We addressed this uncertainty by comparing the adjuvant effect of two different VRP genomes: VRP16M or a new VRP genome

named VRP(-5) which contains a deletion in the core 26S subgenomic promoter and is genetically incapable of producing a subgenomic RNA (Fig. 1A). Mice were primed and boosted with OVA alone or OVA in the presence of a low dose of VRP16M or VRP(-5) (103 IU, which corresponds to 106 GE). (VRP IU are based on in vitro infection of BHK-21 cells; in vivo infectivity is undefined.) After the boost we measured anti-OVA IgG in the serum and anti-OVA IgA in fecal extracts. Both VRP genomes significantly increased antibody responses compared to OVA alone (Fig. 1B and C), with the VRP(-5) genome inducing a significantly stronger mucosal IgA response. These results show clearly that the

26S promoter is not required for the adjuvant effect induced MLN0128 by VRP, so for all subsequent experiments we used the VRP(-5) genome, which will be referred to as simply VRP Trametinib in vivo for the rest of this report. In all previous studies of VRP adjuvant activity the VRP were injected into the footpad, but because this is an impractical route for human vaccines, we assessed whether VRP would be effective by intramuscular (i.m.) delivery. Mice were primed and boosted with OVA and VRP (105 IU) in the footpad or i.m. Anti-OVA serum IgG and fecal IgA titers were significantly increased by both routes of delivery (Fig. 1D and E), indicating that i.m. delivery of VRP is just as effective as footpad delivery. Data shown in Fig. 1 demonstrate that VRP injected into the footpad are an effective adjuvant at a relatively low dose (103 IU). To evaluate the efficacy of lower doses of VRP delivered i.m., we tested the effect of VRP on anti-OVA immunity after i.m.

injection in Balb/c mice using a range of Sitaxentan VRP doses between 102 and 105 IU (105 to 108 GE). Titers of anti-OVA IgG in the serum had a clear dose–response, and all tested doses of VRP significantly increased the anti-OVA titers relative to mice immunized with OVA alone (Fig. 2A). The mucosal response measured in the fecal extracts demonstrated clear induction of anti-OVA IgA antibodies at all tested VRP doses, with the strongest response at ≥104 IU (Fig. 2B). To examine the VRP dose effect on T cell responses, we primed and boosted C57Bl/6 mice i.m. with OVA alone or in the presence of increasing doses of VRP. This mouse strain was used because T cell-reactive OVA peptides are known for this mouse, and it was previously shown that the VRP adjuvant effect is intact in this strain [21]. The dose of OVA used (100 μg) was based on the previous finding that this higher dose was required for a detectable T cell response [21]. After boost, spleen cells harvested from these mice were incubated in vitro with a CD8-specific OVA peptide, and IFN-γ production was measured by intracellular staining and flow cytometric analysis.

The field of “community health” reflects the needs of the community and exemplifies the best of public health research and methods to achieve the shared goal of improving health. The authors

declare that there are no conflicts of interest. The authors thank the following for their review of and comments on this manuscript: Lawrence Barker, Peter Briss, and Leonard Jack. “
“Falling survey response rates present a significant challenge for health research, primarily because of the increasing effects of selective non-response on estimates of the prevalence of health problems and risk behaviour. A typical approach to studying non-response bias is to undertake intensive follow-up of non-respondents and to compare estimates with those obtained using standard Compound C ic50 survey procedures (Wild et al., 2001). An alternative is to compare respondents and non-respondents in surveys imbedded within larger studies (Van Loon et al., 2003). In one such study, involving a postal survey of cancer risk

factors of individuals participating in a larger study of behavioural risk factors for chronic disease, smoking, physical inactivity, obesity, and poorer self-rated health were found to be more prevalent among non-respondents (Van Loon et al., buy MK0683 2003). In a third paradigm, utilising archival records, mortality subsequent to postal and telephone health surveys has been found to be higher among non-respondents (Barchielli and Balzi, 2002 and Cohen and Duffy, 2002), as have sickness absence rates (Martikainen et al., 2007) and hospital utilisation (Gundgaard et al., 2008 and Kjoller and Thoning, 2005). These findings suggest that people with poorer health tend to avoid participating in health surveys.

