Females present larger deficit in heel-rise height at 3 months following an Achilles tendon rupture compared with males.

PURPOSE: There is a lack of knowledge concerning differences between females and males in the early stages after an acute Achilles tendon rupture. This article aims to explore the different factors affecting early function after an Achilles tendon rupture with a validated test battery that includes functional tests, clinical measurements and patient-reported outcome at a 3-month follow-up analysis of a larger prospective study. METHODS: This study was part of the DUSTAR-study (Diagnostic UltraSonography for the choice of Treatment of acute Achilles tendon Rupture) where the main aim was to evaluate if an acute ultrasonography could determine which patients, with an Achilles tendon rupture, should be treated surgically or nonsurgically. At the 3-month follow-up, the results between males and females were compared. RESULTS: One hundred and twenty-seven patients were included at the 3-month follow-up; of these, 102 (80%) were males and 25 (20%) were females. Amongst the females, 11 (44%) were able to perform a single leg heel-rise compared to 48 (47%) of the males; however, the difference was not statistically significant. There was no difference between the sexes in the frequency of completing a single-leg heel-rise at 3 months after injury; however, there were statistically significant differences between the groups when comparing Limb Symmetry Index (LSI) of heel-rise height and heel-rise work. The females had a median heel-rise height LSI/median heel-rise work LSI of 45%/14% compared to males who reached a level of 57%/23% (p = 0.006/p = 0.010). At the 3-month follow-up, the median (range) Achilles tendon Total Rupture Score (ATRS) reported by females was 28.5 (8-51), which had a nonsignificant difference compared to males who reported a median (range) ATRS of 30 (1-86). CONCLUSION: The risk of reduced heel-rise height and worse heel-rise work 3 months after an acute Achilles tendon rupture increases by being a female. Through this knowledge, we highlighted the importance of an individualised treatment for acute Achilles tendon ruptures with better outcome for both males and females. LEVEL OF EVIDENCE: Level II.

COVID-19-associated mortality in individuals with serious mental disorders in Sweden during the first two years of the pandemic- a population-based register study.

BACKGROUND: Reports at the beginning of the COVID-19 pandemic suggested differences in COVID-19-associated mortality between individuals with serious mental disorders (SMD) and the population at large. AIM: To compare the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden over the two main pandemic years. METHODS: We compared the pattern of COVID-19-associated mortality in individuals with and without SMD in Sweden during 2020 and 2021. For SMD, we included psychotic disorder, bipolar disorder, and severe depression. The analysis was based on summary data from the Swedish Board of Health and Welfare covering the entire adult Swedish population. RESULTS: The overall relative risk (RR) for experiencing a COVID-19-associated death was 1.66 (CI 1.50-1.83; p < 0.001) for individuals with SMD versus individuals without SMD. The corresponding RRs were 3.25 (CI 2.84-3.71; p < 0.001) for individuals with psychotic disorder, 1.06 (CI 0.88-1.26; p = 0.54) for individuals with bipolar disorder, and 1.03 (CI 0.80-1.32; p = 0.80) for individuals with severe depression. Compared to their respective counterparts in the non-SMD group, in the psychotic disorder and severe depression group, the RR were higher in women than in men. In the bipolar disorder group, the RR was higher in men than in women. The RR of COVID-19-associated death was generally higher in younger individuals with SMD. Individuals with psychosis between 18 and 59 years had the highest RR of COVID-19-associated death with 7.25 (CI 4.54-11.59; p<0.001). CONCLUSIONS: Individuals with SMD, and particularly those with psychotic disorders, had a higher risk of COVID-19-associated death than the general population. As this is a pattern also seen with other infections, people with SMD may be similarly vulnerable in future pandemics.

The Delayed Presentation of Achilles Tendon Ruptures Is Associated With Marked Alterations in the Gene Expression of COL1A1, MMPs, TIMPs, and IL-6.

