A plain language summary of how well the single-dose Janssen vaccine works and how safe it is.

This is a summary of a publication about the ENSEMBLE trial of the Janssen Ad26.COV2.S vaccine against COVID-19, which was published in the New England Journal of Medicine in April 2021. The ENSEMBLE study started in September 2020 and is still ongoing. The study compared the effectiveness of the vaccine to a placebo in 43,783 adults from Latin America, South Africa, and the United States. Of those, 19,630 got a single dose of the vaccine. Compared to the placebo, the vaccine prevented: 66.9% of moderate to severe-critical COVID-19 cases after 14 days66.1% of moderate to severe-critical COVID-19 cases after 28 days85.4% of severe COVID-19 cases after 28 days100% of people with severe COVID-19 from needing to go to hospital for treatment None of the vaccinated participants died from COVID-19. There were 5 people who got the placebo who died from COVID-19. The vaccine was similarly effective in people from all age groups and different countries, including South Africa, where most cases were caused by the beta variant of the virus that originated there. The people in the study who got the vaccine who went on to get COVID-19 generally had milder and fewer symptoms than those who got the placebo. In most people, the vaccine started working after about 2 weeks. After receiving the vaccine, some people experienced pain at the injection site, headache, tiredness, muscle pain, and nausea. In most cases, these were mild and went away within a few days. Serious side effects were very rare. Blood clots, seizures, and tinnitus were very rare but were more common in the people who got the vaccine than in those who got the placebo. At the time of the study, it was not clear if these were caused by the vaccine or not. ClinicalTrials.gov NCT number: NCT04505722.

Non-traumatic chronic shoulder pain is not associated with changes in rotator cuff interval tendon thickness.

OBJECTIVE: To determine whether the thickness of the rotator interval tendons is different when comparing both symptomatic and non-symptomatic sides in people with chronic shoulder pain, and to those free of pain. Furthermore, to calculate the level of association between the rotator interval tendon thicknesses and perceived shoulder pain-function. DESIGN: A cross-sectional, observational study. METHOD: The supraspinatus, subscapularis and biceps brachii tendon thickness of sixty two patients with chronic shoulder pain were determined from standardized ultrasonography measures performed on both shoulders, whereas only the dominant arm was measured for the control subjects. FINDINGS: Supraspinatus, subscapularis and biceps brachii tendon thickness was comparable between sides in the symptomatic group and was also comparable between the symptomatic and asymptomatic participants. In addition, the correlation between the tendon thickness and shoulder pain-function was non-significant. INTERPRETATIONS: Tendon thickness was unaltered in people with chronic shoulder pain. These findings do not rule out the possibility that other changes in the tendon are present such as changes in the elastic properties and cell population and this should be explored in future studies.

Sensory processing and central pain modulation in patients with chronic shoulder pain: A case-control study.

Chronicity and recurrence in musculoskeletal shoulder pain are highly prevalent and can possibly be attributed to the concept of central sensitization. Available studies suggest a role for central sensitization in explaining chronic shoulder pain, but so far a comprehensive quantitative sensory testing (QST) protocol has not been used. The aim of this study was to gain knowledge on sensory processing and central pain modulatory mechanisms in patients suffering from chronic shoulder pain using such a QST protocol. Fifty study participants, including chronic shoulder pain patients and healthy controls, underwent a standardized, comprehensive psychophysical testing procedure. A static adapted QST protocol (including pressure algometry, vibration and mechanical detection) was applied. Thereafter, all subjects underwent dynamic measures of temporal summation and conditioned pain modulation. Questionnaires assessing psychosocial factors were completed by each subject. No significant differences (P >= .05) were found between patients and controls based on pressure algometry, vibration detection, mechanical detection, temporal summation, and conditioned pain modulation. Moderate positive correlations (r = .5) were found between pressure pain thresholds (PPTs) and the amount of sports participation. Weak-to-moderate negative correlations (r = -.3 à -.5) were found between PPTs and psychosocial factors such as pain catastrophizing. Based on these findings, we can conclude that central sensitization is no characteristic feature in chronic musculo-skeletal shoulder pain but can be present in individual cases.

