Change In Treatment Policy Research Articles

Risk factors for conservative treatment failure in acute osteoporotic vertebral compression fractures (OVCFs)

This study aimed to identify risk factors for failure of conservative treatment of acute osteoporotic vertebral compression fractures (OVCFs). This is a retrospective study of patients presenting with acute OVCFs who were initiated on conservative treatment for 3weeks. Conservative treatment was considered to have failed if patients were not satisfied with pain relief or there were bed rest-related complications. These patients progressed to operation. Patients were divided into a conservative treatment failure group (group A) and a conservative treatment group (group B). X-ray, computed tomography and magnetic resonance imaging of two groups were performed on the first visit to our department due to OVCFs. Recorded data for comparison among groups included age, gender, fracture level, bone mineral density (BMD), body mass index (BMI), modified frailty index (mFI), whether the fractures were multiple (≥ 2 vertebral bodies was defined as multiple vertebral fractures) or combined with old fractures, and whether intervertebral cleft (IVC) was present. We collected data from 173 patients who underwent conservative treatment of acute OVCF in our hospital. Of these, 71 had conservative treatment failure, while 102 patients succeeded in long-term conservative treatment. After logistic regression analysis, age, BMD, BMI, mFI, and IVC were identified as high-risk factors for conservative treatment failure (P < 0.05). Age, BMD, BMI, and mFI were included in receiver operating characteristic curve analysis, the result showed that the cutoff value of age was 73.5years old, of BMI was 23.65kg/m2, of BMD was - 3.45, and mFI was 2.5. According to the results of this study, patients with high-risk factors should be actively observed during conservative treatment, especially for patients with all of the above risk factors, but further research would be required before considering early-stage treatment policy change.

Minimal Increase in Survival Throughout the Years in Patients with Soft Tissue Sarcoma with Synchronous Metastases: Results of a Population-Based Study.

Treatment options for patients with metastatic soft tissue sarcoma (STS) have increased in the last decade. We aimed to examine whether this is associated with improved overall survival (OS) in patients with STS with synchronous metastases. Patients diagnosed with STS and synchronous metastases from 1989 to 2014 were queried from The Netherlands Cancer Registry. Trends in OS were assessed by the Kaplan-Meier method and log-rank test in time intervals of 5 years, for the whole study population and in subgroups for liposarcomas, leiomyosarcoma, and other STS subtypes. A multivariable Cox regression analysis was performed to identify characteristics prognostic for OS. Median OS of the 1,393 identified patients did not improve significantly over the years from 5.8 months in 1989-1994 to 8.1 months in 2010-2014, but there was an evident trend. Median OS was prolonged in the subgroups of liposarcomas (3.6 to 9.3 months), leiomyosarcomas (11.3 to 14.6 months), and other STS subtypes (5.7 to 6.3 months), although there were no significant improvements in OS over the years. Primary tumor site in one of the extremities and surgery in an academic center had a favorable effect on OS, whereas significant negative predictors were no treatment, elderly age, STS subtype other than liposarcoma or leiomyosarcoma, high or unknown grade, and nodal involvement. Although overall survival of patients with STS with synchronous metastases in this nationwide and "real-life" population has improved over the years, the improvement was not statistically significant, despite new treatment options. Treatment of patients with metastatic soft tissue sarcoma (STS) has changed in the past years, with new drugs such as trabectedin (2007) and pazopanib (2012) becoming available. By using data from the nationwide Netherlands Cancer Registry, the impact of these changes in treatment policies on survival is analyzed in a "real-life" population of patients with STS with synchronous metastases, rather than in a strictly selected trial population. Unfortunately, overall survival improved only minimally and not significantly for these patients diagnosed from 1989 to 2014. Hopefully, the advent of novel treatment options, such as eribulin and olaratumab, will further improve the outcome of this patient group.

Prevalence of chloroquine resistance alleles among Plasmodium falciparum parasites in countries affected by malaria disease since change of treatment policy: a systematic review protocol