BACKGROUND: Both acute and chronic Achilles tendon ruptures are affected by alterations in the extracellular matrix during the healing process of the tendon. Yet, these alterations in gene expression patterns are not well characterized. PURPOSE: To characterize temporal and spatial differences in gene expression patterns after an Achilles tendon rupture and to evaluate if cells from chronic Achilles tendon ruptures have the same ability to form new tendon tissue (tendon constructs) as healthy tendon cells. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 35 patients with surgically treated Achilles tendon ruptures were included in the study and divided into 3 groups: acute (<4 weeks), short-term chronic (1-6 months), and long-term chronic (>6 months). Biopsy specimens were collected during surgical repair and were used to analyze the gene expression within the different groups and to compare mRNA levels in the proximal and distal tendon ends. A complementary in vitro experiment was performed to evaluate if cells from chronic Achilles tendon ruptures can form tendon constructs. RESULTS: The mRNA levels for COL1A1 and COL3A1 were significantly higher in the short-term chronic group compared with the acute group (P < .05). Both MMP-1 and MMP-13 had the highest mRNA levels in the acute group (P < .01) compared with the long-term chronic group, while MMP-2 had the highest mRNA level in the short-term chronic group. Significant differences between the proximal and distal tendon ends were only detected for the monocyte and macrophage marker CD163 (P < .05), which was more expressed proximally. Cells extracted from chronic Achilles tendon ruptures displayed a similar ability and effectiveness to form tendon constructs as healthy tendon cells. CONCLUSION: A high collagenase gene activity after an Achilles tendon rupture indicated possible rapid matrix degradation in the acute phase. Chronic ruptures appeared to initiate the healing process even before treatment, indicated by the higher expression of collagen in the short-term chronic group. Cells from chronic Achilles tendon ruptures also displayed an ability to form new tendon tissue in vitro. CLINICAL RELEVANCE: The study shows a rapid increase in collagenase gene expression, which could lead to matrix degradation that continues for months after an Achilles tendon rupture.

Both gastrocnemius aponeurosis flaps and semitendinosus tendon grafts are effective in the treatment of chronic Achilles tendon ruptures - a systematic review.

INTRODUCTION: A chronic Achilles tendon rupture (ATR) is defined as an ATR that has been left untreated for more than four weeks following rupture. This systematic review aims to summarize the outcomes of chronic ATR treated using either a gastrocnemius aponeurosis flap or semitendinosus tendon graft. METHODS: A systematic search was conducted in three databases (PubMed, Scopus and Cochrane), for studies describing outcomes after surgical treatment of chronic ATR using gastrocnemius aponeurosis flaps or semitendinosus tendon grafts with more than 10 patients included. The studies were assessed for quality and risk of bias using the Methodological Items used to assess risk of bias in Non-Randomized Studies (MINORS). RESULTS: Out of the 818 studies identified with the initial search, a total of 36 studies with 763 individual patients were included in this systematic review. Gastrocnemius aponeurosis flap was used in 21 and semitendinosus tendon graft was used in 13 of the studies. The mean (SD) postoperative Achilles tendon Total Rupture Score (ATRS) for patients treated with a gastrocnemius aponeurosis flap was 83 (14) points and the mean (SD) American Orthopaedic Foot and Ankle Score (AOFAS) was 96 (1.7) points compared with ATRS 88 (6.9) points and AOFAS 92 (5.6) points for patients treated with a semitendinosus tendon graft. The included studies generally had low-quality according to MINORS, with a median of 8 (range 2-13) for all studies. CONCLUSION: Both gastrocnemius aponeurosis flaps and semitendinosus tendon grafts give acceptable results with minimal complications and are valid methods for treating chronic ATR. The main difference is more wound healing complications in patients treated with a gastrocnemius aponeurosis flap and more sural nerve injuries in patients treated with a semitendinosus grafts. The current literature on the subject is of mainly low quality and the absence of a patient-related outcome measure validated for chronic ATR makes comparisons between studies difficult. LEVEL OF EVIDENCE: Level IV.

Co-administration of Intravenous Drugs: Rapidly Troubleshooting the Solid Form Composition of a Precipitate in a Multi-drug Mixture Using On-Site Raman Spectroscopy.

