Immunogenicity, safety, and reactogenicity of heterologous COVID-19 primary vaccination incorporating mRNA, viral-vector, and protein-adjuvant vaccines in the UK (Com-COV2): a single-blind, randomised, phase 2, non-inferiority trial.

BACKGROUND: Given the importance of flexible use of different COVID-19 vaccines within the same schedule to facilitate rapid deployment, we studied mixed priming schedules incorporating an adenoviral-vectored vaccine (ChAdOx1 nCoV-19 [ChAd], AstraZeneca), two mRNA vaccines (BNT162b2 [BNT], Pfizer-BioNTech, and mRNA-1273 [m1273], Moderna) and a nanoparticle vaccine containing SARS-CoV-2 spike glycoprotein and Matrix-M adjuvant (NVX-CoV2373 [NVX], Novavax). METHODS: Com-COV2 is a single-blind, randomised, non-inferiority trial in which adults aged 50 years and older, previously immunised with a single dose of ChAd or BNT in the community, were randomly assigned (in random blocks of three and six) within these cohorts in a 1:1:1 ratio to receive a second dose intramuscularly (8-12 weeks after the first dose) with the homologous vaccine, m1273, or NVX. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentrations measured by ELISA in heterologous versus homologous schedules at 28 days after the second dose, with a non-inferiority criterion of the GMR above 0·63 for the one-sided 98·75% CI. The primary analysis was on the per-protocol population, who were seronegative at baseline. Safety analyses were done for all participants who received a dose of study vaccine. The trial is registered with ISRCTN, number 27841311. FINDINGS: Between April 19 and May 14, 2021, 1072 participants were enrolled at a median of 9·4 weeks after receipt of a single dose of ChAd (n=540, 47% female) or BNT (n=532, 40% female). In ChAd-primed participants, geometric mean concentration (GMC) 28 days after a boost of SARS-CoV-2 anti-spike IgG in recipients of ChAd/m1273 (20 114 ELISA laboratory units [ELU]/mL [95% CI 18 160 to 22 279]) and ChAd/NVX (5597 ELU/mL [4756 to 6586]) was non-inferior to that of ChAd/ChAd recipients (1971 ELU/mL [1718 to 2262]) with a GMR of 10·2 (one-sided 98·75% CI 8·4 to ∞) for ChAd/m1273 and 2·8 (2·2 to ∞) for ChAd/NVX, compared with ChAd/ChAd. In BNT-primed participants, non-inferiority was shown for BNT/m1273 (GMC 22 978 ELU/mL [95% CI 20 597 to 25 636]) but not for BNT/NVX (8874 ELU/mL [7391 to 10 654]), compared with BNT/BNT (16 929 ELU/mL [15 025 to 19 075]) with a GMR of 1·3 (one-sided 98·75% CI 1·1 to ∞) for BNT/m1273 and 0·5 (0·4 to ∞) for BNT/NVX, compared with BNT/BNT; however, NVX still induced an 18-fold rise in GMC 28 days after vaccination. There were 15 serious adverse events, none considered related to immunisation. INTERPRETATION: Heterologous second dosing with m1273, but not NVX, increased transient systemic reactogenicity compared with homologous schedules. Multiple vaccines are appropriate to complete primary immunisation following priming with BNT or ChAd, facilitating rapid vaccine deployment globally and supporting recognition of such schedules for vaccine certification. FUNDING: UK Vaccine Task Force, Coalition for Epidemic Preparedness Innovations (CEPI), and National Institute for Health Research. NVX vaccine was supplied for use in the trial by Novavax.

Tibial rotational osteotomy and distal tuberosity transfer for patella subluxation secondary to excessive external tibial torsion: surgical technique and clinical outcome.

