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1.
Molecules ; 26(9)2021 Apr 30.
Article in English | MEDLINE | ID: mdl-33946601

ABSTRACT

A new method combining isotope dilution mass spectrometry (IDMS) and standard addition has been developed to determine the mass fractions w of different elements in complex matrices: (a) silicon in aqueous tetramethylammonium hydroxide (TMAH), (b) sulfur in biodiesel fuel, and (c) iron bound to transferrin in human serum. All measurements were carried out using inductively coupled plasma mass spectrometry (ICP-MS). The method requires the gravimetric preparation of several blends (bi)-each consisting of roughly the same masses (mx,i) of the sample solution (x) and my,i of a spike solution (y) plus different masses (mz,i) of a reference solution (z). Only these masses and the isotope ratios (Rb,i) in the blends and reference and spike solutions have to be measured. The derivation of the underlying equations based on linear regression is presented and compared to a related concept reported by Pagliano and Meija. The uncertainties achievable, e.g., in the case of the Si blank in extremely pure TMAH of urel (w(Si)) = 90% (linear regression method, this work) and urel (w(Si)) = 150% (the method reported by Pagliano and Meija) seem to suggest better applicability of the new method in practical use due to the higher robustness of regression analysis.


Subject(s)
Isotopes/chemistry , Mass Spectrometry/methods , Algorithms , Biofuels/analysis , Biomarkers/blood , Humans , Mass Spectrometry/standards , Models, Theoretical , Silicon/analysis , Sulfur/analysis , Transferrin/analysis
3.
BMC Health Serv Res ; 19(1): 848, 2019 Nov 20.
Article in English | MEDLINE | ID: mdl-31747932

ABSTRACT

BACKGROUND: Universal Health Coverage only leads to the desired health outcomes if quality of health services is ensured. In Tanzania, quality has been a major concern for many years, including the problem of ineffective and inadequate routine supportive supervision of healthcare providers by council health management teams. To address this, we developed and assessed an approach to improve quality of primary healthcare through enhanced routine supportive supervision. METHODS: Mixed methods were used, combining trends of quantitative quality of care measurements with qualitative data mainly collected through in-depth interviews. The former allowed for identification of drivers of quality improvements and the latter investigated the perceived contribution of the new supportive supervision approach to these improvements. RESULTS: The results showed that the new approach managed to address quality issues that could be solved either solely by the healthcare provider, or in collaboration with the council. The new approach was able to improve and maintain crucial primary healthcare quality standards across different health facility level and owner categories in various contexts. CONCLUSION: Together with other findings reported in companion papers, we could show that the new supportive supervision approach not only served to assess quality of primary healthcare, but also to improve and maintain crucial primary healthcare quality standards. The new approach therefore presents a powerful tool to support, guide and drive quality improvement measures within council. It can thus be considered a suitable option to make routine supportive supervision more effective and adequate.


Subject(s)
Primary Health Care/standards , Quality Improvement/standards , Adolescent , Adult , Aged , Attitude of Health Personnel , Child , Child, Preschool , Female , Health Facilities/standards , Health Personnel/standards , Humans , Infant , Infant, Newborn , Male , Middle Aged , Primary Health Care/organization & administration , Quality Indicators, Health Care , Quality of Health Care/standards , Rural Health Services/standards , Tanzania , Universal Health Insurance/organization & administration , Young Adult
4.
BMC Health Serv Res ; 19(1): 55, 2019 Jan 22.
Article in English | MEDLINE | ID: mdl-30670011

