Genomic insights on conservation priorities for North Sea houting and European lake whitefish (Coregonus spp.).

Population genomics analysis holds great potential for informing conservation of endangered populations. We focused on a controversial case of European whitefish (Coregonus spp.) populations. The endangered North Sea houting is the only coregonid fish that tolerates oceanic salinities and was previously considered a species (C. oxyrhinchus) distinct from European lake whitefish (C. lavaretus). However, no firm evidence for genetic-based salinity adaptation has been available. Also, studies based on microsatellite and mitogenome data suggested surprisingly recent divergence (c. 2500 years bp) between houting and lake whitefish. These data types furthermore have provided no evidence for possible inbreeding. Finally, a controversial taxonomic revision recently classified all whitefish in the region as C. maraena, calling conservation priorities of houting into question. We used whole-genome and ddRAD sequencing to analyse six lake whitefish populations and the only extant indigenous houting population. Demographic inference indicated post-glacial expansion and divergence between lake whitefish and houting occurring not long after the Last Glaciation, implying deeper population histories than previous analyses. Runs of homozygosity analysis suggested not only high inbreeding (FROH up to 30.6%) in some freshwater populations but also FROH up to 10.6% in the houting prompting conservation concerns. Finally, outlier scans provided evidence for adaptation to high salinities in the houting. Applying a framework for defining conservation units based on current and historical reproductive isolation and adaptive divergence led us to recommend that the houting be treated as a separate conservation unit regardless of species status. In total, the results underscore the potential of genomics to inform conservation practices, in this case clarifying conservation units and highlighting populations of concern.

Pulmonary superinfection diagnosed with bronchoalveolar lavage at intubation in COVID patients: A Swedish single-centre study.

BACKGROUND: Patients with severe coronavirus disease 2019 (COVID) pneumonia and acute respiratory distress syndrome (C-ARDS) on invasive mechanical ventilation (IMV) have been found to be prone to having other microbial findings than severe acute respiratory syndrome coronavirus 2 (SARS-2)-CoV-19 in the bronchoalveolar lavage (BAL) fluid at intubation causing a superinfection. These BAL results could guide empirical antibiotic treatment in complex clinical situations. However, there are limited data on the relationship between microbial findings in the initial BAL at intubation and later ventilator-associated pneumonia (VAP) diagnoses. OBJECTIVE: To analyse the incidence of, and microorganisms responsible for, superinfections in C-ARDS patients at the time of first intubation through microbial findings in BAL fluid. To correlate these findings to markers of inflammation in plasma and later VAP development. DESIGN: Retrospective single-centre study. SETTING: One COVID-19 intensive care unit (ICU) at a County Hospital in Sweden during the first year of the pandemic. PATIENTS: All patients with C-ARDS who were intubated in the ICU. RESULTS: We analysed BAL fluid specimens from 112 patients at intubation, of whom 31 (28%) had superinfections. Blood levels of the C-reactive protein, procalcitonin, neutrophil granulocytes, and lymphocytes were indistinguishable between patients with and without a pulmonary superinfection. Ninety-eight (88%) of the patients were treated with IMV for more than 48 h and of these patients, 37% were diagnosed with VAP. The microorganisms identified in BAL at the time of intubation are normally found at the oral, pharyngeal, and airway sites. Only one patient had an indistinguishable bacterial strain responsible for both superinfection at intubation and in VAP. CONCLUSIONS: One fourth of the patients with C-ARDS had a pulmonary superinfection in the lungs that was caused by another microorganism identified at intubation. Routine serum inflammatory markers could not be used to identify this complication. Microorganisms located in BAL at intubation were rarely associated with later VAP development.

Risk factors for ventilator-associated lower respiratory tract infection in COVID-19, a retrospective multicenter cohort study in Sweden.

