Factors influencing patient decision-making to undergo shoulder arthroplasty.

Aims: Shoulder arthroplasty is effective in the management of end-stage glenohumeral joint arthritis. However, it is major surgery and patients must balance multiple factors when considering the procedure. An understanding of patients' decision-making processes may facilitate greater support of those considering shoulder arthroplasty and inform the outcomes of future research. Methods: Participants were recruited from waiting lists of three consultant upper limb surgeons across two NHS hospitals. Semi-structured interviews were conducted with 12 participants who were awaiting elective shoulder arthroplasty. Transcribed interviews were analyzed using a grounded theory approach. Systematic coding was performed; initial codes were categorized and further developed into summary narratives through a process of discussion and refinement. Data collection and analyses continued until thematic saturation was reached. Results: Two overall categories emerged: the motivations to consider surgery, and the information participants used to inform their decision-making. Motivations were, broadly, the relief of pain and the opportunity to get on with life and regain independence. When participants' symptoms and restrictions prevented them enjoying life to a sufficient extent, this provided the motivation to proceed with surgery. Younger participants tended to focus on maintaining employment and recreational activities, and older patients were eager to make the most of their remaining lifetime. Participants gathered information from a range of sources and were keen to optimize their recovery where possible. An important factor for participants was whether they trusted their surgeon and were prepared to delegate responsibility for elements of their care. Conclusion: Relief of pain and the opportunity to get on with life were the primary reasons to undergo shoulder arthroplasty. Participants highlighted the importance of the patient-surgeon relationship and the need for accurate information in an accessible format which is relevant to people of different ages and functional demands.

Experimental Evaluation of Higher Order Stability Zones Using a Digitally Operated Quadrupole Mass Filter.

Recent improvements to the comparison-based method of digital waveform generation increased the reproducibility of the waveforms so that the higher-order Mathieu stability zones can be accessed reliably. Digitally driven quadrupole mass filters access these zones using a fixed AC voltage and rectangular waveforms that are defined by a duty cycle. In this context, the duty cycle is the fraction of the waveform period where the waveform remains in the high state. Because digitally driven quadrupoles navigate stability using a duty cycle, there is no need to apply a resolving DC offset between electrode pairs. Accessing the higher stability zones using a conventional resonantly tuned RF requires the use of thousands of AC and DC voltages making the mode of operation less accessible with these devices. Stability zones higher than (1,1) and (2,1) have theoretical resolving powers that are on the order 1,140 and 3,447 at fwhm which drives efforts to practically access these operational conditions. Accessing these zones digitally requires the use of extremely precise waveforms. In a previous effort, waveform generation produced waveforms to reliably access the (1,1) and (2,1) zones without impacting performance. However, recent work found more improvement was needed to reliably access neighboring higher stability zones. Derived from that work, it was determined that a waveform resolution of ∼10 ppm or less was needed to reliably access the (3,1) and (3,2) zones. The present work utilized digital waveforms that achieve this level of precision to experimentally access and characterize attributes of the (3,1) and (3,2) zones. This work dives into the investigation of different beam energies to overcome the destabilizing fringing fields, improve transmission, and their overall effect on the experimental resolving power and signal-to-noise. In addition, the AC voltage of the driving RF was varied to understand the effects on the initial ion beam energy that is needed to achieve balanced separation and how the overall signal-to-noise is affected. Lastly, an assessment was made on the effects of the temporal parameters of a digital mass scan on peak sensitivity, peak fidelity, and overall duration for a scan.

Evaluation of Acute and Convalescent Antibody Concentration Against Pneumococcal Capsular Polysaccharides for the Diagnosis of Pneumococcal Infection in Children with Community-Acquired Pneumonia.

We evaluated whether the quantification of IgG to pneumococcal capsular polysaccharides is an accurate diagnostic test for pneumococcal infection in children with pneumonia in Nepal. Children with pneumococcal pneumonia did not have higher convalescent, or higher fold change, IgG to pneumococcal polysaccharides than children with other causes of pneumonia. Caution is needed in interpreting antibody responses in pneumococcal infections.

Revision rate in metal compared to ceramic humeral head total shoulder arthroplasty and hemiarthroplasty.