There are, however, contrary findings which suggest context specific effects. For example, studies of respiratory health find that respondents have worse respiratory health than non-respondents (Hardie et al., 2003, Kotaniemi et al., 2001 and Verlato et al., 2010). Perhaps in some contexts, less healthy people perceive a greater benefit in responding than healthier people. Differences between respondents and non-respondents have been observed across postal, telephone, aminophylline and face-to-face surveys. There has been a rapid increase in the use of web-based surveys but little is known about non-response bias in this modality. A theoretical framework for studying respondent behaviour is the continuum of resistance model, which posits that willingness of individuals to participate can be inferred from the effort required to elicit participation ( Lin and Schaeffer, 1995). Two methods are used to test the model. In the more commonly used approach, the sampling frame is used to compare the demographic characteristics of those who respond versus those who do not respond.

To quantify IL-4 and IFNγ, fluoresceinated microbeads coated with capture antibodies (IL-4: BVD-1D11; IFN-γ:AN-18) were added to 50 μl BAL fluid and incubated overnight at 4 °C. Cytokines were detected with biotinylated anti-IFNγ (XMG1.2) and -IL-4 (BVD6-24G2), and PE-labeled streptavidin. Fluorescence was measured using a Luminex model 100 XYP (Luminex, Austin, TX, USA). Antibodies were purchased from BD

Biosciences. Naïve and PVM-infected (d. 14 p.i.) donor mice were sacrificed, single cell suspensions prepared of lungs, spleens and MLNs were mixed and stained Selleck PI3K inhibitor with PE-labeled antibodies against CD19, CD4, MHC-II and NKp46 (without Fc-block). Negative selection was performed using a BD Influx (BD check details Biosciences). Recipient mice received 5 × 106 enriched cells in 200 μl PBS i.v., and then were infected with PVM. Intranasal infection with 25 pfu of PVM strain J3666 induced severe but sublethal disease in BALB/c mice, with weight reduction of approximately 15–20% of original body weight (data not shown). During the first days of infection, PVM rapidly replicated to high numbers (Fig. 1A). Viral copy numbers peaked at d. 8 p.i. and then declined. In order to determine their protective capacity, we first studied CD8+ T-cell kinetics during primary PVM infection and compared these with the well-described CD8+ T-cell responses in influenza and hRSV-infected mice [36] and [37]. The relative proportions of CD8+ T-cells in the

airways of PVM-infected mice strongly increased over time (Fig. 1B), and from d. 10 onwards approximately

60% of lymphocytes in the BAL were CD8+ T-cells. In influenza- and hRSV-infected mice, initially, the proportions of CD8+ T-cells in the airways were higher than in PVM-infected mice but then dropped, when relative proportions of CD8+ T-cells in PVM-infected mice were still rising (Fig. 1B). Quantification of virus-specific CD8+ T-cells with MHC class I tetramers containing a dominant epitope of either PVM (P261–269[30]), influenza (NP147–155[38]) or hRSV (M282–90[39]), demonstrated that NP147–155- and M282–90-specific CD8+ T-cells no were detectable at d. 6 p.i. and expanded until d. 8–10 p.i. when a plateau was reached (Fig. 1C). In PVM-infected mice, the BAL did not contain any P261–269-specific CD8+ T-cells at d. 6 p.i, and only a small population of P261–269-specific CD8+ T-cells could be detected at d. 8 p.i. (Fig. 1D and E). The relative proportions of P261–269 tetramer+ CD8+ T-cells further increased until d. 10 p.i. after which levels remained high (Fig. 1D and E). To determine whether PVM-specific CD8+ T-cell were functional, we quantified IFNγ production in virus-specific CD8+ T-cells after ex vivo P261–269 stimulation. Consistent with earlier publications [30] and [37], we found that IFNγ producing P261–269-specific CD8+ T-cells were barely detectable at d. 8 of infection ( Fig. 1F and G) but then increased in numbers.

