Perceptions of Kenyan adults on access to medicines for non-communicable diseases: A qualitative study

In Kenya, noncommunicable diseases (NCDs) account for 27% of all deaths. Adult Kenyans have an 18% chance of dying prematurely from cancers, diabetes, cardiovascular diseases or chronic respiratory diseases. A Novartis Access Initiative is making medicines available to treat cardiovascular diseases, diabetes, chronic respiratory diseases, and breast cancer in 30 countries, including Kenya. Little is known about patients' perceptions of access to medicines for NCDs in Kenya. The study objective was to understand patients' perceptions of access to medicines; as well as barriers and facilitators at the household, community, and healthcare system level. A baseline qualitative study was conducted in eight of 47 counties as part of an evaluation of the Novartis Access Initiative in Kenya. The 84 patients interviewed through a household survey had been diagnosed and treated for an NCD. Although medicines at government facilities were free or cheaper than those sold in private pharmacies, the availability of medicines presented a constant challenge. Patients often resorted to private pharmacies, where NCD medicines cost more than at public facilities. Participants with an NCD took their health seriously and strove to get the medicines, even under difficult circumstances. Buying NCD medicines put a strain on the household budget, especially for the lower-income participants. Some actions to overcome affordability barriers included: borrowing money, selling assets, seeking help from relatives, taking on extra work, buying partial dosages, leaving without the medicines, or resorting to non-medical alternatives. In conclusion, access to NCD medicines is a major challenge for most adults in Kenya. As a result, they engage in complex interactions between public, private facilities and pharmacies to overcome the barriers. The government should ensure well-stocked public sector pharmacies and subsidize prices of medicines for lower-income patients. Integration of industryled access to medicine programs may help governments to obtain low cost supplies

Glycan based detection and drug susceptibility of influenza virus

ABSTRACT: We have developed a panel of synthetic glycans as receptor mimics for the specific capture of influenza viruses. The glycans were printed onto commercial glass slides using a free amine at the end of a spacer to generate a small focused microarray. The microarray was evaluated for its ability to capture three different strains of influenza A virus, two H1N1, A/Brisbane/59/2007 and A/Solomon Islands/3/2006 and one H3N2, A/Aichi/2/1968. We observed an excellent detection ability with some compounds exhibiting clinically relevant (101 plaque forming units) limit of detection. We also tested the drug susceptibility of current antivirals, Zanamivir and Ostelamivir using this microarray and could determine antiviral resistance for these strains

Basal Body Positioning Is Controlled by Flagellum Formation in Trypanosoma brucei

To perform their multiple functions, cilia and flagella are precisely positioned at the cell surface by mechanisms that remain poorly understood. The protist Trypanosoma brucei possesses a single flagellum that adheres to the cell body where a specific cytoskeletal structure is localised, the flagellum attachment zone (FAZ). Trypanosomes build a new flagellum whose distal tip is connected to the side of the old flagellum by a discrete structure, the flagella connector. During this process, the basal body of the new flagellum migrates towards the posterior end of the cell. We show that separate inhibition of flagellum assembly, base-to-tip motility or flagella connection leads to reduced basal body migration, demonstrating that the flagellum contributes to its own positioning. We propose a model where pressure applied by movements of the growing new flagellum on the flagella connector leads to a reacting force that in turn contributes to migration of the basal body at the proximal end of the flagellum

A Cost-Effectiveness Analysis of “Test” versus “Treat” Patients Hospitalized with Suspected Influenza in Hong Kong

BACKGROUND: Seasonal and 2009 H1N1 influenza viruses may cause severe diseases and result in excess hospitalization and mortality in the older and younger adults, respectively. Early antiviral treatment may improve clinical outcomes. We examined potential outcomes and costs of test-guided versus empirical treatment in patients hospitalized for suspected influenza in Hong Kong. METHODS: We designed a decision tree to simulate potential outcomes of four management strategies in adults hospitalized for severe respiratory infection suspected of influenza: "immunofluorescence-assay" (IFA) or "polymerase-chain-reaction" (PCR)-guided oseltamivir treatment, "empirical treatment plus PCR" and "empirical treatment alone". Model inputs were derived from literature. The average prevalence (11%) of influenza in 2010-2011 (58% being 2009 H1N1) among cases of respiratory infections was used in the base-case analysis. Primary outcome simulated was cost per quality-adjusted life-year (QALY) expected (ICER) from the Hong Kong healthcare providers' perspective. RESULTS: In base-case analysis, "empirical treatment alone" was shown to be the most cost-effective strategy and dominated the other three options. Sensitivity analyses showed that "PCR-guided treatment" would dominate "empirical treatment alone" when the daily cost of oseltamivir exceeded USD18, or when influenza prevalence was <2.5% and the predominant circulating viruses were not 2009 H1N1. Using USD50,000 as the threshold of willingness-to-pay, "empirical treatment alone" and "PCR-guided treatment" were cost-effective 97% and 3% of time, respectively, in 10,000 Monte-Carlo simulations. CONCLUSIONS: During influenza epidemics, empirical antiviral treatment appears to be a cost-effective strategy in managing patients hospitalized with severe respiratory infection suspected of influenza, from the perspective of healthcare providers in Hong Kong

