Availability and prescription practice of anti-malaria drugs in the private health sector in Yemen

Introduction: Although the government of Yemen changed the national policy for treating malaria in November 2005 from chloroquine to combination drugs in the form of artesunate + sulphadoxine-pyrimethamine (SP) as first line and lumefantrine + artemether as second line treatment for uncomplicated malaria, clinicians in public and private health facilities continued to prescribe chloroquine because their knowledge about the new treatment policy was poor. Methodology: A non-randomized trial of pre- and post-evaluation of the training and reporting interventions about prescription behaviors and availability of anti-malaria drugs among clinicians and pharmacists in the private sector in three governorates in Yemen was conducted. Results: Adherence of clinicians in the private sector to the new national guidelines for anti-malaria drugs improved from 21% in pre-intervention period to 38% after the intervention for artesunate + SP being prescribed as the first-line treatment. Prescription of lumefantrine + artemether as the second-line anti-malaria treatment was also improved from 18% before the intervention to 22% post-intervention. Unfortunately the combination of halofantrine + SP continued to be frequently prescribed by clinicians in Sana'a city (18%). Artesunate + SP and quinine are increasing their marketing significantly from 8% in the pre-intervention period to 22% post-intervention (P-value 0.001). Conclusions: The study provides evidence of usefulness of the training intervention on the national guidelines for malaria treatment. Additionally, the involvement of private health-care providers in reporting procedures will promote the rational prescription and availability of anti-malaria drugs.

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TERAPI MALARIA PADA ANAK

JURNAL BIOMEDIK (JBM) ◽

10.35790/jbm.7.3.2015.10437 ◽

2015 ◽

Vol 7 (3) ◽

Author(s):

Novi H. Rampengan

Keyword(s):

Severe Malaria ◽

Uncomplicated Malaria ◽

Malaria Infection ◽

Laboratory Tests ◽

Age Groups ◽

Malaria Treatment ◽

Line Treatment ◽

Second Line ◽

First Line ◽

First Line Treatment

Abstract: Malaria is still a health problem in Indonesia because it is endemic in considerable parts of Indonesia. According to Riskesdas 2010, the most frequent causes of malaria were P. falciparum (86.4%) and P. vivax (6.9%), with mortality in all age groups increased more than 2 times in 2006-2009 compared to years before. One of the reasons is the increase of malaria parasite resistence to malaria treatment. Therefore, WHO and Ministry of Health in Indonesia recommend that malaria treatment must be by evidence of malaria infection with laboratory tests and malaria medicine must be in combination form to prevent the occurence of resistence. The first line treatment for uncomplicated malaria cases is DHP and AAQ meanwhile the second line is quinine and doxycycline. Moreover, the first line treatment for severe malaria cases is artesunate IV or artemeter IM and the second line is kinine IV.Keywords: plasmodium, malaria, uncomplicated malaria, severe malaria, combination therapyAbstrak: Malaria masih merupakan masalah di Indonesia karena terdapat endemis di sebagian besar wilayah Indonesia. Menurut Riskesdas tahun 2010 penyebab malaria yang tertinggi ialah P. falciparum (86,4%) dan P. vivax (6,9%) dengan angka kematian untuk semua kelompok umur meningkat >2 kali lipat pada tahun 2006-2009 dibandingkan tahun sebelumnya. Salah satu penyebabnya yaitu meningkatnya resistensi parasit malaria terhadap obat-obat malaria sehingga WHO dan Kemkes merekomendasikan bukti laboratorium terinfeksi malaria dan pemberian obat anti malaria diberikan kombinasi untuk mencegah resistensi. Lini I obat untuk terapi malaria tanpa komplikasi yaitu DHP, AAQ dan lini II kinin + doksisiklin, sedangkan lini I obat untuk terapi malaria berat yaitu artesunat IV atau artemeter IM dan lini II kinin IV.Kata kunci: plasmodium, malaria, malaria tanpa komplikasi, malaria berat, terapi kombinasi

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Current guidelines for malaria treatment in Somalia: evidence-based recommendations

10.36368/shaj.v1i1.249 ◽

2021 ◽

Author(s):

Marian Warsame ◽

Ali Abdulrahman Osman ◽

Abdikarim Hussein Hassan ◽

Abdi Abdulle ◽

Abdikarim Muse ◽

...

