysis of long-term outcome in 60 patients.

AIM: Altemeier's procedure (perineal rectosigmoidectomy) is the operation of choice for rectal prolapse in the elderly. The aims of this prospective observational study were to evaluate its long-term actuarial recurrence risk and the influence of the length of rectosigmoid resection and associated levatorplasty on recurrence rate and continence. METHOD: The perioperative and long-term data for all patients undergoing Altemeier's procedure since 1992 were analysed with regard to mortality, morbidity, continence, anorectal function and recurrence rate. RESULTS: Sixty patients [median age 77 years (35-98)] underwent rectosigmoid resection [median length of bowel 14 (6-60) cm] with associated levatorplasty in 21 (35%). Overall mortality and morbidity were 1.6 and 11.6%, respectively. Manometry showed increased anal sphincter basal pressure and maximal squeeze pressure. We observed a decrease in postoperative rectal compliance (P=0.002). Age, gender, prolapse duration before surgery, levatorplasty and length of resection had no statistically significant relationship with recurrence. Continence improved in 62% and was stable over a median follow-up of 48 (1-186) months. Continence was positively related to a short length of bowel resection, but not to decreased rectal compliance. Actuarial recurrence was 14% at 4 years. CONCLUSION: The long-term recurrence rate after the Altemeier procedure was low and not linked to resection length or to levatorplasty. Improvement in continence was stable over time.

Early and late parameters describing the offset of neuromuscular blockade are highly intercorrelated.

BACKGROUND: Neuromuscular blocking agents have always shown wide inter-individual variability when it comes to their duration of action. This prevents clinicians from anticipating the evolution of the neuromuscular block for any given patient. With this study, we aimed to assess the nature of the relationships existing between different time course parameters used to describe paralysis onset and offset. METHODS: Sixty American Society of Anesthesiologists (ASA) score III-IV anaesthetised patients were randomised to receive a single equipotent dose (2ED95) of either rocuronium, mivacurium or atracurium. We used acceleromyography to monitor neuromuscular transmission. We described the relationships between the time-interval measurements of: onset, the first response (T1) reappearance, T1 25% of control, train-of-four ratio 0.25 and 0.75. Pearson correlation coefficients were calculated. RESULTS: We found no significant relationships between onset and any of the four parameters used to describe the offset. On the other hand, we showed strong and highly significant linear relationships between all the parameters describing the offset for each of the muscle relaxants studied (correlation coefficients ranging from 0.850 to 0.992). CONCLUSIONS: We evidenced strong linear correlations between the four offset time course parameters of spontaneous recovery after a single neuromuscular blocking agents (NMBAs) bolus. Such relationships open up new clinical perspectives concerning quantitative neuromuscular transmission monitoring: the scope of individual valuable anticipation of the patient's recovery.

Microwave freeze-thaw treatment of dose-banded cytotoxics injectable drugs: a review of the literature from 1980 to 2011.

INTRODUCTION: Microwave freeze-thaw treatment (MFTT) of injectable drugs can support the development of centralized intravenous admixtures services (CIVAS). The aim of this review is to collect information about the stability of cytotoxic and hazardous drugs after this treatment. METHODS: The scientific literature about drug stability studies was reviewed. The data describe the name of the drug, the manufacturer, the final concentration, the temperature and time of freezing storage, type of microwave oven, the thawing power, the measurement, the method and the results after treatment and final long-term storage at 5±3°C. RESULTS: From 1980 to 2011, nine drugs (cyclophosphamide, cytarabine, daunorubicine, doxorubicine, epirubicine, fluorouracile, ganciclovir, methotrexate sodium, mitomycine C) were studied after MFTT and the results were presented in 10 publications. The storage freezing temperature ranged from -15°C to -30°C, the time storage from 14 to 364 days, the thaw from moderate to full power. High performance liquid chromatography is mainly used to measure drug concentrations. All drugs are stable during and after the treatment. However, mitomycine needs to be stored at -30°C. The long-term stability after MFTT was evaluated only for the ganciclovir after 7 days, and for fluorouracile after 28 days. The concentration of the seven drugs was measured after one to 11 freezing-thawing cycles with a loss below 5%. CONCLUSIONS: This review can help the hospital pharmacist to take in charge the productions of nine dose-banded ready-to-use injectable cytotoxic and hazardous drugs. Freezing enhances their long-term stability without altering their chemical stability. Validated microwave thawing reduces the time of defrosting of these drugs at the studied concentrations.

