Associations between indoor relative humidity and global COVID-19 outcomes.

Globally, the spread and severity of COVID-19 have been distinctly non-uniform. Seasonality was suggested as a contributor to regional variability, but the relationship between weather and COVID-19 remains unclear and the focus of attention has been on outdoor conditions. Because humans spend most of their time indoors and because most transmission occurs indoors, we here, instead, investigate the hypothesis that indoor climate-particularly indoor relative humidity (RH)-may be the more relevant modulator of outbreaks. To study this association, we combined population-based COVID-19 statistics and meteorological measurements from 121 countries. We rigorously processed epidemiological data to reduce bias, then developed and experimentally validated a computational workflow to estimate indoor conditions based on outdoor weather data and standard indoor comfort conditions. Our comprehensive analysis shows robust and systematic relationships between regional outbreaks and indoor RH. In particular, we found intermediate RH (40-60%) to be robustly associated with better COVID-19 outbreak outcomes (versus RH < 40% or >60%). Together, these results suggest that indoor conditions, particularly indoor RH, modulate the spread and severity of COVID-19 outbreaks.

Additive manufacturing of hierarchical injectable scaffolds for tissue engineering.

We present a 3D-printing technology allowing free-form fabrication of centimetre-scale injectable structures for minimally invasive delivery. They result from the combination of 3D printing onto a cryogenic substrate and optimisation of carboxymethylcellulose-based cryogel inks. The resulting highly porous and elastic cryogels are biocompatible, and allow for protection of cell viability during compression for injection. Implanted into the murine subcutaneous space, they are colonized with a loose fibrovascular tissue with minimal signs of inflammation and remain encapsulation-free at three months. Finally, we vary local pore size through control of the substrate temperature during cryogenic printing. This enables control over local cell seeding density in vitro and over vascularization density in cell-free scaffolds in vivo. In sum, we address the need for 3D-bioprinting of large, yet injectable and highly biocompatible scaffolds and show modulation of the local response through control over local pore size. STATEMENT OF SIGNIFICANCE: This work combines the power of 3D additive manufacturing with clinically advantageous minimally invasive delivery. We obtain porous, highly compressible and mechanically rugged structures by optimizing a cryogenic 3D printing process. Only a basic commercial 3D printer and elementary control over reaction rate and freezing are required. The porous hydrogels obtained are capable of withstanding delivery through capillaries up to 50 times smaller than their largest linear dimension, an as yet unprecedented compression ratio. Cells seeded onto the hydrogels are protected during compression. The hydrogel structures further exhibit excellent biocompatibility 3 months after subcutaneous injection into mice. We finally demonstrate that local modulation of pore size grants control over vascularization density in vivo. This provides proof-of-principle that meaningful biological information can be encoded during the 3D printing process, deploying its effect after minimally invasive implantation.

[Registration of assessments in orthopaedic residents' portfolios is falling short]. / Praktijktoetsen van aiossen onvoldoende geregistreerd.

OBJECTIVE: To evaluate of the number of registered competency assessments in the portfolios of orthopaedic residents in the Netherlands, for whom a competency-based training programme is mandatory. DESIGN: National cohort study. METHOD: We collected data regarding the registered assessments of all orthopaedic residents who finished their training between 2012-2015. We determined the number of registered assessments of 'standard orthopaedic treatments' (evaluating residents' competency in 70 different orthopaedic treatments), objective structured clinical skills evaluations (OSCEs), critically appraised topics (CATs), and 360 degree feedback appraisals. We compared the number of registered assessments in the portfolios with the minimum requirements laid down by the training curriculum. RESULTS: A total of 196 residents finished their training between 2012 and 2015. These residents finished their training with a mean (i.e., percentage of minimally required number of assessments) of 17.0 (34%) 'standard orthopaedic treatments' (level 4 or 5), 13.6 (34%) OSCEs, 2.6 (33%) CATs and 0.2 (4%) 360 degree feedback. CONCLUSION: On average, only one-third of the minimally required number of assessments were registered in the portfolios of orthopaedic residents (OSCEs and standard orthopaedic treatments level 4 or 5). These revelations show that action is needed to improve the way in which the progress of residents is monitored. These findings are going to have an effect on the new curriculum which must be more practical and less complex. Additionally, external quality control will focus more on residents at the end of their training and on the training region involved. This information may serve as a framework for postgraduate training programmes in other scientific associations which also find themselves in the same process of modernisation.