Intravenous drugs are often co-administrated in the same intravenous catheter line due to which compatibility issues, such as complex precipitation processes in the catheter line, may occur. A well-known example that led to several neonatal deaths is the precipitation due to co-administration of ceftriaxone- and calcium-containing solutions. The current study is exploring the applicability of Raman spectroscopy for testing intravenous drug compatibility in hospital settings. The precipitation of ceftriaxone calcium was used as a model system and explored in several multi-drug mixtures containing both structurally similar and clinically relevant drugs for co-infusion. Equal molar concentrations of solutions containing ceftriaxone and calcium chloride dihydrate were mixed with solutions of cefotaxime, ampicillin, paracetamol, and metoclopramide. The precipitate formed was collected as an "unknown" material, dried, and analyzed. Several solid-state analytical methods, including X-ray powder diffraction, Raman spectroscopy, and thermogravimetric analysis, were used to characterize the precipitate. Raman microscopy was used to investigate the identity of single sub-visual particles precipitated from a mixture of ceftriaxone, cefotaxime, and calcium chloride. X-ray powder diffraction suggested that the precipitate was partially crystalline; however, the identity of the solid form of the precipitate could not be confirmed with this standard method. Raman spectroscopy combined with multi-variate analyses (principal component analysis and soft independent modelling class analogy) enabled the correct detection and identification of the precipitate as ceftriaxone calcium. Raman microscopy enabled the identification of ceftriaxone calcium single particles of sub-visual size (around 25 µm), which is in the size range that may occlude capillaries. This study indicates that Raman spectroscopy is a promising approach for supporting clinical decisions and especially for compatibility assessments of drug infusions in hospital settings.

Exploring a case of incompatibility in a complex regimen containing Plasma-Lyte 148 in the pediatric intensive care.

BACKGROUND: In the local pediatric intensive care unit, precipitation was observed in the intravenous catheter upon co-administration of four drugs together with the buffered electrolyte solution (Plasma-Lyte 148, Baxter). Co-infusion of incompatible combinations represents a safety concern. AIMS: To reproduce the clinical case of precipitation. To further explore and understand the risk of precipitation, different combinations of the components as well as the corresponding electrolyte solution with 5% glucose (Plasma-Lyte 148 with 5% glucose) should be investigated. METHODS: Physical compatibility of fentanyl, ketamine, midazolam, and potassium chloride was tested in combination with the buffered electrolyte solutions. The concentrations and infusion rates representative of children 10-40 kg were used to estimate mixing ratios. Analyses detecting visual particles (Tyndall beam) and sub-visual particles (light obscuration technology) were undertaken. Measured turbidity and pH in mixed samples were compared with unmixed controls. RESULTS: Both midazolam and ketamine showed formation of visual and sub-visual particles upon mixing with Plasma-Lyte 148, respectively. Particle formation was confirmed by increased turbidity and a distinct Tyndall effect. pH in mixed samples mirrored the pH of the buffered electrolyte, suggesting that the solubility limits of midazolam, and in some ratios also ketamine, were exceeded. Midazolam also precipitated in combination with the glucose-containing product that held a lower pH, more favorable for keeping midazolam dissolved. CONCLUSIONS: Replication of the case revealed that both midazolam and ketamine contributed to the precipitation. Midazolam and ketamine were both evaluated as incompatible with the buffered electrolyte solution and midazolam also with the buffered electrolyte-glucose solution and should not be co-administered in the same i.v.-catheter line. Fentanyl and potassium chloride were interpreted as compatible with both buffered electrolytes.

Frequently acquired drugs in neonatal intensive care and their physical compatibility.

AIM: Incompatibility of intravenous drugs is dangerous and therefore undesirable. The aim of this study was to identify the most commonly acquired intravenous drugs in five neonatal intensive care units and test these for compatibility. METHODS: The most frequently acquired drugs in five key hospitals in the South-Eastern district of Norway for 2019 and 2020 served as a proxy for the prevalence of use. Representatives were selected from the three most prevalent groups based on the Anatomical Therapeutic Chemical classification system. Co-administration of drug pairs was simulated using clinically relevant concentrations and infusion rates representing mixing ratios in the catheter. Particle formation was assessed by particle counting and size measurement, by visual examination using Tyndall beam, by turbidity and by measuring pH of mixed samples. RESULTS: The most frequently acquired drug groups were anti-infectives, neurological agents and cardiovascular drugs. Compatibility testing revealed that both ampicillin and benzylpenicillin were incompatible with morphine. Flecainide and fluconazole showed no signs of incompatibility with morphine. No information on these combinations in a neonatal-relevant setting is available. CONCLUSION: We recommend to abstain from co-administering ampicillin and benzylpenicillin with morphine in neonatal intensive settings. Morphine co-administered with flecainide and fluconazole in neonatal patients were evaluated as safe.