ABSTRACT

BACKGROUND: Progress in health service quality is vital to reach the target of Universal Health Coverage. However, in order to improve quality, it must be measured, and the assessment results must be actionable. We analyzed an electronic tool, which was developed to assess and monitor the quality of primary healthcare in Tanzania in the context of routine supportive supervision. The electronic assessment tool focused on areas in which improvements are most effective in order to suit its purpose of routinely steering improvement measures at local level. METHODS: Due to the lack of standards regarding how to best measure quality of care, we used a range of different quantitative and qualitative methods to investigate the appropriateness of the quality assessment tool. The quantitative methods included descriptive statistics, linear regression models, and factor analysis; the qualitative methods in-depth interviews and observations. RESULTS: Quantitative and qualitative results were overlapping and consistent. Robustness checks confirmed the tool's ability to assign scores to health facilities and revealed the usefulness of grouping indicators into different quality dimensions. Focusing the quality assessment on processes and structural adequacy of healthcare was an appropriate approach for the assessment's intended purpose, and a unique key feature of the electronic assessment tool. The findings underpinned the accuracy of the assessment tool to measure and monitor quality of primary healthcare for the purpose of routinely steering improvement measures at local level. This was true for different level and owner categories of primary healthcare facilities in Tanzania. CONCLUSION: The electronic assessment tool demonstrated a feasible option for routine quality measures of primary healthcare in Tanzania. The findings, combined with the more operational results of companion papers, created a solid foundation for an approach that could lastingly improve services for patients attending primary healthcare. However, the results also revealed that the use of the electronic assessment tool outside its intended purpose, for example for performance-based payment schemes, accreditation and other systematic evaluations of healthcare quality, should be considered carefully because of the risk of bias, adverse effects and corruption.


Subject(s)
Automation , Primary Health Care , Quality Improvement , Quality Indicators, Health Care , Quality of Health Care/standards , Accreditation/standards , Ambulatory Care Facilities , Factor Analysis, Statistical , Female , Humans , Outcome Assessment, Health Care/methods , Tanzania , Universal Health Insurance
5.
PLoS One ; 13(9): e0202735, 2018.
Article in English | MEDLINE | ID: mdl-30192783

ABSTRACT

Effective supportive supervision of healthcare services is crucial for improving and maintaining quality of care. However, this process can be challenging in an environment with chronic shortage of qualified human resources, overburdened healthcare providers, multiple roles of district managers, weak supply chains, high donor fragmentation and inefficient allocation of limited financial resources. Operating in this environment, we systematically evaluated an approach developed in Tanzania to strengthen the implementation of routine supportive supervision of primary healthcare providers. The approach included a systematic quality assessment at health facilities using an electronic tool and subsequent result dissemination at council level. Mixed methods were used to compare the new supportive supervision approach with routine supportive supervision. Qualitative data was collected through in-depth interviews in three councils. Observational data and informal communication as well as secondary data complemented the data set. Additionally, an economic costing analysis was carried out in the same councils. Compared to routine supportive supervision, the new approach increased healthcare providers' knowledge and skills, as well as quality of data collected and acceptance of supportive supervision amongst stakeholders involved. It also ensured better availability of evidence for follow-up actions, including budgeting and planning, and higher stakeholder motivation and ownership of subsequent quality improvement measures. The new approach reduced time and cost spent during supportive supervision. This increased feasibility of supportive supervision and hence the likelihood of its implementation. Thus, the results presented together with previous findings suggested that if used as the standard approach for routine supportive supervision the new approach offers a suitable option to make supportive supervision more efficient and effective and therewith more sustainable. Moreover, the new approach also provides informed guidance to overcome several problems of supportive supervision and healthcare quality assessments in low- and middle income countries.


Subject(s)
Quality of Health Care/statistics & numerical data , Costs and Cost Analysis , Delivery of Health Care/economics , Health Facilities/economics , Health Facilities/statistics & numerical data , Humans , Tanzania
7.
BMC Health Serv Res ; 16(1): 578, 2016 10 13.
Article in English | MEDLINE | ID: mdl-27737679

ABSTRACT

BACKGROUND: Assessing quality of health services, for example through supportive supervision, is essential for strengthening healthcare delivery. Most systematic health facility assessment mechanisms, however, are not suitable for routine supervision. The objective of this study is to describe a quality assessment methodology using an electronic format that can be embedded in supervision activities and conducted by council health staff. METHODS: An electronic Tool to Improve Quality of Healthcare (e-TIQH) was developed to assess the quality of primary healthcare provision. The e-TIQH contains six sub-tools, each covering one quality dimension: infrastructure and equipment of the facility, its management and administration, job expectations, clinical skills of the staff, staff motivation and client satisfaction. As part of supportive supervision, council health staff conduct quality assessments in all primary healthcare facilities in a given council, including observation of clinical consultations and exit interviews with clients. Using a hand-held device, assessors enter data and view results in real time through automated data analysis, permitting immediate feedback to health workers. Based on the results, quality gaps and potential measures to address them are jointly discussed and actions plans developed. RESULTS: For illustrative purposes, preliminary findings from e-TIQH application are presented from eight councils of Tanzania for the period 2011-2013, with a quality score <75 % classed as 'unsatisfactory'. Staff motivation (<50 % in all councils) and job expectations (≤50 %) scored lowest of all quality dimensions at baseline. Clinical practice was unsatisfactory in six councils, with more mixed results for availability of infrastructure and equipment, and for administration and management. In contrast, client satisfaction scored surprisingly high. Over time, each council showed a significant overall increase of 3-7 % in mean score, with the most pronounced improvements in staff motivation and job expectations. CONCLUSIONS: Given its comprehensiveness, convenient handling and automated statistical reports, e-TIQH enables council health staff to conduct systematic quality assessments. Therefore e-TIQH may not only contribute to objectively identifying quality gaps, but also to more evidence-based supervision. E-TIQH also provides important information for resource planning. Institutional and financial challenges for implementing e-TIQH on a broader scale need to be addressed.


