Association of compounded bevacizumab with postinjection endophthalmitis.

IMPORTANCE: Current draft guidelines set forth by the US Food and Drug Administration for compounded or repackaged medications would greatly limit the availability and use of bevacizumab by ophthalmologists across the country. Little evidence beyond highly publicized case reports exists for or against the need for additional regulation of compounded bevacizumab. OBJECTIVE: To determine whether the distribution of bevacizumab through compounding pharmacies increases the risk for endophthalmitis compared with the distribution of single-use vials of ranibizumab from the manufacturer. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study using medical claims data from ambulatory care centers across the United States that were submitted to a large, national US insurer. Cohorts were created using information on 530 382 intravitreal injections administered from January 1, 2005, through December 31, 2012. Any individual from this data set who received an intravitreal injection of bevacizumab or ranibizumab (n=383 810) and had at least 6 months of data before and 1 month after the injection was eligible. After exclusions (any previous diagnosis of endophthalmitis, multiple injected drugs given on the index day, or intraocular surgery within 15 days of the injection or between the injection and a diagnosis of endophthalmitis), our analysis involved 383 810 intravitreal injections given to 58 612 patients. Data collection and analysis occurred from February 16 through April 7, 2015. MAIN OUTCOMES AND MEASURES: The odds of developing endophthalmitis after an intravitreal injection of bevacizumab compared with ranibizumab. RESULTS: In total, 296 565 injections of bevacizumab were given to 51 116 patients and 87 245 injections of ranibizumab were given to 7496 patients. We found 71 cases of endophthalmitis (49 in the bevacizumab cohort and 22 in the ranibizumab cohort) for an endophthalmitis rate of 0.017% (95% CI, 0.012%-0.021%; 1 case per 6061 injections) for bevacizumab and 0.025% (95% CI, 0.015%-0.036%; 1 case per 3968 injections) for ranibizumab. After controlling for age, race, sex, injection-related diagnosis, and year of injection, we found no significant association with development of endophthalmitis after a bevacizumab injection compared with ranibizumab (odds ratio, 0.66 [95% CI, 0.39-1.09]; P = .11). CONCLUSIONS AND RELEVANCE: The results of this study suggest bevacizumab as currently used across the United States does not increase the risk for endophthalmitis; therefore, additional regulations on the use of repackaged bevacizumab may be unnecessary.

Transient macular edema after intracameral injection of a moderately elevated dose of cefuroxime during phacoemulsification surgery.

IMPORTANCE: Intracameral injection of cefuroxime sodium (1 mg/0.1 mL) has been reported to reduce the risk of endophthalmitis following cataract surgery. In the United States it must be compounded, which is subject to dilution error. We describe a series of 13 eyes that received intracameral injection of cefuroxime sodium, 9 mg/0.1 mL, intraoperatively. OBSERVATIONS: On postoperative day 1, 6 of 13 eyes (46%; 95% CI, 19%-75%) had visual acuity of 20/70 or worse and macular edema. Spectral-domain optical coherence tomography of 2 eyes revealed central subfield thicknesses of 909 and 873 µm. On postoperative day 4, the mean (SD) central subfield thickness was 309 (78) µm in the 6 eyes with diagnosed macular edema, 279 (23) µm in the fellow eyes, and 271 (38) µm in the 7 exposed eyes without macular edema. The mean (SD) time to resolution of macular edema was 5.2 (1.3) days; the final central subfield thickness ranged from 193 to 293 µm. All eyes, except 2 with preexisting ocular comorbidity, had a best-corrected final visual acuity at 1 month of 20/30 or better. Significant corneal edema was not observed. CONCLUSIONS AND RELEVANCE: Intracameral injection of cefuroxime sodium at a dose of 9 mg/0.1 mL was associated with transient macular edema and diminished visual acuity in 6 of 13 exposed eyes (46%), resolving largely within 1 week.

Long-term management of severe ocular surface injury due to methamphetamine production accidents.