Is coracohumeral distance associated with pain-function, and shoulder range of movement, in chronic anterior shoulder pain?

BACKGROUND: The aim of this study was twofold: (i) to assess the intrarater reliability of coracohumeral distance; (ii) to investigate the level of association between coracohumeral distance measured by ultrasonography, and pain-disability and shoulder range of movement, in patients suffering from chronic anterior shoulder pain. METHODS: An observational, cross sectional study was carried out. A convenience sample comprised of 87 patients with chronic anterior shoulder pain was assessed from 3 primary care centres. Main outcomes as pain and function were measured through the shoulder pain and disability index. Furthermore, shoulder range of movement-free of pain in shoulder elevation, as well as coracohumeral distance at both 0 and 60 degrees, were collected. RESULTS: Absence of any correlation was found between coracohumeral distance and shoulder pain and disability index at both 0 and 60 degrees of shoulder elevation. Furthermore, absence of any correlation was found between coracohumeral distance measurements and active shoulder range of movement -free of pain. CONCLUSIONS: There was poor association between coracohumeral distance and shoulder pain and function, as well as with shoulder range of movement, in patients with chronic anterior shoulder pain. Hence, clinicians should consider, not only increasing this space, but also other possibilities in their therapies, when patients with anterior shoulder pain are treated. TRIAL REGISTRATION: ACTRN12614000144617 . Registered: 1st March 2014.

Inter-rater reliability of shoulder measurements in middle-aged women.

OBJECTIVES: To investigate inter-rater reliability of a set of shoulder measurements including inclinometry [shoulder range of motion (ROM)], acromion-table distance and pectoralis minor muscle length (static scapular positioning), upward rotation with two inclinometers (scapular kinematics) and pain pressure thresholds (muscle tenderness) in middle-aged women. DESIGN: Observational study. PARTICIPANTS: Thirty symptom-free middle-aged women (first cohort) were measured by two raters. All measurements with an intraclass correlation coefficient (ICC) below 0.75 were retested after an additional training period in a second cohort of 30 symptom-free middle-aged women. MAIN OUTCOME MEASURES: Inter-rater reliability of all variables was measured with the ICC (95% confidence interval) and standard error of measurement (SEM). RESULTS: Acromion-table distance (ICC=0.91, SEM 0.22 to 0.28% of body length), pectoralis minor muscle length (ICC=0.91, SEM 0.16% of body length), pain pressure thresholds (ICC=0.78 to 0.85, SEM 0.39 to 0.70kg) and abduction ROM (ICC=0.77, SEM 5°) showed good to excellent inter-rater reliability in the first cohort. After an additional training period, forward flexion ROM showed good inter-rater reliability (ICC=0.83, SEM 5°), scapular upward rotation in resting position showed moderate reliability (ICC=0.52, SEM 2°), and other scaption angles showed weak reliability (ICC=0.26 to 0.43, SEM 3 to 8°). CONCLUSIONS: In a battery of clinical tools to evaluate factors contributing to shoulder pain, static scapular positioning and pressure pain thresholds were found to have good to excellent inter-rater reliability in middle-aged women. Additional training is recommended for measurements with a gravity inclinometer.

Does scapular positioning predict shoulder pain in recreational overhead athletes?

The objective of this prospective study is to investigate possible scapular related risk factors for developing shoulder pain. Therefore, a 2-year follow-up study in a general community sports centre setting was conducted. A sample of convenience of 113 recreational overhead athletes (59 women and 54 men) with a mean age of 34 (17-64; SD 12) years were recruited. At baseline, visual observation for scapular dyskinesis, measured scapular protraction, upward scapular rotation and dynamic scapular control were evaluated. 22% (n=25) of all athletes developed shoulder pain during the 24 months following baseline assessment. The Mean Shoulder Disability Questionnaire (SDQ) score for the painful shoulders was 34.8 (6.3-62.5; SD 17.4). None of the scapular characteristics predicted the development of shoulder pain. However, the athletes that developed shoulder pain demonstrated significantly less upward scapular rotation at 45° (p=0.010) and 90° (p=0.016) of shoulder abduction in the frontal plane at baseline in comparison to the athletes that remained pain-free. In conclusion, although these scapular characteristics are not of predictive value for the development of shoulder pain, this study increases our understanding of the importance of a scapular upward rotation assessment among recreational overhead athletes.