Management of occupational asthma: cessation or reduction of exposure? A systematic review of available evidence.

Reduction of exposure to sensitising agents causing occupational asthma has been proposed as an alternative to total avoidance in order to minimise the adverse socio-economic impact of the condition. The aim of this systematic review was to compare the effects of these two management options on asthma and socio-economic outcomes. A bibliographic search was conducted to identify studies examining the outcome of workers with occupational asthma after reduction or cessation of exposure to the causal agent. The changes in asthma symptoms and nonspecific bronchial hyperresponsiveness after reduction or cessation of exposure were described in nine and five studies, respectively. The meta-analysis of pooled data showed that a reduction of exposure was associated with a lower likelihood of improvement (OR 0.16, 95% CI 0.03-0.91) and recovery (OR 0.30, 95% CI 0.11-0.84) of asthma symptoms and a higher risk of worsening of the symptoms (OR 10.23, 95% CI 2.97-35.28) and nonspecific bronchial hyperresponsiveness (OR 5.65, 95% CI 1.11-28.82), compared with complete avoidance of exposure. This systematic review indicates that reduction of exposure cannot be routinely recommended as an alternative to cessation of exposure in the management of occupational asthma. However, further investigations are required before drawing evidence-based conclusions on the cost-effectiveness of this approach.

Case-matched comparison of early and long-term outcomes of everted cervical vein and saphenous vein carotid patch angioplasty.

OBJECTIVES: To compare outcomes after carotid endarterectomy (CEA) with saphenous vein patch closure (SV), with cervical vein (external jugular and common facial) patch closure (CV). DESIGN: A total of 322 cases of CEA was achieved consecutively by using venous patch angioplasty. Propensity scores were calculated followed by a one-to-one basis case-matching. MATERIALS: This resulted into 90 SV and 90 CV matched cases. METHODS: The primary endpoint was the incidence of ipsilateral stroke and transient ischaemic attack at any time during follow-up. RESULTS: Ten-year freedom from stroke was 94.1% ± 3.5% for the SV group and 90.5% ± 4.2% for the CV group (log rank P = 0.230). Ten-year freedom from ipsilateral neurological events (stroke and transient ischaemic attack) was 93.5% ± 3.3% for SV group and 92.4% ± 3.0% for the CV group (log rank P = 0.403). Ten-year freedom from ≥75% stenosis/occlusion was 93.1 ± 4.8% for the SV group and 89.9 ± 6.0% for the CV group (log rank P = 0.481). CONCLUSIONS: CV is a good alternative to SV patching, particularly when the SV needs to be preserved for further use or is unsuitable.

Total perineal reconstruction after abdominoperineal excision for rectal cancer: long-term results of dynamic graciloplasty with Malone appendicostomy.

AIM: This study aimed to assess long-term function after total perineal reconstruction (TPR) with dynamic graciloplasty (DG) and systematic Malone appendicostomy (MA) adjunction after abdominoperineal excision (APR) for rectal cancer. METHOD: From 1999 to 2004, TPR using DG and MA was performed in 10 patients [seven women; median age 40 (range 28-55) years] after APR for rectal cancer (cT2 in one patient, cT3 in six patients and cT4 in three patients). We prospectively recorded early and late morbidity, mortality, oncological outcome, functional results (using the modified Working Party on Anal Sphincter Replacement 'WPASR' scoring system) and quality of life (QoL; using the European Organisation for Research and Treatment of Cancer 'EORTC' QLQ-C30 and QLQ-CR38 questionnaires). RESULTS: There was no procedure-related mortality. One patient required intra-abdominal re-operation. Nine patients required local and multiple revisions [there was one coloperineal anastomosis (CPA) stenosis, five CPA mucosal prolapse, three stenosis related to graciloplasty, two MA stenosis and one MA reflux]. After a median follow up of 78 months, there was no local recurrence and six patients were alive and disease-free. Regarding the functional results, the median modified WPASR score, of 8, after a follow up of 78 months, was good. The overall QoL scores remained stable over time. CONCLUSION: In carefully selected patients who want to avoid definitive abdominal colostomy after APR for rectal cancer, reconstruction involving MA and DG after APR for low rectal cancer is followed by good long-term function and QoL.