BackgroundMalaria remains one of the leading causes of morbidity and mortality in most low- and middle-income countries. Chloroquine is a previously cheap and effective antimalarial agent whose loss to resistance resulted in more than doubling of malaria-related mortality in malaria-endemic countries. Recently, chloroquine sensitivity is re-emerging among Plasmodium falciparum parasites which gives hope for malaria control and treatment efforts globally. The aim of the current review is to establish the prevalence of chloroquine resistance alleles among P. falciparum parasites in malaria-endemic areas after change in malaria treatment policy.Methods/designThe articles will be obtained from search of MEDLINE via PubMed, SCOPUS, and EMBASE data bases. The Mesh terms will be used in article search. Boolean operators (“AND,” “OR”) will be used in article search. The article search will be done independently by two librarians. The PRISMA-P statement will be used to guide the conduct and reporting of the systematic review. STREGA guideline will be used in developing data abstraction form for the review. Data abstraction will be done by two independent reviewers, Kappa statistic will be calculated, and any discrepancies resolved by discussion. Data analysis will be done using STATA ver 13.0. The level of heterogeneity in the articles will be established by using the I2-statistic. Publication bias will be assessed using funnel plot. Random effects analysis will be used.DiscussionThe review seeks to establish the extent of chloroquine resistance reversal in malaria-endemic countries. The evidence generated from this review will help guide policy makers on the potential re-emerging role of chloroquine in malaria treatment.Systematic review registrationThe systematic review protocol has been registered in PROSPERO with registration number CRD42018083957.

“Sisonke - Together We Can”: Conceptualisations of Critically Reflective Communities of Practice Nurses Caring for Women Living with HIV

The dynamic nature of HIV care in the context of South Africa challenges nurses to continually keep abreast of changes in treatment and care policies. Communities of practice (CoPs) are considered an effective method of promoting lifelong learning, enhancing professional development and clinical reasoning through reflective practice. This paper reports on the conceptualisations and meanings that emerged from a critically reflective CoP established among nurses caring for women living with HIV. Based on social constructivismand underpinned on grounded theory, four themes emerged which conceptualised the meaning of a critically reflective CoP, namely: (i) a practice and learning community, (ii) a support network, (iii) collaborative, purposive-driven working to make a difference and (iv) a space that fosters self-determination. The findings of this paper enhance the understanding of organisational learning strategies that can support nurses working in various settings through ongoing learning embedded in evidence-based practice through critical reflection and CoPs.

Effect of enhanced feedback to hospitals that are part of an emerging clinical information network on uptake of revised childhood pneumonia treatment policy: study protocol for a cluster randomized trial

BackgroundThe national pneumonia treatment guidelines in Kenya changed in February 2016 but such guideline changes are often characterized by prolonged delays in affecting practice. We designed an enhanced feedback intervention, delivered within an ongoing clinical network that provides a general form of feedback, aimed at improving and sustaining uptake of the revised pneumonia treatment policy. The objective was to determine whether an enhanced feedback intervention will improve correctness of classification and treatment of childhood pneumonia, compared to an existing approach to feedback, after nationwide treatment policy change and within an existing hospital network.Methods/designA pragmatic, cluster randomized trial conducted within a clinical network of 12 Kenyan county referral hospitals providing inpatient pediatric care to children (aged 2–59 months) with acute medical conditions between March and November 2016. The intervention comprised enhanced feedback (monthly written feedback incorporating goal setting, and action planning delivered by a senior clinical coordinator for selected pneumonia indicators) and this was compared to standard feedback (2-monthly written feedback on multiple quality of pediatric care indicators) both delivered within a clinical network promoting clinical leadership linked to mentorship and peer-to-peer support, and improved use of health information on service delivery. The 12 hospitals were randomized to receive either enhanced feedback (n = 6) or standard feedback (n = 6) delivered over a 9-month period following nationwide pneumonia treatment policy change. The primary outcome is the proportion of all admitted patients with pneumonia (fulfilling criteria for treatment with orally administered amoxicillin) who are correctly classified and treated in the first 24 h. The secondary outcome will be measured over the course of the admission as any change in treatment for pneumonia after the first 24 h.DiscussionThis trial protocol employs a pragmatic trial design during a period of nationwide change in treatment guidelines to address two high-priority areas within implementation research: promoting adoption of health policies and optimizing effectiveness of feedback.Trial registrationClinicalTrials.gov, ID: NCT02817971. Registered retrospectively on 27 June 2016

Treatment Failure of Dihydroartemisinin/Piperaquine for Plasmodium falciparum Malaria, Vietnam.

We conducted a study in Binh Phuoc, Vietnam, in 2015 on the therapeutic efficacy of dihydroartemisinin/piperaquine for Plasmodium falciparum malaria. A high number of treatment failures (14/40) was found, and piperaquine resistance in Vietnam was confirmed. A change in the malaria treatment policy for Vietnam is in process.

Observations from Mortality Trends at The Children's Hospital, Accra, 2003-2013.