Aims: Metal and ceramic humeral head bearing surfaces are available choices in anatomical shoulder arthroplasties. Wear studies have shown superior performance of ceramic heads, however comparison of clinical outcomes according to bearing surface in total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) is limited. This study aimed to compare the rates of revision and reoperation following metal and ceramic humeral head TSA and HA using data from the National Joint Registry (NJR), which collects data from England, Wales, Northern Ireland, Isle of Man and the States of Guernsey. Methods: NJR shoulder arthroplasty records were linked to Hospital Episode Statistics and the National Mortality Register. TSA and HA performed for osteoarthritis (OA) in patients with an intact rotator cuff were included. Metal and ceramic humeral head prostheses were matched within separate TSA and HA groups using propensity scores based on 12 and 11 characteristics, respectively. The primary outcome was time to first revision and the secondary outcome was non-revision reoperation. Results: A total of 4,799 TSAs (3,578 metal, 1,221 ceramic) and 1,363 HAs (1,020 metal, 343 ceramic) were included. The rate of revision was higher for metal compared with ceramic TSA, hazard ratio (HR) 3.31 (95% confidence interval (CI) 1.67 to 6.58). At eight years, prosthesis survival for ceramic TSA was 98.7% (95% CI 97.3 to 99.4) compared with 96.4% (95% CI 95.2 to 97.3) for metal TSA. The majority of revision TSAs were for cuff insufficiency or instability/dislocation. There was no significant difference in the revision rate for ceramic compared with metal head HA (HR 1.33 (95% CI 0.76 to 2.34)). For ceramic HA, eight-year prosthetic survival was 92.8% (95% CI 86.9 to 96.1), compared with 91.6% (95% CI 89.3 to 93.5) for metal HA. The majority of revision HAs were for cuff failure. Conclusion: The rate of all-cause revision was higher following metal compared with ceramic humeral head TSA in patients with OA and an intact rotator cuff. There was no difference in the revision rate for HA according to bearing surface.

Patient-reported outcomes following total shoulder arthroplasty and hemiarthroplasty: an analysis of data from the National Joint Registry.

BACKGROUND: Total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) are used in the management of end-stage glenohumeral arthritis. Improvement in shoulder function and resolution of symptoms are high priorities for patients. The aim of this study was to compare patient-reported outcome measures (PROMs) following TSA and HA. METHODS: Records from the National Joint Registry of England, Wales, Northern Ireland, and the Isle of Man were linked to the PROMs data set. The study included anatomic shoulder arthroplasties performed for osteoarthritis in patients with an intact rotator cuff. Patients with preoperative and postoperative Oxford Shoulder Scores (OSSs) were included. The improvement in OSS at 6 months and 5 years and the trend in scores over time were analyzed for each prosthesis. A cohort of 2002 patients were matched on 10 variables using propensity scores. OSSs at 6 months following TSA vs. HA were compared in the matched sample. RESULTS: There was a significant improvement in the OSS in both groups (P < .001). At 6 months, the OSSs were superior following TSA compared with HA (median 42 vs. 36, P < .001). The median score at 5 years was 44 following TSA and 35 following HA. Score distributions were skewed toward the maximum score. The highest possible score (48) was achieved in 28% (134 of 478) of TSAs and 9% (20 of 235) of HAs at 5 years. The improvement in the preoperative to 6-month OSS reached the minimal clinically important difference of 5.5 in 92% (1653 of 1792) of TSAs and in 80% (416 of 523) of HAs. At 5 years, this improvement was maintained in 91% (339 of 374) of TSAs and 78% (136 of 174) of HAs. CONCLUSION: TSA resulted in superior OSSs at 6 months in patients with osteoarthritis. The median OSS improved from 6 months to 5 years following TSA; however, there was a small decline in scores following HA. A ceiling effect was shown in the OSS following TSA at 5 years.

Immune responses to typhoid conjugate vaccine in a two dose schedule among Nepalese children <2 years of age.