PURPOSE: The aim of this study was to report the clinical features and management of patients with ocular surface damage during methamphetamine production accidents. METHODS: This is a retrospective noncomparative interventional case series of 5 patients with methamphetamine production-related ocular injuries referred to the Cincinnati Eye Institute between 1999 and 2014. RESULTS: Four of 5 cases were white young men with severe bilateral ocular injury and extremely poor vision. All except 1 eye (9 of 10) were diagnosed with total or near-total ocular surface failure. Limbal stem cell transplantation was performed in 8 of 10 eyes. Keratolimbal allograft was followed by penetrating keratoplasty in 7 of 10 eyes. Ocular surface stability was achieved in 7 of 10 eyes after keratolimabl allograft. Postoperative visual acuity was better than 20/200 in 4 of 10 of eyes. Keratolimbal graft rejection occurred in 3 of 10 eyes; the rate of rejection of penetrating keratoplasty was also 3 out of 10 eyes. CONCLUSIONS: Methamphetamine-related accidents can lead to severe bilateral ocular injuries. Although stem cell transplantation procedure success is guarded in most of these patients because of severe conjunctival inflammation and accompanying ocular comorbidities, as well as personality issues, compliant patients can achieve good visual function with ocular surface transplantation and subsequent keratoplasty.

Environmental contamination, product contamination and workers exposure using a robotic system for antineoplastic drug preparation.

Environmental contamination, product contamination and technicians exposure were measured following preparation of iv bags with cyclophosphamide using the robotic system CytoCare. Wipe samples were taken inside CytoCare, in the clean room environment, from vials, and prepared iv bags including ports and analysed for contamination with cyclophosphamide. Contamination with cyclophosphamide was also measured in environmental air and on the technicians hands and gloves used for handling the drugs. Exposure of the technicians to cyclophosphamide was measured by analysis of cyclophosphamide in urine. Contamination with cyclophosphamide was mainly observed inside CytoCare, before preparation, after preparation and after daily routine cleaning. Contamination outside CytoCare was incidentally found. All vials with reconstituted cyclophosphamide entering CytoCare were contaminated on the outside but vials with powdered cyclophosphamide were not contaminated on the outside. Contaminated bags entering CytoCare were also contaminated after preparation but non-contaminated bags were not contaminated after preparation. Cyclophosphamide was detected on the ports of all prepared bags. Almost all outer pairs of gloves used for preparation and daily routine cleaning were contaminated with cyclophosphamide. Cyclophosphamide was not found on the inner pairs of gloves and on the hands of the technicians. Cyclophosphamide was not detected in the stationary and personal air samples and in the urine samples of the technicians. CytoCare enables the preparation of cyclophosphamide with low levels of environmental contamination and product contamination and no measurable exposure of the technicians.

Risks and effectiveness of compounded bioidentical hormone therapy: a case series.

After the publication of the Women's Health Initiative, attitudes towards management of menopausal symptoms changed dramatically. One alternative that has received much media attention is the use of bioidentical hormone therapy (BHT). The media and celebrity endorsements have promoted a number of misconceptions about the risks and benefits associated with the various forms of BHT. This article will review the available evidence regarding the safety and efficacy of BHT in comparison to conventional hormone therapy. We will also review several cases seen in our midlife women's referral clinics, which demonstrate concerns for the safety and efficacy of BHT, including unexplained endometrial cancer in otherwise healthy BHT users. Due to the lack of sufficient data to support the efficacy or safety of BHT, we recommend the use of United States Food and Drug Administration-approved regimens in the management of menopausal symptoms.

Assessment of the risk of needlestick injuries associated with intravitreal injections.

PURPOSE: To assess the overall risk of needlestick injuries (NSIs) associated with intravitreal injection, and more specifically related to the practice of compounding pharmacies of applying informational adhesive stickers to repackaged bevacizumab injection syringes. METHODS: This cross-sectional study involved an online survey of retina specialists in the United States. RESULTS: Of the 717 invited retina specialists, 158 (22%) responded to the online survey. The respondents reported using 1 pair of gloves (51%), no gloves (46%), or 2 pairs of gloves (3%) during intravitreal injection. Repackaged bevacizumab syringes distributed by compounding pharmacy were used by 89% of the respondents, and 63% reported that the adhesive sticker was applied directly to the syringe. Unintentional adhesion between the sticker and hand or glove was experienced by 9% of respondents. At least 1 NSI during intravitreal injection was experienced by 8% of respondents, and sticker-related injury was reported by 3%. The sticker was perceived to increase risk for NSI by 33% of respondents. CONCLUSION: This survey showed that 8% of the responding physicians surveyed have experienced at least one NSI during intravitreal injections, of which approximately one third was attributed to the adhesive sticker. Direct application of misfitting stickers to repackaged syringes by compounding pharmacies may be a practice that can aggravate the risk of NSI.

Effect of microformulation on the bioactivity of an anthocyanin-rich bilberry pomace extract ( Vaccinium myrtillus L.) in vitro.

