Self-assembled enzymatic monolayer directly bound to a gold surface: activity and molecular recognition force spectroscopy studies.

Escherichia coli dihydrofolate reductase (ecDHFR) has one surface cysteine, C152, located opposite and distal to the active site. Here, we show that the enzyme spontaneously assembles on an ultraflat gold surface as a homogeneous, covalently bound monolayer. Surprisingly, the activity of the gold-immobilized ecDHFR as measured by radiographic analysis was found to be similar to that of the free enzyme in solution. Molecular recognition force spectroscopy was used to study the dissociation forces involved in the rupture of AFM probe-tethered methotrexate (MTX, a tight-binding inhibitor of DHFR) from the gold-immobilized enzyme. Treatment of the ecDHFR monolayer with free MTX diminished the interaction of the functionalized tip with the surface, suggesting that the interaction was indeed active-site specific. These findings demonstrate the viability of a simple and direct enzymatic surface-functionalization without the use of spacers, thus, opening the door to further applications in the area of biomacromolecular force spectroscopy.

Anaesthesia and analgesia for ambulatory hysteroscopic surgery.

Although ambulatory hysteroscopy is well established in dedicated centres, there is a delay in its general implementation. One reason for this may be the lack of consensus regarding a protocol for analgesia and anaesthesia in ambulatory hysteroscopy. This review looks at the various methods in use. These include the paracervical or intracervical injection of anaesthetic to establish a block. Topical anaesthetic may be applied to the surface of the endometrium in the uterine cavity or to the cervix. Oral analgesia is also used. A vaginoscopic approach to the uterine cavity without any anaesthesia is also becoming popular. Finally, combinations of the above methods have been employed for hysteroscopic surgical procedures, including the newer generation of endometrial ablation methods.

Improvement in safety monitoring of biologic response modifiers after the implementation of clinical care guidelines by a specialty.

BACKGROUND: Tumor necrosis factor (TNF)-alpha inhibitors and other biologic response modifiers (BRMs) are frequently used to treat a variety of inflammatory diseases. Use of these agents may increase risk of serious infections, malignancies, and other complications such as worsening symptoms of heart failure or demyelinating disease. Because of these risks, a baseline assessment and routine monitoring have been recommended, but standardized guidelines for monitoring have yet to be established. OBJECTIVE: To measure the compliance with the recommended safety monitoring in the Clinical Care Guidelines for BRMs at the University of Illinois Hospitals and Health Sciences System (UI Health). METHODS: The Clinical Care Guidelines for BRMs was developed by a committee of pharmacists, nurses, and physicians based on an assessment of published literature and medication labeling. The guidelines included recommendations for safety monitoring prior to BRM therapy, such as the tuberculosis (TB) test, Hepatitis B surface Antigen (HBsAg) test, liver function test (LFT), complete blood count (CBC), up-to-date vaccinations, risk assessment for cancer, pregnancy testing, monitoring for contraindications with concomitant medications, concomitant disease state risk assessment, and patient education. The guidelines were introduced to UI Health in February 2012 by a systemwide email and by in-services given by the health system's Specialty Pharmacy Service. In-services were given in the clinics known to generate large numbers of BRM orders (e.g., gastroenterology and rheumatology) and at the outpatient center for infused therapies. The purpose of the in-services was to introduce providers to the guidelines and encourage their compliance. To ensure that guideline requirements were met when BRMs were ordered, a process was established to identify BRM orders, assess the orders for compliance with 4 of the safety monitoring tests from the guidelines (TB, HBsAg, LFT, and CBC), and make interventions. When necessary, Specialty Pharmacy Services coordinated with the pharmacists and other providers in the clinic to order lab tests and ensure they were completed prior to the start of therapy. Feedback was provided during the study to proactively improve compliance with the guidelines. After completion of the study, a report containing outpatient prescription orders for BRMs (abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab, and tocilizumab) from August 2011 through July 2012 was generated from the electronic medical record. Retrospective analyses of completion of safety monitoring were conducted for patients administered BRM treatment. Completion rates were compared before and after implementation of guidelines in February 2012. Completion was considered to have occurred when all 4 safety monitoring tests had been conducted -TB (unless known to be positive from a previous test), HBsAg, LFT, and CBC. Completion data from August 2011 through January 2012 were before the guidelines were implemented, and data from February 2012 through July 2012 were after the guidelines. Chi square analyses were performed on completion frequencies in the patients before and after the guidelines were implemented. RESULTS: Of the 320 unique patient BRM orders evaluated in this study, 195 (61%) were generated in the Rheumatology clinic, 99 (31%) in the Gastroenterology clinic, 21 (6.5%) in the Dermatology clinic, and 5 (1.5%) in the Transplant clinic. Before the guidelines were implemented, 54 ( 31%) of 173 patient orders complied with the safety monitoring by having all 4 clinical tests performed at the appropriate time points. After guideline implementation, 88 (60%) of 147 patient orders were compliant and had all 4 clinical tests conducted, which represents a statistically significant improvement in the rate of compliance (Pearson chi square = 26.43, degrees of freedom (df) = 1, P less than 0.0001). This significant improvement in compliance rates after guideline implementation was observed in both the new patient group and the patients with continuing prescription orders/treatment changes. There was also an improvement in patients whose prescriptions were dispensed by UI Health and to a lesser degree those whose prescriptions were dispensed by an outside pharmacy. When the new patient group was analyzed separately (n = 92), 50 patients were treated before the guidelines were implemented, and 42 patients were treated after the guidelines were implemented. Compliance rates with safety monitoring in these 2 groups were 52% pre-implementation and 83% post-implementation, which represented a statistically significant improvement in compliance (Pearson chi square = 10.03, df=1, P = 0.0015). Similar results were observed in the second patient subgroup with continuing prescription orders/treatment change (n = 228). A total of 123 patients were treated before the guidelines were implemented, and 105 were treated after the guidelines were implemented. Compliance rates were 23% pre-implementation compared with 50% post-implementation, which represented a statistically significant improvement in compliance (Pearson chi square = 18.99, df = 1, P less than 0.0001). CONCLUSION: Given the widespread and long-term use of BRMs, safety monitoring and management should be an important part of a comprehensive medication management program for their use. A coordinated effort may have a significant impact on compliance with safety monitoring guidelines.

