Determining the frequency of prescription errors in an Irish hospital.

BACKGROUND: Faults in writing prescriptions are a common source of medical error. Iatrogenic injury due to medication error increases patient morbidity and hospital stay, thereby encouraging litigation. AIM: To assess the accuracy and legibility of the prescriptions in patients' medication charts. METHODS: A cross-sectional observational study examined prescribing records of inpatients randomly selected in two surgical wards. Medication charts were assessed by a committee consisting of a nurse, a pharmacist and a doctor for omission and legibility of prescribing information. RESULTS: Important patient information and medication administration details were frequently omitted from charts. Overall, 27% of individual prescriptions had potential to cause prescription error because of illegibility or omission of medication administration details. CONCLUSIONS: The results of this study demonstrate that prescription error frequently occurs in the clinical workplace and may contribute to medical error. Improving legibility of handwriting and use of novel prescribing devices may reduce prescription error.

Randomized controlled trial of oral vs intravenous therapy for the clinically diagnosed acute uncomplicated diverticulitis.

OBJECTIVE: Despite the high prevalence of hospitalization for left iliac fossa tenderness, there is a striking lack of randomized data available to guide therapy. The authors hypothesize that an oral antibiotic and fluids are not inferior to intravenous (IV) antibiotics and 'bowel rest' in clinically diagnosed acute uncomplicated diverticulitis. METHOD: A randomized controlled trial was constructed in two District General Hospitals. All clinically diagnosed patients presenting with acute uncomplicated diverticulitis were eligible for the study. Oral and IV regimens utilizing ciprofloxacin and metronidazole were compared. The primary outcomes studied were surrogates for resolution of symptoms (including tenderness on day 3 and length of stay) and failure of oral therapy. Secondary endpoints studied were serial constitutional and biomarker trends. RESULTS: There were 41 patients in the oral arm and 38 in the IV arm (n = 79). No patient had to be converted to IV antibiotics from the oral group. There was a complete resolution of symptoms in both groups. Tenderness was equivalent in both groups on day 3. Among secondary endpoints, a serial decrease in C reactive protein was the best serological predictor of resolution for both groups. CONCLUSION: Oral antibiotics are not inferior to intravenous antibiotics in achieving resolution of clinically diagnosed diverticulitis.

Legibility of doctor's signatures: novel approaches to improving an age-old problem.

UNLABELLED: In today's medico-legal environment, the importance of identification of the authors of notes in patient medical charts cannot be overemphasized. We evaluated three different techniques of signing patient notes, over a one month period, in order to determine which technique was the most effective in identifying the author of the note. Surgical NCHDs in our hospital were divided into three groups. Group 1 was asked to sign the notes as they normally would. Group 2 was asked to print their name in block capitals after their signature and Group 3 was given pens with a personal self inking stamp to be used in addition to signing the notes. The number of signatures in all the charts, compliance with the assigned technique and the legibility of signatures were calculated. RESULTS: in Group 1, all NCHDs signed their name when writing notes (100% compliance), however the NCHD's signature was identified only 37% of the time. In Groups 2 (who signed in block capitals) and Group 3 (who used the pen with personalised stamp) the author was identifiable 100% of the time when the respective signing method was used. Using the pen with personalised self inking stamp was significantly more popular (77% compliance) compared to signing in block capitals (46% compliance). In conclusion the pen, with personalised self inking stamp, provides a fast and effective means to clarify signatures of NCHD's documentation, which is not only important in a day to day patient management, but is essential from a medico-legal stand point.

Low molecular weight heparin prophylaxis in day case surgery.