Subject(s)
Automation , Primary Health Care/organization & administration , Quality Assurance, Health Care/organization & administration , Quality of Health Care , Clinical Competence , Delivery of Health Care/organization & administration , Health Facilities , Health Personnel , Humans , Motivation , Tanzania
8.
Int J Epidemiol ; 43(1): 204-15, 2014 Feb.
Article in English | MEDLINE | ID: mdl-24355745

ABSTRACT

BACKGROUND: Between 1997 and 2009, a number of key malaria control interventions were implemented in the Kilombero and Ulanga Districts in south central Tanzania to increase insecticide-treated nets (ITN) coverage and improve access to effective malaria treatment. In this study we estimated the contribution of these interventions to observed decreases in child mortality. METHODS: The local Health and Demographic Surveillance Site (HDSS) provided monthly estimates of child mortality rates (age 1 to 5 years) expressed as cases per 1000 person-years (c/1000py) between 1997 and 2009. We conducted a time series analysis of child mortality rates and explored the contribution of rainfall and household food security. We used Poisson regression with linear and segmented effects to explore the impact of malaria control interventions on mortality. RESULTS: Child mortality rates decreased by 42.5% from 14.6 c/1000py in 1997 to 8.4 c/1000py in 2009. Analyses revealed the complexity of child mortality patterns and a strong association with rainfall and food security. All malaria control interventions were associated with decreases in child mortality, accounting for the effect of rainfall and food security. CONCLUSIONS: Reaching the fourth Millenium Development Goal will require the contribution of many health interventions, as well as more general improvements in socio-environmental and nutritional conditions. Distinguishing between the effects of these multiple factors is difficult and represents a major challenge in assessing the effect of routine interventions. However, this study suggests that credible estimates can be obtained when high-quality data on the most important factors are available over a sufficiently long time period.


Subject(s)
Antimalarials/administration & dosage , Child Mortality , Malaria/drug therapy , Malaria/prevention & control , Mosquito Control/methods , Rural Population/statistics & numerical data , Child , Female , Food Supply , Health Services Accessibility , Humans , Insecticide-Treated Bednets/statistics & numerical data , Malaria/epidemiology , Male , Nutritional Status , Seasons , Socioeconomic Factors , Tanzania/epidemiology
9.
BMC Health Serv Res ; 13: 101, 2013 Mar 16.
Article in English | MEDLINE | ID: mdl-23497025

ABSTRACT

BACKGROUND: Patient Centred Tuberculosis Treatment (PCT) is a promising treatment delivery strategy for Mycobacterium tuberculosis (TB). It aims to improve adherence to treatment by giving patients the choice of having drug intake supervised at the health facility by a medical professional or at home by a supporter of their choice. METHODS: A cross-sectional survey was undertaken in three districts of Tanzania during October 2007, one year after PCT was rolled out nationally. Semi-structured questionnaires were used to assess whether key elements of the PCT approach were being implemented, to evaluate supporters' knowledge, to capture opinions on factors contributing to treatment completion, and to assess how treatment completion was measured. Transcripts from open-ended responses were analysed using framework analysis. RESULTS: Interviews were conducted with 127 TB patients, 107 treatment supporters and 70 health workers. In total, 25.2% of TB patients were not given a choice about the place of treatment by health workers, and only 13.7% of those given a choice reported that they were given adequate time to make their decision. Only 24.3% of treatment supporters confirmed that they were instructed how to complete patients' treatment cards. Proper health education was the factor most frequently reported by health workers as favouring successful completion of TB treatment (45.7%). The majority of health workers (68.6%) said they checked returned blister packs to verify whether patients had taken their treatment, but only 20.0% checked patients' treatment cards. CONCLUSIONS: The provision of choice of treatment location, information on treatment, and guidance for treatment supporters need to be improved. There is a requirement for regular re-training of health workers with effective supportive supervision if successful implementation of the PCT approach is to be sustained.


