1) and VLP ELISA (Fig. 2) data. The target antigens (L1L2 pseudovirus or L1 VLP) were clustered horizontally while the sera were clustered vertically against a heat map representing the Log10-transformed antibody titer data. This approach allowed us to sort the pseudovirus neutralization and VLP ELISA data into clusters of sera displaying similar antigenic profiles. The magnitude and breadth of

the individual serum neutralizing antibody responses against vaccine and non-vaccine types GSK1349572 datasheet permitted intuitive clustering (Fig. 1). Serum samples in Cluster I displayed the highest HPV16 neutralization titers and the broadest coverage of non-vaccine types, while Cluster VI included samples that had intermediate HPV16 neutralization titers and whose

breadth of reactivity extended to HPV31 and HPV33 (Table 1). These data support a generally quantitative relationship between the level of antibodies in vaccinee sera against HPV16 and an ability to recognize non-vaccine types. However, there also appeared to be a number of antibody specificities displayed. Samples within Clusters II, V and VI for example exhibited differential neutralization of HPV33, HPV35 or HPV52, in addition to HPV31 despite similar HPV16 antibody titers. The serological dendrogram based upon VLP ELISA binding titers (Fig. 2) permitted the formation of branches but the ordering of individual sera bore little relation to the arrangement Akt inhibitor in the serological dendrogram based upon the pseudovirus neutralization data. The hierarchical clustering of antibody responses also permitted the ranking of the target antigens. Pseudoviruses HPV31 and HPV33 were the nearest antigenic relatives to HPV16 followed by HPV58 (Fig. 1). HPV52 and HPV35 pseudoviruses

clustered together suggesting a close antigenic relationship between these types. The antigenic dendrogram based upon mafosfamide VLP ELISA data (Fig. 2) was broadly similar such that the nearest antigenic relative to HPV16 was HPV31, followed by two separate clusters of HPV33 and HPV58, and HPV35 and HPV52. These inter-type antigenic relationships had good bootstrap support and differed somewhat from the inter-type genetic distances based upon L1 amino sequence (Fig. 3). Potential differences in cross-neutralizing antibody specificity were addressed by adsorption on, and elution from, individual non-vaccine type VLP. We reasoned that if cross-neutralization was due to antibodies that constitute a minor fraction of the total vaccine antibody repertoire, such an approach should enrich for these specificities in preference to type-specific HPV16 antibodies. Six serum samples (A–F) were selected from Cluster I (Fig. 1) for enrichment and the neutralization titers against pseudoviruses HPV16, HPV31 and another relevant type were determined prior to and post enrichment. Antibodies enriched on non-vaccine type VLP displayed a range of different cross-neutralizing specificities (Fig. 4).

The decline in carriage of VT may have allowed non-vaccine serotypes (NVT) to fill the niche and cause disease, the phenomena known as serotype replacement [2], [3] and [4]. By 2004, 88% of IPD among children <5 years old was due to NVT [2]. Of the NVT, serotype 19A was predominant [2]. Serotype 19A

isolates were identified in IPD cases in the United States [5], [6] and [7] and Korea [8] with increased non-susceptibility to antimicrobials. Even though serotype 19A was known to cause IPD prior to the use of PCV7 [2] and [9], clonal expansion of serotype 19A was also reported [10] and [11]. As a method to protect against serotype replacement disease, pneumococcal conjugate vaccines

(PCV) are increasing in their valences [3], [12] and [13]. selleck products Akt tumor The distribution of pneumococcus constantly changes and varies geographically, complicating the construction and implementation of new PCV [11] and [14]. Although pneumococcal (Pnc) polysaccharides are considered the major virulence factor, Pnc proteins in a vaccine formula could provide serotype-independent protection [14]. The evaluation of these protein-based vaccines, for the most part, has been limited to the mouse model [15]. Briles et al. observed enhanced reduction of nasopharyngeal colonization in mice immunized with the Pnc surface protein A (PspA) and Pnc surface almost adhesin A (PsaA) in comparison to mice immunized with PspA or PsaA alone [16]. PsaA, a common Pnc protein, has been shown to be immunogenic and reduce nasopharyngeal carriage in a mouse model [16], [17] and [18]. Previous studies also showed that PspA mixed with pneumolysin or the combination of Pnc histidine

