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We most welcome the comment by Thakur, van Schayck and Boudewijns on our article on the effects and acceptability of implementing improved cookstoves. Adoption rates of improved cookstoves by local communities are often strikingly low. The authors underline the urge to advance cookstove implementation strategies, and reinforce the approach used in the FRESH AIR project. They highlight several important factors to increase adoption success and call for further research on the topic. We want to build on this comment by reflecting on decades of substantial discrepancies between the disappointing adoption rates of improved cookstoves, and the subsequent failure to adapt implementation strategies accordingly. We argue that it is not necessarily the lack of evidence that impedes the success of implementation strategies for improved cookstoves. Moreover, it is the lack of use of the evidence by implementors. We propose several ideas for overcoming this evidence-to-practice gap.

Background Low-resource settings are disproportionally burdened by chronic lung disease due to early childhood disadvantages and indoor/outdoor air pollution. However, data on the socioeconomic impact of respiratory diseases in these settings are largely lacking. Therefore, we aimed to estimate the chronic lung disease-related socioeconomic burden in diverse low-resource settings across the globe. To inform governmental and health policy, we focused on work productivity and activity impairment and its modifiable clinical and environmental risk factors. Methods We performed a cross-sectional, observational FRESH AIR study in Uganda, Vietnam, Kyrgyzstan, and Greece. We assessed the chronic lung disease-related socioeconomic burden using validated questionnaires among spirometry-diagnosed COPD and/or asthma patients (total N = 1040). Predictors for a higher burden were studied using multivariable linear regression models including demographics (e.g. age, gender), health parameters (breathlessness, comorbidities), and risk factors for chronic lung disease (smoking, solid fuel use). We applied identical models per country, which we subsequently meta-analyzed. Results Employed patients reported a median [IQR] overall work impairment due to chronic lung disease of 30% [1.8–51.7] and decreased productivity (presenteeism) of 20.0% [0.0–40.0]. Remarkably, work time missed (absenteeism) was 0.0% [0.0–16.7]. The total population reported 40.0% [20.0–60.0] impairment in daily activities. Breathlessness severity (MRC-scale) (B = 8.92, 95%CI = 7.47–10.36), smoking (B = 5.97, 95%CI = 1.73–10.22), and solid fuel use (B = 3.94, 95%CI = 0.56–7.31) were potentially modifiable risk factors for impairment. Conclusions In low-resource settings, chronic lung disease-related absenteeism is relatively low compared to the substantial presenteeism and activity impairment. Possibly, given the lack of social security systems, relatively few people take days off work at the expense of decreased productivity. Breathlessness (MRC-score), smoking, and solid fuel use are potentially modifiable predictors for higher impairment. Results warrant increased awareness, preventive actions and clinical management of lung diseases in low-resource settings from health policymakers and healthcare workers.

Cardiogenic shock (CS) due to myocardial infarction (MI) carries 30-day mortality rates as high as 50\of-hospital cardiac arrest (OHCA). Patients with and without OHCA are likely to represent two distinctive entities, which may be problematic to combine in an intervention trial.The aim of the study was to compare CS due to MI patients presenting with and without OHCA in terms of patient characteristics and outcome.In the period from 2010–2017 all patients admitted at two tertiary heart centres in Denmark with CS following MI were individually identified and validated through patient records. The two centres have a catchment area of 3.9 million citizens corresponding to two-thirds of the Danish population.A total of 1716 CS patients were identified, of which 42\mean 63 vs 67 years), more frequently male (85 vs 67\, had higher lactate concentration (median 6.2 vs 5.0 mmol/L) on admission and higher left ventricular ejection fraction (median 30 vs 25\ compared to patients without OHCA (p\lt;0.0001 for all). Patients presenting with OHCA had lower 30-day mortality compared to patients without OHCA (49\7\ respectively, plogrank\lt;0.0001, Figure). Cause of in hospital death differed markedly between the two groups. Not surprisingly, anoxic brain damage was the leading cause of in hospital death in the OHCA group (56\ and only seen in 4\ cardiac failure was the main cause of death in hospital death among patients without OHCA (60\, compared to 27\p\lt;0.0001).Figure 1Among patients with CS due to MI, overall 30-day mortality was significantly lower in patients presenting with OHCA. Anoxic brain damage was the main cause of in hospital death among OHCA patients, whereas fatal heart failure prevailed in patients without OHCA. Combining these two groups in a single trial with one specific intervention seems inappropriate and likely to cause an imbalance in the signal-to-noise ratio.The Danish Heart Foundation and a research grant from Abiomed