Triple Combination Antiviral Drug (TCAD) Composed of Amantadine, Oseltamivir, and Ribavirin Impedes the Selection of Drug-Resistant Influenza A Virus

Widespread resistance among circulating influenza A strains to at least one of the anti-influenza drugs is a major public health concern. A triple combination antiviral drug (TCAD) regimen comprised of amantadine, oseltamivir, and ribavirin has been shown to have synergistic and broad spectrum activity against influenza A strains, including drug resistant strains. Here, we used mathematical modeling along with three different experimental approaches to understand the effects of single agents, double combinations, and the TCAD regimen on resistance in influenza in vitro, including: 1) serial passage at constant drug concentrations, 2) serial passage at escalating drug concentrations, and 3) evaluation of the contribution of each component of the TCAD regimen to the suppression of resistance. Consistent with the modeling which demonstrated that three drugs were required to suppress the emergence of resistance in influenza A, treatment with the TCAD regimen resulted in the sustained suppression of drug resistant viruses, whereas treatment with amantadine alone or the amantadine-oseltamivir double combination led to the rapid selection of resistant variants which comprised ∼100% of the population. Furthermore, the TCAD regimen imposed a high genetic barrier to resistance, requiring multiple mutations in order to escape the effects of all the drugs in the regimen. Finally, we demonstrate that each drug in the TCAD regimen made a significant contribution to the suppression of virus breakthrough and resistance at clinically achievable concentrations. Taken together, these data demonstrate that the TCAD regimen was superior to double combinations and single agents at suppressing resistance, and that three drugs at a minimum were required to impede the selection of drug resistant variants in influenza A virus. The use of mathematical modeling with multiple experimental designs and molecular readouts to evaluate and optimize combination drug regimens for the suppression of resistance may be broadly applicable to other infectious diseases

Comprehensive Analysis Reveals Dynamic and Evolutionary Plasticity of Rab GTPases and Membrane Traffic in Tetrahymena thermophila

Cellular sophistication is not exclusive to multicellular organisms, and unicellular eukaryotes can resemble differentiated animal cells in their complex network of membrane-bound structures. These comparisons can be illuminated by genome-wide surveys of key gene families. We report a systematic analysis of Rabs in a complex unicellular Ciliate, including gene prediction and phylogenetic clustering, expression profiling based on public data, and Green Fluorescent Protein (GFP) tagging. Rabs are monomeric GTPases that regulate membrane traffic. Because Rabs act as compartment-specific determinants, the number of Rabs in an organism reflects intracellular complexity. The Tetrahymena Rab family is similar in size to that in humans and includes both expansions in conserved Rab clades as well as many divergent Rabs. Importantly, more than 90% of Rabs are expressed concurrently in growing cells, while only a small subset appears specialized for other conditions. By localizing most Rabs in living cells, we could assign the majority to specific compartments. These results validated most phylogenetic assignments, but also indicated that some sequence-conserved Rabs were co-opted for novel functions. Our survey uncovered a rare example of a nuclear Rab and substantiated the existence of a previously unrecognized core Rab clade in eukaryotes. Strikingly, several functionally conserved pathways or structures were found to be associated entirely with divergent Rabs. These pathways may have permitted rapid evolution of the associated Rabs or may have arisen independently in diverse lineages and then converged. Thus, characterizing entire gene families can provide insight into the evolutionary flexibility of fundamental cellular pathways