BACKGROUND: Ventilator-associated lower respiratory tract infections (VA-LRTI) increase morbidity and mortality in intensive care unit (ICU) patients. Higher incidences of VA-LRTI have been reported among COVID-19 patients requiring invasive mechanical ventilation (IMV). The primary objectives of this study were to describe clinical characteristics, incidence, and risk factors comparing patients who developed VA-LRTI to patients who did not, in a cohort of Swedish ICU patients with acute hypoxemic respiratory failure due to COVID-19. Secondary objectives were to decipher changes over the three initial pandemic waves, common microbiology and the effect of VA-LTRI on morbidity and mortality. METHODS: We conducted a multicenter, retrospective cohort study of all patients admitted to 10 ICUs in southeast Sweden between March 1, 2020 and May 31, 2021 because of acute hypoxemic respiratory failure due to COVID-19 and were mechanically ventilated for at least 48 h. The primary outcome was culture verified VA-LRTI. Patient characteristics, ICU management, clinical course, treatments, microbiological findings, and mortality were registered. Logistic regression analysis was conducted to determine risk factors for first VA-LRTI. RESULTS: Of a total of 536 included patients, 153 (28.5%) developed VA-LRTI. Incidence rate of first VA-LRTI was 20.8 per 1000 days of IMV. Comparing patients with VA-LRTI to those without, no differences in mortality, age, sex, or number of comorbidities were found. Patients with VA-LRTI had fewer ventilator-free days, longer ICU stay, were more frequently ventilated in prone position, received corticosteroids more often and were more frequently on antibiotics at intubation. Regression analysis revealed increased adjusted odds-ratio (aOR) for first VA-LRTI in patients treated with corticosteroids (aOR 2.64 [95% confidence interval [CI]] [1.31-5.74]), antibiotics at intubation (aOR 2.01 95% CI [1.14-3.66]), and days of IMV (aOR 1.05 per day of IMV, 95% CI [1.03-1.07]). Few multidrug-resistant pathogens were identified. Incidence of VA-LRTI increased from 14.5 per 1000 days of IMV during the first wave to 24.8 per 1000 days of IMV during the subsequent waves. CONCLUSION: We report a high incidence of culture-verified VA-LRTI in a cohort of critically ill COVID-19 patients from the first three pandemic waves. VA-LRTI was associated with increased morbidity but not 30-, 60-, or 90-day mortality. Corticosteroid treatment, antibiotics at intubation and time on IMV were associated with increased aOR of first VA-LRTI.

Comparative effectiveness of pharmacological interventions for hand osteoarthritis: a systematic review and network meta-analysis of randomised trials.

OBJECTIVE: To explore the comparative effectiveness of pharmacological interventions for hand osteoarthritis (OA). METHODS: We systematically searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials from inception until 26 December 2021, for randomised trials of pharmacological interventions for people with hand OA. Two reviewers independently extracted study data and assessed the risk of bias. We calculated the effect sizes for pain (standardised mean differences) using Bayesian random effects models for network meta-analysis (NMA) and pairwise meta-analysis. Based on a pre-specified protocol, we prospectively registered the study at PROSPERO, CRD42021215393. RESULTS: We included 72 trials with 7609 participants. 65 trials (n=5957) were eligible for the quantitative synthesis, investigating 29 pharmacological interventions. Oral non-steroidal anti-inflammatory drugs (NSAIDs) and oral glucocorticoids' NMA effect sizes were -0.18 (95% credible interval -0.36 to 0.02) and -0.54 (-0.83 to -0.24), respectively, compared with placebo, and the result was consistent when limiting evidence to the pairwise meta-analysis of trials without high risk of bias. Intra-articular hyaluronate, intra-articular glucocorticoids, hydroxychloroquine, and topical NSAIDs' NMA effect sizes were 0.22 (-0.08 to 0.51), 0.25 (0.00 to 0.51), -0.01 (-0.19 to 0.18), and -0.14 (-0.33 to 0.08), respectively, compared with placebo. Oral NSAIDs were inferior to oral glucocorticoids with an NMA effect size of 0.36 (0.01 to 0.72). No intervention was superior to placebo when stratifying for thumb and finger OA. CONCLUSION: Oral NSAIDs and glucocorticoids are apparently effective pharmacological interventions in hand OA. Intra-articular therapies and topical NSAIDs were not superior to placebo.