Scapular-focused treatment in patients with shoulder impingement syndrome: a randomized clinical trial.

The purpose of this clinical trial is to compare the effectiveness of a scapular-focused treatment with a control therapy in patients with shoulder impingement syndrome. Therefore, a randomized clinical trial with a blinded assessor was used in 22 patients with shoulder impingement syndrome. The primary outcome measures included self-reported shoulder disability and pain. Next, patients were evaluated regarding scapular positioning and shoulder muscle strength. The scapular-focused treatment included stretching and scapular motor control training. The control therapy included stretching, muscle friction, and eccentric rotator cuff training. Main outcome measures were the shoulder disability questionnaire, diagnostic tests for shoulder impingement syndrome, clinical tests for scapular positioning, shoulder pain (visual analog scale; VAS), and muscle strength. A large clinically important treatment effect in favor of scapular motor control training was found in self-reported disability (Cohen's d = 0.93, p = 0.025), and a moderate to large clinically important improvement in pain during the Neer test, Hawkins test, and empty can test (Cohen's d 0.76, 1.04, and 0.92, respectively). In addition, the experimental group demonstrated a moderate (Cohen's d = 0.67) improvement in self-experienced pain at rest (VAS), whereas the control group did not change. The effects were maintained at three months follow-up.

Efficacy of the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine in women aged 15-25 years with and without serological evidence of previous exposure to HPV-16/18.

In the Phase III PATRICIA study (NCT00122681), the human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (Cervarix(®), GlaxoSmithKline Biologicals) was highly efficacious against HPV-16/18 infections and precancerous lesions in women HPV-16/18 deoxyribose nucleic acid (DNA) negative and seronegative at baseline. We present further data on vaccine efficacy (VE) against HPV-16/18 in the total vaccinated cohort including women who may have been exposed to HPV-16/18 infection before vaccination. In women with no evidence of current or previous HPV-16/18 infection (DNA negative and seronegative), VE was 90.3% (96.1% confidence interval: 87.3-92.6) against 6-month persistent infection (PI), 91.9% (84.6-96.2) against cervical intraepithelial neoplasia (CIN)1+ and 94.6% (86.3-98.4) against CIN2+ [97.7% (91.1-99.8) when using the HPV type assignment algorithm (TAA)]. In women HPV-16/18 DNA negative but with serological evidence of previous HPV-16/18 infection (seropositive), VE was 72.3% (53.0-84.5) against 6-month PI, 67.2% (10.9-89.9) against CIN1+, and 68.8% (-28.3-95.0) against CIN2+ [88.5% (10.8-99.8) when using TAA]. In women with no evidence of current HPV-16/18 infection (DNA negative), regardless of their baseline HPV-16/18 serological status, VE was 88.7% (85.7-91.1) against 6-month PI, 89.1% (81.6-94.0) against CIN1+ and 92.4% (84.0-97.0) against CIN2+ [97.0% (90.6-99.5) when using TAA]. In women who were DNA positive for one vaccine type, the vaccine was efficacious against the other vaccine type. The vaccine did not impact the outcome of HPV-16/18 infections present at the time of vaccination. Vaccination was generally well tolerated regardless of the woman's HPV-16/18 DNA or serological status at entry.

Scapular positioning and movement in unimpaired shoulders, shoulder impingement syndrome, and glenohumeral instability.