Research Project in Strengthening Local Authority in Risk Management. By

In the frameworks of the ITC Projects (SLARIM) Strengthening Local Authorities in Risk Management, a case study was carried out on hazard assessment on Lower Bicol floodplain. The floodplain is located in four provinces in the Philippines. It is an area frequented by Typhoons accompanied with floods. This study was carried out in collaboration with Naga City Municipality, the Philippines, In order to assist the Local authorities in the flood management. 2D flood model Delft-FLS was used to reconstruct one of the flood events caused by the Typhoon Yonning. The Model parameters were the DEM of the floodplain, the DEM of the riverbed, the floodplain and riverbed roughness, and the artificial structures. The model hydrological boundaries were the discharges at the upstream and the tidal fluctuations at the Bay. The model results were compared with water depth information, obtained from the local people, during the fieldwork that was carried out in September 2003 and previous Reports. Then several Scenarios were constructed to simulate other flood events. A methodology was then developed to transform the modelled results into hazard indicators. It was finally concluded the 2D modelling approach is useful for reconstruction of past events. The model results suggest that the flood parameters water depth and flow velocity are not very sensitive to variations in surface roughness. However physical barriers, like embankments so affect flooding significantly. V Acknowledgments The research related to this thesis and the writing process benefited from many people around the globe. Although words are not enough they appear weak and insufficient considering the contributions and strong support, nevertheless, I would like to express my sincere gratitude. First and fore most I thank ..

Active monitoring versus immediate abduction as treatment of stable developmental dysplasia of the hip: a systematic review of the literature

OBJECTIVES: This systematic review aims to compare the effects of active monitoring and abduction treatment on the Graf alpha angle, Acetabular Index (AI) and femoral head coverage in infants with stable developmental dysplasia of the hip (DDH). DESIGN: Systematic review reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: A search of the PubMed, Embase, Cochrane and Web of Science databases was performed in January 2020 and updated in January 2021. ELIGIBILITY CRITERIA: (Non-)randomised studies comparing active monitoring with abduction treatment in infants younger than 4 months with stable DDH were included. DATA EXTRACTION AND SYNTHESIS: All eligible articles were methodologically assessed using the Cochrane risk of bias tools. Data were extracted by summarising the study characteristics and results. RESULTS: Of the six included studies, two randomised studies were of low risk and two of some concerns. Two non-randomised studies were of serious risk. In total, 544 dysplastic hips (439 infants) were investigated, of which 307 were observed and 237 were treated. Two studies reported a faster improvement of the alpha angle and average acetabular coverage in treated hips at 3 months. No differences in AI between the treatment and observation group after 3 months were reported. In total, 38 infants (12%) in the observation group switched to the treatment group. At the final radiograph, 21 observed hips and 32 treated hips were dysplastic. CONCLUSIONS: There were no differences in AI between the treatment and observation group after 3 months in infants up to 4 months of age with stable DDH hips. The switch of 38 infants (12%) from the observation to the treatment group corroborates that not all infantile DDH hips will spontaneously progress into normal hips. The small study population sizes and methodological heterogeneity warrant a large randomised controlled trial to study this research question. PROSPERO REGISTRATION NUMBER: CRD4202123300

Active monitoring versus immediate abduction as treatment of stable developmental dysplasia of the hip:a systematic review of the literature

OBJECTIVES: This systematic review aims to compare the effects of active monitoring and abduction treatment on the Graf alpha angle, Acetabular Index (AI) and femoral head coverage in infants with stable developmental dysplasia of the hip (DDH). DESIGN: Systematic review reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: A search of the PubMed, Embase, Cochrane and Web of Science databases was performed in January 2020 and updated in January 2021. ELIGIBILITY CRITERIA: (Non-)randomised studies comparing active monitoring with abduction treatment in infants younger than 4 months with stable DDH were included. DATA EXTRACTION AND SYNTHESIS: All eligible articles were methodologically assessed using the Cochrane risk of bias tools. Data were extracted by summarising the study characteristics and results. RESULTS: Of the six included studies, two randomised studies were of low risk and two of some concerns. Two non-randomised studies were of serious risk. In total, 544 dysplastic hips (439 infants) were investigated, of which 307 were observed and 237 were treated. Two studies reported a faster improvement of the alpha angle and average acetabular coverage in treated hips at 3 months. No differences in AI between the treatment and observation group after 3 months were reported. In total, 38 infants (12%) in the observation group switched to the treatment group. At the final radiograph, 21 observed hips and 32 treated hips were dysplastic. CONCLUSIONS: There were no differences in AI between the treatment and observation group after 3 months in infants up to 4 months of age with stable DDH hips. The switch of 38 infants (12%) from the observation to the treatment group corroborates that not all infantile DDH hips will spontaneously progress into normal hips. The small study population sizes and methodological heterogeneity warrant a large randomised controlled trial to study this research question. PROSPERO REGISTRATION NUMBER: CRD4202123300