Association between ABCB1 Polymorphisms and Artesunate–Mefloquine Treatment Responses of Patients with Falciparum Malaria on the Thailand–Myanmar Border

2021 ◽  
Author(s):  
Kanyarat Boonprasert ◽  
Nanthawat Kosa ◽  
Poonuch Muhamad ◽  
Anurak Cheoymang ◽  
Kesara Na-Bangchang
Keyword(s):  
Falciparum Malaria ◽  
Multidrug Resistant ◽  
Drug Efflux ◽  
Antimalarial Treatment ◽  
Mutant Genotype ◽  
Genes Encoding ◽  
Treatment Responses ◽  
Endemic Areas ◽  
The Impact ◽  
Larger Sample

A decrease in the clinical efficacy of a 3-day artesunate–mefloquine combination treatment was reported in the areas of multidrug-resistant Plasmodium falciparum along the Thailand–Myanmar border. The current study investigated the possible contribution of genetic polymorphisms of the three major genes encoding drug efflux transporters, ABCB1, ABCG2, and ABCC1, to responses to the aforementioned treatment in 91 patients with acute uncomplicated falciparum malaria residing along the Thailand–Myanmar border. Patients carrying homozygous mutant genotype ABCB1 c.1236C>T (TT) were found to have a three-times higher chance of successful treatment with this combination compared with other genotypes (CC and CT). Furthermore, whole blood mefloquine concentrations in these patients with the TT genotype were significantly lower than those of patients carrying the CC genotype. Patients with heterozygous mutant genotype (CT), however, were three-times more likely to experience treatment failure. No significant association was found with the ABCG2 and ABCC1 gene polymorphisms. The results suggest that ABCB1 c.1236CT polymorphisms could be useful genetic markers for predicting responses to the 3-day artesunate–mefloquine treatment; however, studies using larger sample sizes in different malaria-endemic areas are necessary to confirm this finding. This study highlights the impact of pharmacogenetic factors on antimalarial treatment responses and the basis for the application of control policies in various malaria-endemic areas.

Contact precautions for colonisation with multidrug-resistant organisms and haemodialysis patient quality of life and mood: a pilot case-control study

2019 ◽  
pp. 19-25 ◽  
Author(s):  
Rathika Krishnasamy
Keyword(s):  
Quality Of Life ◽  
Qualitative Interviews ◽  
Social Function ◽  
Multidrug Resistant ◽  
Contact Precautions ◽  
Dialysis Vintage ◽  
Multidrug Resistant Organisms ◽  
And Gender ◽  
The Impact

Background: The rate of multidrug-resistant organisms (MDRO) colonisation in dialysis populations has increased over time. This study aimed to assess the effect of contact precautions and isolation on quality of life and mood for haemodialysis (HD) patients colonised with MDRO. Methods: Patients undergoing facility HD completed the Kidney Disease Quality of Life (KDQOL–SFTM), Beck Depression Inventory (BDI) and Personal Wellbeing-Index Adult (PWI-A). Patients colonised with MDRO were case-matched by age and gender with patients not colonised. Results: A total of 16 MDRO-colonised patients were matched with 16 controls. Groups were well matched for demographics and co-morbidities, other than a trend for older dialysis vintage in the MDRO group [7.2 years (interquartile range 4.6–10.0) compared to 3.2 (1.4–7.6) years, p=0.05]. Comparing MDRO-positive with negative patients, physical (30.5±10.7 vs. 34.6±7.3; p=0.2) and mental (46.5±11.2 vs. 48.5±12.5; p = 0.6) composite scores were not different between groups. The MDRO group reported poorer sleep quality (p=0.01) and sleep patterns (p=0.05), and lower social function (p=0.02). BDI scores were similar (MDRO-positive 10(3.5–21.0) vs. MDRO-negative 12(6.5–16.0), p=0.6). PWI-A scores were also similar in both groups; however, MDRO patients reported lower scores for “feeling safe”, p=0.03. Conclusion: While overall scores of quality of life and depression were similar between groups, the MDRO group reported poorer outcomes in sleep and social function. A larger cohort and qualitative interviews may give more detail of the impact of contact precautions and isolation on HD patients. The necessity for contact precautions for different MDRO needs consideration.