Platelet Function is Preserved After Moderate Cardiopulmonary Bypass Times But Transiently Impaired After Protamine.

OBJECTIVES: Previous studies have described impaired platelet function after cardiopulmonary bypass (CPB). Whether this is still valid in contemporary cardiac surgery is unclear. This study aimed to quantify changes in function and number of platelets during CPB in a present-day cardiac surgery cohort. DESIGN: Prospective, controlled clinical study. SETTING: A single-center university hospital. PARTICIPANTS: Thirty-nine patients scheduled for coronary artery bypass graft surgery with CPB. INTERVENTIONS: Platelet function and numbers were measured at 6 timepoints in 39 patients during and after coronary artery bypass graft surgery; at baseline before anesthesia, at the end of CPB, after protamine administration, at intensive care unit (ICU) arrival, 3 hours after ICU arrival, and on the morning after surgery. MEASUREMENTS AND MAIN RESULTS: Platelet function was assessed with impedance aggregometry and flow cytometry. Platelet numbers are expressed as actual concentration and as numbers corrected for dilution using hemoglobin as a reference marker. There was no consistent impairment of platelet function during CPB with either impedance aggregometry or flow cytometry. After protamine administration, a decrease in platelet function was seen with impedance aggregometry and for some markers of activation with flow cytometry. Platelet function was restored 3 hours after arrival in the ICU. During CPB (85.0 ± 21 min), the number of circulating platelets corrected for dilution increased from 1.73 ± 0.42 × 109/g to 1.91 ± 0.51 × 109/g (p < 0.001). CONCLUSIONS: During cardiac surgery with moderate CPB times, platelet function was not impaired, and no consumption of circulating platelets could be detected. Administration of protamine transiently affected platelet function.

Two-year follow-up of patients with post-COVID-19 condition in Sweden: a prospective cohort study.

Background: Few studies have reported the long-term health effects of COVID-19. The regional population-based Linköping COVID-19 study (LinCoS) included all patients hospitalised due to COVID-19 during the first pandemic wave. Four months post-discharge, over 40% (185/433) experienced persisting symptoms and activity/participation limitations, indicating post-COVID-19 condition (PCC). The present follow-up study aimed to determine the long-term recovery among these patients 24 months post-admission. Methods: This prospective cohort study included all patients from LinCoS with PCC at four months post-discharge. We repeated the same structured interview at a 24-month follow-up to identify persisting symptoms and their impact on daily life. Intercurrent health issues were identified by reviewing medical records. Findings: Of 185 patients with PCC at 4 months post-discharge, 181 were alive at the 24-month assessment and 165 agreed to participate. Of those, 21% (35/165) had been readmitted to hospital for various causes in the interim period. The majority of patients (139/165, 84%) reported persisting problems affecting everyday life at 24 months. Significant improvements were seen in the prevalence and magnitude of some symptoms/limitations compared with four months post-discharge. Cognitive, sensorimotor, and fatigue symptoms were the most common persisting symptoms at 24 months. No clear difference was evident between individuals treated in the intensive care unit (ICU) and non-ICU-treated individuals. Approximately half of those who were on sick leave related to PCC at four months after infection were on sick leave at 24 months. Interpretation: This is one of the first studies to report 2-year outcomes in patients with PCC following COVID-19 hospitalisation. Despite some improvements over time, we found a high prevalence of persisting symptoms and a need for long-term follow-up and rehabilitation post COVID-19 infection. Funding: The study was funded by Region Östergötland.

Outcome of nasal measurements in patients with OSA - Mounting evidence of a nasal endotype.