Subject(s)
Allied Health Personnel , Patient-Centered Care , Professional Competence , Tuberculosis, Pulmonary/drug therapy , Adult , Cross-Sectional Studies , Directly Observed Therapy , Female , Humans , Male , Medication Adherence , Patient Participation , Qualitative Research , Quality of Health Care , Surveys and Questionnaires , Tanzania
10.
BMC Health Serv Res ; 12: 113, 2012 May 09.
Article in English | MEDLINE | ID: mdl-22571384

ABSTRACT

BACKGROUND: Acceptability is a poorly conceptualized dimension of access to health care. Using a study on childhood convulsion in rural Tanzania, we examined social acceptability from a user perspective. The study design is based on the premise that a match between health providers' and clients' understanding of disease is an important dimension of social acceptability, especially in trans-cultural communication, for example if childhood convulsions are not linked with malaria and local treatment practices are mostly preferred. The study was linked to health interventions with the objective of bridging the gap between local and biomedical understanding of convulsions. METHODS: The study combined classical ethnography with the cultural epidemiology approach using EMIC (Explanatory Model Interview Catalogue) tool. EMIC interviews were conducted in a 2007/08 convulsion study (n = 88) and results were compared with those of an earlier 2004/06 convulsion study (n = 135). Earlier studies on convulsion in the area were also examined to explore longer-term changes in treatment practices. RESULTS: The match between local and biomedical understanding of convulsions was already high in the 2004/06 study. Specific improvements were noted in form of (1) 46% point increase among those who reported use of mosquito nets to prevent convulsion (2) 13% point decrease among caregivers who associated convulsion with 'evil eye and sorcery', 3) 14% point increase in prompt use of health facility and 4)16% point decrease among those who did not use health facility at all. Such changes can be partly attributed to interventions which explicitly aimed at increasing the match between local and biomedical understanding of malaria. Caregivers, mostly mothers, did not seek advice on where to take an ill child. This indicates that treatment at health facility has become socially acceptable for severe febrile with convulsion. CONCLUSION: As an important dimension of access to health care 'social acceptability' seems relevant in studying illnesses that are perceived not to belong to the biomedical field, specifically in trans-cultural societies. Understanding the match between local and biomedical understanding of disease is fundamental to ensure acceptability of health care services, successful control and management of health problems. Our study noted some positive changes in community knowledge and management of convulsion episodes, changes which might be accredited to extensive health education campaigns in the study area. On the other hand it is difficult to make inference out of the findings as a result of small sample size involved. In return, it is clear that well ingrained traditional beliefs can be modified with communication campaigns, provided that this change resonates with the beneficiaries.


Subject(s)
Caregivers/psychology , Health Knowledge, Attitudes, Practice , Health Services Accessibility/economics , Malaria, Falciparum/psychology , Patient Acceptance of Health Care/psychology , Rural Population , Seizures, Febrile/therapy , Adult , Animals , Anthropology, Cultural , Anticonvulsants/therapeutic use , Antimalarials/therapeutic use , Caregivers/statistics & numerical data , Child , Cross-Cultural Comparison , Culicidae/parasitology , Female , Fever/complications , Fever/therapy , Humans , Insect Bites and Stings/complications , Interviews as Topic , Malaria, Falciparum/epidemiology , Malaria, Falciparum/therapy , Male , Medicine, African Traditional/economics , Medicine, African Traditional/psychology , Rural Population/statistics & numerical data , Sanitation/standards , Seasons , Seizures, Febrile/ethnology , Seizures, Febrile/etiology , Social Class , Tanzania/epidemiology
11.
PLoS One ; 7(12): e51828, 2012.
Article in English | MEDLINE | ID: mdl-23284782

