Assessing the potential of upper respiratory tract point-of-care testing: a systematic review of the prognostic significance of upper respiratory tract microbes.

OBJECTIVES: Microbial point-of-care testing (POCT) has potential to revolutionize clinical care. Understanding the prognostic value of microbes identified from the upper respiratory tract (a convenient sampling site) is a necessary first step to understand potential for upper respiratory tract POCTs in assisting antimicrobial treatment decisions for respiratory infections (RTIs). The aim was to investigate the relationship between upper respiratory tract microbial detection and disease prognosis, including effects of antimicrobial use. METHODS: Data sources were the MEDLINE and Embase databases. Study eligibility criteria consisted of quantitative studies reporting microbiological and prognostic data from patients of all age groups presenting with RTI. Patients presenting to healthcare or research settings with RTI participated. Interventions included upper respiratory tract swab. The methods used were systematic review and meta-analysis. RESULTS: Searches identified 5156 articles, of which 754 were duplicates and 4258 excluded on title or abstract. A total of 144 full texts were screened; 21 articles were retained. Studies reported data for 15 microbes and 26 prognostic measures (390 potential associations). One hundred and seven (27%) associations were investigated statistically, of which 38 (36%) were significant. Most studies reported only prognostic value of test positive results. Meta-analyses suggested hospitalization duration was longer for patients with respiratory syncytial virus than adenovirus and influenza, but significant heterogeneity was observed between studies. CONCLUSIONS: A quarter of potential prognostic associations have been investigated. Of these, a third were significant, suggesting considerable potential for POCT. Future research should investigate prognostic value of positive and negative tests, and interactions between test results, use of antimicrobials and microbial resistance.

Uva-ursi extract and ibuprofen as alternative treatments for uncomplicated urinary tract infection in women (ATAFUTI): a factorial randomized trial.

OBJECTIVES: The aim was to investigate if offering symptomatic therapy (Uva-ursi or ibuprofen) alongside a delayed prescription would relieve symptoms and reduce the consumption of antibiotics for adult women presenting with acute uncomplicated urinary tract infection (UTI). METHODS: A 2 × 2 factorial placebo controlled randomized trial in primary care. The participants were 382 women aged 18-70 years with symptoms of dysuria, urgency, or frequency of urination and suspected by a clinician to have a lower UTI. The interventions were Uva-ursi extract and/or ibuprofen advice. All women were provided with a delayed or 'back-up' prescription for antibiotics. Missing data were imputed using multiple imputation methods (ISRCTN registry: ISRCTN43397016). RESULTS: An ITT analysis of mean score for frequency symptoms assessed on Days 2-4 found no evidence of a difference between Uva-ursi vs. placebo -0.06 (95% CI -0.33 to 0.21; p 0.661), nor ibuprofen vs. no ibuprofen advice -0.01 (95% CI -0.27 to 0.26; p 0.951). There was no evidence of a reduction in antibiotic consumption with Uva-ursi (39.9% vs. placebo 47.4%; logistic regression odds ratio (OR) 0.59 (95% CI 0.22-1.58; p 0.293) but there was a significant reduction for ibuprofen advice (34.9% vs. no advice 51.0%; OR 0.27 (95% CI 0.10 to 0.72; p 0.009). There were no safety concerns and no episodes of upper tract infection were recorded. CONCLUSIONS: We found no evidence of an effect of either intervention on the severity of frequency symptoms. There is evidence that advice to take ibuprofen will reduce antibiotic consumption without increasing complications. For every seven women given this advice, one less will use antibiotics.

Paracetamol and ibuprofen for the treatment of fever in children: the PITCH randomised controlled trial.