PURPOSE: Recurrent patella subluxation may be secondary to excessive external tibial torsion. The purpose of this study is to evaluate the clinical and radiographic outcome of patients undergoing tibial derotation osteotomy and tibial tuberosity transfer for recurrent patella subluxation in association with excessive external tibial torsion. METHODS: A combined tibial derotation osteotomy and tibial tuberosity transfer was performed in 15 knees (12 patients) with recurrent patella subluxation secondary to excessive external tibial torsion. Clinical evaluation was carried out using preoperative and post-operative Knee Society Score (KSS), Kujala Patellofemoral score, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, the short form-12 (SF-12) and a visual analogue score (VAS) pain scale. RESULTS: The median follow-up period was 84 months (range 15-156) and median patient age was 34 years (range 19-57 years). The median preoperative external tibial torsion was 62° (range 55°-70°), with a median rotational correction of 36° (range 30°-45°) after surgery. Significant improvement (p < 0.05) was found in the KSS part I (37 ± 14 to 89 ± 11 points), KSS part II (25 ± 26 to 85 ± 14 points), Kujala score, the SF-12 outcome, WOMAC score and VAS score (8.8 ± 1.9 to 2.4 ± 1.5). Two patients had a nonunion of the tibial osteotomy site; one patient required bone grafting, while another patient required revision to total knee arthroplasty. CONCLUSION: Patients presenting with recurrent patella subluxation secondary to excessive external tibial torsion >45° who underwent tibial derotation osteotomy and tibial tuberosity transfer achieved a satisfactory outcome in terms of pain relief and improved function. A significant complication was seen in 2/15 patients. LEVEL OF EVIDENCE: Case series, Level IV.

Prospective surveillance study of the management of intussusception in UK and Irish infants.

BACKGROUND: Intussusception is the most common cause of acute intestinal obstruction in infants. This study examined the clinical presentation, management and outcomes of intussusception in this age group. METHODS: Prospective surveillance of intussusception in infants was carried out between March 2008 and March 2009 in the UK and Ireland. Monthly cards were sent to paediatric clinicians who were requested to notify cases of intussusception. RESULTS: The study identified 261 confirmed cases. The commonest presenting symptom/sign was non-bilious vomiting, in 210 (80·5 per cent) of the infants. Abdominal ultrasonography was done in 247 infants (94·6 per cent) and was diagnostic in 242 (98·0 per cent), compared with plain abdominal X-ray, which was diagnostic in 33 (23·6 per cent) of 140 infants. Enema reduction was carried out in 240 (92·0 per cent) of the 261 infants; the majority (237, 98·8 per cent) had pneumatic reduction with a success rate of 61·2 per cent (145 of 237). Surgery was required in 111 infants (42·5 per cent); 92 operations were as a result of unsuccessful enema reduction, and the remaining 19 infants (17·1 per cent) had primary surgery. Forty-four infants (39·6 per cent of operations) needed a bowel resection. The majority of children (238, 91·2 per cent) recovered uneventfully; 21 (8·0 per cent) had sequelae, one child died (0·4 per cent), and the outcome was unknown for one infant. CONCLUSION: This study described current treatment patterns for intussusception in infancy; these represent a benchmark for improved standards of care for this condition.

Total knee replacement with rotational proximal tibial osteotomy for osteoarthritis with severe external tibial torsion and patellar instability.

The management of osteoarthritis of the knee associated with patellar instability secondary to external tibial torsion > 45 degrees is challenging. Patellofemoral biomechanics in these patients cannot be achieved by intra-articular correction using standard techniques of total knee replacement. We reviewed seven patients (eight knees) with recurrent patellar dislocation and one with bilateral irreducible lateral dislocation who had undergone simultaneous total knee replacement and internal tibial derotational osteotomy. All had osteoarthritis and severe external tibial torsion. The mean follow-up was for 47.2 months (24 to 120). The mean objective and functional Knee Society scores improved significantly (p = 0.0001) from 29.7 and 41.5 pre-operatively to 71.4 and 73.5 post-operatively, respectively. In all patients the osteotomies healed and patellar stability was restored. Excessive external tibial torsion should be identified and corrected in patients with osteoarthritis and patellar instability. Simultaneous internal rotation osteotomy of the tibia and total knee replacement is a technically demanding but effective treatment for such patients.

The development of novel and selective p56lck tyrosine kinase inhibitors.

Early T-cell receptor mediated signal transduction involves the activation of several tyrosine protein kinases. One of these tyrosine kinases, p56lck, is expressed primarily in T-cells and Natural Killer (NK) cells and has been shown to be critical for their proliferative and effector functions. Indandiones have been identified as a potent and selective chemical class that inhibits p56lck.