[How representative is the healthcare assessment website Zorgkaart Nederland? The evaluation of medical specialists by patients in the Netherlands]. / Hoe representatief is Zorgkaart Nederland? De waardering van specialisten door patiënten in beeld gebracht.

OBJECTIVE: To describe the number of ratings and the corresponding scores given to medical specialists on the Dutch healthcare assessment website 'Zorgkaart Nederland.nl', and evaluation of this website as tool for evaluation of quality. DESIGN: Explorative descriptive study. METHOD: In July 2015, data were gathered from the public section of the healthcare assessment website 'ZorgkaartNederland.nl'. The number of specialists, the mean ratings per department (group mark), the number of evaluations, the number of medical specialists without a rating and the number of specialists with at least 9 ratings were registered per speciality, per hospital. Outcomes measures were the median number of ratings per speciality and the group score. Data were analysed using descriptive and non-parametric statistics. RESULTS: Each month, 763,000 unique visitors access ZorgkaartNederland.nl; on average, 0.08% of these registers a vote. There were 15,337 medical specialists, spread across 97 hospitals and 2,060 specialities on ZorgkaartNederland.nl, with a total of 45,548 evaluations. Of these, 6,682 (43.4%) specialists were not rated, and 1.165 (7.6%) had ≥ 9 ratings. Additionally, 327 (15.9%) departments were unrated. Surgical departments were evaluated more often, and their grades were significantly higher, than those of non-surgical departments. CONCLUSION: The website ZorgkaartNederland.nl shows ratings for 56.6% of all medical specialists. When the lower limit of at least 9 evaluations per specialist introduced by ZorgkaartNederland.nl was applied, only the grades for 7.6% of all specialists are valid. On average, 0.08% of unique visitors cast a vote. Surgical specialities have a higher number of evaluations and a higher score than non-surgical ones. ZorgkaartNederland.nl in its current form does not constitute a valid tool for evaluation of the quality of medical specialist care in the Netherlands. This article provides recommendations for improvement.

Pseudotumor formation and serum ions after large head metal-on-metal stemmed total hip replacement. Risk factors, time course and revisions in 706 hips.

INTRODUCTION: The incidence and natural course of pseudotumors in metal-on-metal total hip arthroplasties is largely unknown. The objective of this study was to identify the true incidence and risk factors of pseudotumor formation in large head metal-on-metal total hip arthroplasties. MATERIALS AND METHODS: Incidence, time course and risk factors for pseudotumor formation were analysed after large femoral head MoM-THA. We defined a pseudotumor as a (semi-)solid or cystic peri-prosthetic soft-tissue mass with a diameter ≥2 cm that could not be attributed to infection, malignancy, bursa or scar tissue. All patients treated in our clinic with MoM-THA's were contacted. CT scan, metal ions and X-rays were obtained. Symptoms were recorded. RESULTS: After median follow-up of 3 years, 706 hips were screened in 626 patients. There were 228 pseudotumors (32.3 %) in 219 patients (35.0 %). Pseudotumor formation significantly increased after prolonged follow-up. Seventy-six hips (10.8 %) were revised in 73 patients (11.7 %), independent risk factors were identified. Best cutoff point for cobalt and chromium was 4 µg/l (68 and 77 nmol/l). CONCLUSIONS: This study confirms a high incidence of pseudotumors, dramatically increasing after prolonged follow-up. Risk factors for pseudotumors are of limited importance. Pain was the strongest predictor for pseudotumor presence; cobalt chromium and swelling were considered poor predictors. Cross-sectional imaging is the main screening tool during follow-up.

