The geographical distribution and socioeconomic risk factors of COVID-19, tuberculosis and leprosy in Fortaleza, Brazil.

BACKGROUND: Fortaleza (Brazil) is high endemic for coronavirus disease 2019 (COVID-19), tuberculosis (TB) and leprosy. These three diseases share respiratory droplets through coughing or sneezing as the main mode of transmission but differ in incubation time, with COVID-19 having a short and leprosy a long incubation time. Consequently, contacts of a patient are at higher risk of infection and developing these diseases. There might be scope for combined preventive measures, but a better understanding of the geographical distribution and relevant socioeconomic risk factors of the three diseases is needed first. This study aims to describe the geographic distribution of COVID-19, TB and leprosy incidence and to identify common socioeconomic risk factors. METHODS: The total number of new cases of COVID-19, TB and leprosy, as well as socioeconomic and demographic variables, were retrieved from official registers. The geographical distribution of COVID-19, TB and leprosy rates per neighbourhood was visualised in Quantum GIS, and spatial autocorrelation was measured with Moran's I in GeoDa. A spatial regression model was applied to understand the association between COVID-19, TB, leprosy rates, and socioeconomic factors. RESULTS: COVID-19 and TB showed a more homogenous distribution, whereas leprosy is located more in the south and west of Fortaleza. One neighbourhood (Pedras) in the southeast was identified as high endemic for all three diseases. Literacy was a socioeconomic risk factor for all three diseases: a high literacy rate increases the risk of COVID-19, and a low literacy rate (i.e., illiteracy) increases the risk of TB and leprosy. In addition, high income was associated with COVID-19, while low income with TB. CONCLUSIONS: Despite the similar mode of transmission, COVID-19, TB and leprosy show a different distribution of cases in Fortaleza. In addition, associated risk factors are related to wealth in COVID-19 and to poverty in TB and leprosy. These findings may support policymakers in developing (partially combined) primary and secondary prevention considering the efficient use of resources.

Determining target populations for leprosy prophylactic interventions: a hotspot analysis in Indonesia.

BACKGROUND: Leprosy incidence remained at around 200,000 new cases globally for the last decade. Current strategies to reduce the number of new patients include early detection and providing post-exposure prophylaxis (PEP) to at-risk populations. Because leprosy is distributed unevenly, it is crucial to identify high-risk clusters of leprosy cases for targeting interventions. Geographic Information Systems (GIS) methodology can be used to optimize leprosy control activities by identifying clustering of leprosy cases and determining optimal target populations for PEP. METHODS: The geolocations of leprosy cases registered from 2014 to 2018 in Pasuruan and Pamekasan (Indonesia) were collected and tested for spatial autocorrelation with the Moran's I statistic. We did a hotspot analysis using the Heatmap tool of QGIS to identify clusters of leprosy cases in both areas. Fifteen cluster settings were compared, varying the heatmap radius (i.e., 500 m, 1000 m, 1500 m, 2000 m, or 2500 m) and the density of clustering (low, moderate, and high). For each cluster setting, we calculated the number of cases in clusters, the size of the cluster (km2), and the total population targeted for PEP under various strategies. RESULTS: The distribution of cases was more focused in Pasuruan (Moran's I = 0.44) than in Pamekasan (0.27). The proportion of total cases within identified clusters increased with heatmap radius and ranged from 3% to almost 100% in both areas. The proportion of the population in clusters targeted for PEP decreased with heatmap radius from > 100% to 5% in high and from 88 to 3% in moderate and low density clusters. We have developed an example of a practical guideline to determine optimal cluster settings based on a given PEP strategy, distribution of cases, resources available, and proportion of population targeted for PEP. CONCLUSION: Policy and operational decisions related to leprosy control programs can be guided by a hotspot analysis which aid in identifying high-risk clusters and estimating the number of people targeted for prophylactic interventions.

Traditional plant functional groups explain variation in economic but not size-related traits across the tundra biome.