triad proteins, PhtB (BVH-11) and PhtE (BVH-3) enhances the protection against pneumonia in the mouse model [19], [20], [21] and [22]. More than one mechanism of defending against infection is targeted as a result of combining proteins; however, no other pneumococcal antigen as of yet can elicit comparable protection to that of Pnc polysaccharides in conjugate form [22]. In our study, we co-administered PCV7 and rPsaA to increase serotype coverage of PCV7. We evaluated the immune responses and reduction in carriage of PCV7 serotypes 4 and 14, and non-PCV7 serotype 19A in mice. Streptococcus pneumoniae serotype 4 (CSF isolate DS2341-94), 14 (blood isolate D2232-92) and 19A (blood isolate DS3842-03) were used. All strains were provided by the Streptococcus Reference Laboratory at the Centers for Disease Control and Prevention. Serotypes were confirmed through latex agglutination and capsular swelling (Quellung reaction) tests [18]. For PCV7 serotypes 4 and 14, stocks were prepared as before [18] and [23].

The American view [6] is much clearer, specifying relative contra-indications under clinical, social and procedural categories. Clinical contra-indications in the US include thyrotoxicosis and pre-existing vocal paresis alongside criteria applicable to any day case procedure (cardiorespiratory co-morbidity, morbid obesity, etc.). Social factors consider the home PF-06463922 cost environment, availability of primary carer, distance

from hospital, communication difficulties, patient preference and understanding. Within the procedural category, contra-indications include large volume glands and retrosternal extension, plus specific intra-operative factors to reduce the risk of complications; anaesthetic choice, type and extent of surgery, nerve monitoring, haemostasis, parathyroid gland management, wound closure and extubation. For safe postoperative care, there are suggested discharge criteria (absence of neck swelling, dysphagia etc.) and emphasis on the importance of nursing and patient/carer education for the recognition of complications. Unilateral

surgery compared to total thyroidectomy carries a reduced risk of laryngeal nerve dysfunction, postoperative hypocalcaemia and potentially a reduced risk of bleeding and its consequences given the smaller operative field. Indeed, unilateral surgery has been suggested as generally more suitable [16] and [19]. An Austrian groups’ review of over 30,000 thyroidectomies [24] would appear to support this position since no patient in their review developed NVP-AUY922 manufacturer a haematoma after undergoing unilateral

surgery (92 of 8783 procedures, 1% cases) or became symptomatic after 20 hours. Thyroid surgery is unique to other day case procedures in that it is associated with a small but definite risk of life-threatening complications. Mortality incidence from population series are less than one per-cent [10] and [11] but the risk of death following a significant postoperative complication is unquantified. Reliability of more specific outcome data from complications is liable to publication bias, possibly more so in the day case setting where complications are notable by their Casein kinase 1 low incidence in some single centre series. Even in Tuggle’s state-wide review of over 1000 thyroidectomies [17] where the emergency room visit and re-admission rate of 7.8 and 2.3 per-cent respectively seem typical [13] and [16] the total bleed rate of under 0.2% is either a reflection of high volume surgeon performance or under-reporting. The three main risks of thyroid surgery are airway obstruction from haemorrhage/laryngeal oedema, vocal cord paresis and tetany from severe hypocalcaemia. This section will consider these in turn, along with recommendations to mitigate their occurrence and impact. When postoperative complications do occur, their recognition with prompt and effective management is critical.

The seeds were sown at 25 days intervals on 20th May, 15th June and 10th July, 2010 in the experimental plots with 60 × 30 cm spacing. All agronomical management practices were performed as needed. The samples AP24534 supplier of leaves and whole plants were collected at pre flowering and full flowering stages. Samples of whole plant, leaves, spikes and husk were subjected to hydro-distillation for 4 h using a Clevenger-type apparatus to produce oil. The oils were dried over anhydrous sodium sulphate and stored in sealed vial at low temperature before analysis. GC/MS analyzes were performed with a Perkin Elmer Clarus 500 gas chromatograph

equipped with a split/splitless injector (split ratio 50:1) data handling system. The column was Rtx®-5 capillary columns (60 m × 0.32  mm, 0.25 μm film thickness). Helium (He) was the carrier gas at a flow rate 1.0 ml/min. The GC was interfaced with (Perkin Elmer Clarus 500) mass detector operating in the EI+ mode. The mass spectra were generally recorded over 40–500 amu that revealed the total ion current (TIC) chromatograms. Temperature program was used as follows: initial temperature of 60 °C (hold: 2 min) programmed at a rate of 3 °C/min to a final temperature of 220 °C (hold: 5 min). The temperatures of the injector,