BACKGROUND: Previously, the Vi-typhoid conjugate vaccine (Vi-TT) was found to be highly efficacious in Nepalese children under 16 years of age. We assessed the immunogenicity of Vi-TT at 9 and 12 months of age and response to a booster dose at 15 months of age. METHODS: Infants were recruited at Patan Hospital, Kathmandu and received an initial dose of Vi-TT at 9 or 12 months of age with a booster dose at 15 months of age. Blood was taken at four timepoints, and antibody titres were measured using a commercial ELISA kit. The primary study outcome was seroconversion (4-fold rise in antibody titre) of IgG one month after both the doses. FINDINGS: Fifty children were recruited to each study group.Some visits were disrupted by the COVID19 pandemic and occurred out of protocol windows.Both the study groups attained 100 % IgG seroconversion after the initial dose. IgG seroconversion in the 9-month group was significantly higher than in the 12-month group (68.42 % vs 25.8 %, p < 0.001). Among individuals who attended visits per protocol, IgG seroconversion after the first dose occurred in 100 % of individuals (n = 27/27 in 9-month and n = 32/32 in 12-month group). However, seroconversion rates after the second dose were 80 % in the 9-month and 0 % in the shorter dose-interval 12-month group (p < 0.001) (n = 16/20 and n = 0/8, respectively). INTERPRETATION: Vi-TT is highly immunogenic at both 9 and 12 months of age. Stronger response to a booster in the 9-month group is likely due to the longer interval between doses.

The risk of revision is higher following shoulder hemiarthroplasty compared with total shoulder arthroplasty for osteoarthritis: a matched cohort study of 11,556 patients from the National Joint Registry, UK.

BACKGROUND AND PURPOSE: Total shoulder arthroplasty (TSA) and hemiarthroplasty (HA) are used in the management of osteoarthritis of the glenohumeral joint. We aimed to determine whether TSA or HA resulted in a lower risk of adverse outcomes in patients of all ages with osteoarthritis and an intact rotator cuff and in a subgroup of patients aged 60 years or younger. PATIENTS AND METHODS: Shoulder arthroplasties recorded in the National Joint Registry, UK, between April 1, 2012 and June 30, 2021, were linked to Hospital Episode Statistics in England. Elective TSAs and HAs were matched on propensity scores based on 11 variables. The primary outcome was all-cause revision. Secondary outcomes were combined revision/non-revision reoperations, 30-day inpatient complications, 1-year mortality, and length of stay. 95% confidence intervals (CI) were reported. RESULTS: 11,556 shoulder arthroplasties were included: 7,641 TSAs, 3,915 HAs. At 8 years 95% (CI 94-96) of TSAs and 91% (CI 90-92) of HAs remained unrevised. The hazard ratio (HR) varied across follow-up: 4-year HR 2.7 (CI 1.9-3.5), 8-year HR 2.0 (CI 0.5-3.5). Rotator cuff insufficiency was the most common revision indication. In patients aged 60 years or younger prosthesis survival at 8 years was 92% (CI 89-94) following TSA and 84% (CI 80-87) following HA. CONCLUSION: The risk of revision was higher following HA in patients with osteoarthritis and an intact rotator cuff. Patients aged 60 years and younger had a higher risk of revision following HA.

Optimising DTwP-containing vaccine infant immunisation schedules (OptImms) - a protocol for two parallel, open-label, randomised controlled trials.

BACKGROUND: Universal immunisation is the cornerstone of preventive medicine for children, The World Health Organisation (WHO) recommends diphtheria-tetanus-pertussis (DTP) vaccine administered at 6, 10 and 14 weeks of age as part of routine immunisation. However, globally, more than 17 unique DTP-containing vaccine schedules are in use. New vaccines for other diseases continue to be introduced into the infant immunisation schedule, resulting in an increasingly crowded schedule. The OptImms trial will assess whether antibody titres against pertussis and other antigens in childhood can be maintained whilst adjusting the current Expanded Programme on Immunisation (EPI) schedule to provide space for the introduction of new vaccines. METHODS: The OptImms studies are two randomised, five-arm, non-inferiority clinical trials in Nepal and Uganda. Infants aged 6 weeks will be randomised to one of five primary vaccination schedules based on age at first DTwP-vaccination (6 versus 8 weeks of age), number of doses in the DTwP priming series (two versus three), and spacing of priming series vaccinations (4 versus 8 weeks). Additionally, participants will be randomised to receive their DTwP booster at 9 or 12 months of age. A further sub-study will compare the co-administration of typhoid vaccine with other routine vaccines at one year of age. The primary outcome is anti-pertussis toxin IgG antibodies measured at the time of the booster dose. Secondary outcomes include antibodies against other vaccine antigens in the primary schedule and their safety. DISCUSSION: These data will provide key data to inform policy decisions on streamlining vaccination schedules in childhood. TRIAL REGISTRATIONS: ISRCTN12240140 (Nepa1, 7th January 2021) and ISRCTN6036654 (Uganda, 17th February 2021).