The objective was to evaluate the effectiveness and acceptability of locally tailored implementation of improved cookstoves/heaters in low- and middle-income countries. This interventional implementation study among 649 adults and children living in rural communities in Uganda, Vietnam and Kyrgyzstan, was performed after situational analyses and awareness programmes. Outcomes included household air pollution (PM2.5 and CO), self-reported respiratory symptoms (with CCQ and MRC-breathlessness scale), chest infections, school absence and intervention acceptability. Measurements were conducted at baseline, 2 and 6-12 months after implementing improved cookstoves/heaters. Mean PM2.5 values decrease by 31% (to 95.1 µg/m3) in Uganda (95%CI 71.5-126.6), by 32% (to 31.1 µg/m3) in Vietnam (95%CI 24.5-39.5) and by 65% (to 32.4 µg/m3) in Kyrgyzstan (95%CI 25.7-40.8), but all remain above the WHO guidelines. CO-levels remain below the WHO guidelines. After intervention, symptoms and infections diminish significantly in Uganda and Kyrgyzstan, and to a smaller extent in Vietnam. Quantitative assessment indicates high acceptance of the new cookstoves/heaters. In conclusion, locally tailored implementation of improved cookstoves/heaters is acceptable and has considerable effects on respiratory symptoms and indoor pollution, yet mean PM2.5 levels remain above WHO recommendations., European Union’s Horizon 2020 programme under grant agreement no. 680997, TRIAL ID NTR5759, http://www.trialregister.nl/trialreg/admin/rctsearch.asp?Term=23332. The devices, measuring the personal HAP, were funded by Netherlands Enterprise Agency (RVO)

Out-of-hospital cardiac arrest is associated with high mortality and morbidity. Treatment options remain few in refractory cases, but extracorporeal cardiopulmonary resuscitation (eCPR) is increasingly applied to improve the outcome. This article summarizes the use, experience and outcome of eCPR focussing on current knowledge of criteria for selection of relevant patients for treatment.

BACKGROUND The increasing tendency to acquire data by linkage to registries not designed for research has introduced a problem into epidemiological research. The data is often crude or possibly incomplete and, in some cases, it has been proposed to use these registries in the routine acquisition of data for existing epidemiological research registries. This study estimates the validity and completeness of the registration of surgically treated malignant gynaecological diseases in the Danish National Hospital Registry 1977-88. METHODS Completeness was estimated by the method of independent case ascertainment, by comparison with the registration of surgically treated gynaecological cancer cases registered in the Danish Cancer Registry. The validity of the diagnoses was analysed by comparison with the recoding of discharge summaries describing the admission of a 5% random sample. RESULTS The completeness of registration was 87% overall. Ovarian cancer, cervical cancer and cancer of the uterus were registered with a positive predictive value (PPV) of 89-90%. DISCUSSION The results of the study emphasise the need to consider the validation of Danish Hospital Registry data before linkage and analysis. In epidemiological cancer research the Danish Cancer Registry is the better alternative when information on malignant tumours is needed.

From 1990 through 1997 the working schedules for staff surgeons underwent gradual changes. The aim was to comply with patient demands to receive care from few surgeons during hospital care. To evaluate the effect, four controlled or cross sectional studies were conducted. Quality of care was assessed by surgical audit. Patient and surgeon satisfaction was examined with questionnaires and interviews. Changes in costs were evaluated by administrative data. The number of different specialists providing care was reduced by 50%, initially during inpatient care and later also during outpatient care. The patients experienced this change as very satisfying. Hospital stay was reduced, as was time used by specialists on out-of-hours duty. The quality of care did not change neither did the use of diagnostic tests. The specialists appraised the increased individual responsibility in patient care as satisfying. Initiatives should be taken to examine whether other ways of organising work for hospital employed doctors have similar effect.

Udgivelsesdato: 2000-Oct

Seven temporal bones from four human foetuses of crown-rump length 55-62 mm were prepared for electron microscopy and stepwise sectioned. Seven glomera were found along the tympanic and auricular branches and/or in the adventitia of the superior bulb of the jugular vein. The glomus parenchyma was made up of chief cells characterized by a content of membrane-bound, osmiophilic granules 114 nm in mean diameter. The cells were almost completely invested by supporting cells, in which nerve fibres were embedded as well. The numerous vessels contained fenestrae in the endothelium. The fine structure of the tympanojugular glomus is similar to that of the carotid body.ZUSAMMENFASSUNGSieben Schlafenbeine von vier menschlichen Foten (Scheitel-Steiss-Lange 55-62 mm) wurden fur die Elektronenmikroskopie prapariert. Es wurden sieben Glomera gefunden, die in der Nachbarschaft des N. tympanicus und des R. auricularis und/oder in der Adventitia des Bulbus venae jugularis superior lagen. Das Glomusparenchym bestand haupts...

In a systematic study of bladders from consecutively cystectomized patients, 40 primary urinary bladder carcinomas were examined with regard to the type of differentiation. Metaplastic areas were found in 24 of the tumours. A positive reaction of keratin to Kreybergs stain was required for the definition squamous metaplasia. Squamous areas were found in 16 of the tumours. In 4 tumours there was, in addition to squamos metaplasia, glandular metaplasia which was defined as definite glandular tissue with dysplasia of the epithelium. In 4 tumours, glandular metaplasia was also present in addition to the urothelial carcinoma. In 18 cases, metaplastic changes were present in the luminal portion of the tumour from which the biopsy material and desqaminated material originated. The occurrence of metaplasia was related to the degree of differentiation of the urothelial part of the tumour. Metaplastic changes were most frequent in the poorly differentiated tumours. The biopsies obtained pre-operatively permitted of the diagnosis metaplasia being made in 15 cases, while the cytological material suggested metaplastic changes in 4 cases only. The biological function of metaplasia is unknown. The possibility that these areas will react differently to radiation and chemotherapy is present and the frequency of such changes would suggest that their importance should be studied by their registration as mixed forms as stated by WHO.