In cell culture were compared the different release rates of anthocyanins from a bilberry pomace extract encapsulated either in food grade whey protein-based matrix capsules (WPC) or in pectin amid-based hollow spherical capsules (PHS). The impact of the formulations on typical anthocyanin-associated biological end points such as inhibition of the epidermal growth factor receptor (EGFR) and suppression of cell growth in HT29 colon carcinoma cells was assessed. The purpose was to find whether the release rates are sufficient to maintain biological activity and whether encapsulation affected EGFR inhibitory and growth suppressive properties of the extract. Even though anthocyanin release from extract-loaded capsules was proven under cell culture conditions, the inhibitory potential toward the EGFR was diminished. However, nonencapsulated extract as well as both extract-loaded encapsulation systems diminished the growth of HT29 cells to a comparable extent. The loss of EGFR inhibitory properties by encapsulation despite anthocyanin release indicates substantial contribution of other further constituents not monitored so far. Taken together, both applied encapsulation strategies allowed anthocyanin release and maintained biological activity with respect to growth inhibitory properties. However, the loss of EGFR inhibitory effects emphasizes the need for biological profiling to estimate process-induced changes of plant constituent's beneficial potencies.

Medical device on pharmacists' work-related musculoskeletal complaints and burnouts.

This study analysed the total number of consumed vials of chemotherapy drugs during the year 2007 to determine workloads, and investigated the effects of using the Spike medical device in contrast to the use of traditional needles on oncology pharmacists' dispensing time, muscle soreness, work-related burnout and fatigue symptoms. Work-related burnout and physiological symptoms were measured using the Copenhagen Burnout Inventory (CBI) and a visual analogue pain scale. The Spike device significantly reduced the time spent in drawing up fluorouracil (39.46 ± 9.43 s vs. 57.13 ± 13.47 s) or cisplatin (29.65 ± 11.22 s vs. 60.93 ± 20.54 s) compared with traditional needles (P < 0.001). The CBI burnout score improved significantly with the Spike device (53.21 ± 8.58 vs. 73.21 ± 5.42; P = 0.007) because finger and palm muscle soreness complaints and subjective fatigue symptoms for eye tiredness and shoulder-wrist pain were significantly reduced (P < 0.05). Practitioner Summary The pharmacist needs to exert hand strength to counter the vial back-suction pressure to draw out the medical liquid, and confirm the volume during the drawing antineoplastic drug procedure. This study aimed to determine the effects of using a medical device, instead of a needle, on pharmacists' work-related musculoskeletal complaints and burnouts.

The effect of information provision on reduction of errors in intravenous drug preparation and administration by nurses in ICU and surgical wards.

Malpractice in preparation and administration of intravenous (IV) medications has been reported frequently. Inadequate knowledge of nurses has been reported as a cause of such errors. We aimed to evaluate the role of nurses' education via installation of wall posters and giving informative pamphlets in reducing the errors in preparation and administration of intravenous drugs in 2 wards (ICU and surgery) of a teaching hospital in Tehran, Iran. A trained observer stationed in 2 wards in different work shifts. He recorded the nurses' practice regarding the preparation and administration of IV drugs and scored them before and after the education process. 400 observations were evaluated. Of them, 200 were related to before education and 200 were related to after education. On a 0-10 quality scale, mean ± SD scores of before and after education were determined. Mean ± SD scores of before and after education at the 2 wards were 4.51 (± 1.24) and 6.15 (± 1.23) respectively. There was a significant difference between the scores before and after intervention in ICU (P<0.001), surgery (P<0.001), and total two wards (P<0.001). Nurses' education by using wall poster and informative pamphlets regarding the correct preparation and administration of IV drugs can reduce the number of errors.

Effectiveness of compounded bioidentical hormone replacement therapy: an observational cohort study.