Passive surveillance is based on the reporting of confirmed or suspected cases encountered by health care workers. However, as most dengue cases are ambulatory, and not always seen by health care workers, this system results in significant under-reporting. Under-reporting also results from the lack of a universally CDK inhibitor applicable or uniformly applied case definition [16]. Improving the availability and reliability of diagnostics for dengue is a major priority. Recent recommendations from the Asia-Pacific and Americas Dengue Prevention Boards (organised by the Dengue Vaccine

Initiative Consortium) include: making the reporting of dengue mandatory, use of electronic reporting systems, application of minimum reporting requirements and sharing of expertise and data [15]. To obtain support from governments and global decision-makers, a dengue vaccine must be shown to be cost-effective. This requires accurate data on the economic costs of dengue. Dengue is responsible for an annual

estimated global burden of 750,000 disability-adjusted life years (DALY) Cisplatin nmr [6], [17] and [18]. A study across eight countries in Asia and Latin America estimated that the mean cost per hospitalised case of dengue is US$571, of which 76% was direct costs and 24% indirect costs [19]. For ambulatory cases the mean cost per case was US$248, of which 28% was direct costs and 72% indirect costs [19]. Another study estimated the total cost of dengue illness across the Americas (based on data from 2000 to 2007) at US$2149.8

million per year, with a total of 72,772 DALY lost [17]. Ambulatory cases accounted for 73% of the costs, hospitalised cases 24%, Adenosine and deaths 3% [17]. A comprehensive review of health economic studies of dengue burden has recently been published [20]. Such cost studies face two main challenges: (i) it is difficult to incorporate all of the costs of a case of dengue, and (ii) incidence of dengue is considerably under-estimated. Expansion factors are used to adjust for the under-reporting of cases and provide estimates of the true extent of the dengue burden [21]. Expansion factors of 10–27 in Puerto Rico [22], 6 in Panama [23] and 21.3 in Nicaragua [24] have been reported. While different expansion factors for different countries might be expected given differences in surveillance systems, the wide variation observed calls for a systematic and comprehensive analysis of dengue under-reporting. Indeed, reliable expansion factors will be essential to calculate the full cost of dengue. The threshold for vaccine cost-effectiveness recommended by the WHO is a cost per DALY saved of three times the annual per capita gross domestic product (GDP) [25]. For dengue-endemic countries in the Asia-Pacific region this threshold is approximately US$3000. The cost-effectiveness of a dengue vaccine in Southeast Asia was calculated assuming a two-dose schedule and different potential prices per dose [26] and [27].

When withdrawn on day 5, bacterial numbers rapidly fell, and were no longer detectable after 48 h, by day 7 post-colonisation. To investigate the impact of controlled colonisation on immunogenicity and protection, further groups of mice were colonised with

D39Δpab in the presence or absence of PABA for 5 days. Serum anti-D39 IgG level was assessed at 14 and 28 days, prior to pneumonia challenge with WT D39. By day 14 post-colonisation, mice receiving 5 days of PABA supplementation had approximately 10-fold greater median serum IgG against D39 than those not receiving PABA ( Fig. 7B). By day 28, levels were not significantly different between the groups, indicating more rapid development of an antibody response when growth of the auxotrophic bacteria was supported at this level. In mice colonised with D39Δpab alone, there was no evidence of protection (median survival time 3.00 days, overall Selleck JQ1 survival 30%) compared to controls (median time 2.87 days, 20% survival) ( Fig. 7C). In mice where colonisation was

supported with PABA, there was a trend towards longer survival compared with controls (median survival time 6.90 days, overall survival 35%, P = 0.09). Thus, the enhanced immune kinetics suggested that the degree of nasopharyngeal bacterial exposure was directly impacting on subsequent immunogenicity, and Ibrutinib molecular weight could make a contribution towards protection. Live attenuated vaccines must possess both antigens and adjuvants which persist in sufficient quantity in an appropriate location for

enough time to induce a protective response. We have investigated how multiple factors may contribute towards the immunogenicity of a colonising bacterial strain and determine whether the colonisation event is sufficient to induce protection. We have previously shown prior colonisation protects against invasive D39 pneumonia by preventing septicaemia not with no protection at the mucosal level and is dependent on serum antibody [5]. Hence, systemic IgG rather than local immunological responses to colonisation are likely to be the important protective response for this model of S. pneumoniae infection, and this was supported by the close correlation between the serum IgG response and protective efficacy for the different strains studied here. Compared to its WT parent strain, D39Δpab was poorly immunogenic following colonisation. Supplementation with PABA for 5 days restored the ability of D39Δpab to colonise, and enhanced the speed of anti-D39 IgG seroconversion. The majority of mice with PABA supplementation had high titres of anti-D39 IgG, whereas in mice without PABA titres were much more variable. This was associated with a strong trend towards protection. These data support the hypothesis that for a given strain of S. pneumoniae, the duration of colonisation is important in generating protective immunity. Whether the ‘area under the curve’ (reflecting total antigen present over time i.e.

