SummaryBackgroundCytomegalovirus end-organ disease can be prevented by giving ganciclovir when viraemia is detected in allograft recipients. Values of viral load correlate with development of end-organ disease and are moderated by pre-existing natural immunity. Our aim was to determine whether vaccine-induced immunity could do likewise.MethodsWe undertook a phase-2 randomised placebo controlled trial in adults awaiting kidney or liver transplantation at the Royal Free Hospital, London, UK. Exclusion criteria were pregnancy, receipt of blood products (except albumin) in the previous 3 months, and simultaneous multiorgan transplantation. 70 patients seronegative and 70 seropositive for cytomegalovirus were randomly assigned from a scratch-off randomisation code in a 1:1 ratio to receive either cytomegalovirus glycoprotein-B vaccine with MF59 adjuvant or placebo, each given at baseline, 1 month and 6 months later. If a patient was transplanted, no further vaccinations were given and serial blood samples were tested for cytomegalovirus DNA by real-time quantitative PCR (rtqPCR). Any patient with one blood sample containing more than 3000 cytomegalovirus genomes per mL received ganciclovir until two consecutive undetectable cytomegalovirus DNA measurements. Safety and immunogenicity were coprimary endpoints and were assessed by intention to treat in patients who received at least one dose of vaccine or placebo. This trial is registered with ClinicalTrials.gov, NCT00299260.Findings67 patients received vaccine and 73 placebo, all of whom were evaluable. Glycoprotein-B antibody titres were significantly increased in both seronegative (geometric mean titre 12 537 (95% CI 6593–23 840) versus 86 (63–118) in recipients of placebo recipients; p<0·0001) and seropositive (118 395; 64 503–217 272) versus 24 682 (17 909–34 017); p<0·0001) recipients of vaccine. In those who developed viraemia after transplantation, glycoprotein-B antibody titres correlated inversely with duration of viraemia (p=0·0022). In the seronegative patients with seropositive donors, the duration of viraemia (p=0·0480) and number of days of ganciclovir treatment (p=0·0287) were reduced in vaccine recipients.InterpretationAlthough cytomegalovirus disease occurs in the context of suppressed cell-mediated immunity post-transplantation, humoral immunity has a role in reduction of cytomegalovirus viraemia. Vaccines containing cytomegalovirus glycoprotein B merit further assessment in transplant recipients.Funding, Grant R01AI051355 and , Grant 078332. Sponsor: University College London (UCL).

After allotransplantation, cytomegalovirus (CMV) may be transmitted from the donor organ, giving rise to primary infection in a CMV negative recipient or reinfection in one who is CMV positive. In addition, latent CMV may reactivate in a CMV positive recipient. In this study, serial blood samples from 689 kidney or liver transplant recipients were tested for CMV DNA by quantitative PCR. CMV was managed using preemptive antiviral therapy and no patient received antiviral prophylaxis. Dynamic and quantitative measures of viremia and treatment were assessed. Median peak viral load, duration of viremia and duration of treatment were highest during primary infection, followed by reinfection then reactivation. In patients who experienced a second episode of viremia, the viral replication rate was significantly slower than in the first episode. Our data provide a clear demonstration of the immune control of CMV in immunosuppressed patients and emphasize the effectiveness of the preemptive approach for prevention of CMV syndrome and end organ disease. Overall, our findings provide quantitative biomarkers which can be used in pharmacodynamic assessments of the ability of novel CMV vaccines or antiviral drugs to reduce or even interrupt such transmission.

BackgroundLow back pain is a common musculoskeletal disorder defined as pain and soreness, muscle tension, or stiffness in the lumbosacral area of the spine which does not have a specific cause. Low back pain results in high health costs and incapacity to work causing an economic burden to society. The optimal management of non-specific low back pain appears to be undecided. Recently published guidelines support the use of acupuncture for treating non-specific low back pain and it has become a popular alternative treatment modality for patients with low back pain.MethodsA comprehensive systematic literature search was conducted through Medline using Ovid and Medical Subject Headings for randomized controlled trials published in the last 10 years. The outcomes scored were subjective pain scores and functional outcome scores.ResultsEighty two randomized studies were identified, of which 7 met our inclusion criteria. Three studies found a significant difference in pain scores when comparing acupuncture, or sham acupuncture, with conventional therapy or no care. Two studies demonstrated a significant difference between acupuncture treatment and no treatment or routine care at 8 weeks and 3 months. Three studies demonstrated no significant difference between acupuncture and minimal/sham acupuncture with no difference in pain relief or function over 6 to 12 months.ConclusionsThis review provides some evidence to support acupuncture as more effective than no treatment, but no conclusions can be drawn about its effectiveness over other treatment modalities as the evidence is conflicting.

AimsTo compare the gait of unicompartmental knee arthroplasty (UKA) and total knee arthroplasty (TKA) patients with healthy controls, using a machine-learning approach.Patients and Methods145 participants (121 healthy controls, 12 patients with cruciate-retaining TKA, and 12 with mobile-bearing medial UKA) were recruited. The TKA and UKA patients were a minimum of 12 months post-operative, and matched for pattern and severity of arthrosis, age, and body mass index. Participants walked on an instrumented treadmill until their maximum walking speed was reached. Temporospatial gait parameters, and vertical ground reaction force data, were captured at each speed. Oxford knee scores (OKS) were also collected. An ensemble of trees algorithm was used to analyse the data: 27 gait variables were used to train classification trees for each speed, with a binary output prediction of whether these variables were derived from a UKA or TKA patient. Healthy control gait data was then tested by the decision trees at each speed and a final classification (UKA or TKA) reached for each subject in a majority voting manner over all gait cycles and speeds. Top walking speed was also recorded.Results92% of the healthy controls were classified by the decision tree as a UKA, 5% as a TKA, and 3% were unclassified. There was no significant difference in OKS between the UKA and TKA patients (p = 0.077). Top walking speed in TKA patients (1.6 m/s; 1.3 to 2.1) was significantly lower than that of both the UKA group (2.2 m/s; 1.8 to 2.7) and healthy controls (2.2 m/s; 1.5 to 2.7; p < 0.001). ConclusionUKA results in a more physiological gait compared with TKA, and a higher top walking speed. This difference in function was not detected by the OKS.Cite this article: Bone Joint J 2016;98-B(10 Suppl B):16–21.