Factors influencing operationalization of Integrated Disease Surveillance in Malawi.

OBJECTIVES: Malawi's disease surveillance system is built on several different data sources and systems and is informed by the Integrated Diseases Surveillance and Response (IDSR) strategy. This study was carried out as part of a larger multicountry study to identify context-specific factors, which influence the operationalization of integrated disease surveillance. STUDY DESIGN AND METHODS: A total of six focus group discussions were conducted with 43 relevant personnel at the primary and secondary healthcare levels in two districts (Lilongwe and Dowa) and at the national level. The discussions were analyzed and sorted into predefined categories based on the domains of the International Association of Public Health conceptual framework. RESULTS: We found ongoing efforts to enhance integrated disease surveillance operationalization, including the establishment of the Public Health Institute of Malawi for coordination, digitalizing the surveillance system through One Health Surveillance Platform, and improving communication among rapid response teams using WhatsApp. The adoption of World Health Organization's third edition IDSR technical guidelines was also underway. Nonetheless, there were major implementation barriers such as parallel and uncoordinated surveillance systems, priority conditions that cannot be diagnosed at the point of reporting, lack of case definitions and diagnostic codes for priority conditions, reporting forms with unexplained acronyms, illegible data sources, unstable electronic data transfers, inadequate supervision and training, poor enforcement of reporting from private health facilities, high reporting burden, and lack of and feedback to those reporting. CONCLUSIONS: The results fit well into the predefined categories used. The study reveals basic problems with the operationalization, tools, and reporting forms used for IDSR. These findings may have implications for practice and policy in Malawi and other countries where IDSR is the national strategy for surveillance.

TB among refugees from Ukraine in European countries.

BACKGROUND: Since the Russian Federation's invasion of Ukraine, millions of refugees have moved to neighbouring European countries. We assessed the burden of TB in these refugees and surveyed screening approaches. METHODS: We conducted a survey among 30 European Union/European Economic Area and 13 other European countries, requesting population data on migrant residents and refugees with country of birth (COB) Ukraine, the number of TB notifications among people with COB Ukraine and countries' screening policies for refugees from Ukraine. RESULTS: In 2021, the number of migrants born in Ukraine was 1.7 million in the 34 responding countries, and increased with 5.2 million refugees from Ukraine to 6.9 million in 2022. These countries notified 207 TB cases in people with COB Ukraine in 2021 (TB notification rate 12.0/100,000) and 887 in 2022 (TB notification rate 12.8/100,000), of which 228 (26%) had multidrug-resistant/rifampicin-resistant TB (MDR/RR-TB). TB notification rates were higher in countries advising screening for all (16.9/100,000) or specific groups of refugees from Ukraine (14.7/100,000) compared to those without screening (7.2/100,000). CONCLUSION: TB rates found in people from Ukraine were lower than the expected rate of 44 per 100,000, but higher in host countries recommending screening. Our study underscores the need for adequate TB health services for refugees from Ukraine to ensure tailored diagnosis and treatment, especially for MDR/RR-TB.

CONTEXTE: Suite à l'invasion de l'Ukraine par la Fédération de Russie, des millions de réfugiés se sont installés dans les pays européens voisins. Notre étude a porté sur la prévalence de la TB parmi ces réfugiés et a examiné les différentes méthodes de dépistage. MÉTHODES: Nous avons réalisé une enquête auprès de 30 pays de l'Union européenne/de l'Espace économique européen et de 13 autres pays européens, en demandant des données démographiques sur les résidents migrants et les réfugiés dont le pays de naissance (COB, pour l'anglais « country of birth ¼) est l'Ukraine, le nombre de notifications de TB chez les personnes dont le COB est l'Ukraine et les politiques de dépistage des pays pour les réfugiés d'Ukraine. RÉSULTATS: En 2021, le nombre de migrants nés en Ukraine était de 1,7 million dans les 34 (79%) pays ayant répondu à l'enquête, et a augmenté à 5,2 millions en 2022. Ces pays ont notifié 207 cas de TB chez des personnes ayant le COB Ukraine en 2021 (taux de notification de la TB 12,0/100 000) et 887 en 2022 (taux de notification de la TB 12,8/100 000), dont 228 (26%) avaient une TB multirésistante/résistante à la rifampicine (MDR/RR-TB). Les pays qui recommandent le dépistage pour tous ont enregistré des taux de notification de la TB plus élevés (16,9/100 000) tandis que ceux qui ciblent des groupes spécifiques de réfugiés ukrainiens ont signalé (14,7/100 000). En revanche, les pays ne proposant pas de dépistage ont affiché un taux de notification de seulement (7,2/100 000). CONCLUSION: Les personnes originaires d'Ukraine présentaient des taux de TB inférieurs à ceux attendus, soit 44 pour 100 000, tandis que les pays d'accueil recommandant le dépistage affichaient des taux plus élevés. Notre étude met en évidence l'importance de fournir des services de santé appropriés pour la TB aux réfugiés ukrainiens, afin d'assurer un diagnostic et un traitement adaptés, en particulier pour la MDR/RR-TB.