BACKGROUND: The role of Low molecular weight heparins (LMWH) in day case/short-stay surgery is unknown. AIM: To characterise the current national use of LMWH prophylaxis in specific day and short stay surgeries. METHODS: A standardised anonymous postal questionnaire was sent to all consultant general surgeons in Ireland. The operations selected were herniorraphy, anorectal, varicose vein and laparoscopic cholecystectomy. RESULTS: Questionnaires were sent to 82 surgeons in 2003. There was a response rate of 68.3% (56). Fifty-four per cent of respondents said there was a protocol in place for administration of LMWH in day case surgery. Of these 41% were not confident that their protocols were being adhered. Fifty-nine per cent of all respondents said they stratified patients according to individual risk. Thirteen per cent reported occurrence of VTE post day case surgery CONCLUSION: This study demonstrates a heterogeneous pattern of administration of LMWH. In the absence of published validated protocols, the authors suggest a consensus day case protocol.

Immature T lymphocytes after injury characterized by morphology and phenotypic markers.

Changes in the peripheral blood mononuclear cell (PBMC) population in patients following both thermal and nonthermal injury were defined by both morphological characteristics and surface phenotype with the monoclonal antibodies T6, OKT9, OKT10, and OKIa1, using a fluorescence activated flow cytometer with gating to separate small cells of the lymphocyte series from larger forms. Lymphocytes with surface antigens that bind T6, OKT9, and OKT10 are rarely found in the peripheral blood of adult patients, except in those with malignancies of the lymphoid system. In both burn and trauma patients the percentage of lymphocytes in the PBMC population after Ficoll-Hypaque separation was significantly reduced as compared with normal controls due to increases in the number of granulocytes, large granular lymphocytes (LGL), and monocytes, often present in immature forms. T6 cells were found in significantly greater numbers in both burn and nonthermal injury patients than in a control group using both small and wide gate settings on the fluorescence-activated flow cytometer. Significant increases in the number of T9+ cells also were observed in both groups for a prolonged period following injury. Significantly increased numbers of the T10+ and Ia1+ cells were detected in burn patients. The response to injury, therefore, involves the appearance in the peripheral blood of immature cells that may express T6, T9, T10, and Ia1 surface antigens. These cells may be present in quantities otherwise seen only in malignant disease.

Mechanisms of immunosuppression associated with severe nonthermal traumatic injuries in man: production of interleukin 1 and 2.

Depression of cell-mediated immunity in patients following severe traumatic injury has been well documented in vitro and in vivo. However, the exact mechanism of this defect is still controversial. In this study, we have investigated the ability of injured patients' peripheral blood mononuclear cells (PBMC) to produce two important immunoregulatory molecules, interleukin 1 (IL 1) and interleukin 2 (IL 2). Eighteen traumatic injury patients were studied during the course of their hospital stay and their results compared with a group of 18 normal age- and sex-matched controls. The results showed the following. (1) Production of IL 2 by normal PBMC in response to optimal doses of mitogen may vary with sex as well as age. (2) Adherent mononuclear cells from trauma patients produced at least as much IL 1 as normals. (3) IL 2 production, however, was markedly suppressed (normals, 1.6 +/- 0.2 U; traumatic injury, 0.6 +/- 0.1 U; P = 0.001) and persisted for as long as 50 days postinjury. OKT4+ cells were not significantly decreased at any time, nor were OKT8+ suppressor/cytotoxic cells increased at any time. Decreased IL 2 production in patients treated with steroids or those who were septic was not different from that in those patients who were not treated with steroids or were not septic. These results suggest that the cause of the defect in IL 2 production in traumatic injury patients is not related to a lack of the IL 1 signal, producer T cells, or Ia+ monocytes or to increased suppressor T cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Suppression of natural killer-cell function in humans following thermal and traumatic injury.