The purpose of this manuscript is to review the knowledge of scapular positioning at rest and scapular movement in different anatomic planes in asymptomatic subjects and patients with shoulder impingement syndrome (SIS) and glenohumeral shoulder instability. We reviewed the literature for all biomechanical and kinematic studies using keywords for impingement syndrome, shoulder instability, and scapular movement published in peer reviewed journal. Based on the predefined inclusion and exclusion criteria, 30 articles were selected for inclusion in the review. The literature is inconsistent regarding the scapular resting position. At rest, the scapula is positioned approximately horizontal, 35° of internal rotation and 10° anterior tilt. During shoulder elevation, most researchers agree that the scapula tilts posteriorly and rotates both upward and externally. It appears that during shoulder elevation, patients with SIS demonstrate a decreased upward scapular rotation, a decreased posterior tilt, and a decrease in external rotation. In patients with glenohumeral shoulder instability, a decreased scapular upward rotation and increased internal rotation is seen. This literature overview provides clinicians with insight into scapular kinematics in unimpaired shoulders and shoulders with impingement syndrome and instability.

Scapular positioning in overhead athletes with and without shoulder pain: a case-control study.

Abnormalities of scapular positioning are considered important risk factors for developing shoulder disorders. This study analyses the scapular positioning pattern in a group of overhead athletes with and without shoulder pain. In a multi-center blinded case-control study, 36 shoulder pain athletes (19 men, 17 women), were compared with 36 unimpaired athletes free of shoulder pain, matched for gender, age, hand dominance and body mass index. The blinded assessor performed visual observation, the measurement of the distance between the acromion and the table, inclinometry and the kinetic medial rotation test for dynamic scapular control in random order. Athletes with shoulder pain demonstrate scapular asymmetry in the sagittal plane, observed visually as anterior tilting on the painful side. Athletes with shoulder pain show a lack of scapular motor control on their painful side in contrast to their pain-free side. No scapular positioning or motor control differences were found in athletes with or without shoulder pain.

Efficacy of human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine against cervical infection and precancer caused by oncogenic HPV types (PATRICIA): final analysis of a double-blind, randomised study in young women.

BACKGROUND: The human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine was immunogenic, generally well tolerated, and effective against HPV-16 or HPV-18 infections, and associated precancerous lesions in an event-triggered interim analysis of the phase III randomised, double-blind, controlled PApilloma TRIal against Cancer In young Adults (PATRICIA). We now assess the vaccine efficacy in the final event-driven analysis. METHODS: Women (15-25 years) were vaccinated at months 0, 1, and 6. Analyses were done in the according-to-protocol cohort for efficacy (ATP-E; vaccine, n=8093; control, n=8069), total vaccinated cohort (TVC, included all women receiving at least one vaccine dose, regardless of their baseline HPV status; represents the general population, including those who are sexually active; vaccine, n=9319; control, n=9325), and TVC-naive (no evidence of oncogenic HPV infection at baseline; represents women before sexual debut; vaccine, n=5822; control, n=5819). The primary endpoint was to assess vaccine efficacy against cervical intraepithelial neoplasia 2+ (CIN2+) that was associated with HPV-16 or HPV-18 in women who were seronegative at baseline, and DNA negative at baseline and month 6 for the corresponding type (ATP-E). This trial is registered with ClinicalTrials.gov, number NCT00122681. FINDINGS: Mean follow-up was 34.9 months (SD 6.4) after the third dose. Vaccine efficacy against CIN2+ associated with HPV-16/18 was 92.9% (96.1% CI 79.9-98.3) in the primary analysis and 98.1% (88.4-100) in an analysis in which probable causality to HPV type was assigned in lesions infected with multiple oncogenic types (ATP-E cohort). Vaccine efficacy against CIN2+ irrespective of HPV DNA in lesions was 30.4% (16.4-42.1) in the TVC and 70.2% (54.7-80.9) in the TVC-naive. Corresponding values against CIN3+ were 33.4% (9.1-51.5) in the TVC and 87.0% (54.9-97.7) in the TVC-naive. Vaccine efficacy against CIN2+ associated with 12 non-vaccine oncogenic types was 54.0% (34.0-68.4; ATP-E). Individual cross-protection against CIN2+ associated with HPV-31, HPV-33, and HPV-45 was seen in the TVC. INTERPRETATION: The HPV-16/18 AS04-adjuvanted vaccine showed high efficacy against CIN2+ associated with HPV-16/18 and non-vaccine oncogenic HPV types and substantial overall effect in cohorts that are relevant to universal mass vaccination and catch-up programmes. FUNDING: GlaxoSmithKline Biologicals.