Transmyocardial revascularization with CO2 laser in patients with refractory angina pectoris. Clinical results from the Norwegian randomized trial.

OBJECTIVES: The purpose of the study was to evaluate clinical effects, exercise performance and effect on maximal oxygen consumption (MVO2) of transmyocardial revascularization with CO2-laser (TMR) in patients with refractory angina pectoris. BACKGROUND: Transmyocardial laser revascularization is a new method to treat patients with refractory angina pectoris not eligible for conventional revascularization. Few randomized studies comparing TMR with conventional treatment have been published. METHODS: One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized in a 1:1 ratio to receive continued optimal medical treatment (MT) or TMR in addition to MT. The patients were evaluated at baseline and at three and 12 months with end points to symptoms, exercise capacity and MVO2. RESULTS: Transmyocardial laser revascularization resulted in significant relief in angina symptoms after three and 12 months compared to baseline. Time to chest pain during exercise increased from baseline by 78 s after three months (p = NS) and 66 s (p < 0.01) after 12 months in the TMR group, whereas total exercise time and MVO2 were unchanged. No significant changes were observed in the MT group. Perioperative mortality was 4%. One year mortality was 12% in the TMR group and 8% in the MT group (p = NS.) CONCLUSIONS: Transmyocardial laser revascularization was performed with low perioperative mortality and caused significant symptomatic improvement, but no improvement in exercise capacity.

Structure, dynamics and electrostatics of the active site of glutaredoxin 3 from Escherichia coli: comparison with functionally related proteins.

The chemistry of active-site cysteine residues is central to the activity of thiol-disulfide oxidoreductases of the thioredoxin superfamily. In these reactions, a nucleophilic thiolate is required, but the associated pK(a) values differ vastly in the superfamily, from less than 4 in DsbA to greater than 7 in Trx. The factors that stabilize this thiolate are, however, not clearly established. The glutaredoxins (Grxs), which are members of this superfamily, contain a Cys-Pro-Tyr-Cys motif in their active site. In reduced Grxs, the pK(a) of the N-terminal active-site nucleophilic cysteine residue is lowered significantly, and the stabilization of the corresponding thiolate is expected to influence the redox potential of these enzymes. Here, we use a combination of long molecular dynamics (MD) simulations, pK(a) calculations, and experimental investigations to derive the structure and dynamics of the reduced active site from Escherichia coli Grx3, and investigate the factors that stabilize the thiolate. Several different MD simulations converged toward a consensus conformation for the active-site cysteine residues (Cys11 and Cys14), after a number of local conformational changes. Key features of the model were tested experimentally by measurement of NMR scalar coupling constants, and determination of pK(a) values of selected residues. The pK(a) values of the Grx3 active-site residues were calculated during the MD simulations, and support the underlying structural model. The structure of Grx3, in combination with the pK(a) calculations, indicate that the pK(a) of the N-terminal active-site cysteine residue in Grx3 is intermediate between that of its counterpart in DsbA and Trx. The pK(a) values in best agreement with experiment are obtained with a low (<4) protein dielectric constant. The calculated pK(a) values fluctuate significantly in response to protein dynamics, which underscores the importance of the details of the underlying structures when calculating pK(a) values. The thiolate of Cys11 is stabilized primarily by direct hydrogen bonding with the amide protons of Tyr13 and Cys14 and the thiol proton of Cys14, rather than by long-range interactions from charged groups or from a helix macrodipole. From the comparison of reduced Grx3 with other members of the thioredoxin superfamily, a unifying theme for the structural basis of thiol pK(a) differences in this superfamily begins to emerge.

NMR structure of Escherichia coli glutaredoxin 3-glutathione mixed disulfide complex: implications for the enzymatic mechanism.

