A Comparison of Instructions for Use Documents and Manufacturer Produced Administration Videos for Biological Products.

OBJECTIVES: To compare Instructions for Use (IFU) and Manufacturer Produced Administration Videos (MPAV) for biological products to describe if they are highly similar or different. To identify differences between the two that may lead to medication errors and to point out possible solutions to optimize safety. METHODS: We screened 139 biological products having both an IFU and a MPAV. Differences between the IFU and MPAV of each biological product were noted and categorized by importance and how likely it would cause harm to patients. Strategies were discussed based on differences observed. RESULTS: Of the products screened, 51 had an IFU and a MPAV available for evaluation. They were primarily made to support the use of auto-injectors (n = 25) and pre-filled syringes (n = 19). Of this group, we found that 11 had no differences between the IFU and MPAV, while the other 40 had at least one or more identifiable differences. Differences were stratified into the following sub-categories from most to least prevalent: word choice differences, supplementary information, missing information, and unaligned directions. We looked at the distribution of differences per biological product and found an average of two differences per MPAV (IQR 1-3). CONCLUSION: We suggest that when sponsors create or update MPAVs, to focus on aligning critical content between the respective IFU and MPAV. We believe that it is possible for MPAVs to potentially reduce medication errors as a non-text-based media form and that care should be taken to avoid substantial differences in critical content between the IFU and MPAV.

Use of Proprietary Names by Prescribers for Generic Products.

BACKGROUND: Proprietary names are often used when prescribing drug products in the United States. The purpose of this study is to describe prescribers' use of proprietary names for generic products, branded-generic names, on prescription orders and to identify prescribing practice trends to inform the development and evaluation of new proprietary names. METHODS: To identify Abbreviated New Drug Application (ANDA) with branded-generic names approved between January 2003 and December 2012, we utilized the database provided by the FDA Office of Communications, Drugs@FDA . A national outpatient retail prescription database, IMS's Vector One: National (VONA) was used to identify prescribing trends by examining data for branded-generic names identified in Drugs@FDA as they were written on prescriptions for years 2003 to 2012, the last year of data collection for VONA. IMS Health, IMS National Sales Perspectives (IMS NSP) was used to retrieve the date that product sales were first reported (launch date). RESULTS: Our search of Drugs@FDA identified 65 distinct branded-generic names approved between January 2003 and December 2012. Data show that most of these products with branded-generic names are written on prescriptions and sold to pharmacies within a year of FDA approval. In some cases, the use of branded-generic names persists for up to 9 years after drug approval. CONCLUSION: This descriptive study confirmed that branded-generic names are used in prescribing. Thus, evaluation of orthographic and phonetic similarities between proposed proprietary names and branded-generic names is necessary when formulating and evaluating new proprietary names.

Characteristics That May Help in the Identification of Potentially Confusing Proprietary Drug Names.

PURPOSE: This study aimed to provide a descriptive analysis of characteristics that are common among drug name pairs involved in name confusion medication errors. METHODS: We evaluated drug name pairs that contained at least one proprietary name from the Institute for Safe Medication Practices (ISMP) List of Confused Drug Names. For each name pair, we analyzed whether the following characteristics were present: (1) the same first letter, (2) a shared letter string of at least 3 letters, and (3) similarity in the number of letters. Additionally, we obtained the combined Phonetic and Orthographic Computer Analysis (POCA) score. RESULTS: Ninety-nine percent of the drug name pairs reflected at least one of the 3 characteristics analyzed. Additionally, 75% of the names had a combined POCA score of ≥50%. CONCLUSIONS: This descriptive analysis provides some insight into characteristics that may be associated with name confusion, which should be considered when formulating and evaluating proposed proprietary drug names.

A Method of Addressing Proprietary Name Similarity for US Prescription Drugs.

There is an increased risk of medication error and harm to a patient whenever 2 or more drug product names appear alike in sound, look, or meaning. Any ambiguity of the proprietary name ("trade" or "brand" name) of a drug product can lead to errors in ordering, dispensing, or administering medication. A drug's name is a critical identifier, and correct product identification is important to the responsible administration of medicine. This article describes a series of tools created for regulatory reviewers to enhance the review of proprietary names under current federal regulations, with the goal of encouraging further innovation toward the goal of medication safety. These tools include measures of orthographic, phonetic, and semantic similarities and are designed be used together with the existing computerized measures of similarity. It is the hope that highlighting the importance of medication error reporting for the safety review process will further encourage health care professionals to provide adequate and detailed reporting regarding medication errors, which will lead to improvements in the overall safety review process.

More methemoglobin is produced by benzocaine treatment than lidocaine treatment in human in vitro systems.

The clinical use of local anesthetic products to anesthetize mucous membranes has been associated with methemoglobinemia (MetHba), a serious condition in which the blood has reduced capacity to carry oxygen. An evaluation of spontaneous adverse event reporting of MetHba submitted to FDA through 2013 identified 375 reports associated with benzocaine and 16 reports associated with lidocaine. The current study was performed to determine the relative ability of benzocaine and lidocaine to produce methemoglobin (MetHb) in vitro. Incubation of 500µM benzocaine with whole human blood and pooled human liver S9 over 5h resulted in MetHb levels equaling 39.8±1.2% of the total hemoglobin. No MetHb formation was detected for 500µM lidocaine under the same conditions. Because liver S9 does not readily form lidocaine hydrolytic metabolites based on xylidine, a primary metabolic pathway, 500µM xylidine was directly incubated with whole blood and S9. Under these conditions MetHb levels of 4.4±0.4% were reached by 5h. Studies with recombinant cytochrome P450 revealed benzocaine to be extensively metabolized by CYP 1A2, with 2B6, 2C19, 2D6, and 2E1 also having activity. We conclude that benzocaine produces much more MetHb in in vitro systems than lidocaine or xylidine and that benzocaine should be more likely to cause MetHba in vivo as well.