All studies reviewed here used culture to detect respiratory bacteria. Therefore molecular testing of paired NP/OP samples is needed to establish if the recommendations for anatomic site of sampling apply also to studies using molecular detection of pneumococci. Conventional teaching is that nasal specimens are less sensitive than NP samples for detecting pneumococci. We identified only three studies directly comparing NP and nasal sampling methods for detecting pneumococci

in children (Supplementary Table 2). Rapola et al. [12] found that pneumococcal isolation rates from NP aspirates, NP swabs and nasal swabs did not differ. The same conclusion was reached by Carville et al. [13] for NP aspirates and nasal swabs, and Van den Bergh et al. selleck products [14] for NP swabs and nasal swabs. However, in two of these studies children had respiratory symptoms, either acute respiratory infection [12] or rhinorrhea [14], conditions that are known to enhance pneumococcal

carriage and possibly affect the sensitivity of detection from nasal specimens. As such, there is currently insufficient evidence to conclude that nasal swabbing is as effective as NP swabbing for the detection of pneumococcal carriage in healthy children. A fourth comparative study [15] found that NP washes performed better than NP swabs, but concluded that the additional gain was not sufficiently large to offset the discomfort and reduced acceptability to study subjects. Lieberman et al. [16] and Gritzfeld et al. [17] found no difference between NP swabs ABT-888 supplier and NP or nasal washes for the detection of pneumococci in adults with respiratory infection (Supplementary Table 2). The very adults found nasal washes more comfortable than NP swabbing, but nasal washes were not recommended for children because of the level of participant cooperation required [17]. There are potential disadvantages of nasal/NP aspirates and washes for pneumococcal detection; the methods are difficult to standardize, and frequent washes in an individual

hypothetically may disrupt the flora or affect immune responses. Given that nasal or NP washing is generally less well tolerated by children, a single NP swab is preferred for the detection of pneumococcal carriage but washes/aspirates are an acceptable method [15]. NP swabbing techniques may vary across studies unless the investigators adhere closely to the standard method, summarized here. Hold the infant or young child’s head securely. Tip their head backwards slightly and pass the swab directly backwards, parallel to the base of the NP passage. The swab should move without resistance until reaching the nasopharynx, located about one-half to two-thirds the distance from the nostril to ear lobe (Fig. 1). If resistance occurs, remove the swab and attempt again to take the sample entering through the same or the other nostril. Failure to obtain a satisfactory specimen is often due to the swab not being fully passed into the nasopharynx.

For example, hypothalamo-pituitary-adrenal (HPA) activity is not modulated by control, at least in the paradigm described above. Thus, neither the peak nor the decay timecourse of plasma ACTH or corticosterone are reduced by control (Maier et al., 1986). Consistent with these findings, ES and IS produce identical increases in corticotrophin releasing hormone selleck chemicals llc (CRH), arginine vasopressin (AVP), enkephalin, and neurotensin mRNA in the paraventricular nucleus of the hypothalamus (PVN) (Helmreich et al., 1999). Similarly, IS increases circulating thyroid hormones, but ES does so to the same extent (Helmreich et al.,

2012). Autonomic measures show a similar pattern, with ES and IS producing the same size increases in core body temperature, heart rate, mean arterial pressure, systolic blood pressure, and diastolic blood pressure (Thompson et al., 2013). We have also examined a number of peripheral immune measures, and they are also not modulated by stressor control (Maier and Laudenslager, 1988). This does not mean that a paradigm cannot be found in which control reduces these stressor-induced changes, Erlotinib in vivo but it does not do so in the very same paradigm in which control blunts other behavioral and neurochemical outcomes. The implication

is that control, and perhaps other processes that lead to vulnerability or resistance/resilience, do not operate as a generalized sensitizing or damping switch, but rather operate on a specific neural circuit, and only responses to

stressors that are modulated by that circuit will be affected. If it is true that control is detected by the mPFC and then operates by activating output pathways that modulate the DRN, amygdala, and perhaps other structures, only stressor driven changes controlled by those mPFC modulated structures can be blunted (or enhanced). STK38 The stressor-induced responses that are unaffected by control seem to be hypothalamically mediated, and mPFC projections to the hypothalamus emanate from a quite different part of the mPFC than do the projections to the DRN and amygdala (Gabbott et al., 2005). Moreover, projections to the PVN are indirect, via the bed nucleus of the stria terminalis (Spencer et al., 2005). Although the argument is admittedly circular, perhaps control does not activate projections to the hypothalamus, or does so only weakly. Or, perhaps, the tailshock stressor is so intense that hypothalamic activation is so powerful that it cannot be readily modulated. It is tempting to consider that all factors that lead to resistance/resilience do so via a common mechanism. However, the data suggest that this is not so (Christianson and Greenwood, 2014). For example, we (Christianson et al., 2008a) and others (Rogan et al., 2005) have studied the mechanism(s) by which safety signals blunt the consequences of stressor exposure.

