A pilot study of cadre training to promote responsible self-medication in Indonesia: Which is better specific or general modules?

In 2015, the Indonesian Government initiated ‘Smart Use of Medications Movement’ (‘GeMa CerMat’) which included cadre training to promote responsible self-medication. Evaluation of a pilot training conducted across Indonesia suggested the need to improve those training modules. This study aimed to assess cadre’ knowledge gained following training with newly developed general or specific training modules. Five types of modules were developed and used to train cadres at five Community Health Centres (CHCs) in Surabaya, Indonesia: 1) Sidosermo CHC (general-drugs module), 2) Tenggilis CHC (common cold drugs module), 3) Gunung Anyar CHC (analgesic drugs module), 4) Kalirungkut CHC (anti-diarrhoeal drugs module), and 5) Jagir CHC (indigestion drugs module). Cadres’ knowledge improvements were evaluated using pre-/post-test scores and the difference scores depending on the module being tested. Multifactorial ANOVA explored the effects of the type of module on difference scores. A total of 279 cadres across five CHCs were involved in the training, giving response rates from 65% to 93%. There was an increase in the post-test scores after the training with all modules. However, significant differences were reported only for the specific-drugs module groups (all p < .001). Furthermore, the general module group had the lowest difference score (1.12; 95% CI [−0.45, 2.92]) while the common cold module group had the highest gain (5.02; 95% CI [1.95, 5.17]). Multifactorial ANOVA revealed that there was a significant main effect of the type of modules on difference scores [F (4, 263) = 8.37, p <.001]. In conclusion, this preliminary study indicated that the development of modules for specific minor illnesses could be beneficial in facilitating effective community-based training to promote responsible self-medication in Indonesia. The priority for therapeutic areas chosen for the module should be based on the local needs. Further research is required to confirm the findings in broader community members.     

The use of natural interferon alpha conjugated to a monoclonal antibody anti mammary epithelial mucin (Mc5) for the treatment of human breast cancer xenografts

Summary An immunoconjugate composed of natural interferon (nIFN) bound in a noncleavable fashion to a monoclonal antibody (MoAb) recognizing a breast epithelial membrane mucin (Mc5) was used to treat xenografts of a human mammary carcinoma cell line (MCF-7) growing in nude mice. The immunoconjugate (nIFN/Mc5) was administered as 20 intralesional (i.l.) injections to 1 of 2 xenografts in each animal. It was found that nIFN/Mc5 produced a significant enhancement of the growth inhibitory actions of nIFN on the injected tumors. Further enhancement was obtained when nIFN or nIFN together with Mc5 (at a dose 10 times larger than that present in nIFN/Mc5) were added to the immunoconjugate. Biodistribution experiments showed that the uptake of¹²⁵I-nIFN/Mc5 by the tumors was greater and its elimination slower than for¹²⁵I-nIFN alone or conjugated to irrelevant mouse IgG₁. In addition, the immunoconjugate up-regulated the antigenic expression of a breast epithelial membrane mucin by the carcinoma cells, an up-regulation which was not significantly different from that produced by nIFN alone. The contralateral noninjected tumors exposed to systemic levels of the immunoconjugate showed an enhancement of antitumor effects, but to a lesser extent than the injected tumors. These findings suggest that the enhancement of the growth inhibitory action of the immunoconjugate was related to the specific binding of Mc5 which targeted the IFN to the carcinoma cells and impeded its elimination. It is likely that the targeting was favored by the IFN-mediated up-regulation of antigenic expression by the carcinoma cells, thereby producing a cascade of interrelated effects. The results of this study point out the feasibility and potential usefulness of IFN treatment by means of immunoconjugates as well as the worth of pursuing and improving this form of therapy.     

Serosurvey of wild rodents for Rickettsioses (spotted fever, murine typhus and Q fever) in Java Island, Indonesia

The prevalence of antibodies against spotted fever group rickettsia (SFGR), murine typhus and Q fever were investigated in wild rats captured in Indonesia. Sera of 327 rats were collected from Jakarta and Boyolali on Java Island. The prevalences of antibodies against SFGR and murine typhus were 128 (39.1%) and 48 (14.7%), respectively. Antibodies against Q fever were not detected in these serum samples. Antibodies against SFGR were found in all species of rats (20.8–51.9%). The antibody positive rate against murine typhus in Rattus norvegicus (38.0%) was significantly higher than that in other rat species (0–4.8%, p < 0.01). The antibody positive rates against SFGR and murine typhus in rats captured in Jakarta were significantly higher than those in rats captured in Boyolali (p < 0.01). In this survey, all species of rats had antibodies against SFGR, indicating that the 4 species of tested rats (R. norvegicus, R. rattus, R. exulans, R. tiomanicus) were infected with SFGR and that SFGR may infest the whole of Java Island. Most of the rats that were antibody-positive against murine typhus were captured in Jakarta. Therefore, R. norvegicus and R. rattus are likely to be important hosts of murine typhus in Jakarta. The antibody-positive rates against SFGR and murine typhus in rats captured in the dry season were significantly higher than those in rats captured in the rainy season. This may coincide with the active periods of ticks and fleas in Indonesia.     