transfer line and ion source were maintained at 210 °C, 210 °C and 200 °C, respectively. The components of the oils were identified by comparison of their mass spectra with those ON-01910 research buy of commercial libraries (NIST/Pfleger/Wiley)

or with authentic compounds and confirmed by comparison of their retention indices either with those of authentic compounds or with data published in literature. 17 The average oil content in different plant parts were obtained as 0.06–0.10% (whole plant), 0.10–0.14% (leaves), 0.13–0.23% (spike) and 0.10–0.13% (husk) during different sowing times. The highest oil content obtained in all the spike samples at different sowing times, which ranged from 0.16 to 0.23% (D1), 0.15–0.20% (D2) and 0.13–0.18% (D3), whereas lowest oil yield obtained in whole plant, varied between 0.06 and 0.09% (D1), 0.06–0.10% (D2 and D3). Table 1 shows the identified constituents and their relative content in the essential oils obtained Parvulin from whole plant, leaves, spikes and husk of Perilla frutescens at 3 sowing times, D1-seeds sown on 20th May, D2-seeds sown on 15th June and D3-seeds sown on 10th July. D1 stage: The major compound was found as perilla ketone (52.34–90.28%) followed by 1-methyl-2-methylene trans-decalin (4.49–32.98%). The percentage of perilla ketone, the first major compound in all the oils, was found maximum in spikes (90.28%) followed by husk (64.54%), leaves (54.56%) and whole plant (52.34%). 1-Methyl-2-methylene trans-decalin was higher in leaves oil (32.98%) and lower in spikes essential oil (4.49%). The amount of trans-caryophyllene was higher in the essential oil obtained from whole plant (8.54%) and also in husk (5.08%).

4B1). In addition to pharmacological block of glutamate uptake leading to increased activation of AMPA and see more NMDA receptors (Jabaudon et al., 1999, Jabaudon et al., 2000, Cavelier and Attwell, 2005, Le Meur et al., 2007 and Herman and Jahr, 2007), ischemia-induced reversed transport also leads to large increases in extracellular [Glu] and pathological receptor signaling (Rossi et al., 2000). Changes are also predicted by the probe diffusion model probe as a consequence of increases in basal glutamate

release (Fig. 4B3). While the value of extracellular [Glu] in the probe dialysate is predicted to significantly exceed ambient [Glu] in healthy tissue far from the probe, the dialysate concentration is also predicted to change in approximate proportion to changes in glutamate homeostasis in distant tissue (Fig.

4B3). This behavior of the model is consistent with reported changes in dialysate [Glu] in response to factors including transport block, ischemia, and trauma (Benveniste et al., 1984, Hagberg et al., 1985, Baker et al., 2002, Del Arco et al., 2003 and Nyitrai et al., 2006). This work was supported by NIHR15 GM088799 to M.P.K. The authors thank Anastassios Tzingounis for discussions and preliminary kinetic data on transporter density effects. “
“Glutamate (Glu) is the major excitatory neurotransmitter in the nervous Bortezomib purchase system. Glu regulates many brain functions and its synaptic concentration must be precisely controlled to avoid excessive excitation and toxicity. As a matter of fact, the brain has at least two mechanisms to control Glu extracellular concentration. The first is credited mainly to the presence, both on nerve terminals and on astrocytes, of members of a large family of Na+-dependent Glu transporters which bind and take up Glu. This system ensures that the very high concentrations of Glu, transiently present after first synaptic or astrocytic release, are soon decreased to concentrations at which Glu

exerts neither overt excitatory nor excitotoxic activities (Danbolt, 2001 and Sattler and Tymianski, 2001). The second mechanism accounts for the elimination of Glu from brain into blood in the face of an unfavorable concentration gradient between interstitial/cerebrospinal fluids (ISF/CSF) Glu and blood plasma (O’Kane et al., 1999). According to this mechanism, extracellular Glu is transported via Na+-dependent transporters, located on the antiluminal membrane of brain capillaries being concentrated and accumulates into endothelial cells. When its concentration exceeds those found in plasma, Glu is facilitatively transported across the luminal membrane into blood. The brain-to-blood Glu efflux may also involve a glutamate–glutamine (Gln) cycle (yet to be demonstrated) between astroglial end feet and endothelial cells.