5 ml extract solution and observed for white precipitation which indicates presence of tannin. 0.2 g of the extract was shaken with 5 ml of distilled water and then heated to boil. Frothing shows the presence of saponin. 0.2 g of the extract was dissolved in 10% NaOH solution, yellow colouration indicates the presence of flavonoid. To 2 ml of extract solution, added 2 ml of alcohol and few drops of ferric chloride solution and observed for colouration. Five ml of each extract was treated with 2 ml of glacial acetic acid containing one drop of ferric chloride solution. This was under layered with 1 ml of conc. sulphuric Selleck ABT 888 acid. A brown ring at the interface indicated

the present of cardiac glycoside. (A violet ring may appear below the ring while in the acetic acid layer, a greenish ring may formed). 0.5 g extract was boiled with conc. HCl and filtered. 0.5 ml of picric

acid and Mayer’s reagent was added separately to about 1 ml of the filtrate in a different test tube and observed for coloured precipitate or turbidity. To 0.2 g of extract, added 5 ml of chloroform and 5 ml of 105 ammonia solution. The presence of bright pink colour in the aqueous layer indicated the presence of anthraquinone. Five ml of extract solution was mixed in 2 ml of chloroform, and 3 ml of conc. sulphuric acid was added to form a layer. A reddish brown colouration of the interface Everolimus concentration was formed to indicate the presence of terpenoids. Red colour at the lower surface indicates presence of steroid. To 0.5 ml of extract solution, 1 ml of water and heated after adding 5–8 drops of Fehling’s solution. Brick red precipitation indicated the presence of reducing sugar. Antioxidants react with 1, 1-diphenyl-2-picryl-hydrazyl (DPPH) radical and convert it to 1, 1-diphenyl-2-picryl hydrazine. The degree of change in colour from purple to yellow can be used as a measure of the scavenging potential of antioxidant extracts. Aliquots of ethanol extract solutions (1 mg/ml) were taken and made up the volume to 3 ml with methanol. 0.15 ml of freshly prepared DPPH Terminal deoxynucleotidyl transferase solution

was added, stirred and left to stand at room temperature for 30 min in dark. The control contains only DPPH solution in methanol instead of sample while methanol served as the blank (negative control). Absorbance was noted at 517 nm using the Systronics make spectrophotometer (Visiscan 167). The capacity of scavenging free radicals was calculated as scavenging activity (%) = [(Abscontrol−Abssample/Abscontrol)] × 100 where Abscontrol is the absorbance of DPPH radical + methanol; Abssample is the absorbance of DPPH radical + sample extract/standard. The ABTS assay was carried out following the method of Re et al.9 The stock solution included 7 mM ABTS solution and 2.4 mM potassium persulfate solution and mixed them in equal proportion then allowed to react for 12 h at room temperature in the dark and diluted by mixing 1 ml ABTS solution with 60 ml methanol to obtain an absorbance of 0.706 ± 0.

Infants received

NVP prophylaxis for the first 6 weeks of life and cotrimoxazole prophylaxis from 6 weeks of age. Breastfeeding infants continued cotrimoxazole throughout the breastfeeding period while formula-fed infants stopped at 10 weeks if their 6-week HIV-1 test was negative. Infants received Kenyan Expanded Program on Immunization (KEPI) vaccinations, which included BCG and oral poliovirus vaccine (OPV) at birth, OPV and Pentavalent vaccine (diphtheria toxin [Dtx], tetanus toxin [Ttx], whole cell pertussis [Ptx], Hemophilus influenzae type b [Hib] and hepatitis B virus [HBV] surface antigen [HBsAg]) at 6, 10 and 14 weeks of age. Pneumoccocal conjugate vaccine 10, introduced in the course of the study was administered to infants at variable ages. During study visits, a standard questionnaire on infant health and immunization was completed. At 20 weeks, infants were randomized buy U0126 if they had received all scheduled KEPI vaccines, were HIV-1-uninfected, had weight-for-age Z-scores no more than 2 standard deviations below normal, had no acute screening assay or chronic disease, had