Depressed cell-mediated and humoral immune functions have been reported to occur following severe thermal and traumatic injury. In this study we have questioned whether another immune function, natural killing (NK), is also disturbed in these injured patients. Twenty-two thermally injured patients with burns ranging from 5 to 75% of the total body surface area and 15 traumatically injured patients with injury severity scores ranging from 9 to 56 were followed postinjury and compared to 29 age-matched controls. NK activity was measured as the percentage cytotoxicity in chromium-51 release assays with K562 target cells. The more severely burned patients had significantly depressed NK activity for the 40-day period following injury that remained reduced for the duration of the study. Patients with lesser burns had reduced NK-cell function for the initial 10-day period postburn that returned slowly to the normal range. Traumatically injured patients had depressed NK-cell function during the 3- to 6-day period postinjury. The percentage of cells bearing phenotypic markers for the groups in which NK cells are found was either normal or elevated in these patients. A correlation was found between NK activity and interleukin 2 generation by mononuclear cells from these patients. In order to investigate the mechanism of NK suppression in these patients, NK-cell function was studied following the infusion of cortisol, epinephrine, and glucagon into volunteer subjects in amounts known to reproduce serum levels seen following injury of moderate severity. NK-cell function was reduced an average of 66% following infusion, suggesting that the inhibition of NK-cell function seen in patients may be mediated by the stress response to injury.

Abnormalities of antibody production after thermal injury. An association with reduced interleukin 2 production.

Antibody (Ab) production was studied in 25 burned patients who were immunized with 0.5 mg of tetanus toxoid adsorbed. Anti-tetanus toxoid (TT) Ab was measured by hemagglutination, radial immunodiffusion, and an enzyme-linked immunosorbent assay, and the results for the patients were compared with those for five similarly immunized healthy controls. As measured by hemagglutination, 12 (63%) of 19 patients had lower Ab responses than all five controls (P less than .05 by chi 2), and the median Ab response during the period of maximum response was significantly less than that in controls (8 vs 15.5 log2 maximum dilution; P = .014). After the initial response, serum Ab levels were not maintained in patients, in contrast to controls. This pattern was demonstrated by all three assays; enzyme-linked immunosorbent assay demonstrated that IgG anti-TT Ab was the major class of Ab produced. In nine patients interleukin 2 production by T lymphocytes was measured simultaneously; it was significantly depressed throughout the study except during the period from 36 to 45 days. The Ab response was also impaired in this patient group. Since maintained antibody production in response to TT is known to be T-cell dependent, these results suggest that inadequate interleukin 2 production leading to reduced T-cell help may be responsible for the lack of a persistent Ab response in these burned patients.

Changes in T lymphocyte subsets following injury. Assessment by flow cytometry and relationship to sepsis.

The increased susceptibility of severely injured patients to infection and death from sepsis has been attributed to abnormalities in cell-mediated immunity. The authors therefore assessed the relative number of peripheral blood T helper cells and T suppressor/cytotoxic cells and total T lymphocytes identified by the monoclonal antibodies (McA) OKT4, OKT8, and OKT3, respectively, in 25 patients with burns from 5 to 85% total body surface area (TBSA) (mean: 40%) and 21 patients with nonthermal injuries (mean Injury Severity Score (ISS): 21.4). Patients were compared to 21 healthy controls. Cells reacting with the McA were detected by flow cytometry, which enabled the examination of a population of cells the size of T lymphocytes, excluding larger contaminating cells that might bind the McA. Patients with burns of 30% TBSA or greater had a significant reduction (p less than or equal to 0.05) in OKT3+ cells up to 50 days post-burn. Both septic and nonseptic burn patients had reduced numbers of OKT3+ cells, as did patients after nonthermal injury, suggesting that this reduction was due to the injury itself. Patients with smaller burns (less than 30% TBSA) as a group did not have reduced OKT4+ cells, whereas those with larger burns showed significant reductions in OKT4+ cells (P less than or equal to 0.05) at 0 to 5, 6 to 10, 11 to 20, 21 to 30, and 41 to 50 days post-burn. Seven burn patients who became septic 10 days post-burn or later had significantly lower OKT4+ cells within 10 days of injury (mean: 33.75% +/- 7.4 SEM) than 10 patients who remained free of sepsis (mean: 42.2% +/- 5.4, p = 0.004). Patients with uncomplicated nonthermal injuries failed to show any significant reduction in OKT4+ cells. Following thermal injury, a reduction in OKT8+ cells was observed up to 10 days in patients with burns less than 30% TBSA, and up to 20 days in patients with larger burns. In both groups, at no time were increased OKT8+ cells found to correlate with clinical events. In patients with nonthermal injury, OKT8+ cells generally remained near the normal range.