Informed consent, parental awareness, and reasons for participating in a randomised controlled study

BACKGROUND: The informed consent procedure plays a central role in randomised controlled trials but has only been explored in a few studies on children. AIM: To assess the quality of the informed consent process in a paediatric setting. METHODS: A questionnaire was sent to parents who volunteered their child (230 children) for a randomised, double blind, placebo controlled trial of ibuprofen syrup to prevent recurrent febrile seizures. RESULTS: 181 (79%) parents responded. On average, 73% of parents were aware of the major study characteristics. A few had difficulty understanding the information provided. Major factors in parents granting approval were the contribution to clinical science (51%) and benefit to the child (32%). Sociodemographic status did not influence initial participation but west European origin of the father was associated with willingness to participate in future trials. 89% of participants felt positive about the informed consent procedure; however, 25% stated that they felt obliged to participate. Although their reasons for granting approval and their evaluation of the informed consent procedure did not differ, relatively more were hesitant about participating in future. Parents appreciated the investigator being on call 24 hours a day (38%) and the extra medical care and information provided (37%) as advantages of participation. Disadvantages were mainly the time consuming aspects and the work involved (23%). CONCLUSIONS: Parents' understanding of trial characteristics might be improved by designing less difficult informed consent forms and by the investigator giving extra attention and information to non-west European parents. Adequate measures should be taken to avoid parents feeling obliged to participate, rather than giving true informed consent.     

Predisposing,Enabling, and Reinforcing Factors of COVID-19 Prevention Behavior in Indonesia: A Mixed-methods Study

Objectives:To prevent the spread of coronavirus disease 2019 (COVID-19), behaviors such as mask-wearing, social distancing, decreasing mobility, and avoiding crowds have been suggested, especially in high-risk countries such as Indonesia. Unfortunately, the level of compliance with those practices has been low. This study was conducted to determine the predisposing, enabling, and reinforcing factors of COVID-19 prevention behavior in Indonesia.Methods:This cross-sectional study used a mixed-methods approach. The participants were 264 adults from 21 provinces in Indonesia recruited through convenience sampling. Data were collected using a Google Form and in-depth interviews. Statistical analysis included univariate, bivariate, and multivariate logistic regression. Furthermore, qualitative data analysis was done through content analysis and qualitative data management using Atlas.ti software.Results:Overall, 44.32% of respondents were non-compliant with recommended COVID-19 prevention behaviors. In multivariate logistic regression analysis, low-to-medium education level, poor attitude, insufficient involvement of leaders, and insufficient regulation were also associated with decreased community compliance. Based on in-depth interviews with informants, the negligence of the Indonesian government in the initial stages of the COVID-19 pandemic may have contributed to the unpreparedness of the community to face the pandemic, as people were not aware of the importance of preventive practices.Conclusions:Education level is not the only factor influencing community compliance with recommended COVID-19 prevention behaviors. Changing attitudes through health promotion to increase public awareness and encouraging voluntary community participation through active risk communication are necessary. Regulations and role leaders are also required to improve COVID-19 prevention behavior.     

Rearrangement of the T cell receptor gamma-chain gene in childhood acute lymphoblastic leukemia

We analyzed rearrangements of the T cell receptor gamma-chain (T gamma) gene as well as rearrangements of the T cell receptor beta-chain (T beta) gene and immunoglobulin heavy-chain (IgH) gene in 68 children with acute lymphoblastic leukemia (ALL). All 15 patients with T cell ALL showed rearrangements of both T beta and T gamma genes. Twenty-four of 53 non-T, non-B ALL patients (45%) showed T gamma gene rearrangements and only 14 of these also showed T beta gene rearrangements. Only a single patient rearranged the T beta gene in the absence of T gamma gene rearrangement. The rearrangement patterns of the T gamma gene in non-T, non-B ALL were quite different from those observed in T cell ALL, as 20 of 23 patients retained at least one germline band of the T gamma gene. In contrast, all T cell ALL patients showed no retention of germline bands. These data indicate that rearrangement of the T gamma gene is not specific for T cell ALL. Further, the results also suggest that T gamma gene rearrangement precedes T beta gene rearrangement. The combined analysis of rearrangement patterns of IgH, T beta, and T gamma genes provides new criteria for defining the cellular origin of leukemic cells and for further delineation of leukemia cell heterogeneity.     