no history of anaphylaxis reaction to prior vaccination, and baseline laboratory investigations were within normal ranges. MVA.HIVA is a recombinant non-replicating poxvirus, which carries the HIVA transgene inserted into the thymidine kinase locus of the parental MVA genome under the early/late P7.5 promoter [16]. MVA.HIVA was manufactured under current Good Manufacturing Practice conditions by IDT, Germany. It was provided in vials of 200 μl at 5 × 108 plaque-forming units (PFU) ml−1 in 10 mM Tris–HCl

buffer pH 7.7 and 0.9% NaCl, and stored at ADAMTS5 ≤−20 °C. On the day of administration, each vial was thawed at room temperature and given within 1 h of thawing. Infants randomized to vaccine group received a single intramuscular dose of 5 × 107 pfu of MVA.HIVA, while the control group received no treatment. Vaccinated infants were observed in the clinic for 1 h post-vaccination and visited at home after 24 and 48 h to assess for adverse reactions. Randomization was generated at Karolinska Institute using a blocked design and participants were assigned using sealed envelopes. After randomization, medical history and examinations were conducted at 21, 28, 36 and 48 weeks of age. At 21 and 28 weeks, hematology and biochemistry tests were done as described below. Local, systemic and laboratory AEs, and relationship to MVA.HIVA were graded as per Clinical Protocol (Supplementary Information). Palpable lymph nodes, redness and induration were scored according to their diameters. Any Grade 3 or 4 laboratory AE was confirmed by re-test. An internal trial safety monitor reviewed Grade 3 and 4 events in real time and these were reported to the KNH Research Ethics committee. Study procedures were reviewed regularly by an external monitor. An external Data Monitoring and Ethics Committee reviewed safety data at 6-monthly intervals.

“
“Summary of: Machado LAC et al (2010) The effectiveness of the McKenzie method in addition to first-line care for acute low back pain: a randomized controlled trial BMC Medicine 8: 10. [Prepared by Julia Hush, CAP Editor.] Question: Does the addition of McKenzie treatment to first-line care improve symptoms and function for patients with acute low back pain? Design: A randomised controlled trial with concealed allocation and blinded outcome assessment. Setting: 27 primary care medical practices in Sydney, Australia. Participants: Patients aged between 18 to find more 80 years seeking

medical care from a primary care physician for a new episode of acute non-specific low back pain. Nerve root compromise, serious spinal pathology, and recent spinal surgery were exclusion criteria. Randomisation of

148 participants allotted 73 to the McKenzie treatment and first-line care group, and 73 to a first-line care only group. Interventions: Both groups received the following recommended first-line care for acute low back pain: advice to remain active and avoid bed rest, reassurance of a favourable prognosis and instructions to take paracetamol. In addition, the intervention group received selleck chemicals llc McKenzie therapy, commenced within 48 h of their physician consultation. Treatment was provided by 15 accredited McKenzie therapists. Treatment for most patients encouraged directions of movement and postures that centralised pain. Patients received up to 6 treatment sessions over 3 weeks. They were provided with the book Treat Your Own Back, prescribed home exercises, and most were prescribed

lumbar rolls. Outcome measures: Primary outcomes were pain and global perceived effect. Pain was measured during the first 7 days, and at Weeks 1 and 3, with the Numerical Rating Scale scored from 0 (no pain) to 10 (worst pain possible), with a between-group difference of 1 unit considered clinically important. Patient-rated global perceived effect was assessed at 3 weeks on a –5 to 5 scale, anchored 4-Aminobutyrate aminotransferase at ‘vastly worse’ and ‘completely recovered.’ Secondary outcome measures were disability, function, global perceived effect at 1 week, persistent low back pain at 3 months, and use of additional health care services. Results: 138 participants provided data at 3 months. At Week 1, pain was less in the McKenzie treatment group by 0.4 points (95% CI –0.1 to –0.8). At Week 3, pain was less in the McKenzie treatment group by 0.7 points (95% CI –1.2 to –0.1). The groups did not differ on other outcomes. However, patients receiving McKenzie treatment sought less additional health care than those receiving only firstline care (p = 0.002).