Co-administration of drugs with parenteral nutrition in the neonatal intensive care unit-physical compatibility between three components.

There is a lack of compatibility data for intravenous therapy to neonatal intensive care unit (NICU) patients, and the purpose of this study was to contribute with documented physical compatibility data to ensure safe co-administration. We selected Numeta G13E, the 3-in-1 parenteral nutrition (PN) used at our NICU, together with the frequently used drugs morphine, dopamine and cefotaxime in two- but also three-component combinations. Incompatibility may lead to particle formation (precipitation) and oil-droplet growth (emulsion destabilisation), both which are undesirable and pose a safety risk to already unstable patients. We assessed potential particle formation of three mixing ratios for each combination (always including 1 + 1 ratio) using light obscuration, turbidity and pH measurements combined with visual inspection by focused Tyndall beam. Potential droplet-growth and emulsion destabilisation was assessed by estimating PFAT5 from droplet size measurements and counts, mean droplet diameter and polydispersity index from dynamic light scattering, and pH measurements. Mixed samples were always compared to unmixed controls to capture changes as a result of mixing and samples were analysed directly after mixing and after 4 h to simulate long contact time. None of the samples showed any sign of precipitation, neither in the drug-drug nor in the two- or three-component mixture with PN. Neither did we detect any form of emulsion destabilisation. CONCLUSION: Dopamine, morphine and cefotaxime were found to be compatible with NumetaG13E, and it is safe to co-administer these drugs together with this PN in NICU patients. WHAT IS KNOWN: • The need for co-administration of drugs and complex PN admixtures occurs frequently in NICU due to limited venous access. • Available compatibility data are scarce and for combinations of more than two components non-existent. WHAT IS NEW: • Here we report physical compatibility data of two- as well as three-component combinations of frequently used NICU drugs and a 3-in-1 PN admixture. • Co-administration of Numeta G13E with dopamine and morphine, but also with morphine and cefotaxime is safe in NICU.

Endoscopically assisted reconstruction of chronic Achilles tendon ruptures and re-ruptures using a semitendinosus autograft is a viable alternative to pre-existing techniques.

PURPOSE: Achilles tendon ruptures are termed chronic after a delay in treatment for more than 4 weeks. The literature advocates surgical treatment with reconstruction to regain ankle push-off strength. The preferred technique is, however, still unknown and is often individualized. This study aims to present the technique and clinical outcome of an endoscopically assisted free semitendinosus reconstruction of chronic Achilles tendon rupture and Achilles tendon re-ruptures with delayed representation. It is hypothesized that the presented technique is a viable and safe alternative for distal Achilles tendon ruptures and ruptures with large tendon gaps. METHOD: Twenty-two patients (13 males and 9 females) with a median (range) age of 64 (34-73) treated surgically with endoscopically assisted Achilles tendon reconstruction using a semitendinosus autograft were included. The patients were evaluated at 12 months post-operatively for Achilles tendon Total Rupture Score (ATRS), calf circumference, Achilles Tendon Resting Angle (ATRA), heel-rise height and repetitions together with tendon length determined by ultrasonography, concentric heel-rise power and heel-rise work. RESULTS: The patients reported a median (range) ATRS of 76 (45-99) out of 100. The median (range) ATRA on the injured side was 60° (49°-75°) compared with 49.5° (40-61°), p < 0.001, on the non-injured side. Eighteen out of 22 patients were able to perform a single-leg heel-rise on the non-injured side. Sixteen patients out of those 18 (89%) were also able to perform a single heel-rise on the injured side. They did, however, perform significantly lower number of repetitions compared with the non-injured side with a median (range) heel-rise repetitions of 11 (2-22) compared with 26 (2-27), (p < 0.001), and a median (range) heel-rise height of 5.5 cm (1.0-11.0 cm) compared with 9.0 cm (5.0-11.5 cm), (p < 0.001). The median calf circumference was 1.5 cm smaller on the injured side, 37.5 cm compared with 39 cm, when medians were compared. The median (range) tendon length of the injured side was 24.8 cm (20-28.2 cm) compared with 22 cm (18.4-24.2 cm), (p < 0.001), on the non-injured side. CONCLUSION: The study shows that endoscopically assisted reconstruction using a semitendinosus graft to treat chronic Achilles tendon ruptures and re-ruptures with delayed representation produces a satisfactory outcome. The technique can restore heel-rise height in patients with more distal ruptures or large tendon defects and is therefore a viable technique for Achilles tendon reconstruction. LEVEL OF EVIDENCE: IV.