AIM: Plant functional groups are widely used in community ecology and earth system modelling to describe trait variation within and across plant communities. However, this approach rests on the assumption that functional groups explain a large proportion of trait variation among species. We test whether four commonly used plant functional groups represent variation in six ecologically important plant traits. LOCATION: Tundra biome. TIME PERIOD: Data collected between 1964 and 2016. MAJOR TAXA STUDIED: 295 tundra vascular plant species. METHODS: We compiled a database of six plant traits (plant height, leaf area, specific leaf area, leaf dry matter content, leaf nitrogen, seed mass) for tundra species. We examined the variation in species-level trait expression explained by four traditional functional groups (evergreen shrubs, deciduous shrubs, graminoids, forbs), and whether variation explained was dependent upon the traits included in analysis. We further compared the explanatory power and species composition of functional groups to alternative classifications generated using post hoc clustering of species-level traits. RESULTS: Traditional functional groups explained significant differences in trait expression, particularly amongst traits associated with resource economics, which were consistent across sites and at the biome scale. However, functional groups explained 19% of overall trait variation and poorly represented differences in traits associated with plant size. Post hoc classification of species did not correspond well with traditional functional groups, and explained twice as much variation in species-level trait expression. MAIN CONCLUSIONS: Traditional functional groups only coarsely represent variation in well-measured traits within tundra plant communities, and better explain resource economic traits than size-related traits. We recommend caution when using functional group approaches to predict tundra vegetation change, or ecosystem functions relating to plant size, such as albedo or carbon storage. We argue that alternative classifications or direct use of specific plant traits could provide new insights for ecological prediction and modelling.

Integrating patient safety education into early medical education utilizing cadaver, sponges, and an inter-professional team.

BACKGROUND: Introducing patient safety and quality improvement science to medical students is integral to improving healthcare. However, developing and implementing a patient safety curriculum can be challenging in a medical school curriculum that is already densely packed. Our aim was to develop and evaluate the impact of a workshop introducing patient safety and quality improvement science to a large class of first-year medical students. METHOD: As a part of an evolving longitudinal patient safety curriculum, an introductory workshop on patient safety was integrated into an anatomy course. A high impact event (a simulated "retained sponge" discovery during an anatomy dissection lab) was used to introduce medical error. The educational session which followed consisted of a presentation by an interprofessional team utilizing the retained sponge as example of an error. Use of safety tools was introduced and quality improvement science was discussed using the evolution of methods to decrease retained foreign objects during surgery. A patient's story told by a close family member about the personal impact of medical errors was presented. Students then participated in an interactive breakout activity and completed a module on safety. The impact of the workshop was assessed through pre- and post- session tests. RESULTS: Quantitative and qualitative evaluation reflected a positive effect of the session in improving students' safety knowledge and attitudes. Students' mean total knowledge improved from 7.58 to 8.98 (p = 0.000). Mean total attitudes score improved from 47.73 to 50.56 (p = 0.000). Students' comments after the workshop reflected increased awareness and appreciation of the importance of addressing medical errors. CONCLUSION: A workshop introducing patient safety and quality improvement to first year medical students improved knowledge and attitudes regarding safety and increased awareness of the importance of addressing medical errors in their future careers. Integrating patient safety education into an existing foundational science course is a model for teaching patient safety at other medical schools.

Unhealthy behaviour is contagious: an invitation to exploit models for infectious diseases.

We argue that the spread of unhealthy behaviour shows marked similarities with infectious diseases. It is therefore interesting and challenging to use infectious disease methodologies for studying the spread and control of unhealthy behaviour. This would be a great addition to current methods, because it allows taking into account the dynamics of individual interactions and the social environment at large. In particular, the application of individual-based modelling holds great promise to address some major public health questions.

Global plant trait relationships extend to the climatic extremes of the tundra biome.

The majority of variation in six traits critical to the growth, survival and reproduction of plant species is thought to be organised along just two dimensions, corresponding to strategies of plant size and resource acquisition. However, it is unknown whether global plant trait relationships extend to climatic extremes, and if these interspecific relationships are confounded by trait variation within species. We test whether trait relationships extend to the cold extremes of life on Earth using the largest database of tundra plant traits yet compiled. We show that tundra plants demonstrate remarkably similar resource economic traits, but not size traits, compared to global distributions, and exhibit the same two dimensions of trait variation. Three quarters of trait variation occurs among species, mirroring global estimates of interspecific trait variation. Plant trait relationships are thus generalizable to the edge of global trait-space, informing prediction of plant community change in a warming world.

Prospective comparative study of technetium-99m-WBCs and indium-111-granulocytes for the examination of patients with inflammatory bowel disease.