Meniscal allograft transplantation for unicompartmental arthritis of the knee.

Sixty-seven meniscal allografts were transplanted in the knees of 63 patients between 1988 and 1994. Before surgery, all patients experienced refractory disabling knee pain secondary to a prior total meniscectomy with advanced unicompartmental osteoarthritic changes as verified by arthroscopy. At a mean followup of 31 months (range, 1.0-5.5 years), 58 knees (86.6%) attained a good to excellent results-Twenty-one knees received isolated meniscal allografts, with 19 achieving good to excellent results (90.5%). Five knees received a medial or lateral meniscal allograft with an anterior cruciate ligament reconstruction, and 4 (80.0%) obtained good to excellent results. Thirty-four knees received a meniscal allograft in combination with either a valgus high tibial osteotomy, varus high tibial osteotomy, or varus distal femoral osteotomy to correct for preoperative varus or valgus deformities, with 29 (85.3%) attaining good to excellent results. The remaining 7 knees underwent a combined medial meniscal allograft, valgus high tibial osteotomy, and anterior cruciate ligament reconstruction with 6 (85.7%) attaining good to excellent results. The most frequent complication was a traumatic posterior horn tear in 6 knees at a mean of 21 months after surgery (range, 9-43 months), most likely the consequence of unsuccessful healing of the posterior horn of the graft.

Ifosfamide neurotoxicity. A challenge for nurses, a potential nightmare for patients.

The alkylator-like agent ifosfamide, which has been found to be useful in the treatment of a number of solid tumors, can have severe central nervous system (CNS) side effects in addition to causing myelosuppression, nephrotoxicity, nausea and vomiting, pulmonary edema, and interstitial pneumonitis. This article, including a case study and a protocol, prepares nurses to do patient education and to observe, assess, and provide care for patients who may experience the CNS toxicity that ranges from mild changes to severe disturbances of mental state.

Constipation related to narcotic therapy. A protocol for nurses and patients.

Constipation is a well-known side effect of narcotics and can add to the total burden of pain of cancer patients in need of pain medication. There is little literature on this topic, and it has been suggested that one reason is that the definitions are vague and socially bound. It has also been suggested that some physicians consider constipation a trivial problem, resulting in a relative lack of attention to the subject. Although this article addresses narcotic-induced constipation, other types related to poor dietary and exercise habits and to disease are mentioned and may be contributing factors. There are a number of drugs and treatments available to treat the problem, but the emphasis of nursing care should be on prevention of constipation. Senna derivatives have been noted to reverse the major constipating effect of narcotics, i.e., the decrease in propulsive movements of the colon, and it is recommended they be given right along with narcotics as a preventive measure. A protocol that incorporates a schedule of drugs and dosages and specific patient and nursing guidelines for daily evaluation of bowel function, with education about dietary, fluid, and exercise requirements, will help nurses practice prevention and contribute to patients' comfort.

Chronic anterior cruciate ligament deficiency. Long-term results of MacIntosh's lateral substitution reconstruction.

The lateral substitution reconstruction operation described by MacIntosh has been evaluated in 27 patients with chronic anterior cruciate ligament deficiency of the knee. The results, at an average of 11.3 years after operation, have been assessed by a scoring system which allocates a maximum of 25 points each for function and for clinical evaluation. Emphasis was placed on subjective giving way and objective evidence of a positive anterior drawer sign and a positive lateral pivot shift test. A score of 46 to 50 was classified as excellent, 41 to 46 as fair, and less than 41 was a poor result: 52% scored excellent, 26% fair and 22% were poor. Most of those with poor results had had evidence of osteoarthritis at the time of operation. Despite the recorded scores, no less than 75% of the patients at long-term follow-up were subjectively improved, and able to maintain an active life style.

Submucosal accumulation of fat in inflammatory bowel disease: CT/pathologic correlation.

A prominent submucosal layer of decreased attenuation was demonstrated on CT in three patients with inflammatory bowel disease. On pathologic examination this zone proved to be due to extensive submucosal fat accumulation and not active inflammation. The potential significance of this finding is discussed.