Disappointment and frustration, but long-term satisfaction: patient experiences undergoing treatment for a chronic Achilles tendon rupture-a qualitative study.

BACKGROUND: Delayed treatment of Achilles tendon ruptures is generally due to either misdiagnosis or patient delay. When the treatment is delayed more than 4 weeks, the rupture is defined as "chronic", and almost always requires more invasive surgery and longer rehabilitation time compared with acute Achilles tendon ruptures. There is insufficient knowledge of patient experiences of sustaining and recovering from a chronic Achilles tendon rupture. METHODS: To evaluate patients' experiences of suffering a chronic Achilles tendon rupture, semi-structured group interviews were conducted 4-6 years after surgical treatment using a semi-structured interview guide. The data were analyzed using qualitative content analysis described by Graneheim and Lundman. RESULTS: The experiences of ten patients (65 ± 14 years, 7 males and 3 females) were summarized into four main categories: (1) "The injury", where the patients described immediate functional impairments, following either traumatic or non-traumatic injury mechanisms that were misinterpreted by themselves or the health-care system; (2) "The diagnosis", where the patients expressed relief in receiving the diagnosis, but also disappointment and/or frustration related to the prior misdiagnosis and delay; (3) "The treatment", where the patients expressed high expectations, consistent satisfaction with the surgical treatment, and addressed the importance of the physical therapist having the right expertise; and (4) "The outcomes", where the patients expressed an overall satisfaction with the long-term outcome and no obvious limitations in physical activity, although some fear of re-injury emerged. CONCLUSIONS: An Achilles tendon rupture can occur during both major and minor trauma and be misinterpreted by both the assessing health-care professional as well as the patient themselves. Surgical treatment and postoperative rehabilitation for chronic Achilles tendon rupture results in overall patient satisfaction in terms of the long-term outcomes. We emphasize the need for increased awareness of the occurrence of Achilles tendon rupture in patients with an atypical patient history.

Patients with chronic Achilles tendon rupture have persistent limitations in patient-reported function and calf muscle function one year after surgical treatment - a case series.

PURPOSE: Evaluate the one-year postoperative outcomes in patients with Chronic Achilles tendon rupture. METHODS: Patients surgically treated for Chronic Achilles tendon rupture (n = 22, 14 males and 8 females, mean age 61 ± 15) were evaluated by Achilles tendon Total Rupture Score, The Physical Activity Scale, The Foot and Ankle Outcome Score, Calf muscle endurance test, counter movement jump, Hopping, ultrasound measurement of tendon length, Achilles Tendon Resting Angle, dorsi flexion range of motion and calf muscle circumference. Muscle function and tendon length outcomes on the injured side were compared with the healthy side. RESULTS: The patients scored a mean of 62 ± 26 on the Achilles tendon Total Rupture Score. Median scores on the injured compared with the healthy side were lower in heel-rise repetitions (20 vs 24 cm, p = 0.004), hel-rise height (8 vs 10 cm, p < 0.001), heel-rise total work (872 vs 1590 joule, p < 0.001) and hopping ratio (0.37 vs 0.48, p = 0.005). Median calf circumference was smaller (37 vs 38 cm, p = 0.001) and the mean tendon elongation greater on the injured side; Achilles tendon resting angle (55 vs 50°, p < 0.001) and ultrasound (22.4 vs 20.5 cm, p = 0.006). CONCLUSIONS: At one year postoperatively, patients with chronic Achilles tendon rupture reported persistent limitations in subjective foot and ankle function. Heel-rise height and total work as well as hopping ratio were not recovered, and there was an elongation of the injured Achilles tendon compared with the healthy tendon. LEVEL OF EVIDENCE: IV.

Increased Risks of Death and Hospitalization in Influenza/Pneumonia and Sepsis for Individuals Affected by Psychotic Disorders, Bipolar Disorders, and Single Manic Episodes: A Retrospective Cross-Sectional Study.