ObjectiveFacility-based studies provide an unparalleled opportunity to assess interventions deployed in hospitals to reduce child mortality which is not easily captured in the national data. We examined mortality trends at the Princess Marie Louise Children’s Hospital (PML) and related it to interventions deployed in the hospital and community to reduce child mortality and achieve the Millennium Development Goal 4 (MDG 4).MethodsThe study was a cross-sectional review of data on consecutive patients who died at the hospital over a period of 11 years, between 2003 and 2013. The total admissions for each year, the major hospital-based and population-based interventions, which took place within the period, were also obtained.ResultsOut of a total of 37,012 admissions, 1,314 (3.6%) deaths occurred and admissions tripled during the period. The average annual change in mortality was -7.12% overall, -7.38% in under-fives, and -1.47% in children ≥5 years. The majority of the deaths, 1,187 (90.3%), occurred in under-fives. The observed decrease in under-five (and overall) mortality rate occurred in a specific and peculiar pattern. Most of the decrease occurred during the period between 2003 and 2006. After that there was a noticeable increase from 2006 to 2008. Then, the rate slowly decreased until the end of the study period in 2013. There was a concomitant decline in malaria mortality following a pattern similar to the decline observed in other parts of the continent during this period. Several interventions might have contributed to the reduction in mortality including the change in malaria treatment policy, improved treatment of malnutrition and increasing paediatric input.ConclusionUnder-fives mortality at PML has declined considerably; however, the reduction in mortality in older children has been minimal and thus requires special attention. Data collection for mortality reviews should be planned and commissioned regularly in hospitals to assess the effects of interventions and understand the context in which they occur. This will provide benchmarks and an impetus for improving care, identify shortfalls and ensure that the gains in child survival are maintained.

Different patterns of pfcrt and pfmdr1 polymorphism in Plasmodium falciparum isolates from Tehama region, Yemen.

Introduction. Despite the efforts of the malaria control programme, malaria morbidity is still a common health problem in Yemen, with 60% of the population at risk. Plasmodium falciparum is responsible for 99% of malaria cases. The emergence in Yemen of parasite resistance to chloroquine (CQ) prompted the adoption of artemisinin combination therapy (ACT) in 2009, which involves the use of artesunate plus sulphadoxine-pyrimethamine (AS + SP). However, CQ was retained as the drug of choice for vivax malaria. To assess the impact of the change in the malaria treatment policy five years after its introduction, the present study investigated the mutations in the CQ resistance transporter (pfcrt) and multidrug resistance 1 (pfmdr1) genes.Method. A molecular investigation of 10 codons of pfcrt (72–76, 220, 271, 326, 356, and 371) and five codons of pfmdr1 (86, 184, 1034, 1042, and 1246) was conducted on P. falciparum isolates from districts with the highest malaria endemicity in the Hodeidah and Al-Mahwit governorates in Tehama region, Yemen. A total of 86 positive cases of falciparum monoinfection were investigated for the presence of mutations related to CQ and other antimalarials using a PCR-RFLP assay.Results. There was a wide prevalence of pfcrt gene mutations with the pfcrt 76T CQ resistance marker being predominant (97.7%). The prevalence of other pfcrt mutations varied from high (75E: 88%) to moderate (74I: 79.1%, 220S: 69.8%, 271E and 371I: 53.5%) or low (326S: 36%, 72S: 10.5%). Mutated pfcrt 72–76 amino acids haplotypes were highly prevalent (98.8%). Among these, the CVIET classic, old-world African/Southeast Asian haplotype was the most predominant, and was mostly found in the isolates from the Khamis Bani Saad district of Al-Mahwit (93.1%) and the AdDahi district of Hodeidah (88.9%). However, it was only found in 26.3% of the isolates from the Bajil district of Hodeidah. Surprisingly, the SVMNT new-world South American haplotype was exclusively detected in 9.3% of the isolates from the Bajil district of Hodeidah. Mutations at Y184F of pfmdr1 were found in all isolates (100%) from all districts. The mutation for codons 1034C and 86Y were found only in the isolates from the AdDahi and Khamis Bani Saad districts. Overall, the AdDahi and Khamis Bani Saad districts were similar in terms of carrying most of the mutations in the pfcrt and pfmdr1 genes, while there was a lower prevalence of mutation in the isolates from the Bajil district.Conclusion. The high prevalence of mutations in pfcrt 5 years after the official cessation of CQ use against P. falciparum suggests that there is sustained CQ pressure on P. falciparum isolates in the study area. Moreover, the low prevalence of mutations in the pfmdr1 gene could be a good indicator of the high susceptibility of P. falciparum isolates to antimalarials other than CQ. A new strategy to ensure the complete nationwide withdrawal of CQ from the private drug market is recommended.