Glycoprotein D-independent spread of pseudorabies virus infection in cultured peripheral nervous system neurons in a compartmented system.

The molecular mechanisms underlying the directional neuron-to-epithelial cell transport of herpesvirus particles during infection are poorly understood. To study the role of the viral glycoprotein D (gD) in the directional spread of herpes simplex virus (HSV) and pseudorabies virus (PRV) infection, a culture system consisting of sympathetic neurons or epithelial cells in different compartments was employed. We discovered that PRV infection could spread efficiently from neurons to cells and back to neurons in the absence of gD, the viral ligand required for entry of extracellular particles. Unexpectedly, PRV infection can also spread transneuronally via axo-axonal contacts. We show that this form of interaxonal spread between neurons is gD independent and is not mediated by extracellular virions. We also found that unlike PRV gD, HSV-1 gD is required for neuron-to-cell spread of infection. Neither of the host cell gD receptors (HVEM and nectin-1) is required in target primary fibroblasts for neuron-to-cell spread of HSV-1 or PRV infection.

Mannan-binding lectin (MBL) gene polymorphisms in ulcerative colitis and Crohn's disease.

The inflammatory bowel diseases (IBD), Crohn's disease (CD), and ulcerative colitis (UC), are complex multifactorial traits involving both environmental and genetic factors. Mannan-binding lectin (MBL) plays an important role in non-specific immunity and complement activation. Point mutations in codons 52, 54 and 57 of exon 1 of the MBL gene are associated with decreased MBL plasma concentrations and increased susceptibility to various infectious diseases. If these MBL mutations could lead to susceptibility to putative IBD-etiological microbial agents, or could temper the complement-mediated mucosal damage in IBD, MBL could function as the link between certain microbial, immunological and genetic factors in IBD. In this study, we investigated the presence of the codon 52, 54 and 57 mutations of the MBL gene in 431 unrelated IBD patients, 112 affected and 141 unaffected first-degree relatives, and 308 healthy control individuals. In the group of sporadic IBD patients (n = 340), the frequency of the investigated MBL variants was significantly lower in UC patients when compared with CD patients (P = 0.01) and with controls (P = 0.02). These results suggest that MBL mutations which decrease the formation of functional MBL could protect against the clinical development of sporadic UC, but not of CD. This could be explained by the differential T-helper response in both diseases.

Analysis of the CC chemokine receptor 5 (CCR5) delta-32 polymorphism in inflammatory bowel disease.

The inflammatory bowel diseases (IBD) Crohn's disease (CD) and ulcerative colitis (UC) are complex multifactorial traits involving both environmental and genetic factors. Recent studies have shown the important role of pro-inflammatory cytokines and chemokines, including RANTES, in IBD. RANTES is the natural ligand for the CC-chemokine receptor 5 (CCR5). The chromosomal location of the CCR5 gene on 3p21 coincides with an IBD-susceptibility locus identified by genome-wide scanning. A 32-bp deletion (A32) in the CCR5 gene results in a nonfunctional receptor and is found with high frequency in Caucasians. In this study, we investigated the presence of the CCR5delta32 allele in a large cohort of IBD patients and in a healthy control population. Blood samples were obtained from 538 unselected IBD cases (433 unrelated IBD patients: 289 CD, 142 UC, 2 indeterminate colitis; 105 affected first-degree relatives) and 135 unaffected first-degree family members. Of the IBD patients, 36% had familial IBD with at least two members being affected. There were no significant differences in the CCR5delta32 mutation frequency between IBD patients and healthy controls, nor between CD and UC patients. There was no correlation between the CCR5delta32 genotype and the age at IBD-diagnosis, the frequency of surgical intervention, or disease localization. Only the association between CCR5delta32 homozygosity and the presence of anal lesions in CD patients was statistically significant (P=0.007). Analysis by the transmission/disequilibrium test showed no significant transmission distortion to the probands or their clinically silent siblings. Based on these results, it is unlikely that the CCR5delta32 allele is an important marker for predisposition to IBD.

