Variable Patterns of Continuous Morphine Infusions at End of Life.

BACKGROUND: Continuous morphine infusions (CMIs) treat pain and dyspnea at the end of life (EOL). CMIs may be initiated at an empiric rate and/or are rapidly escalated without proper titration. OBJECTIVE: The study objective was to evaluate CMI patterns at the EOL. METHODS: This single-center, retrospective chart review evaluated adult patients who died while receiving CMI at EOL. Patient demographics and opioid dosing information were extracted from an electronic medical record. Twenty-four hour IV morphine equivalent was calculated prior to CMI initiation and at the time of death. RESULTS: Of the 190 patient charts, 63.2% (n=120) received no bolus doses prior to CMI initiation. Mean 24-hour IV morphine equivalent prior to CMI initiation was 49.3 mg (range: 0-1200 mg, SD 384.9) and at time of death was 267.1 mg (12.0-5193.2 mg, SD 442.2), representing an increase of +442%. Mean CMI starting rate was 3.3 mg/hour (0.4-30.0 mg/hour, SD 3.6) with titration at time of death to a mean of 7.7 mg/hour (0.4-70.0 mg/hour, SD 9.4), representing an increase of +130%. Mean number of CMI rate adjustments was 2.5 (0-5, SD 3.3); and number of bolus doses administered between titrations was 4.2 (0-27, SD 4.8). Mean time from CMI initiation to death was 15.5 hours (0.05-126.9 hours, SD 21.7). There was a negative association between rate of infusion increase per hour and total number of hours on CMI (r=-0.2, p=0.0062). CONCLUSIONS: Hospitalized patients at EOL had a much higher 24-hour IV morphine equivalents and CMI rates at time of death compared to CMI initiation. Variability was observed in the number of CMI rate adjustments and the number of bolus doses administered.

Nucleoside analog studies indicate mechanistic differences between RNA-editing adenosine deaminases.

Adenosine deaminases acting on RNA (ADAR1 and ADAR2) are human RNA-editing adenosine deaminases responsible for the conversion of adenosine to inosine at specific locations in cellular RNAs. Since inosine is recognized during translation as guanosine, this often results in the expression of protein sequences different from those encoded in the genome. While our knowledge of the ADAR2 structure and catalytic mechanism has grown over the years, our knowledge of ADAR1 has lagged. This is due, at least in part, to the lack of well defined, small RNA substrates useful for mechanistic studies of ADAR1. Here, we describe an ADAR1 substrate RNA that can be prepared by a combination of chemical synthesis and enzymatic ligation. Incorporation of adenosine analogs into this RNA and analysis of the rate of ADAR1 catalyzed deamination revealed similarities and differences in the way the ADARs recognize the edited nucleotide. Importantly, ADAR1 is more dependent than ADAR2 on the presence of N7 in the edited base. This difference between ADAR1 and ADAR2 appears to be dependent on the identity of a single amino acid residue near the active site. Thus, this work provides an important starting point in defining mechanistic differences between two functionally distinct human RNA editing ADARs.

Small-incision manual extracapsular cataract surgery in Ghana, West Africa.

PURPOSE: To evaluate the results of small-incision manual extracapsular cataract extraction surgery (ECCE) in a district hospital in West Africa. SETTING: Margret Marquart Catholic Hospital, Ghana, West Africa. METHODS: This prospective study consisted of 200 eyes of 193 patients who had small-incision manual ECCE between January 1999 and May 2000. For comparison, the charts of 32 patients (32 eyes) operated on between July and December 1998 using a limbal incision (control group) were retrospectively analyzed. Outcome measures included intraoperative and postoperative complications, postoperative visual acuity, and refractive astigmatism. RESULTS: In the small-incision ECCE group, self-sealing wounds were achieved in 129 eyes (64.5%). Vitreous loss occurred in approximately 3% of eyes in both the small-incision and control groups. The final visual acuities were similar between the 2 groups, with more than 90% of eyes in both groups achieving a final best corrected visual acuity of at least 20/60. Eyes in the small-incision group had faster visual recovery (P <.001), a lower incidence of fibrinous iritis (P =.02), and were more likely to have round pupils (P <.001) than eyes in the control group. The main complication of small-incision surgery was moderate corneal edema, which persisted until at least the 1-week visit in 14 eyes (7%). At the most recent visit, 1 eye in the small-incision group (0.5%) had bullous keratopathy. CONCLUSION: In a district hospital in West Africa, small-incision manual ECCE surgery yielded faster visual rehabilitation and had a lower incidence of fibrinous iritis than standard ECCE surgery.