We estimated the seasonal influenza vaccine effectiveness (VE) as 1 minus the OR, expressed as a percentage. Among the 773 eligible children, 69 (9%) were excluded (Fig. 1). The main reason for exclusion was lack of informed consent either to collect the nasopharyngeal swab (n = 25) or to be included in the study (n = 10). Pictilisib The 704 remaining children were classified as cases (262 children tested positive for one of the influenza viruses) and controls (442 children who tested negative). The percentage of hospitalised children was 56% (n = 148)

among cases and 75% (n = 332) among controls. Overall, the age of the enrolled children ranged from 6 months to 16 years. The proportion of cases ranged from 12% to 56% in the 11 centres. In 69% of cases and 55% of controls the test was performed the same day of symptom onset. In 97% of cases and in 93% of controls the test was carried out within 2 days. Among cases, B virus was detected in 126 children (48%), A(H1N1) in 59 (23%), unspecified A virus in 33 (13%), A(H1N1)pdm09 in 22 (8%) and A(H3N2) in 22 (8%). In the 2012–2013 season the virology unit of one clinical centre was able to characterise 40 of the 126 cases positive for influenza B selleck screening library virus: they all resulted belonging to B/Yamagata/16/88 lineage. Cases and controls were similar with regard to gender and prevalence of chronic diseases, whereas a statistically significant

difference was observed for age (46 months in cases and 29 months in controls) (Table 1). The median duration of symptoms before the visit to the ED was similar in the two groups (3 days vs. 2), as it was the

level of fever (median of 39 °C in both groups). According to the ILI definition all children heptaminol presented fever ≥38 °C. Cough was the most frequently associated symptom in both cases and controls (85% vs. 83%), followed by rhinorrhea, malaise, sore throat and asthenia. Vomiting or diarrhoea were more frequently reported in younger children (40% in patients up to 5 years and 21% in older ones). Sixty-eight percent of children were hospitalised through the EDs and the mean duration of hospitalisation was not statistically different in cases and controls (3.6 and 4.3 days respectively). Only 25 children (4%) were vaccinated against influenza: seven of the 262 cases and 18 of the 442 controls (they had been vaccinated between October and mid-January). The date of vaccination was not available for six children (one case and five controls). However, it is likely that these children were vaccinated at least 14 days before hospital admission, since they were hospitalised between the end of January and February. Twelve out of the 25 vaccinated children (46%) reported a chronic disease (asthma, allergy, cardiomyopathy, spinal muscular atrophy [SMA 1 or 2], immunodeficiency, aplastic anaemia, coeliac disease, West syndrome). The overall age-adjusted VE was 38% (95% CI: −52% to 75%) (Table 2).

The correlation between the antibody concentration in sera and intestinal washes in each animal was performed calculating the Pearson’s correlation coefficient r. The lymphoproliferative response between groups was analyzed using one-way

ANOVA and Tukey’s post test. Statistical significance was defined as P ≤ 0.05. Graphpad 4.0 software was used for analysis. Vi-specific serum PFI-2 antibodies were assessed in mice subcutaneously immunized with Vi-CRM197, unconjugated Vi, free CRM197 or PBS. Two weeks after priming (day 13), both Vi-CRM197 and Vi immunized mice developed a significant serum Vi-specific IgM response with a geometric mean titer [GMT] of 1280 and 425 respectively (P < 0.001 versus PBS immunized mice; Fig. 1A and Table S1). IgM titers induced by the glycoconjugate were significantly higher than those observed in Vi immunized mice (P < 0.01) ( Fig. 1A and Table S1). After boosting, Vi-specific IgM significantly Hydroxychloroquine decreased (P < 0.05) while IgG significantly increased in Vi-CRM197-immunized mice (GMT of 1689 after priming [day 13] and of 4560 after boosting [day 24], P < 0.01) and persisted until day 60 with titers

significantly higher compared to mice immunized with Vi or CRM197 alone (P < 0.001; Fig. 1B and Table S2). In Vi-immunized mice the IgG response did not significantly increase after boosting, and persisted up to day 60 with a GMT of about 256 (P < 0.001 versus