Assessing the implementation of COVID-19 structured reporting templates for chest radiography: a scoping review.

Objective: One of the common modalities used in imaging COVID-19 positive patients is chest radiography (CXR), and serves as a valuable imaging method to diagnose and monitor a patients' condition. Structured reporting templates are regularly used for the assessment of COVID-19 CXRs and are supported by international radiological societies. This review has investigated the use of structured templates for reporting COVID-19 CXRs. Methods: A scoping review was conducted on literature published between 2020 and 2022 using Medline, Embase, Scopus, Web of Science, and manual searches. An essential criterion for the inclusion of the articles was the use of reporting methods employing either a structured quantitative or qualitative reporting method. Thematic analyses of both reporting designs were then undertaken to evaluate utility and implementation. Results: Fifty articles were found with the quantitative reporting method used in 47 articles whilst 3 articles were found employing a qualitative design. Two quantitative reporting tools (Brixia and RALE) were used in 33 studies, with other studies using variations of these methods. Brixia and RALE both use a posteroanterior or supine CXR divided into sections, Brixia with six and RALE with four sections. Each section is scaled numerically depending on the level of infection. The qualitative templates relied on selecting the best descriptor of the presence of COVID-19 radiological appearances. Grey literature from 10 international professional radiology societies were also included in this review. The majority of the radiology societies recommend a qualitative template for reporting COVID-19 CXRs. Conclusion: Most studies employed quantitative reporting methods which contrasted with the structured qualitative reporting template advocated by most radiological societies. The reasons for this are not entirely clear. There is also a lack of research literature on both the implementation of the templates or comparing both template types, indicating that the use of structured radiology reporting types may be an underdeveloped clinical strategy and research methodology. Advances in knowledge: This scoping review is unique in that it has undertaken an examination of the utility of the quantitative and qualitative structured reporting templates for COVID-19 CXRs. Moreover, through this review, the material examined has allowed a comparison of both instruments, clearly showing the favoured style of structured reporting by clinicians. At the time of the database interrogation, there were no studies found had undertaken such examinations of both reporting instruments. Moreover, due to the enduring influence of COVID-19 on global health, this scoping review is timely in examining the most innovative structured reporting tools that could be used in the reporting of COVID-19 CXRs. This report could assist clinicians in decision-making regarding templated COVID-19 reports.

COVID-19 vaccine effectiveness and variants in Nepal: study protocol for a test-negative case-control study with SARS-CoV-2 genetic sequencing.

INTRODUCTION: Inactivated, viral vector and mRNA vaccines have been used in the Nepali COVID-19 vaccination programme but there is little evidence on the effectiveness of these vaccines in this setting. The aim of this study is to describe COVID-19 vaccine effectiveness in Nepal and provide information on infections with SARS-CoV-2 variants. METHODS AND ANALYSIS: This is a hospital-based, prospective test-negative case-control study conducted at Patan Hospital, Kathmandu. All patients >18 years of age presenting to Patan Hospital with COVID-19-like symptoms who have received a COVID-19 antigen/PCR test are eligible for inclusion. The primary outcome is vaccine effectiveness of licensed COVID-19 vaccines against laboratory-confirmed COVID-19 disease.After enrolment, information will be collected on vaccine status, date of vaccination, type of vaccine, demographics and other medical comorbidities. The primary outcome of interest is laboratory-confirmed SARS-CoV-2 infection. Cases (positive for SARS-CoV-2) and controls (negative for SARS-CoV-2) will be enrolled in a 1:4 ratio. Vaccine effectiveness against COVID-19 disease will be analysed by comparing vaccination status with SARS-CoV-2 test results.Positive SARS-CoV-2 samples will be sequenced to identify circulating variants and estimate vaccine effectiveness against common variants.Measuring vaccine effectiveness and identifying SARS-CoV-2 variants in Nepal will help to inform public health efforts. Describing disease severity in relation to specific SARS-CoV-2 variants and vaccine status will also inform future prevention and care efforts. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University of Oxford Tropical Ethics Committee (OxTREC) (ref: 561-21) and the Patan Academy of Health Sciences Institutional Review Board (ref: drs2111121578). The protocol and supporting study documents were approved for use by the Nepal Health Research Council (NHRC 550-2021). Results will be disseminated in peer-reviewed journals and to the public health authorities in Nepal.