Incomplete reversal of genotypic resistance of Plasmodium falciparum to chloroquine after a decade of change in malaria treatment policy in Uganda

Incomplete reversal of genotypic resistance of Plasmodium falciparum to chloroquine after a decade of change in malaria treatment policy in Uganda

Policy analysis for deciding on a malaria vaccine RTS,S in Tanzania.

BackgroundTraditionally, it has taken decades to introduce new interventions in low-income countries. Several factors account for these delays, one of which is the absence of a framework to facilitate comprehensive understanding of policy process to inform policy makers and stimulate the decision-making process. In the case of the proposed introduction of malaria vaccines in Tanzania, a specific framework for decision-making will speed up the administrative process and shorten the time until the vaccine is made available to the target population.MethodsQualitative research was used as a basis for developing the Policy Framework. Interviews were conducted with government officials, bilateral and multilateral partners and other stakeholders in Tanzania to assess malaria treatment policy changes and to draw lessons for malaria vaccine adoption.ResultsThe decision-making process for adopting malaria interventions and new vaccines in general takes years, involving several processes: meetings and presentations of scientific data from different studies with consistent results, packaging and disseminating evidence and getting approval for use by the Ministry of Health and Social Welfare (MOHSW). It is influenced by contextual factors; Promoting factors include; epidemiological and intervention characteristics, country experiences of malaria treatment policy change, presentation and dissemination of evidence, coordination and harmonization of the process, use of international scientific evidence. Barriers factors includes; financial sustainability, competing health and other priorities, political will and bureaucratic procedures, costs related to the adoption and implementations of interventions, supply and distribution and professional compliance with anti-malarial drugs.ConclusionThe framework facilitates the synthesis of information in a coherent way, enabling a clearer understanding of the policy process, thereby speeding up the policy decision-making process and shortening the time for a malaria vaccine to become available.

Perception of the efficacy of artemisinin-based combination therapy (ACT) and chloroquine prescription pattern and among nurses in South-West Nigeria

Background-Malaria remains a threat to millions of children despite the recent advances recorded in the fight against the disease which remain the 3 rd largest killer of children below the age of 5 years in endemic regions. Drug resistant plasmodium species continues to limit the fight against malaria, while the spread of fake and substandard antimalarial drugs has been recognized as a major problem across Africa because of its association with drug resistant parasite. We aim to find out the prescription pattern of chloroquine among nurses in South-West Nigeria and perception of artemisinin-based combination therapy (ACT). Design and methods-About 180 pre-tested questionnaires were administered to randomly selected nurses out of which 155 were sufficiently completed and suitable for analysis. Results-Majority (56.1%) still have confidence in the efficacy of CQ which was still being prescribed by 45.2% of the respondents. CQ was mostly prescribed by those who had previous ACT treatment failure experience (54.3%) with their patients, P=0.03; as well as those who believe that ACT resistance malaria is now in circulation (44.3%). Fifty (32.3%) of our respondents claimed that they had come across fake and substandard ACT, from which 40.0% now prescribe CQ. Discussion-The high rate of CQ prescription in this study showed that many of the health workers were still resistant to the change in antimalarial treatment policy, which is related to unsatisfactory experience with ACT. Additional measures are urgently required to verify this experience so as to win the confidence of healthcare workers away from chloroquine. Keywords: Artemisinin-based combination therapy (ACT), chloroquine, substandard antimalarial

Patient perspectives of methadone formulation change in British Columbia, Canada: outcomes of a provincial survey.

BackgroundIn British Columbia, Canada, methadone maintenance treatment formulation transitioned from the oral liquid compound Tang™-flavoured methadone to the ten-times more concentrated cherry-flavoured Methadose™ in February 2014. We quantitatively describe perceptions and reported consequences among a sample of patients on methadone maintenance treatment following this transition.MethodsA province-wide survey was used. Bivariable analyses utilized independent samples t-tests, Phi associations, and Chi-square tests. Multivariable logistic regression analyses evaluated factors related to dependent variables – namely, increases in dose, pain, dope sickness, and the need to supplement with additional opioids.ResultsFour hundred five methadone maintenance treatment patients from fifty harm reduction sites across British Columbia reported transitioning to Methadose™ in February 2014. The majority (n = 258; 73.1 %) heard about the formulation change from their methadone provider or pharmacist. Adjusted models show worse taste was positively associated with reporting an increasing dose (OR = 2.46; CI:1.31–4.61), feeling more dope sick (OR = 3.39; CI:1.88–6.12), and worsening pain (OR = 4.65; CI:2.45–8.80). Feeling more dope sick was positively associated with dose increase (OR = 2.24; CI:1.37–3.66), and supplementing with opioids (OR = 8.81; CI:5.16–15.05).ConclusionsMethadone maintenance treatment policy changes in British Columbia affect a structurally vulnerable population who may be less able to cope with transitions and loss of autonomy. There may be a psychosocial component contributing to the perception of Methadose™ tasting worse, and increased dope sickness, pain, and dose. Our study shows the pronounced negative impacts medication changes can have on patients without informed, coordinated efforts. We stress the need to engage all stakeholders allowing for communication about the reasons, risks and consequences of medication policy changes and provision of additional psychosocial support.