PBS and CRM197 groups; Fig. 1B and Table S2). The IgG response detected in mice immunized Oxalosuccinic acid with Vi-CRM197 was about 8 times higher than that induced by unconjugated polysaccharide Vi after the primary immunization and about 18 times higher after boosting. These data demonstrate that the glycoconjugate was more efficient in stimulating antibody isotype switching. The analysis of Vi-specific serum IgG subclasses 10 days after boosting (day 24) showed a predominance of IgG1 in mice immunized with Vi-CRM197 (P < 0.001 versus other subclasses; Table S3) that were significantly higher than those observed in mice immunized with Vi antigen alone (P ≤ 0.001; Fig. 1C). These data corroborate the IgG subclass switch observed with other polysaccharides, such as pneumococcal and meninogococcal polysaccharides and their respective conjugate vaccines [13], [14] and [15]. No significant levels of serum Vi-specific IgA were detected in any group. Mice immunized with Vi-CRM197 developed a CRM197-specific serum IgG response with a subclass distribution similar to that observed for anti-Vi IgG (data not shown). This work therefore shows that boosting with Vi-CRM197 induces a significant increase of serum IgG typical of secondary antibody response to T-dependent antigens, and a dominance of the IgG1 subclass.

We now

extend those findings by presenting results from the blinded analysis conducted at the end of the first four years of follow-up. These results focus on the according to protocol (ATP) efficacy findings submitted to the FDA under BB-IND #7920; separate GSK J4 datasheet submissions focus on findings from intent-to-treat and naïve analyses from our trial [12] and [23]. This analysis presents a double-blind randomized controlled trial of an HPV-16/18 vaccine among healthy women 18–25 years old. The study was approved by the Institutional Review Boards in Costa Rica and the US. Detailed methods have been published [11]. In brief, potential participants from a census were invited between June 2004 and December 2005. Eligible women who agreed to participate (N = 7466; estimated to provide >80% power to observe expected differences between arms) were randomized with equal chance to the HPV-16/18 (HPV arm) or Hepatitis A vaccine (control arm), offered in three doses over approximately six months. Blinding to arm assignment was maintained throughout the 48-month follow-up

and until the analytic datafile was frozen. At enrollment, a pelvic exam I-BET151 ic50 was performed on sexually experienced women. Exfoliated cells were collected for cytology, HPV DNA, and other tests. At the 6-month visit, women were asked to provide a self-collected cervical specimen for HPV testing. Blood was collected Sodium butyrate from participants. Each participant was scheduled for annual follow-up examinations (median follow-up time = 53.8 months; inter-quartile range: 50.5–57.0), at which time a pelvic examination was performed on sexually active women, and exfoliated cells and blood were collected. On a pre-defined subset, an additional visit approximately one month following the last vaccine dose was performed where blood

was collected for immunological assessment. Cytology was classified using the Bethesda system. Women with low-grade squamous intraepithelial lesions (LSIL) or HPV positive atypical squamous cells of undetermined significance (ASC-US) were followed semi-annually. The colposcopy referral algorithm used in our trial parallels that used for the PATRICIA trial [6]. Specifically, a repeat LSIL/HPV positive ASC-US, an ASC-US-rule out high-grade SIL (ASC-H), high-grade squamous intraepithelial lesions or more severe disease (HSIL+), or glandular abnormalities prompted colposcopy and treatment as needed [11]. HPV testing using the Hybrid Capture 2 test was performed on enrollment specimens plus specimens from women with an ASC-US cytology during follow-up for clinical management [11]. Broad spectrum PCR-based HPV DNA testing was performed on specimens based on amplification and broad spectrum probe hybridization using the SPF10 HPV DNA enzyme immunoassay system followed by typing using the LiPA25 version 1 line detection system and HPV-16 and -18 type specific testing [11].

However even with a practice of routine NPA testing for respiratory related illness, not

all children will have specimens collected for laboratory confirmation. In our analysis we have made estimates of possible increased disease burden had all children had specimens taken. The laboratory surveillance at PWH suggested that up to 1.6% of infants aged above 6 days and below 6 months of age and 5.2% of children Rho kinase inhibition aged above 6 days to below 18 years are admitted to hospital as a result of influenza infection. We adjusted the CMS flu diagnosis estimates using factors derived from linking our laboratory surveillance results at PWH to the CMS coded diagnoses and then extrapolated these adjustments to the whole of Hong Kong. These adjusted rates were generally higher than the unadjusted rates (Fig. 2 and Fig. 3). During the A(H1N1)pdm09 pandemic in 2009/10 the proportion of children aged above 6 days to below 18 years admitted to hospital who had a diagnosis of influenza almost doubled (9.8%). Reasons for this increase incidence during 2009/2010 GSK-J4 could reflect a genuine increase in disease burden or alternatively