BACKGROUND: Bioidentical Hormone Replacement Therapy (BHRT) is believed it to be a safer and equally effective alternative to Conventional Hormone Therapy for the relief of menopausal symptoms; however, data are needed to support these claims. The objective of this study is to evaluate the effectiveness of compounded BHRT provided in six community pharmacies. METHODS: This was an observational cohort study of women between the ages of 18-89 who received a compounded BHRT product from January 1, 2003 to April 30, 2010 in six community pharmacies. Data included patient demographics, comorbidities, therapeutic outcomes, and hormone therapies. Women self-rated menopausal symptoms as absent, mild, moderate, or severe. Descriptive statistics were used to characterize the patient population, BHRT use, and adverse events. Patient symptom severity was compared at baseline and 3 to 6 months follow-up using the Wilcoxon signed-rank test. RESULTS: Women (n = 296) receiving BHRT at Oakdell Pharmacy had a mean (standard deviation) age of 52 (9) years. The most common BHRT dosage forms utilized were topical (71%) and oral (43%). Compounded BHRT regimens were generally initiated at low doses regardless of route. Women experienced a 25% decrease in emotional lability (p < 0.01), a 25% decrease in irritability (p < 0.01), and a 22% reduction in anxiety (p = 0.01) within 3 to 6 months. These women also experienced a 14% reduction in night sweats (p = 0.09) and a 6% reduction in hot flashes (p = 0.50). CONCLUSIONS: This study demonstrates that compounded BHRT improves mood symptoms. Larger studies are needed to examine the impact on vasomotor symptoms, myocardial infarction and breast cancer.

Occupational kidney disease among Chinese herbalists exposed to herbs containing aristolochic acids.

OBJECTIVE: Many Chinese herbs contain aristolochic acids (ALAs) which are nephrotoxic and carcinogenic. The objective of this study was to identify whether exposure to herbs containing ALAs increased the risk of kidney disease among Chinese herbalists. METHODS: A nested case-control study was carried out on 6538 Chinese herbalists registered between 1985 and 1998. All incident cases of chronic renal failure reported to the Database of Catastrophic Illness of the National Health Insurance Bureau between 1995 and 2000 were defined as the case group. Up to four controls without renal failure were randomly matched to each case by sex and year of birth. A structured questionnaire survey was administered between November and December 2002. The Mantel-Haenszel method and conditional logistic regression were used to estimate the risks. RESULTS: 40 cases and 98 matched controls were included in the final analysis. After adjusting for age, frequent analgesic use, and habitual consumption of alcohol, fermented or smoked food, we found manufacturing and selling Chinese herbal medicine (OR 3.43, 95% CI 1.16 to 10.19), processing, selling or dispensing herbal medicines containing Fangji (OR 4.17, 95% CI 1.36 to 12.81), living in the workplace (OR 3.14, 95% CI 1.11 to 8.84) and a history of taking of herbal medicines containing Fangji (frequently or occasionally) (OR 5.42, 95% CI 1.18 to 24.96) were significantly associated with renal failure. CONCLUSION: Occupational exposure to and consumption of herbs containing ALAs increases the risk of renal failure in Chinese herbalists.

[Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC): evaluation, prevention and policies to avoid occupational exposure for operating room personnel]. / Chimiohyperthermie intrapéritonéale : évaluation, prévention et gestion des risques professionnels au bloc opératoire.

To develop a treatment strategy for peritoneal carcinomatosis using a combination of extended peritoneal resections, local destructive procedures and hyperthermic intraperitoneal chemotherapy creates great concern between healthcare workers involved in these procedures. New professional risks exist: risk of exposure to cytotoxic drugs, environmental risks (inhalation of smoke, aerosolization of chemotherapy agents). Information, education and training of healthcare workers is mandatory in order to ensure proper evaluation, prevention, and management of professional exposure risks in coordination with the occupational health office.

Effect of processing methods on colouration of human serum albumin preparations.

Human serum albumin is a well tolerated therapeutic for the treatment of hypovolemia. Despite all commercial human albumin preparations being derived from plasma, these products can have a highly variable colour. Albumin samples derived from ethanol precipitation and chromatographic fractionation procedures were evaluated for bilirubin and biliverdin levels and by spectrophotometry. It was shown that albumin derived from a chromatographic process, which had a bilirubin:albumin ratio similar to that observed in plasma, had a vibrant yellow appearance. The albumin derived from ethanol precipitation had undetectable levels of bilirubin, and the amber colour of this product was attributed mainly to residual haem. The presence of bilirubin during pasteurisation led to oxidation to biliverdin, with a resultant colour change from yellow to yellow/green. Given that the antioxidant properties of bilirubin are well established, it is possible that bilirubin helps protect albumin from oxidation during the pasteurisation step.

[Continuous training program for technicians handling antineoplastic drugs and occupational exposure risk]. / Formation continue des manipulateurs de cytotoxiques et prévention du risque de contamination.