OBJECTIVES: To establish the relative clinical effectiveness and cost-effectiveness of paracetamol plus ibuprofen compared with paracetamol and ibuprofen separately for time without fever, and the relief of fever-associated discomfort in young children who can be managed at home. DESIGN: The trial design was a single-centre (multisite), individually randomised, blinded, three-arm trial comparing paracetamol and ibuprofen together with paracetamol or ibuprofen separately. SETTING: There were three recruitment settings, as follows: 'local' where research nurses were recruited from NHS primary care sites; 'remote' where NHS sites notified the study of potentially eligible children; and 'community' where parents contacted the study in response to local media advertisements. PARTICIPANTS: Children aged between 6 months and 6 years with fever > or = 37.8 degrees C and < or = 41 degrees C due to an illness that could be managed at home. INTERVENTIONS: The intervention was the provision of, and advice to give, the medicines for up to 48 hours: paracetamol every 4-6 hours (maximum of four doses in 24 hours) and ibuprofen every 6-8 hours (maximum of three doses in 24 hours). Every parent received two bottles, with at least one containing an active medicine. Parents, research nurses and investigators were blinded to treatment allocation by the use of identically matched placebo medicines. The dose of medicine was determined by the child's weight: paracetamol 15 mg/kg and ibuprofen 10 mg/kg per dose. RESULTS: For additional time without fever in the first 4 hours, use of both medicines was superior to use of paracetamol alone [adjusted difference 55 minutes, 95% confidence interval (CI) 33 to 77 minutes; p < 0.001] and may have been as good as ibuprofen (adjusted difference 16 minutes, 95% CI -6 to 39 minutes; p = 0.2). Both medicines together cleared the fever 23 minutes (95% CI 2-45 minutes; p = 0.015) faster than paracetamol alone, but no faster than ibuprofen alone (adjusted difference -3 minutes, 95% CI 24-18 minutes; p = 0.8). For additional time without fever in the first 24 hours, both medicines were superior to paracetamol (adjusted difference 4.4 hours, 95% CI 2.4-6.3 hours; p < 0.001) or ibuprofen (adjusted difference 2.5 hours, 95% CI 0.6-4.5 hours; p = 0.008) alone. No reduction in discomfort or other fever-associated symptoms was found, although power was low for these outcomes. An exploratory analysis showed that children with higher discomfort levels had higher mean temperatures. No difference in adverse effects was observed between treatment groups. The recommended maximum number of doses of paracetamol and ibuprofen in 24 hours was exceeded in 8% and 11% of children respectively. Over the 5-day study period, paracetamol and ibuprofen together was the cheapest option for the NHS due to the lower use of health-care services:14 pounds [standard deviation (SD) 23 pounds] versus 20 pounds (SD 38 pounds) for paracetamol and 18 pounds (SD 40 pounds) for ibuprofen. Both medicines were also cheapest for parents because the lower use of health care services resulted in personal saving on travel costs and less time off work: 24 pounds (SD 46 pounds) versus 26 pounds (SD 63 pounds) for paracetamol and 30 pounds (SD 91 pounds) for ibuprofen. This more than compensated for the extra cost of medication. However, statistical evidence for these differences was weak due to lack of power. Overall, a quarter of children were 'back to normal' by 48 hours and one-third by day 5. Five (3%) children were admitted to hospital, two with pneumonia, two with bronchiolitis and one with a severe, but unidentified 'viral illness'. CONCLUSIONS: Young children who are unwell with fever should be treated with ibuprofen first, but the relative risks (inadvertently exceeding the maximum recommended dose) and benefits (extra 2.5 hours without fever) of using paracetamol plus ibuprofen over 24 hours should be considered. However, if two medicines are used, it is recommended that all dose times are carefully recorded to avoid accidentally exceeding the maximum recommended dose. Manufacturers should consider supplying blank charts for this purpose. Use of both medicines should not be discouraged on the basis of cost to either parents or the NHS. Parents and clinicians should be aware that fever is a relatively short-lived symptom, but may have more serious prognostic implications than the other common symptom presentations of childhood.

Relationship between medication adherence and blood pressure in primary care: prospective study.

There is good evidence from randomised trials (RCTs) that treating high blood pressure is effective in reducing cardiovascular risk, but people with high blood pressure can find it difficult to take antihypertensive medication regularly. The relationship between adherence and achieved blood pressure is far from clear.

Euclidean distance matrix analysis of surgical changes in prepubertal craniofacial microsomia patients treated with an inverted L osteotomy.