it could reflect changes in admission policy e.g. all suspected A(H1N1)pdm09 infections, including mild cases, were recommended for admission. Measures for severity of illness in the current study were length of stay, intensive care unit admission and outcome. Severity of influenza as measured by mortality else and

length of stay did not appear to be greater in the 6M group as compared to the 18Y group. The median length of stay for the A(H1N1)pdm09 admissions was similar to the that of the non-A(H1N1)pdm09 influenza admissions (Appendix 12) but when categorised into groups, a greater proportion of children with A(H1N1)pdm09 had a length of stay less than 2 days (Table 3), possibly reflecting less severe disease or a greater proportion of admissions with mild disease. However the number of intensive care unit admissions with any CMS diagnosis of influenza was highest during 2009/10. Incidence estimates based on adjustment factor 3 (PWH laboratory confirmed influenza rate) tended to be higher than the other incidence estimates except during 2009/10 (Fig. 2), possibly reflecting a sustained high level of routine NPA testing for influenza during the whole study period at PWH, but with other HA hospitals only increasing their NPA testing for influenza from 2009/10. Limitations to our incidence estimates include a number of assumptions related to admissions to public HA hospitals and the resident Hong Kong population. The proportion of admissions to public hospitals has fallen in recent years and there has been a marked increase in the number of mothers from mainland China delivering in Hong Kong.

One four-arm trial (Itoh et al 2007) compared traditional Chinese acupuncture with acupuncture directed at ‘trigger points’, acupuncture directed to regions adjacent to ‘trigger points’, and sham acupuncture. The three acupuncture groups in this trial were combined to create a single pair-wise comparison. Pooled outcomes

from five trials (Itoh et al 2007, Nabeta and Kawakita 2002, Petrie and Hazleman 1986, Vas et al 2006, White et al 2004) showed no significant difference in pain outcomes between acupuncture and control at the conclusion of a course of treatment (WMD –12, 95% CI –23 to 0.1). Pooled results from the three trials (Petrie and Hazleman 1986, Vas et al 2006, White et al 2004) that reported

medium-term pain outcomes showed acupuncture to be no more Selleck BYL719 effective selleck chemicals llc than control (WMD –4, 95% CI –15 to 7), consistent with the single trial (White et al 2004) that reported long-term pain outcomes (MD –4, 95% CI –13 to 7). Pooled outcomes from five trials (Itoh et al 2007, Petrie and Hazleman 1986, Vas et al 2006, White et al 2004, Witt et al 2006) showed a significant but small difference in disability outcomes in favour of acupuncture at the conclusion of treatment (WMD –8, 95% CI –13 to –2). Pooled outcomes from the three trials (Petrie and Hazleman 1986, White et al 2004, Witt et al 2006) that reported medium-term disability outcomes Levetiracetam demonstrated that acupuncture was not more effective than control (WMD –1, 95% CI –2 to 0.3), consistent with the single trial (White et al 2004) that reported long-term disability outcomes (MD –4, 95% CI –10 to 2). Exercise: Five trials investigated exercise for non-specific neck pain. One three-arm trial ( Kjellman and Oberg 2002)

compared McKenzie exercise with general exercise and with sham ultrasound. Four trials compared various exercise approaches with minimal intervention. The exercise approaches included ‘proprioceptive’ exercises ( Revel et al 1994), a combined program of neck stabilisation, relaxation, eye fixation, behavioural support, and posture training ( Taimela et al 2000), group gymnastic exercises ( Takala et al 1994), and muscle strengthening ( Viljanen et al 2003). Pooled outcomes from three trials (Kjellman and Oberg 2002, Revel et al 1994, Taimela et al 2000) showed significant reduction in pain at the conclusion of a course of specific exercises (WMD –12, 95% CI –22 to –2). The single trial that reported medium- (MD –6, 95% CI –17 to 5) and long-term (MD 1, 95% CI –12 to 14) pain outcomes for specific exercise programs did not demonstrate similar benefit (Kjellman and Oberg 2002). One trial (Kjellman and Oberg 2002) showed no significant difference in disability at the conclusion of a course of specific exercises (MD –3, 95% CI –10 to 4) and medium- (MD –3, 95% CI –11 to 5) and long-term (MD 2, 95% CI –6 to 10) follow-up.