Prioritising drugs for single patient (n-of-1) trials in palliative care.

Many of the drugs prescribed commonly to palliative care patients have potentially significant side-effects and are of unproven benefit. The acquisition of evidence to support the prescribing of these drugs has been very slow. Single patient trials (SPTs) (also known as n-of-1 trials) offer a potential means of obtaining the evidence necessary to support or refute the use of several of the drugs and interventions whose use is currently based on physician experience or anecdote alone. A list of SPTs considered "most urgent", for commonly employed treatments and for the most common and most troublesome symptoms in palliative care is presented. These are drugs for which the gap between evidence and practice is greatest, where the evidence of efficacy is most lacking, where significant side effects potentially lead to the greatest morbidity, or where cost is a major patient burden. Although not all the drugs used in palliative care are suitable, SPTs provide a potential alternative method of gathering evidence in palliative care.

Preference for place of care and place of death in palliative care: are these different questions?

Place of death is at times suggested as an outcome for palliative care services. This study aimed to describe longitudinal preferences for place of care and place of death over time for patients and their caregivers. Longitudinal paired data of patient/caregiver dyads from a prospective unblinded cluster randomised control trial were used. Patients and caregivers were separately asked by the palliative care nurse their preference at that time for place of care and place of death. Longitudinal changes over time for both questions were mapped; patterns of agreement (patient and caregiver; and preference for place of death when last asked and actual placed of death) were analysed with kappa statistics. Seventy-one patient/caregiver dyads were analysed. In longitudinal preferences, preferences for both the place of care (asked a mean of >6 times) and place of death (asked a mean of >4 times) changed for patients (28% and 30% respectively) and caregivers (31% and 30%, respectively). In agreement between patients and caregivers, agreement between preference of place of care and preferred place of death when asked contemporaneously for patients and caregivers was low [56% (kappa 0.33) and 36% (kappa 0.35) respectively]. In preference versus actual place of death, preferences were met for 37.5% of participants for home death; 62.5% for hospital; 76.9% for hospice and 63.6% for aged care facility. This study suggests that there are two conversations: preference for current place of care and preference for care at the time of death. Place of care is not a euphemism for place of death; and further research is needed to delineate these. Patient and caregiver preferences may not change simultaneously. Implications of any mismatch between actual events and preferences need to be explored.

The effectiveness of local adaptation of nationally produced clinical practice guidelines.

BACKGROUND: Local adaptation is often reported in the literature to be an important strategy in achieving local ownership and relevance of guidelines in order to increase the likelihood of their uptake and implementation. However, the process is also potentially time-consuming and costly. OBJECTIVE: The aim of this study was to determine the impact of local adaptation of nationally produced clinical practice guidelines (CPGs) on the knowledge, attitude and reported practices of GPs. METHODS: Two Divisions of General Practice in Adelaide, Australia were selected and randomized to adapt a nationally produced CPG (on Stroke Prevention) by the National Health and Medical Research Council or use the original version. The order of the interventions was reversed for a second guideline (on management of Lower Urinary Tract Symptoms in Men). An identical multifaceted dissemination strategy was adopted for both sets of guidelines in the two divisions. Prior to the intervention, a random sample of 200 GPs from each Division was sent a postal survey about their knowledge, attitudes and reported practices. This was repeated 3 months after the dissemination phase. RESULTS: Sixty-one per cent (243/400) of the GPs responded to the initial survey and, of these, 76% (184/243) responded to the follow-up survey. Overall, awareness of both sets of guidelines was significantly increased. For stroke, 38% of respondents across both Divisions reported that their practice had changed as a result of the guidelines. For management of lower urinary tract symptoms in men, the corresponding proportion was 52%. Agreement with specific recommendations from both guidelines was also increased following their dissemination. However, these changes were independent of whether or not the guidelines had been locally adapted. The local adaptation process involved no substantive change in content and was estimated to cost AUD$5600 (per Division) independent of the costs of the dissemination process. CONCLUSIONS: Whilst this study found significant changes in knowledge, attitude and reported practice as a result of disseminating guidelines, it did not find any additional effect from the local adaptation process itself. This suggests that the emphasis and investment in promoting guideline implementation should be placed on multifaceted dissemination strategies rather than local adaptation per se.

Streptococcus pneumoniae antibiotic resistance in Northern Territory children in day care.