scholarly journals Impact of Roommates on MDRO Spread in Nursing Homes

2020 ◽  
Vol 41 (S1) ◽  
pp. s66-s67
Author(s):  
Gabrielle M. Gussin ◽  
Ken Kleinman ◽  
Raveena D. Singh ◽  
Raheeb Saavedra ◽  
Lauren Heim ◽  
...  
Keyword(s):  
Nursing Home ◽  
Nursing Homes ◽  
Secondary Analysis ◽  
Nursing Home Residents ◽  
Multidrug Resistant ◽  
Healthcare Intervention ◽  
Odds Ratios ◽  
Care Needs ◽  
Environmental Cleaning ◽  
The Impact

Background: Addressing the high burden of multidrug-resistant organisms (MDROs) in nursing homes is a public health priority. High interfacility transmission may be attributed to inadequate infection prevention practices, shared living spaces, and frequent care needs. We assessed the contribution of roommates to the likelihood of MDRO carriage in nursing homes. Methods: We performed a secondary analysis of the SHIELD OC (Shared Healthcare Intervention to Eliminate Life-threatening Dissemination of MDROs in Orange County, CA) Project, a CDC-funded regional decolonization intervention to reduce MDROs among 38 regional facilities (18 nursing homes, 3 long-term acute-care hospitals, and 17 hospitals). Decolonization in participating nursing homes involved routine chlorhexidine bathing plus nasal iodophor (Monday through Friday, twice daily every other week) from April 2017 through July 2019. MDRO point-prevalence assessments involving all residents at 16 nursing homes conducted at the end of the intervention period were used to determine whether having a roommate was associated with MDRO carriage. Nares, bilateral axilla/groin, and perirectal swabs were processed for methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococcus (VRE), extended-spectrum β-lactamase (ESBL)–producing Enterobacteriaceae, and carbapenem-resistant Enterobacteriaceae (CRE). Generalized linear mixed models assessed the impact of maximum room occupancy on MDRO prevalence when clustering by room and hallway, and adjusting for the following factors: nursing home facility, age, gender, length-of-stay at time of swabbing, bedbound status, known MDRO history, and presence of urinary or gastrointestinal devices. CRE models were not run due to low counts. Results: During the intervention phase, 1,451 residents were sampled across 16 nursing homes. Overall MDRO prevalence was 49%. In multivariable models, we detected a significant increasing association of maximum room occupants and MDRO carriage for MRSA but not other MDROs. For MRSA, the adjusted odds ratios for quadruple-, triple-, and double-occupancy rooms were 3.5, 3.6, and 2.8, respectively, compared to residents in single rooms (P = .013). For VRE, these adjusted odds ratios were 0.3, 0.3, and 0.4, respectively, compared to residents in single rooms (P = NS). For ESBL, the adjusted odds ratios were 0.9, 1.1, and 1.5, respectively, compared to residents in single rooms (P = nonsignificant). Conclusions: Nursing home residents in shared rooms were more likely to harbor MRSA, suggesting MRSA transmission between roommates. Although decolonization was previously shown to reduce MDRO prevalence by 22% in SHIELD nursing homes, this strategy did not appear to prevent all MRSA transmission between roommates. Additional efforts involving high adherence hand hygiene, environmental cleaning, and judicious use of contact precautions are likely needed to reduce transmission between roommates in nursing homes.Funding: NoneDisclosures: Gabrielle M. Gussin, Stryker (Sage Products): Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Clorox: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Medline: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes. Xttrium: Conducting studies in which contributed antiseptic product is provided to participating hospitals and nursing homes.

scholarly journals THU0389 OBESITY IS A STRONG PREDICTOR OF WORSE CLINICAL OUTCOMES AND TREATMENT RESPONSES TO BIOLOGICS IN PATIENTS WITH ANKYLOSING SPONDYLITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 429.2-429
Author(s):  
L. Hu ◽  
X. Ji ◽  
F. Huang
Keyword(s):  
Ankylosing Spondylitis ◽  
Disease Activity ◽  
Clinical Outcomes ◽  
Normal Weight ◽  
Low Grade ◽  
Hla B27 ◽  
Treatment Responses ◽  
The Impact ◽  
Overweight Or Obesity