Glutaredoxins (Grxs) catalyze reversible oxidation/reduction of protein disulfide groups and glutathione-containing mixed disulfide groups via an active site Grx-glutathione mixed disulfide (Grx-SG) intermediate. The NMR solution structure of the Escherichia coli Grx3 mixed disulfide with glutathione (Grx3-SG) was determined using a C14S mutant which traps this intermediate in the redox reaction. The structure contains a thioredoxin fold, with a well-defined binding site for glutathione which involves two intermolecular backbone-backbone hydrogen bonds forming an antiparallel intermolecular beta-bridge between the protein and glutathione. The solution structure of E. coli Grx3-SG also suggests a binding site for a second glutathione in the reduction of the Grx3-SG intermediate, which is consistent with the specificity of reduction observed in Grxs. Molecular details of the structure in relation to the stability of the intermediate and the activity of Grx3 as a reductant of glutathione mixed disulfide groups are discussed. A comparison of glutathione binding in Grx3-SG and ligand binding in other members of the thioredoxin superfamily is presented, which illustrates the highly conserved intermolecular interactions in this protein family.

NMR structure of oxidized glutaredoxin 3 from Escherichia coli.

A high precision NMR structure of oxidized glutaredoxin 3 [C65Y] from Escherichia coli has been determined. The conformation of the active site including the disulphide bridge is highly similar to those in glutaredoxins from pig liver and T4 phage. A comparison with the previously determined structure of glutaredoxin 3 [C14S, C65Y] in a complex with glutathione reveals conformational changes between the free and substrate-bound form which includes the sidechain of the conserved, active site tyrosine residue. In the oxidized form this tyrosine is solvent exposed, while it adopts a less exposed conformation, stabilized by hydrogen bonds, in the mixed disulfide with glutathione. The structures further suggest that the formation of a covalent linkage between glutathione and glutaredoxin 3 is necessary in order to induce these structural changes upon binding of the glutathione peptide. This could explain the observed low affinity of glutaredoxins for S-blocked glutathione analogues, in spite of the fact that glutaredoxins are highly specific reductants of glutathione mixed disulfides.

Direct NMR observation of the Cys-14 thiol proton of reduced Escherichia coli glutaredoxin-3 supports the presence of an active site thiol-thiolate hydrogen bond.

The active site of Escherichia coli glutaredoxin-3 (Grx3) consists of two redox active cysteine residues in the sequence -C11-P-Y-C14-H-. The 1H NMR resonance of the cysteine thiol proton of Cys-14 in reduced Grx3 is observed at 7.6 ppm. The large downfield shift and NOEs observed with this thiol proton resonance suggest the presence of a hydrogen bond with the Cys-11 thiolate, which is shown to have an abnormally low pKa value. A hydrogen bond would also agree with activity data of Grx3 active site mutants. Furthermore, the activity is reduced in a Grx3 H15V mutant, indicating electrostatic contributions to the stabilization of the Cys-11 thiolate.

Lipid entrapment and cellular changes in the rat myocard, lung and liver after long-term parenteral nutrition with lipid emulsion. A light microscopic and ultrastructural study.

We have demonstrated organ damage after long-term administration of lipid-based parenteral nutrition, possibly initiated by intravascular pooling of lipid and phagocytes, in both rats and pigs. To evaluate whether accumulation of lipid could simply be caused by mechanical filtration, a comparative study of three separate capillary beds was performed. Rats were given lipid emulsion (n = 5) or isotonic saline (n = 4) through central venous catheters for 3 weeks. Using both light and electron microscopy, lipid accumulation and structural changes in the rat myocard were compared to those in the lung and liver. The study provides evidence that within myocardial capillaries both peripheral blood monocytes and endothelial cells performed phagocytosis of lipid droplets following administration of lipid emulsion, but no large-scale intravascular pooling of lipid resulted. Morphometry of the myocard detected no lipid increase in the myocytes from the rats given lipid emulsion compared with controls and in neither were there any stigmata of vasculitis or myocardial damage, in contrast to the lung and liver, where intravascular pooling of lipid and phagocytes was seen. This indicates that phagocytosis was an important mechanism involved in entrapment and elimination of lipid.

Pulmonary intravascular macrophages appear in rats after long-term administration of lipid emulsion and amino acid solution. An ultrastructural morphometric study.