In murine models, therapeutic efficacy of adoptive immunotherapy (AIT) of cancer with lymphokine activated killer (LAK) cells is seen only when applied together with substantial doses of interleukin-2 (IL-2), probably because this cytokine is imperative for both motility and viability of the LAK cells. We wanted to investigate whether IL-2 in addition mediates an immunostimulatory activation and expansion of endogenous effector cells contributing to tumor regression. Using an immunoperoxidase technique, we have been able to longitudinally analyze the accumulation of tumor infiltrating lymphocytes expressing the pan-T cell/activated lymphocyte phenotype (Thy1.2), the natural killer (NK) cell phenotype (AsGM,) as well as the cytotoxic T (CD8) cell phenotype within experimental established B16 pulmonary melanoma metastases in C57BL/6 mice during the first 48 h after high dose IL-2 monotherapy. Whereas a substantial and selective infiltration of AsGM1+ lymphocytes in tumor tissue was seen (262 and 937 cells per sq.mm malignant tissue at 0 and 48 h, respectively), only a minor increase in accumulation of CD8+ cells was seen (106 and 171 cells per sq.mm tumor tissue at 0 and 48 h, respectively). The addition of adoptive transfer with lymphokine-activated adherent NK (A-NK) cells to the high-dose IL-2 treatment resulted in more than a 1.5 fold increase in infiltrating AsGM1+ cells compared to IL-2 therapy alone (1520 compared to 937 AsGM1+ cells per sq.mm malignant tissue). No substantial accumulation of CD8+ cells was observed in this setting either. In contrast, the treatment with high dose IL-2 together with adoptive transfer of mitogen-stimulated, lymphokine-activated T killer (T-LAK) cells increased the infiltration of CD8+ cells 10-fold compared to IL-2 monotherapy (2078 compared to 171 CD8+ cells per sq.mm malignant tissue, respectively). Interestingly, infiltration of both endogenous and exogenous cells continued over time, since the effector-to-tumor cell ratio in metastatic tissue dramatically increased from 1:8 and 1:6 at 16 h to 1:3 and 1:2 at 48 h after adoptive transfer of A-NK and T-LAK cells, respectively. These data underline the longevity of LAK cells in vivo and highlight the importance of IL-2 treatment in recruiting endogenous immune cells to tumor areas.

Eighty patients scheduled for elective cholecystectomy were randomly allocated to application of fibrin adhesive (Beriplast) to the gallbladder bed or to a control group. No significant difference was found between the two groups in regard to amount of postoperatively drained secretion or in drainage time. Fibrin adhesive thus had no effect on secretion of peritoneal fluid after simple cholecystectomy.

The circulatory pattern of IL-2 activated natural killer (A-NK) cells was studied in C57BL/6 mice bearing 10 day-old pulmonary and subcutaneous (s.c.) metastases of the B16 melanoma in order to evaluate the roles of the concentration of A-NK cells in the blood and of tumor blood flow on accumulation of A-NK cells in tumors. Kinetic studies of the presence of A-NK cells in peripheral blood after adoptive transfer revealed that these cells rapidly disappear from the blood. Via intravital microscopy of animals with exposed lung tissue, we have shown that the vast majority of transferred A-NK cells become efficiently arrested within the lung microcirculation at their first encounter with this organ, thereby explaining the fast disappearance of the cells from the bloodstream. Despite the low number of A-NK cells circulating in the blood, systemically injected A-NK cells (20 million per mouse) localized significantly (70-80 million cells/g) into most pulmonary metastases within 8-16 hours. In contrast, very few A-NK cells (0.2 million cells/g) were found in the s.c. metastases. Based on measurements of tumor blood flow (showing a classic inverse relationship between tumor size and tumor blood flow) and the blood concentration of A-NK cells, we estimated the highest intratumoral density of A-NK cells that theoretically can be generated by A-NK cells transported to the tumor by way of the blood. In s.c. tumors, the observed density of A-NK cells was at all times lower (10-50 fold) than the estimated density, indicating that only a few percent of the A-NK cells arriving at these tumors become retained in them. In contrast, the observed density of A-NK cells in pulmonary metastases was at all times higher (2-3 fold) than the estimated density. This finding indicates that A-NK cells might not reach the pulmonary metastases solely by way of the blood stream. In conclusion, i.v. injected A-NK cells become immediately entrapped in the lungs and, consequently, circulate poorly. While lung metastases become significantly infiltrated by i.v. injected A-NK cells, metastases in organs down-stream from the lungs become poorly infiltrated. We hypothesize that only a part of the A-NK cells found in lung metastases 8-16 hours following injection reach these metastases by way of the blood-vascular system. They might also migrate into the metastases from the surrounding normal lung tissue.