BACKGROUND: Increased nasal resistance as measured by 4-phase rhinomanometry is associated with a paucity of apneas relative to hypopneas in obstructive sleep apnea (OSA) patients. The ratio of hypopneas to apneas for a given apnea hypopnea index (AHI) may influence treatment choice. This study aimed to investigate if OSA patients with an elevated hypopnea apnea ratio are associated with differences in acoustic rhinometry measurements. METHODS: One hundred and thirty-nine (n = 139) OSA patients (AHI >5) were enrolled in this prospective case-control study (all male). OSA Diagnosis was established through a type three sleep study. Both acoustic rhinometry and 4-phase rhinomanometry were performed on all patients at baseline and after decongestion. Possible associations between apnea-hypopnea index, oxygen desaturation index, nadir oxygen saturation, apnea index, hypopnea index, hypopnea to apnea ratio and body mass index and were analysed using multiple logistic and linear regression models. RESULTS: The acoustic rhinometry measurements minimal cross-sectional area, total volume and minimal cross-sectional areas are significantly smaller in patients with increased nasal resistance as measured by 4-phase rhinomanometry (P < 0.01). No consistent statistically significant associations were found between the acoustic rhinometry variables, and the respiratory variables analysed in the sleep studies. OSA patients with an elevated hypopnea apnea ratio are more than 4 times more likely to present with increased nasal resistance measured by 4-phase rhinomanometry (OR = 4.4, 95% CI [1.5-13.2], P < 0.01). CONCLUSIONS: Acoustic rhinometry is significantly associated with 4-phase rhinomanometry. However, acoustic rhinometry measurements are not associated with the respiratory indices routinely measured in OSA in a clinical setting. 4-phase rhinomanometry is a more suitable method for detecting clinically relevant nasal obstruction in obstructive sleep apnea patients.

Improved 60-day survival but impaired general health in Swedish ICU-COVID patients: An ambidirectional population-based study.

BACKGROUND: Survival among critically ill COVID-19 patients varies between countries and time periods. Mortality rates up to 60% have been reported in intensive care units (ICUs). Standard-of-care has evolved throughout the pandemic. The purpose of the study was to explore management and mortality of COVID-19 ICU-patients during the first pandemic wave and assess their post-ICU health status. METHODS: We conducted an exploratory observational ambidirectional population-based study of ICU-patients with COVID-19 in a Swedish county during 1 March-30 June 2020. Primary outcome was 60-day mortality with secondary outcomes including treatments, complications, self-reported general health and dyspnoea post-discharge. Patients were consecutively divided into equal tertiles with cut-offs on April 4 and April 20, 2020, to analyse time trends. RESULTS: One hundred patients, median age was 63 years, were included, and 60-day mortality rate was 22%. Ninety-one percent had moderate/severe ARDS and 88% required mechanical ventilation. In the first tertile of patients 60-day mortality was 33%, declining to 15% and 18% in the following two. This reduction paralleled increased use of thromboprophylaxis, less steep rise of treated ICU-patients per day and expanded ICU resources. Four months post-discharge, 63% of survivors reported self-assessed decline in general health retrospectively compared to prior COVID-19. CONCLUSIONS: In this cohort, the initial 60-day mortality quickly declined, despite continuous admittance of critically ill patients. This was parallel to adaptation to increased workload and more intense thromboembolic prophylaxis. A majority of survivors reported declined general health four months after discharge. Further studies on long-term health status of ICU-survivors are indicated.

Quantification of platelet function - a comparative study of venous and arterial blood using a novel flow cytometry protocol.