In a prospective comparative study of 14 patients with inflammatory bowel disease (IBD), the abilities of 99mTc-HMPAO labeled white blood cells (WBCs) and 111In-granulocytes to assess the presence and location of active disease were compared. The two examinations were carried out within 2 wk of each other. Scintigraphically concordant positive or discordant segments were evaluated by radiologic or endoscopic examination performed within 14 days. When bowel segments were compared, concordance was found for 102/111 (91.8%) segments between 99mTc-WBC images obtained at 1 hr after injection and 3-hr 111In-granulocyte images. For five of five 99mTc-WBCs positive/111In-granulocyte negative segments, it could be proven that the 99mTc-WBC result was caused by active disease. For patients, 99mTc-WBC scintigraphy detected four more patients with active disease than 111In-granulocytes (11 and 7 patients, respectively). Technetium-WBCs was superior in the assessment of active disease, especially for small bowel segments. We conclude that early imaging 1 hr after the injection of 99mTc-WBCs can reliably replace 111In-granulocyte scintigraphy in IBD patients because the radiopharmaceutical is available on a daily basis. Thus, there is less radiation burden to the patient and cell separation is simpler and less time-consuming.

Feasibility study on the retention of superporous hydrogel composite polymer in the intestinal tract of man using scintigraphy.

In recent years, many complex oral drug delivery systems have been developed using various polymers in order to achieve better drug targeting and drug absorption in the intestinal tract. Superporous hydrogel (SPH) and SPH composite (SPHC)-based drug delivery systems were also developed for the targeted delivery of peptide drugs into the intestinal tract. In the present study, the retention time of SPHC polymer is studied in man using the scintigraphy technique. To that purpose, SPHC polymers were radiolabelled with Tc-99m and administered orally in an enteric-coated gelatin capsule. The location of the radiolabelled polymer was monitored in five healthy volunteers while the subjects were sitting in front of a large field of view gamma camera. The results showed that enteric-coated gelatin capsules remained in the stomach for 75 to 150 min after oral administration to fasted volunteers and that the SPHC polymers thereafter attached to the upper part of the small intestine for at least 45 to 60 min due to their mechanical fixation properties. No discomfort was observed in any of the volunteers after oral administration of these polymers, which indicates that they are safe to be applied for oral drug delivery systems in man.

Experiments on a new phosphine-peptide chelator for labelling of peptides with Tc-99m.

A phosphine-containing ligand providing a N-[N-[3-(diphenylphosphino)propionyl]glycyl]-L-S-benzyl-cystein (PNNS) donor atomset for the chelation of 99mTc was studied in labelling experiments with a model peptide (tetragastrin, cholecystokinin-fragment). The peptide was conjugated to the ligand chelator by active ester chemistry either before or after radiolabelling. Both the chelator-conjugate and the preformed chelate approaches resulted in the same radiolabelled isomers of the ligand peptide. Sequence and reaction conditions influence yield and purity.

99mTc-labeling experiments on CCK(4) by a direct method.

99mTc-labeling studies have been performed on CCK(4) fragment of cholecystokinin, starting from 99mTc-pertechnetate, by using tin(II)pyrophosphate or tin(II)gluconate as reducing agents, together with NaBH(4) acting as a stabilizing agent of tin(II). Gluconate has been used as exchange ligand in the carrier added experiments and in the syntheses of 99Tc-CCK(4) and Re-CCK(4) complexes to be able to reproduce at macroscopic level the same chemical reactions occurring at non carrier added conditions. 99mTc-labeling yields higher than 95% have been achieved depending on Sn(II) concentration, CCK(4)/gluconate ratio, reaction time and applied temperature. The species produced with 99mTc, 99Tc, and cold rhenium nuclides have been compared by means of HPLC measurements, which showed similar retention times and thus probably the same species in the three situations.

Technetium-99m nanocolloid for the scintigraphic assessment of inflammatory bowel disease in the colon: its value in comparison with indium-111-labelled granulocytes.

The usefulness of 99mTc-nanocolloid for the assessment of localization and disease activity of colitis in patients suffering from inflammatory bowel disease (IBD) was investigated in 10 patients. Results of 99mTc-nanocolloid scintigraphy were compared with Indium-111 autologous granulocyte scintigraphy and the activity index according to Van Hees. In none of the patients a true positive result of the 99mTc-nanocolloid scintigraphy was encountered, while 111In-granulocyte scintigraphy was positive in 7 of 10 patients with active disease. Radioactivity became visible in the small bowel starting 2 h after injection of 99mTc-nanocolloid most likely because of excretion by the liver of degradation products of the radiopharmaceutical. The authors conclude that despite a previous communication 99mTc-nanocolloid cannot replace 111In-granulocytes for the assessment of IBD patients with active colitis.

A new method for 99Tcm-labelling of proteins with an application to clot detection with an antifibrin monoclonal antibody.