Training and regular evaluation of technicians involved in the preparation of antineoplastic agents seems essential to reduce occupational exposure. In this way, a continuous training program was established. Technicians were asked to prepare a safe simulated liquid cytotoxic drug with a fluorescein solution (10 mg/L). After, occupational exposure with this solution was simulated. Ultra-violet light (365 nm) was employed to determine surface contamination. This continuous training program is tested and validated with pharmacy technicians. All people handling these drugs (physicians, nurses, pharmacy staff) can use this program. Short mandatory training courses are stimulating and well appreciated.

Evaluation of occupational exposure to antiblastic drugs in an Italian hospital oncological department.

The determination of the current antiblastic drug contamination levels in an Italian hospital oncology ward was carried out. Statistical evaluation of data aiming to identify potential exposure causes was performed. Cyclophosphamide (CP), ifosfamide (IF) and 5-fluorouracil (5-FU) were determined by wipe tests, extracted with diatomaceous earths and quantified by GC/MSMS or HPLC/UV. Data were analysed with respect to the potential contamination levels of sampled surfaces, and various amounts of handled analyte. chi(2) tests and Spearman correlation coefficients were calculated. Median concentration levels of 0.086, 0.071, 2.363 microg/dm(2) were obtained, (CP, IF, 5-FU, respectively). 3.8 and 13.5% of investigated surfaces showed CP and IF concentrations higher than 1 microg/dm(2) (up to 26.96 microg/dm(2)) and 13.4% of samples contained 5-FU concentrations in the range 20-208.9 microg/dm(2). Analytes' concentration levels were dependent on sampling sites, with significant correlations showing a progressive contamination decrement going from workbenches, floor, hood planes and other surfaces. A diffuse contamination (traces of all the three analytes) was found on all investigated surfaces, even when analytes had not been used during the sampling days. A significant correlation (rho s=0.303, p=0.001) between the measured analyte concentration and the analyte handled amount was found only in the case of IF. The risk management strategy should be improved, as suggested by the measured and widespread levels of contamination. Since contamination also depends on other factors attributable to working modalities and cleaning procedures, the obtained results suggest that performance of specific training courses as well as scheduling environmental monitoring plans to achieve an actual decrement of the observed contamination levels should be implemented.

How to combine hygiene and radiation protection for radiopharmaceuticals preparation? Analysis in France and propositions.

Radiopharmaceuticals for intravenous administration are considered as sterile medicinal products. Their preparation in hospitals involves adherence to regulations on radiation protection as well as to sterility requirements for parenteral administration. These two basic aspects are often opposite, making the working conditions difficult to define. Official texts that have included hygiene and radiation protection do not precisely state how to combine these two aspects in practice. Thus, after an analysis of the bibliography available, this review will show that even if hospital radiopharmacy departments in France are not able to work in total aseptic environments, some measures can be taken in order to improve preparation conditions.

Outbreak of Serratia marcescens infections following injection of betamethasone compounded at a community pharmacy.

BACKGROUND: In June 2001, following the report of 4 patients with Serratia marcescens meningitis who received epidural injections of betamethasone compounded at a community pharmacy, we initiated an outbreak investigation. METHODS: All patients who received injections of betamethasone from the production lot common to the 4 patients were evaluated. A case patient was defined as a patient who received compounded betamethasone and had S. marcescens isolated from a sterile site or clinical and laboratory evidence of infection. We cultured all recovered betamethasone, environmental specimens from the pharmacy, and medications recovered from an ambulatory surgery center. The California Board of Pharmacy reviewed the procedures used to prepare the betamethasone. RESULTS: We identified 11 patients with culture-confirmed S. marcescens (8 patients) or clinical infection (3 patients) following injection of compounded betamethasone from 25 May through 31 May 2001. Case patients had meningitis (5 patients, with 3 deaths), epidural abscesses (5 patients), or an infected hip (1 patient). S. marcescens was isolated from 35 (69%) of 51 betamethasone vials recovered, from pharmacy specimens of 1% carboxymethylcellulose stock solution, from pharmacy surfaces, and from multiple parenteral materials used at the ambulatory surgery center. Pulsed-field gel electrophoresis patterns of S. marcescens isolates of representative specimens from patients, the betamethasone, the pharmacy, and the ambulatory surgery center were identical. Deficient practices in compounding of betamethasone included inadequate autoclaving temperatures and failure to perform terminal sterilization. CONCLUSIONS: This outbreak of serious S. marcescens infection followed improper compounding of betamethasone in a community pharmacy. Enforceable national standards for pharmaceutical compounding are needed to reduce the risk of such outbreaks.