ABSTRACT

BACKGROUND: Non-adherence to tuberculosis (TB) treatment is the leading contributor to the selection of drug-resistant strains of Mycobacterium tuberculosis and subsequent treatment failure. Tanzania introduced a TB Patient Centred Treatment (PCT) approach which gives new TB patients the choice between home-based treatment supervised by a treatment supporter of their own choice, and health facility-based treatment observed by a medical professional. The aim of this study was to assess the extent and determinants of adherence to anti-TB therapy in patients opting for home-based treatment under the novel PCT approach. METHODS: In this cross-sectional study, the primary outcome was the percentage of patients adherent to TB therapy as detected by the presence of isoniazid in urine (IsoScreen assay). The primary analysis followed a non-inferiority approach in which adherence could not be lower than 75%. Logistic regression was used to examine the influence of potentially predictive factors. RESULTS: A total of 651 new TB patients were included. Of these, 645 (99.1%) provided urine for testing and 617 patients (95.7%; 90%CI 94.3-96.9) showed a positive result. This result was statistically non-inferior to the postulated adherence level of 75% (p<0.001). CONCLUSIONS: Adherence to TB therapy under home-based Directly Observed Treatment can be ensured in programmatic settings. A reliable supply of medication and the careful selection of treatment supporters, who preferably live very close to the patient, are crucial success factors. Finally, we recommend a cohort study to assess the rate of adherence throughout the full course of TB treatment.


Subject(s)
Antitubercular Agents/therapeutic use , Directly Observed Therapy , Medication Adherence/statistics & numerical data , Mycobacterium tuberculosis/drug effects , Patient Compliance/statistics & numerical data , Tuberculosis/drug therapy , Adolescent , Adult , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Self Administration/statistics & numerical data , Tanzania , Treatment Outcome , Young Adult
12.
Malar J ; 9: 163, 2010 Jun 15.
Article in English | MEDLINE | ID: mdl-20550653

ABSTRACT

BACKGROUND: The ACCESS programme aims at understanding and improving access to prompt and effective malaria treatment. Between 2004 and 2008 the programme implemented a social marketing campaign for improved treatment-seeking. To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO) was created in Tanzania in 2006. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP) to artemether-lumefantrine (ALu) in 2007 and subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on understanding and treatment of malaria was studied in rural Tanzania. The data also enabled an investigation of the determinants of access to treatment. METHODS: Three treatment-seeking surveys were conducted in 2004, 2006 and 2008 in the rural areas of the Ifakara demographic surveillance system (DSS) and in Ifakara town. Each survey included approximately 150 people who had suffered a fever case in the previous 14 days. RESULTS: Treatment-seeking and awareness of malaria was already high at baseline, but various improvements were seen between 2004 and 2008, namely: better understanding causes of malaria (from 62% to 84%); an increase in health facility attendance as first treatment option for patients older than five years (27% to 52%); higher treatment coverage with anti-malarials (86% to 96%) and more timely use of anti-malarials (80% to 93-97% treatments taken within 24 hrs). Unfortunately, the change of treatment policy led to a low availability of ALu in the private sector and, therefore, to a drop in the proportion of patients taking a recommended malaria treatment (85% to 53%). The availability of outlets (health facilities or drug shops) is the most important determinant of whether patients receive prompt and effective treatment, whereas affordability and accessibility contribute to a lesser extent. CONCLUSIONS: An integrated approach aimed at improving understanding and treatment of malaria has led to tangible improvements in terms of people's actions for the treatment of malaria. However, progress was hindered by the low availability of the first-line treatment after the switch to ACT.


Subject(s)
Antimalarials/therapeutic use , Health Services Accessibility , Malaria/drug therapy , Patient Acceptance of Health Care , Rural Health Services/supply & distribution , Antimalarials/supply & distribution , Child , Child, Preschool , Commerce , Cross-Sectional Studies , Data Collection , Family Characteristics , Female , Health Knowledge, Attitudes, Practice , Humans , Infant , Malaria/epidemiology , Male , Private Sector , Rural Population , Social Marketing , Socioeconomic Factors , Tanzania/epidemiology
13.
Malar J ; 8: 144, 2009 Jun 29.
Article in English | MEDLINE | ID: mdl-19563640