Impact of gas formation kinetics on dough development and bread quality.

The baking performance and gas retention capacity of wheat dough depends on production rate and total volume of CO2 during fermentation. This study aims to examine the effect of the CO2 formation kinetics and the gas volume fraction on the structural integrity of wheat dough and the resulting bread quality. The gas release characteristics were evaluated using a rheofermentometer with varied concentrations of compressed yeast and instant dry yeast (CY and IDY respectively). For this purpose, the maximum CO2 formation rate was calculated through the derivation of hydrostatic pressure curves measured in the rheofermentometer. For CY, the time when gas escapes the dough matrix (Tx, time of porosity) as well as the corresponding gas volume depended on the gas formation rate, whereas the gas retention capacity of wheat dough leavened with IDY was not affected by the CO2 formation rate. Although the dough leavened with IDY showed improved extensibility during fermentation, the specific bread volume was 21% below that of the samples leavened with CY. These results indicate that an increase in the maximum gas formation rate considerably affects the structural integrity of the dough matrix. Because of the reduction of the loaf volume, the effect is reinforced by the application of IDY.

The contribution of glutathione to the destabilizing effect of yeast on wheat dough.

Any factor which impairs the development of the gluten network affects the gas retention capacity and the overall baking performance. This study aimed to examine why rising yeast concentrations (Saccharomyces cerevisiae) decrease the dough elasticity in an asymptotic manner. Since in 27 commercial fresh and dry yeasts up to 81 mg glutathione (GSH) per 1g dry sample were found. Through the addition of reduced GSH in dough without yeast, the extent of dough weakening was analysed. Indeed rheological measurements confirmed that yeast-equivalent levels of GSH had a softening effect and during 3h fermentation the weakening coefficient increased from 0.3% to 20.4% in a Rheofermentometer. The present results indicate that free -SH compounds, as represented by GSH, considerably contribute to the softening of dough through dead yeast cells.

The relation between titanium taper corrosion and cobalt-chromium bearing wear in large-head metal-on-metal total hip prostheses: a retrieval study.

BACKGROUND: Revision of hip implants due to adverse tissue reactions to metal debris has been associated with wear and corrosion of the metal-on-metal bearing articulation and the modular taper interface. Bearing articulation wear is increased in conditions of poor lubrication, which can also lead to high friction moments that may cause corrosion at the taper interface. This suggests that wear of the bearing and increased corrosion of the taper interface should occur simultaneously, which was investigated in this study. METHODS: Forty-three large-diameter cobalt-chromium bearings of the same design, implanted with a titanium stem using a titanium adapter, were retrieved at revision at a single center. Retrievals were grouped according to visual inspection of the female taper surface of the adapter into slight and severe corrosion groups. Volume change of bearing and taper surfaces was assessed using a coordinate measurement machine. Serum ion concentrations were determined for forty-three patients, whereas tissue metal concentration was measured for twelve patients. RESULTS: Severe taper corrosion was observed in 30% of the retrievals. Corrosion was observed either as material deposition or wear. The overall bearing wear rate was significantly higher in the group with severe taper corrosion than in the group with slight corrosion (7.2 ± 9.0 mm(3)/yr versus 3.1 ± 6.8 mm(3)/yr, respectively; p = 0.023) as were the serum cobalt (40.5 ± 44.9 µg/L versus 15.2 ± 23.9 µg/L, respectively; p = 0.024) and chromium ion concentrations (32.7 ± 32.7 µg/L versus 12.0 ± 15.1 µg/L, respectively; p = 0.019). Serum metal ion concentrations were more consistent indicators of wear than tissue metal concentrations. CONCLUSIONS: The increased bearing articulation wear and serum metal ion concentrations in cases with taper interface corrosion support the hypothesis that increased friction in the joint articulation is one of the factors responsible for simultaneous articulation and taper damage. However, independent taper or bearing damage was also observed, suggesting that other factors are involved in the process.