Optimization of a Digital Mass Filter for the Isolation of Intact Protein Complexes in Stability Zone 1,1.

Digital mass filters are advantageous for the analysis of large molecules due to the ability to perform ion isolation of high-m/z ions without the generation of very high radio frequency (RF) and DC voltages. Experimentally determined Mathieu stability diagrams of stability zone 1,1 for capacitively coupled digital waveforms show a voltage offset between the quadrupole rod pairs is introduced by the capacitors which is dependent on the voltage magnitude of the waveform and the duty cycle. This changes the ion's a value from a = 0 to a < 0. These effects are illustrated for isolation for single-charge states for various protein complexes up to 800 kDa (GroEL) for stability zone 1,1. Isolation resolving power (m/Δm) of approximately 280 was achieved for an ion of m/z 12,315 (z = 65+ for 800.5 kDa GroEL D398A), which corresponds to an m/z window of 44.

Experimental Validation of the Digital Tandem Mass Filter.

This work presents the experimental evaluation of a digital tandem mass filter that is composed of two digitally operated low-resolution mass filters in series whose mass windows are shifted with respect to each other. The overlap of the mass windows allows the resolution (Δm) of ions to be narrowed to provide better resolving power, while the acceptance of the tandem mass filter is defined by the acceptance of the first low-resolution quadrupole. Our experiments show that digital operation fulfills the promise of the tandem mass filter for providing better ion transmission at the same or better resolving power as a single quadrupole mass filter. It allows the user to continuously adjust the resolving power and sensitivity to meet current needs. Most importantly, the observed resolving power/sensitivity characteristics are the same at any mass and m/z.

Effect of Jitter on Digital Mass Filter Analysis in Higher Stability Zones.

Waveform reproducibility is a critical factor for performing high resolution mass analysis with digitally operated quadrupole mass filters and traps operating in higher stability zones. In this work, Hill equation-based stability calculations were used to define the effect of period jitter on mass analysis in higher stability zones. These calculations correlate well with experimental observations in higher stability zones. Comparison of experiment to theory supplies the basis for defining jitter-based expectations and limits for mass analysis in higher zones.

Superior capsule reconstruction, partial cuff repair, graft interposition, arthroscopic debridement or balloon spacers for large and massive irreparable rotator cuff tears: a systematic review and meta-analysis.

BACKGROUND: Multiple non-arthroplasty surgical techniques are described for the management of large and massive irreparable rotator cuff tears. There is currently no consensus on the best management strategy. Our aim was to compare clinical outcomes following arthroscopic debridement, arthroscopic partial cuff repair, superior capsule reconstruction, balloon spacers or graft interposition for the management of large and massive irreparable rotator cuff tears. METHODS: A comprehensive search was performed of the following databases: Medline, Embase, CINAHL and Cochrane Database of Systematic Reviews. Data were extracted from relevant studies published since January 2000 according to the pre-specified inclusion criteria. The primary outcome was the post-operative improvement in shoulder scores. Meta-analysis of the primary outcome was performed. Secondary outcomes included retear rates and complications. RESULTS: Eighty-two studies were included reporting the outcomes of 2790 shoulders. Fifty-one studies were included in the meta-analysis of the primary outcome. The definition of an irreparable tear varied. All procedures resulted in improved shoulder scores at early follow-up. Shoulder scores declined after 2 years following balloon spacers, arthroscopic debridement and partial cuff repair. High retear rates were seen with partial cuff repairs (45%), graft interposition (21%) and superior capsule reconstruction (21%). CONCLUSIONS: Large initial improvements in shoulder scores were demonstrated for all techniques despite high retear rates for reconstructive procedures. Shoulder scores may decline at mid- to long-term follow-up.

Biceps Tenodesis cannot be used as primary treatment option in baseball pitchers with intact rotator cuff muscles.