Studies of platelet function in surgical patients often involve both arterial and venous sampling. Possible effects of different sampling sites could be important, but have not been thoroughly investigated. We aimed to compare platelet function in arterial and venous blood samples using a novel flow cytometry protocol and impedance aggregometry. Arterial and venous blood was collected before anesthesia in 10 patients undergoing cardiac surgery of which nine was treated with acetylsalicylic acid until the day before surgery. Flow cytometry included simultaneous analysis of phosphatidylserine exposure, active conformation of the fibrinogen receptor (PAC-1 binding), α-granule and lysosomal release (P-selectin and LAMP-1 exposure) and mitochondrial membrane integrity. Platelets were activated with ADP or peptides activating thrombin receptors (PAR1-AP/PAR4-AP) or collagen receptor GPVI (CRP-XL). Leukocyte-platelet conjugates and P-selectin exposure were evaluated immediately in fixated samples. For impedance aggregometry (Multiplate®), ADP, arachidonic acid, collagen and PAR1-AP (TRAP) were used as activators. Using impedance aggregometry and in 27 out of 37 parameters studied with flow cytometry there was no significant difference between venous and arterial blood sampling. Arterial blood showed more PAC-1 positive platelets when activated with PAR1-AP or PAR4-AP and venous blood showed more monocyte-platelet and neutrophil-platelet conjugates and higher phosphatidylserine exposure with CRP-XL alone and combined with PAR1-AP or PAR4-AP. We found no differences using impedance aggregometry. In conclusion, testing of platelet function by flow cytometry and impedance aggregometry gave comparable results for most of the studied parameters in venous and arterial samples. Flow cytometry identified differences in PAC-1 binding when activated with PAR1-AP, exposure of phosphatidyl serine and monocyte/neutrophil-platelet conjugates, which might reflect differences in blood sampling technique or in flow conditions in this patient cohort with coronary artery disease. These differences might be considered when comparing data from different sample sites, but caution should be exercised if a different protocol is used or another patient group is studied.

Diet and food selection by fish larvae in turbid and clear water shallow temperate lakes.

Fish larvae play an important structuring role for their prey and show ontogenetic shifts in diet. Changes in diet differ between species and habitats and may also be affected by turbidity (eutrophication). We investigated the diet (stomach content) and the food selection (ratio of ingested prey and prey availability) of roach and perch larvae in a clear lake and of roach, perch and pikeperch larvae in a turbid lake multiple times during spring to autumn. The diet of the fish larvae changed with size, and for roach and perch larvae between the lakes. Coexisting species of fish larvae had different diets in the two lakes, pointing to resource partitioning; yet, in the clear lake, medium-sized larvae had a high diet overlap, suggesting a competitive relationship at this developmental stage. In the clear lake, roach larvae showed diel differentiation in diet, while perch demonstrated diet shifts between habitats, which probably aided in reducing competition and also evidenced an effect of light on the larval prey capture and/or predator-fish larvae interactions. In the turbid lake, roach and perch larvae did not reveal differences in diet between habitats or time of the day, owing to homogeneity of food items and poor light conditions. However, the diet of pikeperch larvae differed between day and night following daily variations in the abundance of its preferred prey. The roach larvae were highly selective for Bosmina, Daphnia and benthic cladocerans, perch larvae generally consumed what was available, while pikeperch primarily preyed on cyclopoid copepodites. We conclude that turbidity acted as a cover for fish larvae in the turbid lake. Under eutrophication-induced turbidity scenarios the effects of fish larvae on their prey are stronger (i.e., high selectivity for several resources) than that of larvae in clear waters, creating a negative feedback on the path to restore water clarity.

Prehospital delay is an important risk factor for mortality in community-acquired bloodstream infection (CA-BSI): a matched case-control study.