Membrane glycoproteins and platelet cytoskeleton in immune complex- induced platelet activation

To clarify the mechanism of platelet activation by immune complexes and the possible involvement of surface glycoproteins (GPs), we studied platelet activation induced by heat-aggregated IgG (HAG). We examined the effects of monoclonal antibodies (MoAbs) against GPIb, GPIIb/IIIa, and the Fc receptor on resting platelets and on platelets stimulated by HAG. HAG increased the cytosolic ionized calcium concentration ([Ca2+]i) and stimulated protein (P47 and P20) phosphorylation, phosphatidic acid (PA) synthesis, serotonin secretion, and platelet aggregation. IV.3, an anti-Fc gamma RII receptor MoAb, inhibited HAG binding to platelets and all subsequent platelet responses. Like IV.3, MoAbs against GPIIb/IIIa (Tab, 10E5, AP-3) or GPIb (AP-1, 6D1) strongly inhibited platelet activation by HAG. However, while anti-GPIIb/IIIa MoAbs inhibited binding of IV.3 and HAG to platelets, anti-GPIb MoAbs had little effect on platelet binding of IV.3 or HAG. These observations suggest a close topographical and functional association of GPIIb/IIIa with Fc gamma RII in the platelet response to HAG. Cytochalasin B, an inhibitor of actin polymerization, also inhibited platelet activation but not HAG or IV.3 binding. Measurement of the fluorescence of 7-nitrobenz-2-oxa-1,3-(NBD)-phallacidin, a specific marker for filamentous actin (F-actin), showed that both cytochalasin B and AP-1 blocked the increase of F-actin induced by HAG. The common effects of anti-GPIb MoAbs and of cytochalasin B suggest that unlike the activity of GPIIb/IIIa, the ability of anti-GPIb to inhibit the activation of platelets by immune complexes is associated with perturbation of the cytoskeleton.     

Human myeloid alpha 3-fucosyltransferase is involved in the expression of the sialyl-Lewis(x) determinant, a ligand for E- and P-selectin

The sialyl-Lex determinant (NeuAc alpha 2-->3Gal beta 1-->4[Fuc alpha- 1-->3]GlcNAc) has been identified as a major ligand in the selectin- mediated adhesion of neutrophils and monocytes to activated endothelium or platelets. This carbohydrate epitope is formed by the sequential action of alpha 3-sialyltransferase and alpha 3-fucosyltransferase on N- acetyllactosamine (Gal beta 1-->4GlcNAc) disaccharide termini of glycoconjugates. We have addressed the role of the human myeloid alpha 3-fucosyltransferase in the expression of this epitope at the leucocyte surface by determining its activity in human-mouse leukemic cell hybrids (WEGLI), normal human granulocytes and chronic myeloid leukemia (CML) cells using sialylated and desialylated glycoproteins and oligosaccharides as acceptor substrates. In contrast to what has been reported for the myeloid-type enzyme, we found that the alpha 3- fucosyltransferase of the cells studied can use sialylated acceptors be it that the activity is several times lower than with asialo- substrates. Characterization of the product obtained with a sialylated oligosaccharide indicated that the enzyme can catalyze the formation of the sialyl-Le(x) structure. Flow cytometry of the WEGLI cells using a sialyl-Le(x)-specific monoclonal antibody (MoAb) showed that these cells indeed express sialyl-Lex at their surface, provided that they contain human chromosome 11. Earlier the presence of this chromosome had been correlated with the expression of alpha 3-fucosyltransferase activity. In addition to sialyl-Le(x), WEGLI cells containing chromosome 11 showed high-expression levels of related structures recognized by antibodies VIM-2 and VIM-8, suggesting that fucose addition can occur at both distal and proximal GlcNAc residues in poly- N-acetyl-lactosaminoglycan sequences. Based on the human chromosome contents it could be ruled out that the alpha 3-fucosyltransferase of WEGLI cells is a Lewis-type alpha 3/4- or plasma-type alpha 3- fucosyltransferase, the genes of which have been mapped to chromosome 19. It is concluded that the enzyme studied is of the myeloid-type and indeed is involved in the synthesis of sialyl-Le(x) (and also VIM-2 and VIM-8 structures) in leukocytes provided that its expression is at a sufficiently high level.