Pattern of Uncomplicated Malaria Treatment and Antimalarial Prescription Practices among Health Workers in the Littoral Region of Cameroon: An Assessment of Ten Years Post-Malaria Treatment Policy Change

Following highly prevalent Plasmodium resistant strains to antimalarial monotherapies in malaria endemic countries, uncomplicated malaria treatment policy changed to artemisinine-based combination therapies (ACTs). After adoption of this new treatment policy in a country, sufficient care is needed to be taken to prevent occurrence of resistance to the latest drugs. As Cameroon shifted to ACT in 2004, this study aimed to assess knowledge and practices of health workers in government health facilities of the Littoral region regarding mild malaria management in health facilities as well as according to prescription qualities of ACTs in leaflets received in pharmacies. A total of 66 physicians and 16 nurses were questioned in 10 health facilities and 503 medical leaflets with ACTs prescriptions were viewed in 17 pharmacies. All medical workers questioned correctly were defined mild malaria and were aware of the antimalarial policy change in Cameroon. Overall ACTs prescription for mild malaria management in children and adult patients was 72.2% and 87.8% respectively. An important proportion of health workers prescribed antimalarial monotherapies and non recommended antimalarial for uncomplicated malaria treatment. 31.7% of participants did not systematically recommend laboratory diagnostic test before antimalarial prescription. Of leaflets viewed in pharmacies, ACTs were prescribed by physicians, nurses and laboratory technicians. Age was the only criteria for ACTs prescription. Appropriate ACTs quality prescription ranged between 81.2% and 94.4%. Of the ACTs prescribed, blisters had the highest (92.9%) appropriate quality prescription and solutions the lowest (83.3%). According to qualification of prescribers, physicians had the highest score (93.1%) of appropriate quality prescription and laboratory technicians the lowest score (28.1%). For all ACTs containing medical leaflets, concomitant medications were recorded namely antipyretic (73.9%), antibiotic (21.9%), non steroid anti-inflammatory (19.9%) or vitamins (18.1%). Data gathered indicated that although health workers were aware of uncomplicated malaria treatment policy change in Cameroon, mild malaria mismanagement was prevailing in health facilities of the Littoral region and ACTs quality prescription in medical leaflets was not optimal. Therefore, awareness is still needed among prescribers in order to prevent or at least slow the occurrence of Plasmodium resistant strains to ACTs in Cameroon.

Safety and Efficacy of Mini-CHOP-R Chemotherapy for Treatment of Diffuse Large B Cell Lymphoma in Very Elderly Patients: A Quality Assurance Study