Background:Obesity population are rising rapidly and have become a major health issue. Studies have shown that obesity is a low-grade inflammatory status characterized by increase in proinflammatory cytokines.Objectives:To examine the impact of overweight or obesity on disease activity and treatment responses to biologics in patients with ankylosing spondylitis (AS) in a real-world setting.Methods:Body mass index (BMI) is available in 1013 patients from the Chinese Ankylosing Spondylitis Imaging Cohort (CASPIC). Differences in clinical outcomes (such as BASDAI, ASDAS, BASFI, and ASAS HI) and treatment responses to biologics (ΔBASDAI and ΔASDAS) over 3, 6, 9, and 12 months are assessed between BMI categories (normal weight BMI <24 kg/m2; overweight BMI=24-28 kg/m2; obesity BMI ≥28 kg/m2) using Kruskal-Wallis test. The association between BMI and clinical characteristics and treatment responses to biologics was determined, and multivariate median regression analyses were conducted to adjust for confounders (such as age, gender, smoke, and HLA-B27).Results:Among 1013 patients with AS, overweight accounts for 33%, while obesity for 12.4%. There were significant differences between patients who were obese or overweight and those with a normal weight regarding clinical outcomes (BASDAI: 2.90/2.56 vs 2.21; ASDAS-CRP: 2.20/1.99 vs 1.81; BASFI: 2.13/1.69 vs 1.38; ASAS HI: 6.87/5.29 vs 5.12 and BASMI: 2.35/1.76 vs 1.62; all P<0.05). After adjusting for age, gender, smoke, and HLA-B27, obesity remained associated with higher disease activity (BASDAI: β=0.55, P=0.005; ASDAS-CRP: β=0.40, P<0.001), poorer functional capacity (BASFI: β=0.58, P=0.001), worse health index (ASAS HI: β=1.92, P<0.001) and metrology index (BASMI: β=0.71, P=0.013). For TNFi users, BMI was found to be negatively correlated with changes in disease activity (ΔBASDAI and ΔASDAS) in the multivariate regression model (all P<0.05), and overweight and obese patients showed an unsatisfactory reduction in disease activity during 3-month, 6-month, 9-month, and 12-month follow-up period, compared to normal weight patients (all P<0.05).Conclusion:Overweight or obesity impacts greatly on clinical outcomes and treatment responses to biologics in patients with ankylosing spondylitis, which argues strongly for obesity management to become central to prevention and treatment strategies in patients with AS.References:[1]Maachi M, Pieroni L, Bruckert E, et al. Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women. Int J Obes Relat Metab Disord 2004;28:993–7.Figure 1.Changes of disease activity for TNFi users during 3-, 6-, 9- and 12-month follow-up according to BMI categories. a: vs. normal weight, P<0.05 in 3 months; b: vs. normal weight, P<0.05 in 6 months; c: vs. normal weight, P<0.05 in 9 months; d: vs. normal weight, P<0.05 in 12 months.Acknowledgments:We appreciate the contribution of the present or former members of the CASPIC study group.Disclosure of Interests:None declared

scholarly journals Management of superficial and deep surgical site infection: an international multidisciplinary consensus

2021 ◽  
Author(s):  
Gabriele Sganga ◽  
Mohamed Baguneid ◽  
Pascal Dohmen ◽  
Evangelos J. Giamarellos-Bourboulis ◽  
Emilio Romanini ◽  
...  
Keyword(s):  
Length Of Hospital Stay ◽  
Surgical Site Infections ◽  
Early Discharge ◽  
Multidrug Resistant ◽  
Steering Committee ◽  
Resistant Bacteria ◽  
Modified Delphi ◽  
Hospital Stays ◽  
New Treatment ◽  
The Impact