OBJECTIVES: The aim of this study was to identify prehospital and early hospital risk factors associated with 30-day mortality in patients with blood culture-confirmed community-acquired bloodstream infection (CA-BSI) in Sweden. METHODS: A retrospective case-control study of 1624 patients with CA-BSI (2015-2016), 195 non-survivors satisfying the inclusion criteria were matched 1:1 with 195 survivors for age, gender and microorganism. All forms of contact with a healthcare provider for symptoms of infection within 7 days prior CA-BSI episode were registered. Logistic regression was used to analyse risk factors for 30-day all-cause mortality. RESULTS: Of the 390 patients, 61% (115 non-survivors and 121 survivors) sought prehospital contact. The median time from first prehospital contact till hospital admission was 13 hours (6-52) for non-survivors and 7 hours (3-24) for survivors (p<0.01). Several risk factors for 30-day all-cause mortality were identified: prehospital delay OR=1.26 (95% CI: 1.07 to 1.47), p<0.01; severity of illness (Sequential Organ Failure Assessment score) OR=1.60 (95% CI: 1.40 to 1.83), p<0.01; comorbidity score (updated Charlson Index) OR=1.13 (95% CI: 1.05 to 1.22), p<0.01 and inadequate empirical antimicrobial therapy OR=3.92 (95% CI: 1.64 to 9.33), p<0.01. In a multivariable model, prehospital delay >24 hours from first contact remained an important risk factor for 30-day all-cause mortality due to CA-BSI OR=6.17 (95% CI: 2.19 to 17.38), p<0.01. CONCLUSION: Prehospital delay and inappropriate empirical antibiotic therapy were found to be important risk factors for 30-day all-cause mortality associated with CA-BSI. Increased awareness and earlier detection of BSI in prehospital and early hospital care is critical for rapid initiation of adequate management and antibiotic treatment.

Obstructive sleep apnea in Norwegian adults with achondroplasia: a population-based study.

BACKGROUND: Previous studies have found a high prevalence of obstructive sleep apnea (OSA) in children with achondroplasia, but clinical studies on this complication in adults with achondroplasia are lacking. OBJECTIVES: This population-based, cross-sectional study investigated the prevalence, severity, and predictive factors of OSA in Norwegian adults with achondroplasia. METHODS: We collected clinical data on 49 participants. Participants without a preexisting diagnosis of OSA had an overnight sleep registration. OSA was defined as an apnea-hypopnea index (AHI) ≥ 5 plus characteristic clinical symptoms, or AHI ≥ 15. We used the Berlin Questionnaire to assess clinical symptoms of OSA. RESULTS: OSA was found in 59% (29/49) of the participants (95% confidence interval 44 to 73%), of whom 59% (17/29) had moderate to severe OSA (AHI ≥ 15), and 48% (14/29) were previously undiagnosed. Variables predictive of OSA were: excessive daytime sleepiness; unrested sleep; loud snoring; observed nocturnal breathing stops; hypertension; age > 40 years; and BMI > 30 kg/m2. CONCLUSION: OSA was highly prevalent in Norwegian adults with achondroplasia, which we believe is representative of this population worldwide. Follow-up of adults with achondroplasia should include assessment of symptoms and signs of OSA, with a low threshold for conducting an overnight sleep registration if findings suggestive of OSA are present.

A Rapid Method for Postmortem Vitreous Chemistry-Deadside Analysis.

Vitreous fluid is commonly collected for toxicological analysis during forensic postmortem investigations. Vitreous fluid is also often analyzed for potassium, sodium, chloride and glucose for estimation of time since death, and for the evaluation of electrolyte imbalances and hyperglycemia, respectively. Obtaining such results in the early phase of a death investigation is desirable both in regard to assisting the police and in the decision-making prior to the autopsy. We analyzed vitreous fluid with blood gas instruments to evaluate/examine the possible impact of different sampling and pre-analytical treatment. We found that samples from the right and left eye, the center of the eye as well as whole vitreous samples gave similar results. We also found imprecision to be very low and that centrifugation and dilution were not necessary when analyzing vitreous samples with blood gas instruments. Similar results were obtained when analyzing the same samples with a regular multi-analysis instrument, but we found that such instruments could require dilution of samples with high viscosity, and that such dilution might impact measurement accuracy. In conclusion, using a blood gas instrument, the analysis of postmortem vitreous fluid for electrolytes and glucose without sample pretreatment produces rapid and reliable results.

Protamine stimulates platelet aggregation in vitro with activation of the fibrinogen receptor and alpha-granule release, but impairs secondary activation via ADP and thrombin receptors.