A new method is described for labelling proteins with 99Tcm. Labelling of fibrinogen resulted in a radiochemical yield of about 80%. After clotting this 99Tcm-labelled fibrinogen with trombin, an equal percentage of the radioactivity was found in the clot illustrating the retained biological behaviour of this labile protein after our labelling procedure. Labelling of a monoclonal antibody (MoAb) directed against fibrin resulted in a labelling percentage of about 70%. Immunoreactivity of this antifibrin (Y22) is hardly affected by the procedure as demonstrated by a double-sandwich enzyme immunoassay (EIA). Perfusion experiments on a gamma camera in which a plasma clot in a glass chamber was perfused with plasma containing 99Tcm-labelled Y22 revealed an excellent uptake of activity by the clot within 2 h. Finally an animal experiment is presented which showed clear visualization of the thrombi in the jugular vein and the abdomen of a rabbit by scintigraphy after the administration of 99Tcm-labelled antifibrin (Y22).

Is radiolabelled sucralphate scintigraphy of any use in the diagnosis of inflammatory bowel disease?

Previous optimistic reports led us to undertake a study to determine the value of 99Tcm-sucralphate scintigraphy in the assessment of localization and extent of active inflammatory bowel disease. Eight patients were studied; four had Crohn's disease (three small bowel and one colon localization) and four patients had ulcerative colitis. The results obtained by scintigraphy were compared with those obtained by diagnostic radiology and/or endoscopy. In five patients indium-111 granulocyte scintigraphy was also performed. 99Tcm-sucralphate scans showed total discrepancy with standard investigations in four patients and partial discrepancy in the other four. Furthermore, it was difficult from the images to decide whether the radiolabelled sucralphate indicated true inflammation or normal distribution of the radiopharmaceutical. Patient acceptability was very low due to frequent scanning times and the recommended purgation which was not well tolerated and is contraindicated in severely ill patients. We conclude that this technique is not a good screening test for diagnosing inflammatory bowel disease and we have, therefore, discontinued the study.

New peptide and protein drugs.

A view is presented on a number of recent developments, the present state and the perspectives, especially from a pharmacotherapeutic viewpoint, for peptide and protein drugs. The expanding use and the increasing experience create new pharmacotherapeutic modalities. Peptide and protein drugs comprise among others proteins isolated from human sources, and peptides and proteins made by biotechnology including monoclonal antibodies, recombinant human hormones, cytokines and growth factors. In the field of vaccine development also innovation is taking place. Optimal application schemes of these drugs may not have been reached and (clinical) pharmacists should contribute to the optimization. Since recombinant technology has abolished scarcity for a number of these drugs--especially 'physiological' substances--special ethical problems regarding an unlimited application or expansion of the indications may arise.

A new method for protein labeling with 99mTc.

A method is described for labeling proteins with 99mTc, the radionuclide of choice in diagnostic nuclear medicine. Labeling efficiency, stability of label attachment and retained biological behaviour, e.g. immunoreactivity of monoclonal antibodies after radiolabeling are demonstrated. An application of a 99mTc-labeled anti-fibrin monoclonal antibody in radioimmunoimaging of thrombi is presented.

Peptide radiopharmaceuticals in nuclear medicine.

This article reviews the labelling of peptides that are recognised to be of interest for nuclear medicine or are the subject of ongoing nuclear medicine research. Applications and approaches to the labelling of peptide radiopharmaceuticals are discussed, and drawbacks in their development considered.

Comparison of four commercially available 81Rb-81mKr generators: quality testing using a breathing lung phantom.

Four commercially available 81Rb-81mKr generators, including their elution systems, were compared. Considerable differences in useful output between the various generators were found. When a standardized elution system was used, the differences became much less. Differences in the tubing and inaccuracy of the flow meters were found to be the major causes of the original differences. The user should be aware of a loss of output that may occur when the generator is eluted with dry air.

A new 99mTc labelling method for leucocytes: in vitro and in vivo comparison with 99mTc-HMPAO.