AbstractSurgical site infections represent a considerable burden for healthcare systems. To obtain a consensus on the impact and future clinical and economic needs regarding SSI management in an era of multidrug resistance. A modified Delphi method was used to obtain consensus among experts from five European countries. The Delphi questionnaire was assembled by a steering committee, verified by a panel of experts and administered to 90 experts in 8 different surgical specialities (Abdominal, Cancer, Cardiac, General surgery, Orthopaedic, Thoracic, Transplant and Vascular and three other specialities (infectious disease, internal medicine microbiology). Respondents (n = 52) reached consensus on 62/73 items including that resistant pathogens are an increasing matter of concern and increase both treatment complexity and the length of hospital stay. There was strong positive consensus on the cost-effectiveness of early discharge (ED) programs, improvement of quality of life with ED and association between increased length of stay and economic burden to the hospital. However, established ED protocols were not widely available in their hospitals. Respondents expressed a positive consensus on the usefulness of antibiotics that allow ED. Surgeons are aware of their responsibility in an interdisciplinary team for the treatment of SSI, and of the impact of multidrug-resistant bacteria in the context of SSI. Reducing the length of hospital stays by applying ED protocols and implementing new treatment alternatives is crucial to reduce harm to patients and costs for the hospital.

scholarly journals Feasibility of onchocerciasis elimination using a “test-and-not-treat” strategy in Loa loa co-endemic areas

2020 ◽  
Author(s):  
David J Blok ◽  
Joseph Kamgno ◽  
Sebastien D Pion ◽  
Hugues C Nana-Djeunga ◽  
Yannick Niamsi-Emalio ◽  
...  
Keyword(s):  
Adverse Events ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Treatment Duration ◽  
Loa Loa ◽  
Serious Adverse Events ◽  
Endemic Areas ◽  
The Individual ◽  
The Impact ◽  
Main Strategy

Abstract Background Mass drug administration (MDA) with ivermectin is the main strategy for onchocerciasis elimination. Ivermectin is generally safe but associated with serious adverse events in individuals with high Loa loa microfilarial densities (MFD). Therefore, ivermectin MDA is not recommended in areas where onchocerciasis is hypo-endemic and L. loa is co-endemic. To eliminate onchocerciasis in those areas, a test-and-not-treat (TaNT) strategy has been proposed. We investigated whether onchocerciasis elimination can be achieved using TaNT and the required duration. Methods We used the individual-based model ONCHOSIM to predict the impact of TaNT on onchocerciasis microfilarial (mf) prevalence. We simulated pre-control mf prevalence levels from 2-40%. The impact of TaNT was simulated under varying levels of participation, systematic non-participation and exclusion from ivermectin due to high L. loa MFD. For each scenario, we assessed the time to elimination, defined as bringing onchocerciasis mf prevalence below 1.4%. Results In areas with 30-40% pre-control mf prevalence, the model predicted that it would take between 14 and 16 years to bring the mf prevalence below 1.4% using conventional MDA, assuming 65% participation. TaNT would increase the time to elimination by up to 1.5 years, depending on the level of systematic non-participation and the exclusion rate. At lower exclusion rates (≤2.5%), the delay would be less than six months. Conclusions Our model predicts that onchocerciasis can be eliminated using TaNT in L. loa co-endemic areas. The required treatment duration using TaNT would be only slightly longer than in areas with conventional MDA, provided that participation is good.

A comparative clinical trial of artemether and the sequential regimen of artemether-mefloquine in multidrug resistant falciparum malaria

1995 ◽  
Vol 36 (6) ◽  
pp. 1079-1083 ◽  
Author(s):  
Juntra Karbwang ◽  
Kesara Na-Bangchang ◽  
Aurathai Thanavibul ◽  
Prasart Laothavorn ◽  
Monthira Ditta-in ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Falciparum Malaria ◽  
Multidrug Resistant ◽  
Comparative Clinical Trial ◽  
Sequential Regimen

Evaluation of the Impact of P-Glycoprotein (P-gp) Drug Efflux Transporter Blockade on the Systemic and Ocular Disposition of P-gp Substrate

2008 ◽  
Vol 24 (3) ◽  
pp. 290-300 ◽  
Author(s):  
Srinivasan Senthilkumari ◽  
Thirumurthy Velpandian ◽  
Nihar R. Biswas ◽  
Narayanan Sonali ◽  
Supriyo Ghose
Keyword(s):  
Drug Efflux ◽  
Efflux Transporter ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
The Impact