Heparin and protamine are fundamental in the management of anticoagulation during cardiac surgery. Excess protamine has been associated with increased bleeding. Interaction between protamine and platelet function has been demonstrated but the mechanism remains unclear. We examined the effect of protamine on platelet function in vitro using impedance aggregometry, flow cytometry, and thrombin generation. Platelets were exposed to protamine at final concentrations of 0, 20, 40, and 80 µg/mL, alone or together with adenosine diphosphate (ADP) or thrombin PAR1 receptor-activating peptide (TRAP). We found that in the absence of other activators, protamine (80 µg/mL) increased the proportion of platelets with active fibrinogen receptor (binding of PAC-1) from 3.6% to 97.0% (p < .001) measured with flow cytometry. Impedance aggregometry also increased slightly after exposure to protamine alone. When activated with ADP or TRAP protamine at 80 µg/mL reduced aggregation, from 73.8 ± 29.4 U to 46.9 ± 21.1 U (p < .001) with ADP and from 126.4 ± 16.1 U to 94.9 ± 23.7 U (p < .01) with TRAP. P-selectin exposure (a marker of alpha-granule release) measured by median fluorescence intensity (MFI) increased dose dependently with protamine alone, from 0.76 ± 0.20 (0 µg/mL) to 10.2 ± 3.1 (80 µg/mL), p < .001. Protamine 80 µg/mL by itself resulted in higher MFI (10.16 ± 3.09) than activation with ADP (2.2 ± 0.7, p < .001) or TRAP (5.7 ± 2.6, p < .01) without protamine. When protamine was combined with ADP or TRAP, there was a concentration-dependent increase in the alpha-granule release. In conclusion, protamine interacts with platelets in vitro having both a direct activating effect and impairment of secondary activation of aggregation by other agonists.

Impact of nasal resistance on the distribution of apneas and hypopneas in obstructive sleep apnea.

BACKGROUND: This study aims to investigate how increased nasal resistance affects respiratory variables in obstructive sleep apnea (OSA). In this setting, to assess how nasal resistance, as measured by 4-phase rhinomanometry, affects the distribution of hypopneas and apneas when measured with routine Sleep Polygraphy (PG). METHODS: PG recordings were analysed and 4-phase rhinomanometry was conducted. Crude differences between groups were compared using Mann-Whitney Wilkoxon test. Odds for higher nasal resistance were modelled using logistic regression. All tests were two-sided. P < 0.05 was considered statistically significant. RESULTS: In sum, 126 OSA patients referred to our center examined with PG were included. OSA Patients with a higher ratio of hypopneas relative to apneas are more than three times more likely (OR = 3.72, 95%CI [1.30-10.66], p = 0.015) to have increased nasal resistance as measured by 4-phase rhinomanometry, compared to those who have a lower ratio of hypopneas relative to apneas, regardless of OSA severity. The median Hypopnea to Apnea Ratio (HAR) in the low nasal resistance group was 0.8 compared to 2.6 in the high nasal resistance group (p = 0.000). The median apnea index in the low nasal resistance group was 13.6, in the high nasal group it was 5.2 (p = 0.001). CONCLUSIONS: Our investigation shows that OSA patients presenting with increased nasal resistance demonstrate significant differences in the distribution of hypopneas and apneas. OSA patients with increased nasal resistance exhibit a significantly lower apnea index and a higher hypopnea to apnea ratio compared to OSA patients presenting with low nasal resistance. Thus, analysis of the HAR in sleep studies is a useful tool to identify patients who may potentially have nasal obstruction as part of their respiratory pathophysiology. We therefore recommend that OSA patients with a predominance of hypopneas relative to apneas should undergo further nasal measurements.

Cost analysis comparison between peripherally inserted central catheters and implanted chest ports in patients with cancer-A health economic evaluation of the PICCPORT trial.