Individuals with severe mental disorders (SMDs) such as psychotic disorders, bipolar disorders, and single manic episodes have increased mortality associated with COVID-19 infection. We set up a population-based study to examine whether individuals with SMD also had a higher risk of hospitalization and death from other infectious conditions. Anonymized and summarized data from multiple Swedish patient registers covering the entire Swedish population were supplied by the Swedish National Board of Health and Welfare. The frequencies of hospitalizations and deaths associated with influenza/pneumonia and sepsis in individuals with SMD were compared with the rest of the population during 2018-2019. Possible contributing comorbidities were also examined, of which diabetes, cardiovascular disease, chronic lung disease, and hypertension were chosen. A total of 7,780,727 individuals were included in the study; 97,034 (1.2%) cases with SMD and 7,683,693 (98.8%) controls. Individuals with SMD had increased risk of death associated with influenza/pneumonia (OR = 2.06, 95% CI [1.87-2.27]) and sepsis (OR = 1.61, 95% CI [1.38-1.89]). They also had an increased risk of hospitalization associated with influenza/pneumonia (OR = 2.12, 95% CI [2.03-2.20]) and sepsis (OR = 1.89, 95% CI [1.75-2.03]). Our results identify a need for further evaluation of whether these individuals should be included in prioritized risk groups for vaccination against infectious diseases other than COVID-19.

The economic cost and patient-reported outcomes of chronic Achilles tendon ruptures.

PURPOSE: While most Achilles tendon ruptures are dramatic and diagnosed quickly, some are missed, with a risk of becoming chronic. A chronic Achilles tendon rupture is defined as a rupture that has been left untreated for more than 4 weeks. By mapping the health economic cost of chronic Achilles tendon ruptures the health-care system might be able to better distribute resources to detect these ruptures at an earlier time. METHOD: All patients with a chronic Achilles tendon rupture who were treated surgically at Sahlgrenska University Hospital or Kungsbacka Hospital between 2013 and 2018 were invited to participate in the study. The patients were evaluated postoperatively using the validated Achilles tendon Total Rupture Score (ATRS). The health-care costs were assessed using clinical records. The production-loss costs were extracted from the Swedish Social Insurance Agency. The cost of chronic Achilles tendon ruptures was then compared with the cost of acute ruptures in a previous study by Westin et.al. RESULTS: Forty patients with a median (range) age of 66 (28-86) were included in the study. The mean total cost (± SD) for the patients with a chronic Achilles tendon rupture was 6494 EUR ± 6508, which is 1276 EUR higher than the mean total cost of acute ruptures. Patients with chronic Achilles tendon ruptures reported a mean (min-max) postoperative ATRS of 73 (14-100). CONCLUSION: Missing an Achilles tendon rupture will entail higher health-care costs compared with acute ruptures. Health-care resources can be saved if Achilles tendon ruptures are detected at an early stage.

Y-Site Physical Compatibility of Numeta G13E with Drugs Frequently Used at Neonatal Intensive Care.

Preterm neonates require parenteral nutrition (PN) in addition to intravenous drug therapy. Due to limited venous access, drugs are often co-administered with PN via the same lumen. If incompatible, precipitation and emulsion destabilization may occur with the consequent risk of embolism and hyper-immune reactions. Information on intravenous compatibility is scarce. Our aim was to analyse the compatibility of Numeta G13E with paracetamol, vancomycin and fentanyl because of the frequency of their use. A panel of methods was chosen to assess precipitation (sub-visual particle counting, turbidity measurement, Tyndall beam effect and pH measurement) and emulsion destabilization (mean droplet diameter measurement and sub-visual counting of oil droplets, followed by estimation of PFAT5 (percentage of fat residing in globules larger than 5 µm) and pH measurement). Samples in clinically relevant mixing ratios were tested immediately and after 4 h. All samples of drugs mixed with Numeta G13E were compared to unmixed controls. None of the tested drugs precipitated in contact with Numeta G13E, and we did not see any sign of emulsion destabilization when clinically relevant mixing ratios were applied. These results are reassuring. However, when contact time exceeds the established norm, caution in the form of filter utilisation and close inspection is advised.