Background Surgeons remain hesitant to perform biceps tenodesis in athletes with type II superior labrum anterior-to-posterior tears due to the lack of reported clinical outcomes for individual overhead throwing sports and associated concerns that this may predispose the joint to instability. This study aimed to assess the effect of biceps tenodesis on shoulder stability for major overhead throwing sports to aid sport-specific surgical decision-making for athletes with type II superior labrum anterior-to-posterior tears. METHODS: This is a combined modelling and experimental study. Motion data and external forces were measured from 13 participants performing five overhead throwing motions. These data served as input into a musculoskeletal shoulder model that quantifies shoulder stability and muscle loading. FINDINGS: The loading of the long head of the biceps brachii decreases significantly following biceps tenodesis in three overhead throwing motions (p = 0.02). The loss in joint stability following biceps tenodesis is compensated by a non-significant increase in rotator cuff muscle force which maintains shoulder stability across all overhead throwing motions, except baseball pitching (p = 0.01). The presence of a full-thickness supraspinatus tear post biceps tenodesis further decreases shoulder stability in four of the five overhead throwing motions (p = 0.01). INTERPRETATION: The study findings demonstrate that an increase in rotator cuff muscle force maintains joint stability for all overhead throwing motions post biceps tenodesis, except baseball pitching. As the presence of a full-thickness tear of the supraspinatus significantly reduces joint stability, biceps tenodesis may be used as a primary treatment in overhead throwing athletes with intact rotator cuff muscles, except baseball pitchers. LEVEL OF EVIDENCE: Controlled Laboratory Study; Level of Evidence 3.

Protocolised MRI as an adjunct to CT in the diagnosis of femoral neck fracture in high energy ipsilateral femoral shaft fractures - A break-even analysis.

BACKGROUND: In high-energy femoral shaft fractures (FSFs), ipsilateral femoral neck fractures (FNFs) can be missed by conventional trauma computed topography (CT) imaging, resulting in increased treatment costs and patient complications. Preliminary evidence suggests that a rapid, limited-sequence pelvis and hip magnetic resonance imaging (MRI) protocol can identify these occult fractures and be feasibly implemented in the trauma setting. This study aims to establish the economic break-even point for implementing such an MRI protocol in all high-energy FSFs. METHODS: We used an adapted break-even economic tool to determine whether the costs of a targeted MRI protocol can be offset by cost-savings achieved through prevention of missed fractures (thus avoiding prolonged admission and re-operation). Sensitivity analyses were performed to demonstrate reliability of the economic modelling across a range of assumptions. RESULTS: Assuming a baseline of FNFs missed on CT of 12%, an MRI cost of £129 and cost of treating each missed FNF of £2457.5, the equation yielded a break-even rate of 7% and absolute risk reduction (ARR) of 5%, indicating that for every 100 FSFs, MRI would need to diagnose 5 of the 12 missed FNF to be economically viable (number needed to treat (NNT)=20). Economic viability was maintained even at double the cost of MRI, while increasing the cost of treating each complication served to reduce the ARR further, increasing cost-savings. CONCLUSION: A rapid, limited-sequence MRI protocol to exclude occult ipsilateral FNFs in all high-energy FSFs appears to be economically justified measure. Further research exploring the feasibility of such a protocol, as well as the role of intra-operative fluoroscopy in this context, is required.

Effect of the of 10-valent pneumococcal conjugate vaccine in Nepal 4 years after introduction: an observational cohort study.