ABSTRACT

BACKGROUND: Convulsions is one of the key signs of severe malaria among children under five years of age, potentially leading to serious complications or death. Several studies of care-seeking behaviour have revealed that local illness concepts linked to convulsions (referred to as degedege in Tanzanian Kiswahili) called for traditional treatment practices while modern treatment was preferred for common fevers. However, recent studies found that even children with convulsions were first brought to health facilities. This study integrated ethnographic and public health approaches in order to investigate this seemingly contradictory evidence. Carefully drawn random samples were used to maximize the representativity of the results. METHODS: The study used a cultural epidemiology approach and applied a locally adapted version of the Explanatory Model Interview Catalogue (EMIC), which ensures a comprehensive investigation of disease perception and treatment patterns. The tool was applied in three studies; i) the 2004 random sample cross-sectional community fever survey (N = 80), ii) the 2004-2006 longitudinal degedege study (N = 129), and iii) the 2005 cohort study on fever during the main farming season (N = 29). RESULTS: 71.1% of all convulsion cases were brought to a health facility in time, i.e. within 24 hours after onset of first symptoms. This compares very favourably with a figure of 45.6% for mild fever cases in children. The patterns of distress associated with less timely health facility use and receipt of anti-malarials among children with degedege were generalized symptoms, rather than the typical symptoms of convulsions. Traditional and moral causes were associated with less timely health facility use and receipt of anti-malarials. However, the high rate of appropriate action indicates that these ideas were not so influential any more as in the past. Reasons given by caretakers who administered anti-malarials to children without attending a health facility were either that facilities were out of stock, that they lacked money to pay for treatment, or that facilities did not provide diagnosis. CONCLUSION: The findings from this sample from a highly malaria-endemic area give support to the more recent studies showing that children with convulsions are more likely to use health facilities than traditional practices. This study has identified health system and livelihood factors, rather than local understandings of symptoms and causes relating to degedege as limiting health-seeking behaviours. Improvements on the supply side and the demand side are necessary to ensure people's timely and appropriate treatment: Quality of care at health facilities needs to be improved by making diagnosis and provider compliance with treatment guidelines more accurate and therapies including drugs more available and affordable to communities. Treatment seeking needs to be facilitated by strengthening livelihoods including economic capabilities.


Subject(s)
Community Health Services/statistics & numerical data , Health Knowledge, Attitudes, Practice , Medicine, African Traditional/statistics & numerical data , Patient Acceptance of Health Care , Seizures, Febrile/therapy , Antimalarials/therapeutic use , Child, Preschool , Culture , Family , Female , Fever/complications , Fever/therapy , Health Care Surveys , Humans , Infant , Malaria/complications , Malaria/therapy , Male , Seizures, Febrile/ethnology , Seizures, Febrile/etiology , Tanzania/epidemiology , Time Factors
14.
Bioorg Med Chem Lett ; 19(7): 1960-5, 2009 Apr 01.
Article in English | MEDLINE | ID: mdl-19250826

ABSTRACT

A novel series of matriptase inhibitors based on previously identified tribasic 3-amidinophenylalanine derivatives was prepared. The C-terminal basic group was replaced by neutral residues to reduce the hydrophilicity of the inhibitors. The most potent compound 22 inhibits matriptase with a K(i) value of 0.43 nM, but lacks selectivity towards factor Xa. By combination with neutral N-terminal sulfonyl residues several potent thrombin inhibitors were identified, which had reduced matriptase affinity.


Subject(s)
Amidines/chemistry , Phenylalanine/chemistry , Serine Endopeptidases/chemistry , Serine Proteinase Inhibitors/chemistry , Sulfonamides/chemistry , Administration, Oral , Amidines/pharmacology , Animals , Factor Xa/metabolism , Factor Xa Inhibitors , Phenylalanine/analogs & derivatives , Phenylalanine/pharmacology , Rats , Serine Endopeptidases/metabolism , Serine Proteinase Inhibitors/pharmacology , Sulfonamides/pharmacology , Thrombin/antagonists & inhibitors , Thrombin/metabolism
15.
Bioorg Med Chem Lett ; 19(1): 67-73, 2009 Jan 01.
Article in English | MEDLINE | ID: mdl-19036586

ABSTRACT

Replacement of the N-terminal beta-alanyl-amide moiety in previously identified matriptase inhibitors by non-charged aryl groups caused a slightly decreased potency and partially reduced selectivity, especially towards thrombin. However, some of these analogues are still potent matriptase inhibitors with K(i)-values <10nM. In contrast, improved activity was observed for newly designed tribasic analogues, especially for compound 21, which inhibits matriptase with an K(i)-value of 80pM.