Depression of cellular immunity after multiple trauma in the absence of sepsis.

We have previously reported that severe burn injury was regularly accompanied by impaired lymphocyte responses to T cell mitogens, circulating suppressor lymphocytes, and serum factors suppressive of lymphocyte activation. However, in burned patients it was difficult to determine whether these manifestations of suppressed immunity were predictive of, or the result of, sepsis which was ubiquitous in this population. In an attempt to clarify this issue, we have studied 31 patients with multiple trauma (without burns) mean age, 31 years; average injury severity score, 22; range, 9-56; in whom sepsis was less common. Patients were tested for lymphocyte response to the T cell mitogens PHA and Con A, the percentage of circulating putative suppressor (OKT8) and helper (OKT4) T cells using monoclonal antibodies, circulating suppressor cell activity as revealed by functional assays, and serum suppression of lymphocyte activation. Patients were compared with ten normal volunteers (mean age, 32) studied simultaneously. Significant suppression (greater than 50% compared with controls) in lymphocyte responses to mitogens 1 to 5 days after injury was seen in 12 patients, was accompanied by a shift in the ratio of helper (OKT4) to suppressor (OKT8) T cells (patients, 0.96:1; normals, 1.82:1; p less than 0.01), and was followed by the appearance of significant (greater than 50%) serum suppressive activity in six of the 12 patients. Circulating suppressor cell activity as revealed by functional assays was also seen early after injury in three of 12 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Inadequate interleukin 2 production. A fundamental immunological deficiency in patients with major burns.

We studied the production of the two major mediators of cellular immune responses, Interleukin 1 (IL-1) and Interleukin 2 (IL-2), by the peripheral blood mononuclear cells of 23 burn patients (16 men, seven women, mean age 48.9 years) compared with 23 matched controls (16 men, seven women, mean age 46.7 years). Serial measurements were made of IL-1 production by adherent mononuclear cells after stimulation with lipopolysaccharide and of IL-2 production by lymphocytes after stimulation with phytohemagglutinin (PHA). Eighty determinations of IL-2 production by lymphocytes from 12 patients with greater than 30% body surface area burn revealed a mean IL-2 production of 0.71 u as compared with a mean of 1.23 u for patients with less than 30% burns (p = 0.04). Patients with greater than 30% body surface area burns had significantly reduced IL-2 production (p less than or equal to 0.05) until 60 days after injury, whereas those with smaller burns had reduced IL-2 production only at 20-29 and 30-39 days postburn. Nine burn patients with systemic sepsis showed significantly lower IL-2 production (p = 0.03) at 10-29 days postburn than nonseptic patients, and significantly less IL-2 production during septic episodes. Eight patients with greater than 50% suppression of lymphocyte response to PHA produced less IL-2 (0.4 u) than patients with less than 50% suppression, (1.07 u, p = 0.004). IL-1 production was significantly elevated as compared with controls (4.45 u vs. 3.6 u, p = 0.05) early after injury, but was subsequently within the normal range regardless of burn size. The percentage of circulating helper T-lymphocytes, the principal source of IL-2, was also reduced, although this did not always correlate with IL-2 production, which remained depressed after recovery of the helper T-cell population. These results indicate that failure to produce IL-2, a powerful mediator of cellular immune responses, is an important mechanism underlying the defective cell mediated immunity seen in burn patients.

The effect of short term postoperative intravenous feeding upon cell-mediated immunity and serum suppressive activity in well nourished patients.