Background: Diffuse Large B Cell Lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma. Very elderly patients with DLBCL, defined as patients who are 80 years of age or older, have inferior outcomes related to co-morbid illness, poor performance status, and intolerance of full dose chemotherapy. In 2011, a phase II study of DLBCL in very elderly patients suggested a dose attenuated protocol of CHOP-R (mini-CHOP-R) reduced adverse effects while maintaining efficacy (Lancet Oncology 2011). Based on these results, the mini-CHOP-R protocol became the standard of care for very elderly patients at the London Regional Cancer Program (LRCP) in London, Ontario, Canada in November 2011. These patients had previously received either standard dose CHOP-R or a modified version in which the dose was reduced at the discretion of the treating clinician. Objective: This quality assurance study compares safety and efficacy outcomes among very elderly patients with DLBCL treated before and after adoption of the mini-CHOP-R treatment protocol. Methods: Outcomes of very elderly patients with DLBCL treated at LRCP with mini-CHOP-R between November 2011 - November 2014 were compared to the outcomes of patients treated in the 5 years preceding the treatment policy change. Results: Seventy-three patients were evaluated in this study. Thirty-seven patients (16M/21F; median age 83, range 80-93) treated with mini-CHOP-R comprised the study group, and thirty-six patients (16M/20F; median age 83, range 80-97) who received standard or 'clinician-modified' CHOP-R comprised the historical control group. The two groups differed in stage and ECOG status but were otherwise similar. Thirty-three (89%) study patients had advanced stage disease vs. 15 (42%) patients in the control group (p= 0.018). Thirty-three (89%) mini-CHOP-R patients had an ECOG &gt; 1 compared to 13 (36%) controls (p=0.0013). Study patients received a median of 6 cycles of mini-CHOP-R compared to 4.28 cycles in the CHOP-R cohort (p=0.11). Granulocyte-colony stimulating factors were used as primary prophylaxis in the majority of patients in both cohorts. Chemotherapy side effects necessitated dose reductions in 6 (16%) mini-CHOP-R patients vs. 24 (67%) control patients. This was mainly due to the difference in febrile neutropenia, which complicated 4/178 mini-CHOP-R cycles (2%) compared to 16/181 CHOP-R cycles (9%). Cardiac complications were observed in 1 (3%) mini-CHOP-R patient, compared with 3 (8%) controls. Response rates of mini-CHOP-R treated patients compared favorably to controls, with overall response rates of 31/37 (84%) vs. 30/36 (83%), complete responses of 20 (54%) vs. 19 (53%), and partial responses of 11 (30%) vs. 11 (31%). Six patients in each group progressed on treatment. The 1-year overall survival and 1-year progression-free survival rates were 60% and 51% in mini-CHOP-R study group compared to 56% and 53% in control group. Conclusions: Results with mini-CHOP-R have been encouraging so far. Despite the more aggressive disease (higher stage, inferior ECOG) in mini-CHOP-R patients compared to controls treated with CHOP-R, similar response rates were achieved, with fewer adverse effects and better tolerability, which is of particular importance in very elderly patients. Longer follow up will be necessary to determine durability of responses. Disclosures No relevant conflicts of interest to declare.

Emergence of sulfadoxine–pyrimethamine resistance in Indian isolates of Plasmodium falciparum in the last two decades

Genotyping the sulfadoxine–pyrimethamine (SP) genes will help in identifying the genes under drug selection and the emergence of resistance in dhfr and dhps genes. India is an important hotspot for studying malaria due to the immense climatic diversity prevalent in the country. The central and eastern parts of the country are most vulnerable sites where malaria cases are reported throughout the year. From different regions of the country 173 field isolates were genotyped at various loci in dhfr and dhps genes collected between 1994 and 2013. This encompasses the period before antimalarial resistance emerged and the period after the use of combination therapy was made mandatory in the country. We observed the rise of resistant SP alleles from very low frequencies (in the year 1994) to steadily rising (in the year 2000) and maintaining this increasing trend subsequently (in the year 2013) as shown by the sequence analysis of dhfr and dhps genes. This study assessed the prevalence of mutations in dhfr and dhps genes associated with SP resistance in samples indicative of increase in resistance levels of Plasmodium falciparum to SP even after the change in malaria treatment policy in the country.

Treatment policy change to dihydroartemisinin-piperaquine contributes to the reduction of adverse maternal and pregnancy outcomes.

BackgroundIn Papua, Indonesia, maternal malaria is prevalent, multidrug resistant and associated with adverse outcomes for mother and baby. In March 2006, anti-malarial policy was revised for the second and third trimester of pregnancy to dihydroartemisinin–piperaquine (DHP) for all species of malaria. This study presents the temporal analysis of adverse outcomes in pregnancy and early life following this policy change.MethodsFrom April 2004 to May 2010, a standardized questionnaire was used to collect information from all pregnant women admitted to the maternity ward. A physical examination was performed on all live birth newborns. The relative risks (RR) and the associated population attributable risks (PAR) of adverse outcomes in women with a history of malaria treatment to the risk in those without a history of malaria during the current pregnancy were examined to evaluate the temporal trends before and after DHP deployment.ResultsOf 6,556 women enrolled with known pregnancy outcome, 1,018 (16%) reported prior anti-malarial treatment during their pregnancy. The proportion of women with malaria reporting treatment with DHP rose from 0% in 2004 to 64% (121/189) in 2010. In those with history of malaria during pregnancy, the increasing use of DHP was associated with a 54% fall in the proportion of maternal malaria at delivery and a 98% decrease in congenital malaria (from 7.1% prior to 0.1% after policy change). Overall policy change to more effective treatment was associated with an absolute 2% reduction of maternal severe anaemia and absolute 4.5% decrease in low birth weight babies.ConclusionsIntroduction of highly effective treatment in pregnancy was associated with a reduction of maternal malaria at delivery and improved neonatal outcomes. Ensuring universal access to arteminisin combination therapy (ACT) in pregnancy in an area of multidrug resistance has potential to impact significantly on maternal and infant health.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0794-0) contains supplementary material, which is available to authorized users.