Intravascular macrophages have rarely been seen in normal lungs of humans and rats, but in rats endotoxaemia has induced their presence. To study whether substrates used for parenteral nutrition could have a similar stimulatory effect on mononuclear phagocytes, rats were given lipid emulsion (n=5), amino acid solution (n=5), or isotonic saline (n=5) through central venous catheters for 3 weeks. Structural changes in the lung microvessels were evaluated using electron microscopy. The areal fraction of pulmonary intravascular mononuclear phagocytes was 19.6% (SD=8.2) in rats given lipid emulsion (p<0.05) and 8.2% (SD=8.2) in rats given amino acid solution n.s. compared to 2.4% (SD= 4.0) in rats given saline. The increase in areal fraction was mainly due to an increase in cell numbers. In rats given lipid emulsion the intravascular phagocytes were only slightly larger than in rats given saline, but had the morphological features of mature macrophages. The study demonstrates that lipid emulsion recruits pulmonary intravascular macrophages in rats, indicating a stimulatory effect on the mononuclear phagocyte system. The effect was less pronounced with amino acid solution.

Development of granulomas and vascular fibrocellular proliferation in the lungs of pigs receiving long-term lipid-based parenteral nutrition.

The lungs of pigs receiving long-term total parenteral nutrition (TPN) have been studied. A total of 20 pigs were tentatively infused with TPN through central venous catheters for 7 weeks. To secure adequate nutrition and gastrointestinal absorbance of nutrients, an additional full oral diet was given to eight of these animals. Fifteen control animals received Ringer solution through central venous catheters in addition to the oral diet. All animals infused with TPN for 7 weeks developed lung granulomas, a finding not observed in control animals. No lung granulomas were seen in three TPN animals sacrificed after 3 to 5 weeks owing to illness. All TPN animals also developed tissue reactions suggesting long-standing lung vascular inflammation. Similar vascular changes were seen in seven control animals that had bacterial infection or endotoxemia. The total amount of neutral fat in lung homogenate tended to increase in animals given TPN, and the linoleic acid content was significantly increased. In conclusion, long-term TPN caused lung granulomas in pigs. Vascular damage seemed to be accelerated by bacterial infection as well as by the TPN. The tissue reactions presumably involved long-term activation of monocytes/macrophages.

Is atrial fibrillation caused by extracorporeal circulation?

BACKGROUND: Atrial fibrillation is the most common rhythm disturbance encountered after open heart operations, with a reported incidence up to 40%. Despite its high incidence and clinical relevance its etiology remains obscure. It has been hypothesized that atrial fibrillation might be related to extracorporeal circulation. We performed a retrospective study (January 1, 1997 to December 31, 1997) comparing the incidence of atrial fibrillation in 3 groups of patients revascularized with and without extracorporeal circulation. METHODS: The first group comprised patients with coronary artery disease operated on with standard revascularization technique with cardiopulmonary bypass (n = 685). The second group included patients who had minimally invasive coronary artery bypass grafting without the use of extracorporeal circulation (n = 19). Patients in the third group had off-pump transmyocardial laser revascularization (n = 19). RESULTS: There was no significant difference in the incidence of atrial fibrillation in the group that had conventional coronary artery bypass and the group that had minimally invasive coronary artery bypass without cardiopulmonary bypass. The incidence of atrial fibrillation was significantly lower in the transmyocardial laser group compared with the other two groups. CONCLUSIONS: The present study found that postoperative atrial fibrillation is not caused solely by extracorporeal circulation, but patients who had transmyocardial laser revascularization had a significantly lower incidence of atrial fibrillation.

Perioperative cardiac function and predictors for adverse events after transmyocardial laser treatment.

BACKGROUND: Previous studies have reported that mortality and morbidity after transmyocardial laser treatment (TML) mainly occur perioperatively. The present study was designed to evaluate left-ventricular function and identify risk factors for cardiac-related adverse events in this phase. METHODS: Forty-nine patients were studied. The inclusion criteria were angina pectoris Canadian Cardiovascular Society Angina Score (CCSAS) class III and IV refractory to medical therapy and untreatable by coronary artery bypass graft or percutaneous transluminal coronary angioplasty, age less than 75 years, left ventricular ejection fraction greater than or equal to 30%, and myocardial regions with reversible ischemia. Hemodynamic data and cardiac adverse events were registered. The follow-up time was 30 days. RESULTS: A transient decrease in mean cardiac index (CI) was observed, reaching its minimum immediately after end of the surgical procedure (1.8+/-0.4, p<0.01 vs. baseline). Two patients (4%) died during the postoperative period (30 days). Seventeen patients (35%) experienced adverse cardiac-related events, where CCSAS class IV, unprotected left main stem stenosis, and diabetes mellitus were identified as risk factors in a multivariate analysis. CONCLUSIONS: A transient impairment of left ventricular function was observed after TML. The morbidity and mortality after TML were almost exclusively cardiac-related, identifying CCSAS class IV, unprotected left main stem stenosis, and diabetes as risk factors.