Burnout and quality of life among orthopaedic trainees in a modern educational programme: importance of the learning climate.

We aimed to determine quality of life and burnout among Dutch orthopaedic trainees following a modern orthopaedic curriculum, with strict compliance to a 48-hour working week. We also evaluated the effect of the clinical climate of learning on their emotional well-being. We assessed burnout, quality of life and the clinical climate of learning in 105 orthopaedic trainees using the Maslach Burnout Inventory, linear analogue scale self-assessments, and Dutch Residency Educational Climate Test (D-RECT), respectively. A total of 19 trainees (18%) had poor quality of life and 49 (47%) were dissatisfied with the balance between their personal and professional life. Some symptoms of burnout were found in 29 trainees (28%). Higher D-RECT scores (indicating a better climate of learning) were associated with a better quality of life (r = 0.31, p = 0.001), more work-life balance satisfaction (r = 0.31, p = 0.002), fewer symptoms of emotional exhaustion (r = -0.21, p = 0.028) and depersonalisation (r = -0,28, p = 0.04). A reduced quality of life with evidence of burnout were still seen in a significant proportion of orthopaedic trainees despite following a modern curriculum with strict compliance to a 48-hour working week. It is vital that further work is undertaken to improve the quality of life and reduce burnout in this cohort.

Venous thromboembolism during hip plaster cast immobilisation: review of the literature.

INTRODUCTION: There is a paucity of data regarding the risk of deep vein thrombosis during hip plaster cast immobilisation. The purpose of this article was to review the available evidence regarding the incidence of symptomatic venous thromboembolism (VTE) during hip plaster cast immobilisation. METHODS AND MATERIALS: All papers describing hip plaster cast immobilisation published in the English literature retrieved from PubMed, EMBASE and the Cochrane database were reviewed. Articles regarding children, hip dysplasia, congenital hip dislocation and Legg-Calvé-Perthes were excluded. A total of three papers were available for analysis. We also describe a case of pulmonary embolism during hip cast immobilisation. RESULTS: The overall incidence of symptomatic VTE during hip plaster cast immobilisation was 0% in 343 patients. The incidence of symptomatic VTE in hip cast brace was 2.3% (range 0-3%). DISCUSSION: Our systematic review of the literature showed a paucity of data regarding the incidence of VTE during hip plaster cast immobilisation. We describe the first case of pulmonary embolism during hip plaster cast immobilisation. We recommend that patients who are fitted with a hip plaster cast should be routinely screened for additional risk factors. When risk factors are present, patients should be considered for pharmacological thromboprophylaxis.

Ten-year follow-up on Dutch orthopaedic blood management (DATA III survey).

INTRODUCTION: Hip and knee arthroplasties are frequently complicated by the need for allogeneic blood transfusions. This survey was conducted to assess the current use of perioperative blood-saving measures and to compare it with prior results. MATERIALS AND METHODS: All departments of orthopaedic surgery at Dutch hospitals were sent a follow-up survey on perioperative blood-saving measures, and data were compared to the results of two surveys conducted 5 and 10 years earlier. RESULTS: The response rate was 94 out of 108 departments (87%). Most departments used erythropoietin prior to hip and knee replacements at the expense of preoperative autologous blood donation. The use of intraoperative autologous retransfusion in revision hip (56 vs. 54%) as well as revision knee arthroplasty (26 vs. 24%), was virtually unchanged. Postoperative autologous retransfusion is still used by the majority of departments after both primary arthroplasty and revision of hip (58/53%) and knee (65/61%). CONCLUSIONS: Currently, just as in 2007, the majority of Dutch orthopaedic departments uses erythropoietin, normothermia and postoperative autologous retransfusion with hip and knee arthroplasty. Intraoperative retransfusion is used mainly with hip revision arthroplasty. Other effective blood management modalities such as tranexamic acid have not been widely implemented.