BACKGROUND: A reliable central venous access device is a cornerstone in the treatment of cancer. Both peripherally inserted central catheters (PICC) and totally implanted chest ports (PORT) are commonly used for the delivery of chemotherapy. Both types of catheter can cause adverse events such as catheter-related deep venous thrombosis (CR-DVT), infection and mechanical complications. METHOD: We conducted a randomized controlled trial including 399 patients with cancer and performed a health economic evaluation investigating the cost related to PICCs and PORTs using several clinically relevant dimensions from a healthcare perspective. The cost was determined using process and cost estimate models. RESULT: PICCs are associated with a higher total cost when compared with PORTs. Combining the costs of all categories, the prize per inserted device was 824.58 EUR for PICC and 662.34 EUR for PORT. When adjusting for total catheter dwell time the price was 6.58 EUR/day for PICC and 3.01 EUR/day for PORT. The difference in CR-DVT was the main contributor to the difference in cost. The daily cost of PICC is approximately twice to that of PORT. CONCLUSION: We have demonstrated that the cost from a healthcare perspective is higher in cancer patients receiving a PICC than to those with a PORT. The difference is driven mainly by the cost related to the management of adverse events. Our findings are relevant to anaesthetists, oncologists and vascular access clinicians and should be considered when choosing vascular access device prior to chemotherapy.

Clinical impact of peripherally inserted central catheters vs implanted port catheters in patients with cancer: an open-label, randomised, two-centre trial.

BACKGROUND: Centrally inserted totally implanted vascular access ports (PORTs) and peripherally inserted central catheters (PICCs) are widely used for the administration of chemotherapy. Our aim was to study the incidence of catheter-related deep venous thrombosis in patients with cancer receiving chemotherapy through either a PICC or a PORT. METHODS: Adults with non-haematological cancer (mainly breast and colorectal) from two Swedish oncology centres were included and followed for up to 1 yr. Patients were randomly assigned to receive a single-lumen PICC or PORT. The primary end point was the occurrence of a clinically significant catheter-related deep venous thrombosis, and the secondary end point was a composite of adverse events related to the catheter: insertion complication, thrombosis, occlusion, infection, and mechanical problems. RESULTS: The trial recruited 399 participants (PICC, n=201; PORT, n=198) between March 2013 and February 2017. The PICCs were associated with 16 (8%) deep venous thromboses compared with two (1%) in the PORT group (HR=10.2; 95% confidence interval, 2.3-44.6; P=0.002). The overall incidence of composite adverse events was higher for patients with a PICC compared with those with a PORT (HR=2.7; 95% confidence interval, 1.6-4.6; P<0.001). CONCLUSIONS: PICCs are associated with higher risk for catheter-related deep venous thrombosis and other adverse events when compared with PORTs. This increased risk should be considered when choosing a vascular access device for chemotherapy, especially in patients with solid malignancy. CLINICAL TRIAL REGISTRATION: NCT01971021.

Delay of appropriate antibiotic treatment is associated with high mortality in patients with community-onset sepsis in a Swedish setting.

Early appropriate antimicrobial therapy is crucial in patients with sepsis and septic shock. Studies often focus on time to first dose of appropriate antibiotics, but subsequent dosing is equally important. Our aim was to investigate the impact of fulfillment of early treatment, with focus on appropriate administration of first and second doses of antibiotics, on 28-day mortality in patients with community-onset severe sepsis and septic shock. A retrospective study on adult patients admitted to the emergency department with community-onset sepsis and septic shock was conducted 2012-2013. The criterion "early appropriate antibiotic treatment" was defined as administration of the first dose of adequate antibiotics within 1 h, and the second dose given with less than 25% delay after the recommended dose interval. A high-risk patient was defined as a septic patient with either shock within 24 h after arrival or red triage level on admittance according to the Medical Emergency Triage and Treatment System Adult. Primary endpoint was 28-day mortality. Of 90 patients, less than one in four (20/87) received early appropriate antibiotic treatment, and only one in three (15/44) of the high-risk patients. The univariate analysis showed a more than threefold higher mortality among high-risk patients not receiving early appropriate antibiotic treatment. Multivariable analysis identified early non-appropriate antibiotic treatment as an independent predictor of mortality with an odds ratio for mortality of 10.4. Despite that the importance of early antibiotic treatment has been established for decades, adherence to this principle was very poor.