A descriptive study of stress fractures in competitive event horses in the UK

2004 ◽  
Vol 1 (4) ◽  
pp. 233-238
Author(s):  
Emma Hayton ◽  
Jennifer C Sneddon
Keyword(s):  
Stress Fracture ◽  
Descriptive Study ◽  
Stress Fractures ◽  
Anatomical Location ◽  
True Prevalence ◽  
Fracture Prevalence ◽  
The Uk ◽  
The Impact ◽  
Larger Sample ◽  
Age Category

AbstractThe impact of stress fractures on competitive event horses in the UK is completely unknown. Ninety-one replies to 450 questionnaires sent to competitive event riders across the UK indicated that 11 horses, representing 12% of the responders, had a confirmed stress fracture. As data on the total number of horses owned or ridden by the riders were not available, the true prevalence of stress fractures in this sample of horses could not be directly assessed. Within the bounds of this study, competitive level of the rider had a significant effect on stress fracture prevalence (X2(0.05, df. 2) = 24.74, P<0.05), as did years of eventing experience (X2(0.05, df. 1) = 27.80, P<0.01). Training regime was also influential (X2(0.05,df. 1) = 26.30, PX20.01). There was a predominance of fractures in geldings (X2(0.05, df. 1) = 24.45, P<0.03); however, geldings constituted 82% of reported cases. Thoroughbred cross horses had a significantly lower incidence of stress fractures than Thoroughbreds (X2(0.05, df. 1) = 20.82, P<0.01) but constituted only 18% of the sample. Horses in the oldest age category (9–12 years) had 6% of all stress fractures (X2(0.05, df. 2) = 24.54, P<0.1). All fractures occurred on the foreleg at the knee or below, with no significant effect of anatomical location. Seventy-three per cent of horses were not competing when diagnosed (X2(0.05, df. 1) = 22.27, P<0.1). These data indicate that useful preliminary data were yielded by the questionnaire and that further research with a larger sample size is justified.

scholarly journals Multidrug resistant P-glycoprotein positive L1210/VCR cells are also cross-resistant to cisplatin via a mechanism distinct from P-glycoprotein-mediated drug efflux activity

2009 ◽  
Vol 28 (4) ◽  
pp. 391-403 ◽  
Author(s):  
L. Gibalová ◽  
J. Sedlák ◽  
M. Labudová ◽  
M. Barančík ◽  
A. Reháková ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Drug Efflux ◽  
P Glycoprotein

5. Does It Matter What Your Employees Do Outside of Work? - Off-Duty Conduct and its Implications for Organizations and their Employees

2016 ◽  
Author(s):  
Matei Olaru
Keyword(s):  
Drug Trafficking ◽  
Political Protest ◽  
Preliminary Conclusion ◽  
Five Factors ◽  
Organization Analysis ◽  
Explicit Mention ◽  
Drug Manufacturing ◽  
Tax Fraud ◽  
The Impact ◽  
Larger Sample

This research is among the first to explore the phenomenon of off-duty conduct and its implications for organizations and their employees. This research reviewed cases of offdutyconduct to understand the nature of conduct that faced arbitration, the discipline imposed for the conduct, and the arguments made by the parties about the impact of theconduct on the organization itself. In 1967, a case in Ontario (Re Millhaven Fibres Ltd. & Oil, Chemical and Atomic Workers I.U. Loc. 9-670,[[1967] O.L.A.A. No. 4]) set out five factors to evaluate the impact of an employee’s off-duty conduct on the organization. Analysis was based on explicit mention of one or more Millhaven principles. The research included 116 diverse Canadian arbitration cases. Examples of infractions in the sample pool include: theft, drug trafficking, vandalism, assault, tax fraud, murder, sexual assault, drug manufacturing, impaired driving, political protest, and defamatory statements. Trend analyses led to the preliminary conclusion that employers will use reputational damage (one of the five Millhaven principles) as an umbrella defense in arbitration. These findings raise the question of the effectiveness of the reputation Millhaven principle as a valid argument. The initial findings from this   research also shed some light on organizations’ reactions to the off-duty conduct of their employees. Further research of interest will include a larger sample with reputation specific grievances to determine if an  abnormally large number of reputation-based grievances are allowed.

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