Reduction of blood loss with the use of a new combined intra-operative and post-operative autologous blood transfusion system compared with no drainage in primary total hip replacement.

Autologous retransfusion and no-drainage are both blood-saving measures in total hip replacement (THR). A new combined intra- and post-operative autotransfusion filter system has been developed especially for primary THR, and we conducted a randomised controlled blinded study comparing this with no-drainage. A total of 204 THR patients were randomised to autologous blood transfusion (ABT) (n = 102) or no-drainage (n = 102). In the ABT group, a mean of 488 ml (sd 252) of blood was retransfused. The mean lowest post-operative haemoglobin level during the hospital stay was higher in the autotransfusion group (10.6 g/dl (7.8 to 13.9) vs 10.2 g/dl (7.5 to 13.3); p = 0.01). The mean haemoglobin levels for the ABT and no-drainage groups were not significantly different on the first day (11.3 g/dl (7.8 to 13.9) vs 11.0 g/dl (8.1 to 13.4); p = 0.07), the second day (11.1 g/dl (8.2 to 13.8) vs 10.8 g/dl (7.5 to 13.3); p = 0.09) or the third day (10.8 g/dl (8.0 to 13.0) vs 10.6 g/dl (7.5 to 14.1); p = 0.15). The mean total peri-operative net blood loss was 1464 ml (sd 505) in the ABT group and 1654 ml (sd 553) in the no-drainage group (p = 0.01). Homologous blood transfusions were needed in four patients (3.9%) in the ABT group and nine (8.8%) in the no-drainage group (p = 0.15). No statistically significant difference in adverse events was found between the groups. The use of a new intra- and post-operative autologous blood transfusion filter system results in less total blood loss and a smaller maximum decrease in haemoglobin levels than no-drainage following primary THR.

High incidence of pseudotumour formation after large-diameter metal-on-metal total hip replacement: a prospective cohort study.

Peri-articular soft-tissue masses or 'pseudotumours' can occur after large-diameter metal-on-metal (MoM) resurfacing of the hip and conventional total hip replacement (THR). Our aim was to assess the incidence of pseudotumour formation and to identify risk factors for their formation in a prospective cohort study. A total of 119 patients who underwent 120 MoM THRs with large-diameter femoral heads between January 2005 and November 2007 were included in the study. Outcome scores, serum metal ion levels, radiographs and CT scans were obtained. Patients with symptoms or an identified pseudotumour were offered MRI and an ultrasound-guided biopsy. There were 108 patients (109 hips) eligible for evaluation by CT scan at a mean follow-up of 3.6 years (2.5 to 4.5); 42 patients (39%) were diagnosed with a pseudotumour. The hips of 13 patients (12%) were revised to a polyethylene acetabular component with small-diameter metal head. Patients with elevated serum metal ion levels had a four times increased risk of developing a pseudotumour. This study shows a substantially higher incidence of pseudotumour formation and subsequent revisions in patients with MoM THRs than previously reported. Because most revision cases were identified only after an intensive screening protocol, we recommend close monitoring of patients with MoM THR.

In vitro study of the antimicrobial effects of radiological contrast agents used in arthrography.

Aspiration arthrography using an iodinated contrast medium is a useful tool for the investigation of septic or aseptic loosening of arthroplasties and of septic arthritis. Previously, the contrast media have been thought to cause false negative results in cultures when present in aspirated samples of synovial fluid, probably because free iodine is bactericidal, but reports have been inconclusive. We examined the influence of the older, high osmolar contrast agents and the low osmolar media used currently on the growth of ten different micro-organisms capable of causing deep infection around a prosthesis. Five media were tested, using a disc diffusion technique and a time-killing curve method in which high and low inocula of micro-organisms were incubated in undiluted media. The only bactericidal effects were found with low inocula of Escherichia coli and Pseudomonas aeruginosa in ioxithalamate, one of the older ionic media. The low and iso-osmolar iodinated contrast media used currently do not impede culture. Future study must assess other causes of false negative cultures of synovial fluid and new developments in enhancing microbial recovery from aspirated samples.

