Physical interventions and injection techniques for reducing injection pain during routine childhood immunizations: systematic review of randomized controlled trials and quasi-randomized controlled trials.

BACKGROUND: Vaccine injections are the most common reason for iatrogenic pain in childhood. With the steadily increasing number of recommended vaccinations, there has been a concomitant increase in concern regarding the adequacy of pain management. Physical interventions and injection techniques that minimize pain during vaccine injection offer an advantage over other techniques because they can be easily incorporated into clinical practice without added cost or time. Their effectiveness, however, has not previously been studied using a systematic approach. OBJECTIVE: The purpose of this review was to determine the effectiveness of physical interventions and injection techniques for reducing pain during vaccine injection in children. METHODS: MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials databases were searched to identify randomized controlled trials (RCTs) and quasi-RCTs that determined the effect of physical interventions and injection techniques on pain during injection of vaccines in children 0 to 18 years of age, using validated child self-reported pain or assessments of child distress or pain made by others (parent, nurse, physician, observer). We sought to determine the effects of: (1) different formulations of the same vaccine; (2) position of the child during injection; (3) intramuscular versus subcutaneous injection; (4) cooling of the skin at the injection site with ice before injection; (5) stroking the skin or applying pressure close to the injection site before and during injection; (6) order of vaccine injection when 2 vaccines were administered sequentially; (7) simultaneous versus sequential injection of 2 vaccines; (8) vaccine temperature; (9) aspiration before injection; (10) anatomic location of injection; (11) aspects of the needle (gauge, length, angle of insertion, speed of injection); and (12) combinations of these interventions. All meta-analyses were performed using a fixed-effects model. RESULTS: Nineteen RCTs involving 2814 infants and children (0-18 years of age) were included in the systematic review. One study included children >or=16 years and adults (n = 150). Interventions with positive findings are summarized here. In 2 trials that used child self-reports of pain during administration of measles-mumps-rubella vaccine (total, 680 children with complete data), the Priorix vaccine caused less pain than the M-M-R(II) vaccine (standardized mean difference [SMD], -0.66; 95% CI, -0.81 to -0.50; P < 0.001). In 3 trials (404 children), the number needed to treat (NNT) with Priorix to prevent 1 child from crying was 3.2 (95% CI, 2.6-4.2). In 4 trials (281 infants and children), sitting children up or having parents hold infants appeared to cause less pain than the supine position, but the difference was not statistically significant; however, significant heterogeneity was found among the studies, and a qualitative approach was used for data analysis. A benefit was observed for 3 of the 4 studies; the SMD ranged from -0.4 to -0.8 (P < 0.05 for all analyses). The negative findings observed for the remaining study may have been the result of methodologic heterogeneity. Stroking the skin close to the injection site before and during injection reduced pain in 1 trial (66 children; SMD, -0.53; P = 0.03). One study (120 children) found that when diphtheria-polio-tetanus-acellular pertussis-Haemophilus influenzae type b (DPTaP-Hib; Pentacel) and pneumococcus (Prevnar) were injected sequentially during the same office visit, observer- and parent-reported pain scores were lower when DPTaP-Hib was injected first (SMD, -0.40 and -0.57, respectively; P

Population-based pharmacoeconomic model for adopting capecitabine/docetaxel combination treatment for anthracycline-pretreated metastatic breast cancer.

PURPOSE: To model the cost-effectiveness of adopting capecitabine/docetaxel combination therapy in place of single-agent taxane therapy for women in the province of Ontario, Canada, receiving treatment for anthracycline-pretreated metastatic breast cancer. METHODS: Clinical effectiveness and economic data were combined in a population model, from the perspective of a universal health care system. Estimates of clinical effectiveness and medical resource utilization were derived prospectively during a phase III randomized controlled trial comparing single-agent docetaxel with capecitabine/docetaxel combination therapy. Population data were obtained from the Cancer Care Ontario Registry and provincial prescription claims data. RESULTS: During 1999-2000, 542 patients were eligible for taxane monotherapy. As capecitabine/docetaxel treatment confers a median 3-month survival benefit compared with docetaxel monotherapy, the projected survival gain in these patients was 136 life-years. The results of the cost-effectiveness analysis demonstrate that the survival benefit provided by the addition of capecitabine to single-agent docetaxel is afforded at a small incremental cost of Canadian $3,691 per life-year gained. Hospitalization costs for treatment of adverse events were less for patients receiving capecitabine/docetaxel combination therapy than for those receiving docetaxel monotherapy. The results were robust for adjustments in treatment costs and adverse effects costs. CONCLUSION: Due to its 3-month survival gain and small incremental treatment cost, capecitabine/docetaxel is judged to be a highly cost-effective treatment in anthracycline-pretreated advanced breast cancer. From the perspective of the Ontario health care system, the addition of capecitabine to docetaxel in this patient population is a clinically appropriate and economically acceptable treatment strategy.

Relationship between daily dose frequency and adherence to antihypertensive pharmacotherapy: evidence from a meta-analysis.

BACKGROUND: Rates of patient adherence (compliance) to pharmacotherapy range from <5% to >90%. Negative determinants include multiple daily dosing (MDD), chronic duration, and asymptomatic disease. Reports suggest that once-daily (QD) dosing may improve adherence, but their findings are inconclusive. OBJECTIVE: The purpose of this study was to compare the rates of adherence with QD, twice-daily (BID), and MDD antihypertensive drug regimens. METHODS: MEDLINE, Embase, and International Pharmaceutical Abstracts databases were searched to identify comparative trials of patient adherence to antihypertensive medication in solid, oral formulations. Data were combined using a random-effects meta-analytic model. RESULTS: Eight studies involving a total of 11,485 observations were included (1,830 for QD dosing, 4405 for BID dosing, 4147 for dosing >2 times daily [>BID], and 9655 for MDD), in which the primary objective was to assess adherence. The average adherence rate for QD dosing (91.4%, SD = 2.2%) was significantly higher (Z = 4.46, P < 0.001) than for MDD (83.2%, SD = 3.5%). This rate was also significantly higher (Z = 2.22, P = 0.026) than for BID dosing (92.7% [SD = 2.3%] vs 87.1% [SD = 2.9%]). The difference in adherence rates between BID dosing (90.8%, SD = 4.7%) and >BID dosing (86.3%, SD = 6.7%) was not significant (Z = 1.82, P = 0.069). CONCLUSIONS: The results of this meta-analysis demonstrate that with antihypertensive medications, QD dosing regimens are associated with higher rates of adherence than either BID or MDD regimens.