Subject(s)
Amidines/chemical synthesis , Serine Endopeptidases/drug effects , Serine Proteinase Inhibitors/chemical synthesis , Amidines/pharmacology , Animals , Dose-Response Relationship, Drug , Humans , Serine Proteinase Inhibitors/chemistry , Serine Proteinase Inhibitors/pharmacology , Structure-Activity Relationship , Thrombin/antagonists & inhibitors
16.
BMC Public Health ; 8: 317, 2008 Sep 16.
Article in English | MEDLINE | ID: mdl-18793448

ABSTRACT

BACKGROUND: Malaria is still a leading child killer in sub-Saharan Africa. Yet, access to prompt and effective malaria treatment, a mainstay of any malaria control strategy, is sub-optimal in many settings. Little is known about obstacles to treatment and community-effectiveness of case-management strategies. This research quantified treatment seeking behaviour and access to treatment in a highly endemic rural Tanzanian community. The aim was to provide a better understanding of obstacles to treatment access in order to develop practical and cost-effective interventions. METHODS: We conducted community-based treatment-seeking surveys including 226 recent fever episodes in 2004 and 2005. The local Demographic Surveillance System provided additional household information. A census of drug retailers and health facilities provided data on availability and location of treatment sources. RESULTS: After intensive health education, the biomedical concept of malaria has largely been adopted by the community. 87.5% (78.2-93.8) of the fever cases in children and 80.7% (68.1-90.0) in adults were treated with one of the recommended antimalarials (at the time SP, amodiaquine or quinine). However, only 22.5% (13.9-33.2) of the children and 10.5% (4.0-21.5) of the adults received prompt and appropriate antimalarial treatment. Health facility attendance increased the odds of receiving an antimalarial (OR = 7.7) but did not have an influence on correct dosage. The exemption system for under-fives in public health facilities was not functioning and drug expenditures for children were as high in health facilities as with private retailers. CONCLUSION: A clear preference for modern medicine was reflected in the frequent use of antimalarials. Yet, quality of case-management was far from satisfactory as was the functioning of the exemption mechanism for the main risk group. Private drug retailers played a central role by complementing existing formal health services in delivering antimalarial treatment. Health system factors like these need to be tackled urgently in order to translate the high efficacy of newly introduced artemisinin-based combination therapy (ACT) into equitable community-effectiveness and health-impact.


Subject(s)
Fever/therapy , Malaria/therapy , Poverty , Rural Health Services/statistics & numerical data , Adolescent , Adult , Analysis of Variance , Antimalarials/economics , Antimalarials/therapeutic use , Child , Cross-Sectional Studies , Female , Fever/etiology , Health Care Surveys , Humans , Logistic Models , Male , Patient Acceptance of Health Care/psychology , Patient Acceptance of Health Care/statistics & numerical data , Rural Health Services/supply & distribution , Tanzania
17.
BMC Public Health ; 8: 157, 2008 May 09.
Article in English | MEDLINE | ID: mdl-18471299

ABSTRACT

BACKGROUND: Throughout Africa, the private retail sector has been recognised as an important source of antimalarial treatment, complementing formal health services. However, the quality of advice and treatment at private outlets is a widespread concern, especially with the introduction of artemisinin-based combination therapies (ACTs). As a result, ACTs are often deployed exclusively through public health facilities, potentially leading to poorer access among parts of the population. This research aimed at assessing the performance of the retail sector in rural Tanzania. Such information is urgently required to improve and broaden delivery channels for life-saving drugs. METHODS: During a comprehensive shop census in the districts of Kilombero and Ulanga, Tanzania, we interviewed 489 shopkeepers about their knowledge of malaria and malaria treatment. A complementary mystery shoppers study was conducted in 118 retail outlets in order to assess the vendors' drug selling practices. Both studies included drug stores as well as general shops. RESULTS: Shopkeepers in drug stores were able to name more malaria symptoms and were more knowledgeable about malaria treatment than their peers in general shops. In drug stores, 52% mentioned the correct child-dosage of sulphadoxine-pyrimethamine (SP) compared to only 3% in general shops. In drug stores, mystery shoppers were more likely to receive an appropriate treatment (OR = 9.6), but at an approximately seven times higher price. Overall, adults were more often sold an antimalarial than children (OR = 11.3). On the other hand, general shopkeepers were often ready to refer especially children to a higher level if they felt unable to manage the case. CONCLUSION: The quality of malaria case-management in the retail sector is not satisfactory. Drug stores should be supported and empowered to provide correct malaria-treatment with drugs they are allowed to dispense. At the same time, the role of general shops as first contact points for malaria patients needs to be re-considered. Interventions to improve availability of ACTs in the retail sector are urgently required within the given legal framework.