Death and venous thromboembolism after lower extremity amputation.

BACKGROUND: Lower extremity amputation is often performed in patients with end-stage vascular disease and is considered a high-risk procedure. Uncertainty exists about the rate of venous thromboembolism (VTE) in these patients. OBJECTIVES: To establish the incidence of death and venous thromboembolism after lower extremity amputation. METHODS: A prospective cohort study was performed to establish the incidences of death and VTE after lower extremity amputation, as detected by bilateral complete compression ultrasonography and ventilation-perfusion scintigraphy performed preoperatively and around day 14 postoperatively. Standard low-molecular-weight heparin thromboprophylaxis was given during the study period. A secondary outcome was the incidences of mortality and symptomatic venous thromboembolic complications during 8 weeks of postoperative follow-up. RESULTS: Forty-nine patients (53 amputations) were ultimately included in the intention-to-treat analysis. Five patients died within the 2-week period and an additional seven patients died during the 8 weeks clinical follow-up period. The total mortality rate therefore was 12 of 53 amputations [22.6%; 95% confidence interval (CI), 12.3-36.2%]. Six patients developed pulmonary embolisms (of which two were fatal) and one patient developed an asymptomatic contralateral distal deep venous thrombosis, resulting in a total VTE rate of 7 out of 53 amputations (13.2%; 95% CI, 5.47-25.3%). CONCLUSION: Lower extremity amputation is accompanied by a high mortality rate from sepsis, and respiratory and vascular causes. This study shows that VTE substantially contributes to the morbidity and mortality after lower extremity amputation despite adequate pharmacological thromboprophylaxis in this vulnerable population of patients.

Comparing consensus guidelines on thromboprophylaxis in orthopedic surgery.

BACKGROUND: Different guidelines exist regarding the prevention of venous thromboembolism (VTE) in orthopedic surgery. OBJECTIVES: We aimed to compare (inter)national guidelines and analyse differences. METHODS: MEDLINE, the Cochrane Library and the internet were searched for guidelines on the prevention of VTE in orthopedic surgery. From these, we constructed a table comparing the different antithrombotic regimens during different orthopedic surgical and plaster cast treatments. RESULTS: Eleven guidelines from nine different countries and one international guideline were included. Few guidelines advise on thrombosis prophylaxis after plaster cast immobilization, (prolonged) arthroscopic surgery and isolated lower extremity trauma. Different opinions exist on the sole use of aspirin and mechanical prophylaxis and on the use of vitamin K antagonists after major hip and knee surgery. CONCLUSION: Based on the same available literature, different guidelines recommend different thromboprophylactic regimens. Ideally, the grade of recommendation should be based on the same level of evidence world-wide. Whilst there is no agreement on the relevance of different endpoints (e.g. asymptomatic DVT), it is very difficult to reach a consensus. Thromboprophylaxis guidelines should be reviewed and updated on a regular basis, because the evidence is evolving rapidly.

Porous-coated femoral components with or without hydroxyapatite in primary uncemented total hip arthroplasty: a systematic review of randomized controlled trials.

The purpose of this systematic review was to determine the clinical and radiologic benefit of hydroxyapatite coating in uncemented primary total hip arthroplasty. A database of Medline articles published up to September 2007 was compiled and screened. Eight studies involving 857 patients were included in the review. Pooled analysis for Harris hip score as a clinical outcome measure demonstrated no advantage of the hydroxyapatite coating (WMD: 1.49, P = 0.44). Radiologically, both groups showed equal presence of endosteal bone ingrowth (RR: 1.04, P = 0.66) and radioactive lines (RR: 1.02, P = 0.74) in the surface area of the prosthesis. This meta-analysis demonstrates neither clinical nor radiologic benefits on the application of a hydroxyapatite coating on a femoral component in uncemented primary total hip arthroplasty.