Toward a wiki guide for obstetrics and gynecology trainees in Ireland.

BACKGROUND: The present paper describes the implementation of a novel, web-based, comprehensive national information hub for trainees in obstetrics and gynecology in Ireland. This was a unique development in the context of an entire medical specialty and was aligned with the communication strategy of the governing professional body. To date, trainee doctors working in Ireland undergo an incoherent and inconsistent new-staff induction and handover. In the healthcare setting, staff integration can have a major impact on the quality of patient care. METHODS: A free wiki software platform (PBworks) was used for the website, and freely available software (Google Analytics) was used to determine user interaction and level of engagement. RESULTS: In the first year, 442 user visits were recorded. The average duration of site visits was 4 minutes 39 seconds, which compared favorably with the 4-minute duration for visits to Wikipedia. CONCLUSION: The project was successful as a proof concept and in practice. Other medical faculties have expressed an interest in adopting the concept and developing it for their trainees. The concept is widely applicable to other countries, with the negligible cost relevant to resource-poor areas.

Psychiatric morbidity following endometrial ablation and its association with genuine menorrhagia.

OBJECTIVE: To explore the relation between pre-operative psychiatric morbidity, menstrual blood loss and psychiatric outcome in women receiving endometrial ablation for heavy periods. DESIGN: A prospective cohort study. SETTING: The menorrhagia clinic at Leeds General Infirmary. POPULATION: One hundred and twenty consecutive women referred to the Clinic for endometrial ablation. METHODS: Psychiatric interview and actual menstrual blood loss measurements at presentation pre-operatively and one year post endometrial ablation. MAIN OUTCOME MEASURE: Psychiatric status using the semi-structured interview, Present State Examination, with measurement of menstrual blood loss. RESULTS: Endometrial ablation was performed on 92 women. Of the 87 women evaluated 51 (59%) had clinically significant psychiatric symptoms, mainly depression and anxiety. Psychiatric morbidity fell to 21.8% at one year after endometrial ablation. Women with the best psychiatric outcome (6% post-operative psychiatric morbidity) were those with genuine menorrhagia (> or =80 mL) and low psychiatric morbidity pre-operatively. Those who fared worst (39% post-operative psychiatric morbidity) were women with high pre-operative psychiatric morbidity and low menstrual blood loss. Of seven women with very low losses [mean 19 mL (SD 17)] who did not proceed to surgery after counselling, six (86%) had significant psychiatric morbidity. CONCLUSIONS: Pre-operative psychiatric status and menstrual blood loss are predictors of outcome of surgery for women with reported heavy periods.