Persistence of chloroquine-resistant haplotypes of Plasmodium falciparum in children with uncomplicated Malaria in Lagos, Nigeria, four years after change of chloroquine as first-line antimalarial medicine.

BackgroundIn Nigeria, despite the change in National malaria drug policy to artemisinin combination therapy (ACT) in 2005 due to widespread chloroquine resistance, chloroquine (CQ) is still widely used in the treatment of malaria because it is cheap, affordable and accessible. The use of ACT for the management of uncomplicated malaria is currently being promoted. The employment of genetic markers to track circulating chloroquine-resistant parasites are useful in elucidating likely poor efficacy of chloroquine, especially in settings where it is not recommended for the treatment of uncomplicated falciparum malaria. This study determined the prevalence of pfcrt haplotypes and point mutations in pfmdr1 genes four years after the change in antimalarial treatment policy from CQ to the ACTs in Lagos, a commercial city in South-West, Nigeria.MethodsThis was a cross sectional study on uncomplicated malaria in children less than 12 years that presented with fever and other symptoms suggestive of malaria. Parasite DNA was extracted from 119 patients out of 251 children who were positive for Plasmodium falciparum by microscopy and amplified. The occurrence of haplotypes was investigated in pfcrt gene using probe-based qPCR and single nucleotide polymorphisms in pfmdr1 gene using nested PCR.ResultsOne hundred and nine (109) of the 119 children with P falciparum infection (91.6%) harbourd parasites with the mutant pfcrt haplotype (CVIET). Out of this, 4.2% comprised a mixture of genotypes encoding CVMNK and CVIET, while 4.2% had the wild type (CVMNK). Furthermore, the frequency of point mutations in pfmdr1 was 62.2% and 69.0% for codons Y86 and F184 respectively. There were no mutations at codons 1034, 1042 and 1246 of the Pfmdr1 genes.ConclusionThe high frequency of the CQ-resistant haplotypes (CVIET) and mutations in Pfmdr1 associated with CQ resistance in P. falciparum among these children suggest that CQ-resistant parasites are still in circulation. Continuous use of chloroquine may continue to increase the level of mutations in pfcrt and pfmdr1genes. There is need to strengthen current case management efforts at promoting ACT use as well as urgently restricting access to chloroquine by the National drug regulatory agency, National Agency for Food Drug Administration and Control (NAFDAC).Virtual SlidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2069472010142303

Safety and Efficacy of Dose Attentuated R-CHOP Chemotherapy for Treatment of Diffuse Large B Cell Lymphoma in the Very Elderly: A Cohort Study

Background: Diffuse Large B Cell Lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma, and is frequently diagnosed in elderly patients. Elderly patients with DLBCL are known to have worse outcomes than younger patients with the same disease, in part due to comorbidities and poor performance status that may decrease their ability to tolerate treatment. A recent phase II study (Lancet Oncology 2011;12:460-8) demonstrated that patients with DLBCL who were older than 80 years of age had excellent tolerability while still maintaining efficacy when treated with an attenuated dose of R-CHOP called “R-mini-CHOP”. This paper prompted a change in treatment policy of very elderly patients with DLBCL at the London Regional Cancer Program. In November 2011, we began treating all DLBCL patients > 80 (and select patients aged 70-79 with significant comorbidities) with the R-mini-CHOP regimen rather than with standard R-CHOP or a ‘randomly dose-attenuated version’ of R-CHOP, which had been our practice prior to the policy change.Objective: This quality assurance study was undertaken in order to monitor and ensure the safety and efficacy of this practice change.Methods: Data was collected prospectively on all elderly patients with DLBCL who were initiated on R-mini-CHOP between November 2011 and January 2013. A retrospective chart review was also performed on patients > 80 treated at our centre in the preceding 10 years, after R-CHOP became standard treatment in elderly patients with DLBCL. We used 16 patients > 80 who received full dose R-CHOP between January 2010 and November 2011 as a historical control group for our prospective cohort.Results: Since November 2011, 17 patients (median age 81, range 71-90) have been treated with R-mini-CHOP and were enrolled in this quality assurance study. All 17 patients had stage III or IV disease. In contrast, only 6/16 patients in the retrospective group were advanced stage (p=0.00004). 12/17 R-mini-CHOP patients (70.6%) had an ECOG > 1, vs. 7/16 R-CHOP patients (43.8%, p=0.070). No dose modifications have been required in patients on R-mini-CHOP. 11/16 patients on R-CHOP underwent dose reductions due to side effects of chemotherapy. The majority of patients in both cohorts received primary prophylaxis with neupogen/neulasta. Five patients remain on R-mini-CHOP, all showing evidence of clinical response. Follow-up is too short to report on PFS or OS, but overall response rate thus far is 10/12 (83%) with 7 CRs (58.3%) and 3 PRs (25%). This compares favorably to the retrospective group who had an ORR of 13/16 (81%, p=0.30), 7 CRs (43.8%) and 6 PR’s (37.5%). One patient in each group had stable disease at the end of treatment. One mini-R-CHOP patient progressed on treatment and ultimately died of lymphoma. In the retrospective cohort, 4 deaths occurred secondary to infectious complications of chemotherapy during treatment period.C onclusions: Results with R-mini-CHOP have been encouraging so far. Despite the more aggressive disease (higher stage, inferior ECOG) in our R-mini-CHOP patients compared to the historical controls treated with R-CHOP, similar response rates are being achieved, with fewer adverse effects and better tolerability. Ongoing enrollment and longer follow-up will further help define the role of R-mini-CHOP in the very elderly patient population.Updated results with longer followup will be presented at the meeting. DisclosuresNo relevant conflicts of interest to declare.