BACKGROUND: There is evidence that the rapid rise in Streptococcus pneumoniae (SP) antimicrobial resistance seen in other countries may have commenced in Australia. Streptococcus pneumoniae carriage and resistance levels are described for urban Northern Territory children in day care. METHODS: A prospective cohort study was conducted of 250 children in nine Darwin day care centres between 24 March and 15 September 1997. Each fortnight nasopharyngeal swabs were collected from children, and parents were interviewed about medications administered. RESULTS: Streptococcus pneumoniae was detected in 52% (1028/1974) of all nasopharyngeal swabs. Streptococcus pneumoniae was isolated from 92% (231/250) of children at some time. Penicillin resistance was found in 30% (312/1028) of isolates using a screening test. Of these, 256 (82%) had resistance confirmed by E-test. Two hundred and one (20% of all isolates) had intermediate penicillin resistance and 55 (5% of all isolates) had high level resistance. Ceftriaxone resistance was found in 19% of children's first isolates. Resistance to other antibiotics was also common: co-trimoxazole 45%, erythromycin 17%, tetracycline 17% and chloramphenicol 13%. A total of 17% (172/1028) of the isolates were multiresistant. The average fortnightly proportion of children given antibiotics was 16% (405/2476). CONCLUSION: Levels of intermediate and high level penicillin resistance in this day care population are consistent with previous data from the Northern Territory, and considerably higher than the rest of Australia. The national trend of increasing pencillin resistance is likely to continue.

A prospective study of the impact of community-based azithromycin treatment of trachoma on carriage and resistance of Streptococcus pneumoniae.

In February 1995, single-dose azithromycin was given to children with trachoma and their household contacts who were children. For children with trachoma, rates of carriage of pneumococci immediately before treatment with azithromycin and 2-3 weeks, 2 months, and 6 months after treatment were 68% (54 of 79), 29% (11 of 38), 78% (29 of 37), and 87% (34 of 39), respectively. The proportion of carriage-positive children with azithromycin-resistant Streptococcus pneumoniae strains was 1 of 54 (1.9%) before treatment and then 6 of 11 (54.5%), 10 of 29 (34.5%), and 2 of 34 (5.9%) at follow-up visits. The profile of pneumococcal serotypes changed after azithromycin treatment. Azithromycin-resistant strains (serotypes 10F, 23A, and 45) were isolated from 1 (1.3%) of 79 pretreatment swab specimens, from 16 (21.3%) of 75 swab specimens collected up to 2 months after treatment, and from 2 (6%) of 32 obtained 6 months after treatment. Mathematical modeling showed a more rapid appearance of azithromycin-resistant pneumococcal strains in previously colonized children than in previously noncolonized children. Thus, it appears that the selective effect of azithromycin allowed the growth and transmission of preexisting azithromycin-resistant strains. More research is needed to clarify the clinical relevance and implications of azithromycin use.

Carriage of multiple ribotypes of non-encapsulated Haemophilus influenzae in aboriginal infants with otitis media.

Ribotyping with the restriction enzyme XbaI was used to study the dynamics of Carriage of non-encapsulated Haemophilus influenzae (NCHi) in Aboriginal infants at risk of otitis media. Carriage rates of NCHi in the infants in the community were very high; the median age for detection was 50 days and colonization was virtually 100% by 120 days of age and persisted at a high level throughout the first year of life [1]. Eighteen different ribotypes of NCHi were identified from 34 positive swabs taken from 3 infants over a period of 9 months. The same ribotypes were recovered for up to 3 months from consecutive swabs of individual infants, and 12 of 27 swabs (44.4%) yielded two ribotypes from four colonies typed. Statistical analysis suggested that most swabs would have been positive for two ribotypes if enough colonies had been typed although the second most frequent ribotype was detected on average in only 13% of strains. Early colonization and carriage of multiple ribotypes of NCHi may help to explain the chronicity of carriage and thus the persistence of otitis media in Aboriginal infants.

Increasing severity of invasive group A streptococcal disease in Australia: clinical and molecular epidemiological features and identification of a new virulent M-nontypeable clone.

We conducted a 12-year review of all cases of group A streptococcal (GAS) bacteremia that were seen at Royal Children's Hospital in Melbourne, Australia, from 1982 through 1993. Forty-two cases were identified. There was a trend towards increased incidence of infections, as well as a clear increase in their severity, during the study period; more previously healthy children were affected during the last 6 years of the study (80% of cases) than during the first 6 years (47% of cases), and more complications occurred during the latter period than during the former (40% vs. 20%, respectively, with an 88% complication rate over the last 12 months). Seventy-four GAS isolates (41 invasive, 23 noninvasive, and 10 indeterminate) were analyzed. An M type 1 clone that was positive for the pyrogenic exotoxin A gene (speA) and that has been found to cause invasive disease in the Northern Hemisphere was most frequent among invasive isolates. Molecular typing also identified a genetically distinct strain that was virulent, mucoid, and M nontypable. Invasive GAS disease in Melbourne has become increasingly aggressive. Newer typing methods should be used in conjunction with traditional serotyping in order to maintain epidemiological surveillance of virulent strains.