Sören Berg

Background: Mortality among critically ill COVID‐19 patients has varied globally. In Sweden, geographic differences in mortality have also been observed. The current study aimed to determine whether mortality differences persist after adjusting for differences in case‐mix, and to identify potential independent factors contributing to regional variations in mortality. Methods: We conducted a multicenter cohort study including adult patients admitted to seven hospital ICUs across three Swedish healthcare counties between March 1, 2020 and July 31, 2021. These ICUs include one university hospital, three county hospitals and three local hospitals, and cover the intensive care infrastructure for approximately one million inhabitants. Patients were assigned to the hospital of initial ICU admission, even if transferred later during the course. Patient characteristics, disease severity, respiratory support, and treatments were registered. Primary outcome was 90‐day mortality. A mixed‐effects Cox proportional hazards model was used. Results: Seven hundred and forty seven patients were included. The unadjusted 90‐day mortality varied significantly, with the highest rate at 30%, and the lowest at 8.5% ( p < 0.001). After adjustment for baseline confounders (Charlson comorbidity index, sex, SAPS3, age, smoking status, BMI), calendar time and healthcare county (random intercept), all hospitals were significantly associated with increased 90‐day mortality compared with the lowest mortality hospital. Hazard ratios ranged from 2.38 to 5.06. Conclusion: Among patients admitted to ICU due to COVID‐19, we observed a difference in mortality related to the hospital of first ICU admission. This difference persisted after adjustment for calendar time, baseline confounders, and healthcare county. Potential explanations are lacking within the current study. Future studies should focus on comprehensive evaluation of both organizational and contextual determinants of mortality. Editorial Comment: This analysis from 3 Swedish counties (7 hospitals) for COVID ICU cases presents factors and relations to mortality risk, including factors for first admission to university‐larger‐, or smaller hospital. An association was observed for higher risk if the first ICU admission was in a smaller hospital, though recognizing that this is a dataset coming from a small set of hospitals.

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.

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.

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 mu g/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 mu g/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 mu g/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 mu g/mL) to 10.2 +/- 3.1 (80 mu g/mL), p < .001. Protamine 80 mu g/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.

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.

The Swedish healthcare system has an increased need for nurses and physicians, and the number of International Educated Nurses (IENs) and International Medical Graduates (IMGs) seeking job opportunities and a license to practice in Sweden is rising. This study explored how IENs and IMGs describe their experience of getting a license to practice, their perceptions of working in Sweden and of how their intercultural competence is utilized. A qualitative study based on semi-structured interviews with 11 IENs and 11 IMGs. The interviews were conducted between 2015 and 2017. The data were analyzed using qualitative content analysis. Three main themes were identified: ‘Getting a license – a different story,’ ‘The work is familiar, yet a lot is new,’ ‘Trying to master a new language.’ The time to obtain a license to practice and finding a job was shorter for IENs and IMGs coming from European countries than for those from non-European countries. Some of the experiences of getting a license to practice and of entering a new workplace in another country were the same for nurses and physicians. In general, both IENs and IMGs felt welcomed and used their intercultural competence at work. Lack of language skills was regarded as the main problem for both professions, while workplace introduction was shorter for IMGs than for IENs. Problems related to language and culture are often underestimated, therefore organizations and managers employing IENs and IMGs should provide longer workplace introduction to facilitate the acculturation process. More time-efficient language courses specifically adapted to IENs and IMGs could make the transition easier and shorten the time to obtain a license to practice for both professions.

Objectives: Platelet dysfunction is an important cause of postoperative bleeding after cardiac surgery. Protamine is routinely used for reversal of heparin after cardiopulmonary bypass (CBP), but may affect platelet aggregation. We assessed changes in platelet function in relation to protamine administration. Design: Platelet aggregation was analyzed by impedance aggregometry before and after protamine administration in 25 adult cardiac surgery patients. Aggregation was also studied after in vitro addition of heparin and protamine. The activators adenosine diphosphate (ADP), thrombin receptor activating peptide-6 (TRAP), arachidonic acid (AA) and collagen (COL) were used. Results: Platelet aggregation was reduced by approximately 50% after in vivo protamine administration; ADP 640 ± 230 (AU*min, mean ± SD) to 250 ± 160, TRAP 939 ± 293 to 472 ± 260, AA 307 ± 238 to 159 ± 143 and COL 1022 ± 350 to 506 ± 238 (all p < 0.001). Aggregation was also reduced after in vitro addition of protamine alone with activators ADP from 518 ± 173 to 384 ± 157 AU*min p < 0.001, and AA 449 ± 311 to 340 ± 285 (p < 0.01) and protamine combined with heparin (1:1 ratio) with activators ADP to 349 ± 160 and AA to 308 ± 260 (both p < 0.001); and COL from 586 ± 180 to 455 ± 172 (p < 0.05). Conclusions: Protamine given after CPB markedly reduces platelet aggregation. Protamine added in vitro also reduces platelet aggregation, by itself or in combination with heparin.