The CarboMedics valve: midterm follow-up with analysis of risk factors.

BACKGROUND: This study examined the midterm results with the CarboMedics prosthetic valve. METHODS: From 1987 through 1991 a total of 569 patients received the CarboMedics prosthesis. RESULTS: Early mortality was 4.9% and related to emergency operation, presence of diabetes mellitus, coronary artery disease, preoperative New York Heart Association class, duration of cardiopulmonary bypass, and aortic cross-clamp time. Midterm follow-up with respect to mortality was 100% complete. All patients were followed up in the hospital after 1 year. In addition 86% of the patients responded to a questionnaire. Mean follow-up was 3 years (range, 0 to 5.6 years). Cumulative survival at 1 and 4 years was 91.2% +/- 1.2% and 83.7% +/- 1.8%, respectively. Five patients experienced obstructive valve thrombosis (0.3%/patient-year), 16 patients had major thromboembolic events (0.9%/patient-year), and 10 patients had major warfarin-related bleeding (0.6%/patient-year) requiring hospitalization or blood transfusions. Eight patients were reoperated on for paraprosthetic leak (0.4%/patient-year). Prosthetic valve endocarditis developed in 4 patients (0.2%/patient-year). No structural valve failure was observed. CONCLUSIONS: Midterm follow-up demonstrates that the CarboMedics mechanical prosthesis is reliable and has an acceptable rate of valve-related complications.

Effects of glucose-insulin-potassium infusion on glycogen levels in cardiac and skeletal muscles in rats.

The effects of loading with glucose-insulin-potassium on the glycogen contents of the heart and peripheral musculature were studied in rats. One group of animals was given intravenous infusion of high concentrations of glucose containing insulin and potassium for 3 days. A control group received the same volume of saline. The hearts and rectus femoris muscles were then analysed for levels of glycogen. It was found that loading with glucose-insulin-potassium induced a decrease in cardiac stores of glycogen while there were no changes in glycogen stores of peripheral musculature as compared to the control animals.

Organ changes in pigs after longterm parenteral nutrition.

When nutritional substrates used in clinical parenteral nutrition are given to rats a number of organ changes have been reported. These could be a species-related effect without significance outside the experimental laboratory. The reproduction of such organ changes in a large unrelated species would increase their importance. Longterm complete parenteral nutrition (CPN) was given to piglets. Nutritional substrates accepted in human parenteral nutrition were used, and the animals were parenterally fed for 6 and 12 weeks. Autopsy demonstrated an increased splenic weight. Epithelioid cell infiltration was found in the liver, spleen and lung. Osmiophilic fat droplets and vascular inflammation were seen in the pulmonary arteries. No signs of infections were found.

[Serious complications related to use of corn starch powder on surgical gloves]. / Alvorlige komplikasjoner ved bruk av maisstivelse på kirurgiske hansker.

Cornflour has been used as a lubricant on surgical gloves since 1947. Serious complications have been reported after deposition of cornflour powder in the human body. The best known complication is granulomatous peritonitis, but cornflour granulomas have also been found in the heart, the kidneys and the central nervous system. Maltesercross, when seen in polarized light in the microscope, is pathognomonic. Malignancy and other granulomatous inflammations are actual differential diagnoses. Nowadays gloves free of lubricating powder are commercially available.

A simple technique for subcutaneous fasciotomy.

A special instrument was devised for semiblind fasciotomy in the treatment of chronic anterior compartment syndrome of the leg. The instrument has been used to treat 133 legs, with satisfactory results.

Use of dextran to prevent intraperitoneal adhesions caused by maize starch powder.

Experimental studies in rats demonstrated that maize starch powder used as lubricant in surgical gloves induces intraperitoneal granulomatosis with formation of adhesions. The possible use of dextran 70 to minimize these adhesions was investigated. By grading the formation of adhesions, it was found that dextran given intraperitoneally reduced the extent of adhesions.