Cause or Effect? Selective Serotonin Reuptake Inhibitors and Falls in Older Adults: A Systematic Review.

A 2012 update of the Beers criteria categorizes selective serotonin reuptake inhibitors (SSRIs) as potentially inappropriate medications in all older adults based on fall risk. The application of these recommendations, not only to frail nursing home residents, but to all older adults, may lead to changes in health policy or clinical practice with harmful consequences. A systematic review of studies on the association between SSRIs and falls in older adults was conducted to examine the evidence for causation. Twenty-six studies met the inclusion criteria. The majority of studies were observational and suggest an association between SSRIs and falls. The direction of the relationship--causation or effect--cannot be discerned from this type of study. Standardized techniques for determining likely causation were then used to see if there was support for the hypothesis that SSRIs lead to falls. This analysis did not suggest causation was likely. There is no Level 1 evidence that SSRIs cause falls. Therefore, changes in the current treatment guidelines or policies on the use of SSRIs in older adults based on fall risk may not be justified at this time given the lack of an established evidence base. Given its significance to public health, well-designed experimental studies are required to address this question definitively.

Genetic mutations in Plasmodium falciparum and Plasmodium vivax dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) in Vanuatu and Solomon Islands prior to the introduction of artemisinin combination therapy

BackgroundPlasmodium falciparum and Plasmodium vivax are endemic in Vanuatu and the Solomon Islands. While both countries have introduced artemether-lumefantrine (AL) as first-line therapy for both P. falciparum and P. vivax since 2008, chloroquine and sulphadoxine-pyrimethamine (SP) were used as first-line therapy for many years prior to the introduction of AL. Limited data are available on the extent of SP resistance at the time of policy change.MethodsBlood spots were obtained from epidemiological surveys conducted on Tanna Island, Tafea Province, Vanuatu and Temotu Province, Solomon Islands in 2008. Additional samples from Malaita Province, Solomon Islands were collected as part of an AL therapeutic efficacy study conducted in 2008. Plasmodium vivax and P. falciparum dhfr and dhps genes were sequenced to detect nucleotide polymorphisms.ResultsAll P. falciparum samples analysed (n =114) possessed a double mutant pfdhfr allele (C59R/S108N). Additionally, mutation A437G in pfhdps was detected in a small number of samples 2/13, 1/17 and 3/26 from Tanna Island, Vanuatu and Temotu and Malaita Provinces Solomon Islands respectively. Mutations were also common in pvdhfr from Tanna Island, Vanuatu, where 33/51 parasites carried the double amino acid substitution S58R/S117N, while in Temotu and Malaita Provinces, Solomon Islands 32/40 and 39/46 isolates carried the quadruple amino acid substitution F57L/S58R/T61M/S117T in DHFR respectively. No mutations in pvdhps (n =108) were detected in these three island groups.ConclusionPrior to the introduction of AL, there was a moderate level of SP resistance in the P. falciparum population that may cause SP treatment failure in young children. Of the P. vivax isolates, a majority of Solomon Islands isolates carried quadruple mutant pvdhfr alleles while a majority of Vanuatu isolates carried double mutant pvdhfr alleles. This suggests a higher level of SP resistance in the P. vivax population in Solomon Islands compared to the sympatric P. falciparum population and there is a higher level of SP resistance in P. vivax parasites from Solomon Islands than Vanuatu. This study demonstrates that the change of treatment policy in these countries from SP to ACT was timely. The information also provides a baseline for future monitoring.