Physico-chemical analysis of several injectable drug in ready-to-use infusion after microwave freeze-thaw treatment and final storage at 5 ± 3 °C.

OBJECTIVE: In hospitals, the majority of the reconstitution of injectable drugs are carried out right before the administration to the patient by the nursing staff. The risks and errors related on their preparation and administration are numerous. The standardization, the centralization of these preparations and reconstitution by the hospital pharmacy make it possible to reduce the various risks and errors To enhance the number of drugs taken in charge, it is necessary to develop the long-term stability of ready-to-use drugs. Freezing seems an easy method but defrosting takes too much time. Some authors develop the concept of microwave treatment and apply this to different drugs. A characteristic of these studies was nevertheless the short period of study after thawing. METHODS: Long-term stability studies were started for different drugs mainly used in the hospital, and verify their stability after freezing at temperature<- 25°C, long-term storage (1 to 4 months), microwave-thawing and long-term storage at 5 ± 3°C. RESULTS: Sixteen molecules were tested and preserve more than 90% of their initial concentration the day of defrosting by microwave oven like this value a certain number of days at 5 ± 3°C. All the analyses were carried out by HPLC. CONCLUSION: The microwave freeze/thawing treatment allows the production of more important batches, makes profit of this technique in workload and material beyond a certain produced quantity. The described results encourage to check the possibilities of taking in charge other molecules regularly used in the Hospital Institutions.

Long-term stability of temocillin in dextrose 5% and in sodium chloride 0.9% polyolefin bags at 5 ± 3°C after freeze-thaw treatment.

INTRODUCTION: The aim of this study was to investigate the stability of a mixture of temocillin 20mg/ml in 5% dextrose and in 0.9% sodium chloride polyolefin bags after freezing, microwave thawing and long-term storage at 5±3°C. METHODS: The stability of ten polyolefin bags containing 20mg/ml of temocillin, five bags in 5% dextrose and five bags in 0.9% sodium chloride, prepared under aseptic conditions was studied after freezing for 1 month at -20°C, thawing in a microwave oven with a validated cycle, and stored at 5±3°C. Over 30 days, temocillin concentrations were measured by high-pressure liquid chromatography. Visual inspections, microscope observation, spectrophotometric measurements and pH measurements were also performed. RESULTS AND DISCUSSION: No precipitation occurred in the preparations but minor colour change was observed. No microaggregate was observed with optical microscopy or revealed by a change of absorbance. Based on a shelf life of 95% residual potency, temocillin infusions were stable at least 11 days in 5% dextrose and 14 days in 0.9% sodium chloride after freezing and microwave thawing (corresponding at the period where 95% lower confidence limit of the concentration-time profile remained superior to 95% of the initial concentration). During this period, the pH values of drug solutions have been observed to decrease without affecting chromatographic parameters. CONCLUSION: Within these limits, temocillin in 5% dextrose and in 0.9% sodium chloride infusions may be prepared and frozen in advance by a centralized intravenous admixture service then thawed before use in clinical units.

Whole-body MRI (WB-MRI) versus axial skeleton MRI (AS-MRI) to detect and measure bone metastases in prostate cancer (PCa).

OBJECTIVE: To compare whole-body MRI (WB-MRI) and axial skeleton MRI (AS-MRI) in detecting and measuring bone metastases in patients with prostate cancer (PCa). METHODS: WB-MRI and AS-MRI examinations were performed in 60 patients with PCa at high risk of metastases. Two radiologists separately categorised the AS-MRI and WB-MRI as negative or positive for metastases, and measured focal metastases using the "Response evaluation criteria in solid tumours" (RECIST) criteria transposed to bone. One radiologist reviewed all examinations 2 months later. Inter- and intraobserver agreements in establishing the presence/absence of metastases were calculated. Bland-Altman plots were used to assess measurement agreement between AS-MRI and WB-MRI. RESULTS: Strong to perfect inter- and intraobserver agreements were found between AS-MRI and WB-MRI in defining the presence/absence of bone metastases. There were no patients with isolated "peripheral" metastases at WB-MRI, missed at AS-MRI. There was no difference in lesion count between the two radiologists. AS-MRI and WB-MRI provided statistically equivalent RECIST values for one radiologist and slightly lower values at AS-MRI for the other. CONCLUSIONS: In our series of PCa patients, AS-MRI and WB-MRI were equivalent in determining the presence/absence of bone metastases and provided similar evaluation of the metastatic burden.