A retrospective study to assess the morbidity associated with transurethral prostatectomy in patients on antiplatelet or anticoagulant drugs.

UNLABELLED: What's known on the subject? and What does the study add? There is controversy over the use of anti-platelet and anti-coagulant drugs in men undergoing TURP with contradictory evidence on the effect of the drugs on bleeding following the operation, particularly for aspirin. If anti-platelet or anti-coagulant drugs are not stopped for TURP, there is an unacceptable burden of bleeding. If the drugs are stopped there is an unacceptable rate of cardiovascular events. OBJECTIVE: • To determine the morbidity associated with perioperative management of antiplatelet (AP) or anticoagulant (AC) medication and transurethral prostatectomy. PATIENTS AND METHODS: • A retrospective review was performed on 163 consecutive patients undergoing transurethural prostatectomy. • Patients were grouped according to the perioperative management of AP and AC medications: control patients not prescribed any AP/AC drugs (group 1), those on AP/AC who had ceased them perioperatively (group 2) and those whose AP/AC were continued (group 3). • Warfarin was withheld perioperatively for all patients. • Morbidity associated with increased blood loss and cardiovascular or cerebrovascular events was recorded and differences were analysed with SPSS version 16 software. RESULTS: • There was a statistically significant increase in bleeding-associated morbidity in group 2 (13/65) and group 3 (6/7) compared with the controls (9/91) (P < 0.01). • Cardiovascular and cerebrovascular events were only seen in group 2 (6/65), statistically significantly higher than the event rate in the other groups (P ≤ 0.01). • All cardiovascular or cerebrovascular events occurred in patients prescribed these medications for secondary prevention. CONCLUSION: • Patients taking AP or AC medications have a higher rate of perioperative bleeding compared with those who are not taking any. • However, for patients prescribed AP or AC medication for secondary prevention, withholding these medications results in an increased rate of cardiovascular and cerebrovascular complications. • Careful consideration of the risks and other management options should be undertaken before performing transurethural prostatectomy in this high risk group of patients.

Matching health needs of refugee children with services: how big is the gap?

OBJECTIVES: To document the health needs of refugee children accessing comprehensive refugee health services in New South Wales (NSW), to match needs with available services and establish gaps in services. METHODS: We collated clinical data on all children aged under 14 years attending the three refugee specific clinics seeing children in NSW in 2005. We compared these data to the number of refugee children settling in NSW in 2005. RESULTS: NSW received 1,557 refugee children (<14 years) in 2005. Around one in five (n=331) was seen in a refugee specific clinic. Most were asymptomatic. Of those tested, 25% had anaemia, 27% were serology positive for schistosomiasis, 16% had evidence of current or recent malaria, 25% were tuberculin skin test positive, 69% were hepatitis B non-immune and 20% had low vitamin D levels. Most children needed catch up immunisation. Other problems included chronic health, developmental and behavioural problems. Screening tests varied across sites. Follow up was problematic for most. CONCLUSIONS: A small proportion of refugee children arriving in NSW have access to comprehensive screening and assessment, in spite of significant health needs. There is variation in screening practices, and follow up is poor. There is a high pick up rate for diseases of personal and public health significance. IMPLICATIONS: There is a strong moral and public health imperative to provide appropriately resourced, culturally competent and comprehensive health care to optimise refugee children's wellbeing.

Destabilization of DJ-1 by familial substitution and oxidative modifications: implications for Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by oxidative stress and protein aggregation. Both toxic phenomena are mitigated by DJ-1, a homodimeric protein with proposed antioxidant and chaperone activities. The neuroprotective function of DJ-1 is modulated by oxidation of cysteine 106, a residue that may act as an oxidative stress sensor. Loss-of-function mutations in the DJ-1 gene have been linked to early onset PD, and age-dependent over-oxidation of DJ-1 is thought to contribute to sporadic PD. The familial mutant L166P fails to dimerize and is rapidly degraded, suggesting that protein destabilization accounts for the dysfunction of this mutant. In this study, we investigated how the structure and stability of DJ-1 are impacted by two other pathogenic substitutions (M26I and E64D) and by over-oxidation with H2O2. Whereas the recombinant wild-type protein and E64D both adopted a stable dimeric structure, M26I showed an increased propensity to aggregate and decreased secondary structure. Similar to M26I, over-oxidized wild-type DJ-1 exhibited reduced secondary structure, and this property correlated with destabilization of the dimer. The engineered mutant C106A had a greater thermodynamic stability and was more resistant to oxidation-induced destabilization than the wild-type protein. These results suggest that (i) the M26I substitution and over-oxidation destabilize dimeric DJ-1, and (ii) the oxidation of cysteine 106 contributes to DJ-1 destabilization. Our findings provide a structural basis for DJ-1 dysfunction in familial and sporadic PD, and they suggest that dimer stabilization is a reasonable therapeutic strategy to treat both forms of this disorder.