Thirty-four patients undergoing elective abdominal aortic aneurysmectomy were studied, and they were randomly allocated to a "fed group receiving amino acid dextrose solutions intravenously and fat emulsions or an "unfed" group receiving standard postoperative care. Cell-mediated immunity was measured by lymphocyte count, the in vitro response to the T-cell mitogen PHA and determination of T-cell subsets using monoclonal antibodies. Serum suppressive activity was measured by the ability of the sera of the patient to suppress the response of normal lymphocytes to PHA. Feeding was continued for three to five days postoperatively until satisfactory oral intake was achieved. There was no significant improvement in lymphocyte count or blastogenesis postoperatively in the "fed" group, and operation did not lead to any alteration in the ratio of T-cell subsets, although there was a fall in T-cell count (OKT3 positive cells). We conclude that short term parenteral nutrition in well nourished patients, postoperatively, does not abrogate the depression of cell-mediated immunity which occurs after extensive operative procedures.

Depressed immune response in burn patients: use of monoclonal antibodies and functional assays to define the role of suppressor cells.

Recent experimental evidence has suggested that circulating suppressor leukocytes play an important role in mediating the suppression of immunity seen in burn patients. In order to shed further light on the relationship between suppressor cells and depressed cellular immunity 22 patients were studied (mean age 37) who had suffered severe burns of greater than 30% body surface area. Simultaneous studies were performed on 14 control laboratory personnel (mean age 32). Monoclonal antibodies were used to identify T-lymphocyte subsets known to have suppressor/cytotoxic (OKT8) and helper/inducer (OKT4) function, respectively. In addition, serial measurements were made of the response of circulating lymphocytes to the T-cell mitogen phytohemagglutinin (PHA). An inversion of the normal ratio between suppressor/cytotoxic and helper/inducer subsets (normal 0.55:1, postburn 1.4:1; p less than 0.001) occurred soon after burn injury, reached a peak in five to seven days and then returned gradually to normal levels by 14 days. A diminished response of patients' lymphocytes to PHA (57 +/- 10% SD suppression as compared with normal controls at five to seven days) corresponded with high suppressor to helper cell ratios and returned to normal at the same time. Functional assays, which recognize only high levels of activity, demonstrated circulating suppressor cells in nine patients during this same period but became negative by 14 days. These early immunologic modulations were not predictive of morbidity or mortality. Later in the postburn course, systemic sepsis in eight patients was associated with a return of increased suppressor to helper cell ratios and decreased mitogen (PHA) responsiveness. At this time functional assays demonstrated circulating suppressor cells in six patients. Five of these six patients died of sepsis. It was concluded that severe burn injury regularly induces an early transient increase in circulating suppressor cells accompanied by a depression of lymphocyte activation. A later (greater than 14 days postburn) increase in suppressor cells to levels detectable by functional assays is closely correlated with mortality from sepsis.

Piribedil (ET 495) in the treatment of Parkinson's disease combined with amantadine or levodopa.

The further therapeutic benefit of piribedil when combined with amantadine or Levodopa was studied by a double-blind, cross-over trial in 15 patients with Parkinson's disease. A significant improvement at the 5 per cent level for akinesia, gait, speech disorder and facial expression occurred when piribedil was added to Levodopa; and a more highly significant improvement at the 1 per cent level for akinesia, facial expression and finger dexterity occurred with piribedil and amantadine. No significant improvement occurred for special timed tests. Improvement was associated with side effects in both groups of patients. Side effects occurred with both placebo and active piribedil. Only nausea during piribedil and Levodopa treatment reached statistical significance when compared with the placebo. Piribedil did not give rise to any haematological or biochemical complications. Our findings suggest that piribedil is of further therapeutic benefit when added to amantadine or Levodopa. It was suggested that the improvement which occurred together with amantadine could be due to the combined action of both drugs on dopamine receptors.