BACKGROUND: In Nepal, Streptococcus pneumoniae (pneumococcus) is a common cause of bacterial pneumonia in children, and is a major health concern. There are few data on the effect of vaccination on the disease or colonisation with pneumococci in the nasopharynx of children in this setting. The 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine infant immunisation schedule in Nepal in 2015. We aimed to investigate the effect of the introduction of PCV10 on pneumococcal carriage and disease in children in Nepal. METHODS: We did an observational cohort study in children in Nepal. The hospital surveillance study took place in Patan Hospital, Kathmandu, and community studies in healthy children took place in Kathmandu and Okhaldhunga district. For the surveillance study, all children admitted to Patan Hospital between March 20, 2014, and Dec 31, 2019, aged between 2 months and 14 years with clinician-suspected pneumonia, were eligible for enrolment. For the community study, healthy children aged 0-8 weeks, 6-23 months, and 24-59 months were recruited from Kathmandu, and healthy children aged 6-23 months were recruited from Okhaldhunga. We assessed the programmatic effect of PCV10 introduction using surveillance for nasopharyngeal colonisation, pneumonia, and invasive bacterial disease from 1·5 years before vaccine introduction and 4·5 years after vaccine introduction. For the surveillance study, nasopharyngeal swabs, blood cultures, and chest radiographs were obtained from children admitted to Patan Hospital with suspected pneumonia or invasive bacterial disease. For the community study, nasopharyngeal swabs were obtained from healthy children in the urban and rural settings. Pneumonia outcomes were analysed using log-binomial models and adjusted prevalence ratios (aPR) comparing each calendar year after the introduction of the vaccine into the national programme with the pre-vaccine period (2014-15), adjusted for calendar month, age, and sex. FINDINGS: Between March 20, 2014, and Dec 31, 2019, we enrolled 2051 children with suspected pneumonia, and 11 354 healthy children (8483 children aged 6-23 months, 761 aged 24-59 months, and 2110 aged 0-8 weeks) to assess nasopharyngeal colonisation. Among clinical pneumonia cases younger than 2 years, vaccine serotype carriage declined 82% (aPR 0·18 [95% CI 0·07-0·50]) by 2019. There was no decrease in vaccine serotype carriage in cases among older unvaccinated age groups. Carriage of the additional serotypes in PCV13 was 2·2 times higher by 2019 (aPR 2·17 [95% CI 1·16-4·05]), due to increases in serotypes 19A and 3. Vaccine serotype carriage in healthy children declined by 75% in those aged 6-23 months (aPR 0·25 [95% CI 0·19-0·33]) but not in those aged 24-59 months (aPR 0·59 [0·29-1·19]). A decrease in overall vaccine serotype carriage of 61% by 2019 (aPR 0·39 [95% CI 0·18-0·85]) was also observed in children younger than 8 weeks who were not yet immunised. Carriage of the additional PCV13 serotypes in children aged 6-23 months increased after PCV10 introduction for serotype 3 and 19A, but not for serotype 6A. The proportion of clinical pneumonia cases with endpoint consolidation on chest radiographs declined from 41% in the pre-vaccine period to 25% by 2018, but rose again in 2019 to 36%. INTERPRETATION: The introduction of the PCV10 vaccine into the routine immunisation programme in Nepal has reduced vaccine serotype carriage in both healthy children and children younger than 2 years with pneumonia. Increases in serotypes 19A and 3 highlight the importance of continued surveillance to monitor the effect of vaccine programmes. This analysis demonstrates a robust approach to assessing vaccine effect in situations in which pneumococcal disease endpoint effectiveness studies are not possible. FUNDING: Gavi, the Vaccine Alliance and the World Health Organization.

Why do older adults stand-up differently to young adults?: investigation of compensatory movement strategies in sit-to-walk.

Functional motor redundancy enables humans to move with distinct muscle activation patterns while achieving a similar outcome. Since humans select similar strategies, there seems to be an optimal control. However, older adults move differently to young adults. The question is whether this is this due to an altered reinforcement scheme, altered sensory inputs, or due to alterations in the neuromusculoskeletal systems, so that it is no longer optimal or possible to execute the same movement strategies. The aim of this study was to analyse natural compensation strategies in the vital daily-life-task, sit-to-walk, in relation to neuromuscular capacity and movement objectives in younger (27.2 ± 4.6 years, N = 27, 14♀) and elderly (75.9 ± 6.3 years, N = 23, 12♀) adults. Aspects of the neuromuscular system that are prone to age-related decline and feasible to quantify were assessed (i.e. strength, nerve conductivity, fear of falling). Kinematics and muscle activity were recorded and joint kinetics were estimated using biomechanical models. Elderly men consistently used their arms when standing up. This strategy was not associated with a lack of or a reduction in strength, but with a reduction, but no lack of, ankle joint range of motion, and with increased fear of falling. The results show that humans preferentially maintain a minimum threshold of neuromuscular reserve to cope with uncertainties which results in compensation prior to coming up against physical limitations. Smaller base of support while standing up, a compensatory strategy with possibly greater risk of falls, was associated with muscular weakness, and longer nerve conduction latencies.