Prevalence of CCR5 and CCR2 HIV-coreceptor gene polymorphisms in Belgium.

Polymorphisms of the chemokine receptor genes CCR5 and CCR2 are associated with resistance to HIV-1 infection or delayed progression to AIDS. Few data are available on their combined prevalence in healthy subjects; we therefore examined the occurrence of CCR5-Delta32 and CCR2-64I polymorphisms in a sample of 310 healthy Belgians. Allele frequencies were 0.119 and 0.074 for CCR5-Delta32 and CCR2-64I, respectively. Genotype distributions for both polymorphisms were found to be in accordance with Hardy-Weinberg equilibrium, but a significant (p = 0.002) linkage disequilibrium between CCR5-Delta32 and CCR2-64I was observed. The high prevalence of CCR5-Delta32 and CCR2-64I in Belgians may need to be taken into account in the design of studies of antiretroviral treatments.

Usefulness of immunochromatographic detection of antibodies to Mycobacterium tuberculosis as an adjunct to auramine staining for rapid diagnosis of tuberculosis in a low-prevalence setting.

A novel immunochromatographic membrane-based assay for the detection of specific IgG antibodies to Mycobacterium tuberculosis was evaluated in patients with active tuberculosis in a low-prevalence population. The sensitivity of the test for detecting active tuberculosis was 41.5% (17/41 patients positive); its specificity in a group of patients with other lung diseases was 91.4% (3/35 false positive), while in a group of 47 healthy controls it was 100%. The sensitivity of the immunochromatographic test equaled that of auramine staining, but different subsets of tuberculosis patients were detected by the two tests. The suboptimal sensitivity of this immunochromatographic test implies that, even though it could be a useful adjunct, it cannot be a replacement for the diagnosis of tuberculosis by other microbiological methods along with clinical and radiological data.

Evaluation of Glucocard Memory 2 and Accutrend sensor blood glucose meters.

The performance and practicability of 2 blood glucose meters (Glucocard Memory 2 and Accutrend sensor) were evaluated. Both glucose meters produced acceptably precise results in the hyper- and normoglycaemic concentration ranges. In the hypoglycaemic concentration range, the imprecision of Accutrend sensor was much higher than recommended by the American Diabetes Association. Within-run coefficients of variation for Glucocard Memory 2 were 6.3%, 3.9% and 2.4% at glucose concentrations of 1.7 mmol/l, 5.8 mmol/l and 11.7 mmol/l, respectively: for Accutrend sensor these were 15.2%, 5.0% and 1.2% at respective concentrations of 0.9 mmol/l, 4.2 mmol/l and 19.6 mmol/l. Between-day coefficients of variation for Glucocard Memory 2 were 4.8% and 3.5% at glucose concentrations of 3.9 mmol/l and 17.2 mmol/l, respectively and for Accutrend sensor they were 3.8% and 2.9% at glucose concentrations of 3.8 mmol/l and 18.7 mmol/l, respectively. Results were linear over a range of 1.6 mmol/l -29.7 mmol/l for Glucocard Memory 2 and 1.6 mmol/l -33.3 mmol/l for Accutrend sensor. Results of both blood glucose meters correlated closely with the hexokinase/glucose-6-phosphate dehydrogenase laboratory method. Ninety-eight percent of both Glucocard Memory 2 and Accutrend sensor results were within 20% of the comparison method values. Ninety-three percent of the Glucocard Memory 2 and 96% of the Accutrend sensor results were within 15% of the comparison method results. An inverse relation between the glucose readings and haematocrit values was observed for both blood glucose meters in the hyperglycaemic range and this effect was more pronounced for Accutrend sensor. In the normo- and hypoglycaemic ranges the effect was insignificant and absent, respectively. Minimum sample volume for Glucocard Memory 2 was 3 microliters and for Accutrend sensor it was 9 microliters. Lower sample volumes gave erroneous results. Presenting more than the required volume had no effect on results.