A new method for the labelling of mixed leucocytes with 99mTc-tropolone was optimized and compared with a 99mTc-HMPAO leucocyte labelling procedure in vitro and in vivo. In the present study, leucocytes obtained from patients suffering from Crohn's disease, were isolated and labelled with 99mTc-HMPAO or labelled according the new 99mTc-tropolone procedure using 9.8 mM tropolone, 1 microM stannous chloride and 0.8 mM potassium borohydride (KBH4) at pH 5.5-6. Labelling efficiency with 99mTc-tropolone yielded 92 +/- 3%, which is higher compared to the 99mTc-HMPAO labelling procedure (64 +/- 13%) using 10(8) of leucocytes. In vitro stability and viability of both the tropolone and the HMPAO labelled cells was investigated. The viability test of the 99mTc-labelled leucocytes was performed in autologous plasma at 37 degrees C and compared with unlabelled leucocytes. After 18 hours of incubation a significant (P < 0.05) higher stability was observed for 99mTc-tropolone labelled leucocytes (84 +/- 5%) compared with that of 99mTc-HMPAO labelled leucocytes (73 +/- 5%). The viability of the 99mTc-labelled leucocytes observed for both labelling procedures was similar to unlabelled leucocytes. In vivo experiments were performed in mice. 99mTc-tropolone or 99mTc-HMPAO labelled murine mixed leucocytes were injected in mice, with a Staphylococcus aureus ATCC 25923 thigh infection. Analysis of scintigraphic images yielded a faster clearance of the 99mTc-tropolone labelled leucocytes. This was most likely due to a significant (P < 0.02) higher liver uptake at 4 hours after administration of the 99mTc-tropolone labelled leucocytes (19%) in comparison with 99mTc-HMPAO labelled cells (9%). Faster and significant (P < 0.02) higher accumulation of the 99mTc-tropolone labelled leucocytes was observed at the site of infection compared with 99mTc-HMPAO labelled leucocytes at all time-intervals after the administration of the 99mTc-labelled leucocytes. The new 99mTc-tropolone leucocyte labelling procedure, offers an attractive low-cost agent for research purposes.

Are activity indices helpful in assessing active intestinal inflammation in Crohn's disease?

We have investigated the correlation of 24 h and 48 h faecal Indium-111 excretion with each other and with several clinical activity indices for Crohn's disease (CD): Crohn's disease activity index (CDAI), activity index (AI), simple index (SI), Oxford score, and laboratory parameters, such as ESR, serum albumin, orosomucoid, C-reactive protein, alpha-l-antitrypsin (alpha 1-AT) faecal concentration, and alpha 1-AT clearance in 58 CD patients (37 with small bowel and 21 with colonic disease). A significant correlation was found between 24 and 48 h faecal Indium-111 excretion for small bowel (r = 0.708, p less than 0.0001) and colonic disease (r = 0.994, p less than 0.0001). The median faecal Indium-111 excretion for colonic involvement (4%; 0.15-50% median and range) was significantly (p less than 0.005) higher than that for small bowel disease (0.45%; 0.03-2.9%). No significant correlation was found between faecal Indium-111 excretion and any activity index in the patients with small bowel disease, while in the group of patients with colonic localisation only the AI showed a significant correlation (r = 0.593, p less than 0.02). Faecal Indium-111 excretion was significantly correlated with alpha 1-AT clearance (r = 0.712, p less than 0.0001) and faecal alpha 1-AT concentration (r = 0.750, p less than 0.0001) in small bowel and in colonic localisation (r = 0.530, p less than 0.02 and r = 0.444, p less than 0.05). Serum albumin was significantly correlated only in the group of patients with colonic disease (r = -0.593, p less than 0.05). The present study shows poor agreement between activity indices, serum parameters of activity and faecal Indium-111 excretion. As a good correlation was found with the alpha1-clearance, which reflects losses into the gut, these results may suggest that faecal Indium excretion does not only reflect activity of inflammation, but my relate to the extent of intestinal ulceration.

A prospective comparison of 99mTc-labeled polyclonal human immunoglobulin and 111In granulocytes for localization of inflammatory bowel disease.

There is a need for an easily prepared radiopharmaceutical agent for the detection of inflammation and infection. In a group of 14 patients with inflammatory bowel disease (IBD), the detection of actively involved intestinal segments by nonspecific human polyclonal immunoglobulin (IgG) labeled with 99mTc was compared with that of 111In granulocytes. To determine the specificity of 99mTc-IgG scintigraphy, 8 control patients without clinical indications of intestinal inflammation were examined. 99mTc-IgG was found in the left colon in 8 and in the right colon in 7 of the 8 controls 4 hours after the injection. At that time of scintigraphy only 4 IBD patients exhibited a more intense accumulation at the site of the intestinal segments with active disease. In contrast, in a randomized comparison with 111In granulocytes scintigraphy was positive in 11 patients with the latter technique. Moreover, fewer diseased segments were seen in the 4 patients with positive 99mTc-IgG scintigraphy (6 versus 12 with 111In granulocytes). In view of the low sensitivity and specificity, it is concluded that 99mTc-IgG is not suitable for the scintigraphic staging of IBD patients.