Subject(s)
Antimalarials/therapeutic use , Health Knowledge, Attitudes, Practice , Malaria/drug therapy , Pharmacies , Process Assessment, Health Care , Adult , Case Management , Child , Commerce , Educational Status , Humans , Linear Models , Logistic Models , Rural Health Services , Surveys and Questionnaires , Tanzania
18.
Malar J ; 7: 7, 2008 Jan 09.
Article in English | MEDLINE | ID: mdl-18184430

ABSTRACT

BACKGROUND: The Kilombero Valley is a highly malaria-endemic agricultural area in south-eastern Tanzania. Seasonal flooding of the valley is favourable to malaria transmission. During the farming season, many households move to distant field sites (shamba in Swahili) in the fertile river floodplain for the cultivation of rice. In the shamba, people live for several months in temporary shelters, far from the nearest health services. This study assessed the impact of seasonal movements to remote fields on malaria risk and treatment-seeking behaviour. METHODS: A longitudinal study followed approximately 100 randomly selected farming households over six months. Every household was visited monthly and whereabouts of household members, activities in the fields, fever cases and treatment seeking for recent fever episodes were recorded. RESULTS: Fever incidence rates were lower in the shamba compared to the villages and moving to the shamba did not increase the risk of having a fever episode. Children aged 1-4 years, who usually spend a considerable amount of time in the shamba with their caretakers, were more likely to have a fever than adults (odds ratio = 4.47, 95% confidence interval 2.35-8.51). Protection with mosquito nets in the fields was extremely good (98% usage) but home-stocking of antimalarials was uncommon. Despite the long distances to health services, 55.8% (37.9-72.8) of the fever episodes were treated at a health facility, while home-management was less common (37%, 17.4-50.5). CONCLUSION: Living in the shamba does not appear to result in a higher fever-risk. Mosquito nets usage and treatment of fever in health facilities reflect awareness of malaria. Inability to obtain drugs in the fields may contribute to less irrational use of drugs but may pose an additional burden on poor farming households. A comprehensive approach is needed to improve access to treatment while at the same time assuring rational use of medicines and protecting fragile livelihoods.


Subject(s)
Malaria/therapy , Adolescent , Adult , Child , Child, Preschool , Endemic Diseases , Family Characteristics , Fever/diagnosis , Fever/therapy , Humans , Infant , Longitudinal Studies , Malaria/epidemiology , Malaria/prevention & control , Multivariate Analysis , Patient Acceptance of Health Care , Risk Factors , Tanzania/epidemiology
20.
Malar J ; 6: 83, 2007 Jun 29.
Article in English | MEDLINE | ID: mdl-17603898

ABSTRACT

BACKGROUND: Prompt access to effective treatment is central in the fight against malaria. However, a variety of interlinked factors at household and health system level influence access to timely and appropriate treatment and care. Furthermore, access may be influenced by global and national health policies. As a consequence, many malaria episodes in highly endemic countries are not treated appropriately. PROJECT: The ACCESS Programme aims at understanding and improving access to prompt and effective malaria treatment and care in a rural Tanzanian setting. The programme's strategy is based on a set of integrated interventions, including social marketing for improved care seeking at community level as well as strengthening of quality of care at health facilities. This is complemented by a project that aims to improve the performance of drug stores. The interventions are accompanied by a comprehensive set of monitoring and evaluation activities measuring the programme's performance and (health) impact. Baseline data demonstrated heterogeneity in the availability of malaria treatment, unavailability of medicines and treatment providers in certain areas as well as quality problems with regard to drugs and services. CONCLUSION: The ACCESS Programme is a combination of multiple complementary interventions with a strong evaluation component. With this approach, ACCESS aims to contribute to the development of a more comprehensive access framework and to inform and support public health professionals and policy-makers in the delivery of improved health services.


Subject(s)
Antimalarials/therapeutic use , Health Services Accessibility , Malaria/drug therapy , Program Development , Rural Health Services/supply & distribution , Adult , Child, Preschool , Female , Health Promotion/methods , Humans , Infant , Male , Pharmacies , Pregnancy , Rural Population , Social Marketing , Tanzania
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