OBJECTIVES: Correction of craniofacial microsomia (CFM) presents several challenges concerning the modality of surgical intervention. The aim of this study was to assess early and late surgical outcome, by undertaking Euclidean distance matrix analysis (EDMA) of CFM patients exhibiting an unilateral mandibular deformity that was surgically corrected by an inverted L osteotomy and autogenous bone graft. DESIGN: Longitudinal study. Preoperative, approximately =1-year postoperative and approximately 3-year postoperative assessments of 14 consecutive children (mean age 9 years) with CFM. Posteroanterior cephalographs were scanned and five homologous mandibular landmarks were digitized in triplicate (< 1% digitization error). Average mandibular geometries, scaled to an equivalent size, were generated using a generalized rotational fit program (Procrustes superimposition) and subjected to EDMA. RESULTS: The mean pre- and both postoperative mandibular configurations differed statistically (p < .01). Early postoperative improvements in mandibular form were noted; increases in length arising in the treated mandibular body (approximately =19%) and ramus (approximately =13%). Comparing early and late postoperative configurations, a decrease of approximately =22% in the late postoperative mandibular body length was evident, but the ramus maintained steady vertical growth (approximately =7%). Comparing the preoperative and late postoperative configurations, the decrease observed in the mandibular body on the treated side was reduced to approximately =8% while the ramus maintained good growth (approximately =20%) on that side. CONCLUSION: Mandibular morphology is improved significantly in CFM patients surgically treated by an inverted L osteotomy, but relapse in the mandibular body is evident after approximately =3 years. Nevertheless, ramus growth proceeds well after the surgical reconstruction.

Mandibular transformations in prepubertal patients following treatment for craniofacial microsomia: thin-plate spline analysis.

To analyze correction of mandibular deformity using an inverted L osteotomy and autogenous bone graft in patients exhibiting unilateral craniofacial microsomia (CFM), thin-plate spline analysis was undertaken. Preoperative, early postoperative, and approximately 3.5-year postoperative posteroanterior cephalographs of 15 children (age 10+/-3 years) with CFM were scanned, and eight homologous mandibular landmarks digitized. Average mandibular geometries, scaled to an equivalent size, were generated using Procrustes superimposition. Results indicated that the mean pre- and postoperative mandibular configurations differed statistically (P<0.05). Thin-plate spline analysis indicated that the total spline (Cartesian transformation grid) of the pre- to early postoperative configuration showed mandibular body elongation on the treated side and inferior symphyseal displacement. The affine component of the total spline revealed a clockwise rotation of the preoperative configuration, whereas the nonaffine component was responsible for ramus, body, and symphyseal displacements. The transformation grid for the early and late postoperative comparison showed bilateral ramus elongation. A superior symphyseal displacement contrasted with its earlier inferior displacement, the affine component had translocated the symphyseal landmarks towards the midline. The nonaffine component demonstrated bilateral ramus lengthening, and partial warps suggested that these elongations were slightly greater on the nontreated side. The affine component of the pre- and late postoperative comparison also demonstrated a clockwise rotation. The nonaffine component produced the bilateral ramus elongations-the nontreated side ramus lengthening slightly more than the treated side. It is concluded that an inverted L osteotomy improves mandibular morphology significantly in CFM patients and permits continued bilateral ramus growth.

Morphometry of the mandible in prepubertal craniofacial microsomia patients following an inverted L osteotomy.

The aim of this study was to undertake finite element modeling of craniofacial microsomia (CFM) patients who exhibited a unilateral mandibular deformity that was surgically corrected by an inverted L osteotomy and autogenous bone graft. Preoperative, 1-year, and 3-year postoperative anteroposterior cephalographs of 14 consecutive children (mean age, about 9 years) with CFM were employed. All cephalographs were scanned, and 8 homologous mandibular landmarks were digitized in triplicate (digitization error < 1%; P > 0.05). Average mandibular geometries, scaled to an equivalent size, were generated using Procrustes superimposition and subjected to analysis of variance. Results showed that while the mean pre- and early postoperative mandibular configurations marginally failed to differ statistically, finite element modeling of the affected mandibular ramus showed a positive allometry (a lengthening by about 10% to 12%) and marked anisotropy, presumably reflecting the surgical procedure carried out in that region. For the preoperative and late postoperative means, the configurations were statistically different (P < 0.002), showing a lengthening of the ramus (about 14%) while the unoperated side had a high degree of isotropy. The early and late postoperative configurations were also statistically different (P < 0.002). The operated ramus showed an increase in length (about 15%), but the corpus showed a decrease in size (about 10%) and marked anisotropy that reflected remodeling associated with the surgical procedure. Although mandibular morphology is improved in CFM patients who are surgically treated by an inverted L osteotomy, some relapse is evident due to deficient growth, localized in the mandibular ramus and body of the affected side.