Keyword(s):

Case Management ◽

Financial Support ◽

Treatment Guidelines ◽

Malaria Treatment ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Treatment Policy ◽

Efficacy Studies ◽

First Line Treatment

Case management – rapid diagnosis and prompt administration of artemisinin-based combination therapy (ACT) – is a fundamental pillar of recommended malaria interventions in Somalia. Unfortunately, the emergence and spread of drug resistant falciparum parasites continues to pose a considerable threat to effective case management. With technical and financial support from WHO, the efficacy of recommended ACTs has been regularly monitored in sentinel sites since 2003. These studies provided evidence that supported the adoption of artesunate-sulfadoxine/pyrimethamine as first-line treatment in 2005 and artemether-lumefantrine as second-line treatment in 2011. Efficacy studies conducted between 2011 and 2015 showed high artesunate-sulfadoxine/pyrimethamine treatment failure rates of 12.3% - 22.2%, above the threshold (10%) for a change of treatment policy as recommended by WHO. This was also associated with high prevalence of quadruple and quintuple mutations in the dihydrofolate reductase (Pfdhfr) and dihydropteroate synthase (Pfdhps) genes, which are associated with sulfadoxine/pyrimethamine resistance. Based on these findings, national malaria treatment guidelines were updated in 2016, with artesunate-sulfadoxine/pyrimethamine replaced by artemether-lumefantrine as first-line treatment and dihydroartemisinin-piperaquine recommended as second-line treatment. Subsequent efficacy studies in 2016 and 2017 confirmed that both the current first- and second-line treatments remain highly efficacious (cure rate above 97%). Technical and financial support from WHO has been instrumental in generating evidence that informs malaria treatment policy and should therefore continue to ensure that effective treatments are available to malaria patients in the country.

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A Rational Sequencing of Anti-Angiogenic Agents as Second-Line Treatment Choice for mCRC Patients Progressing After a Bevacizumab-Based First Line

healthbook TIMES Oncology Hematology ◽

10.36000/hbt.oh.2020.03.010 ◽

2020 ◽

pp. 14-19

Author(s):

Sara De Dosso

Keyword(s):

Acquired Resistance ◽

Predictive Biomarker ◽

Cancer Therapies ◽

Vascular Endothelial ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Vegf Pathway ◽

Effective Choice ◽

Endothelial Growth Factor

A large proportion of patients with metastatic colorectal cancer (mCRC) experience disease progression after first-line treatment with chemotherapy and bevacizumab, an anti-angiogenic agent, as a result of acquired resistance. However, blocking angiogenesis by targeted therapy towards the vascular endothelial growth factor (VEGF) pathway still forms an essential part of the second-line treatment strategy. Although three approved evidence-based choices for angiogenic agents (continuing treatment with bevacizumab, ramucirumab and aflibercept) are currently available in the second line, making the most effective choice is challenging due to the lack of studies directly comparing these agents. Moreover, despite huge investigational efforts, no predictive biomarker for anti-angiogenic cancer therapies could be identified so far.

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Efficacy and Toxicity of Addition of Bevacizumab to Chemotherapy in Patients with Metastatic Colorectal Cancer

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207322666190119162352 ◽

2019 ◽

Vol 21 (10) ◽

pp. 718-724 ◽

Cited By ~ 2

Author(s):

Wen-Cong Ruan ◽

Yue-Ping Che ◽

Li Ding ◽

Hai-Feng Li

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Metastatic Colorectal Cancer ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

Clinical Prognosis ◽

Line Therapy ◽

Significant Difference

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

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Immediate hypersensitivity reaction followed by successful oral desensitization to ursodiol

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00578-7 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Erika Yue Lee ◽

Christine Song

Keyword(s):

Hypersensitivity Reaction ◽

Primary Biliary Cholangitis ◽

Line Treatment ◽

Second Line ◽

Immediate Hypersensitivity ◽

First Line ◽

Case Presentation ◽

Desensitization Protocol ◽

First Line Treatment ◽

Oral Desensitization

Abstract Background Immediate hypersensitivity reaction to ursodiol is rare and there is no previously published protocol on ursodiol desensitization. Case presentation A 59-year-old woman with primary biliary cholangitis (PBC) developed an immediate hypersensitivity reaction to ursodiol—the first-line treatment for PBC. When she switched to a second-line treatment, her PBC continued to progress. As such, she completed a novel 12-step desensitization protocol to oral ursodiol. She experienced recurrent pruritus after each dose following desensitization, which subsided after a month of being on daily ursodiol. Conclusion Immediate hypersensitivity reaction to ursodiol is uncommon. Our case demonstrated that this novel desensitization protocol to ursodiol could be safely implemented when alternative options are not available or have proven inferior in efficacy.

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Patient profiles as an aim to optimize selection in the second line setting: the role of aflibercept

Clinical & Translational Oncology ◽

10.1007/s12094-021-02568-y ◽

2021 ◽

Author(s):

B. González Astorga ◽

F. Salvà Ballabrera ◽

E. Aranda Aguilar ◽

E. Élez Fernández ◽

P. García-Alfonso ◽

...

Keyword(s):

Colorectal Cancer ◽

Therapeutic Option ◽

Scientific Evidence ◽

Treatment Options ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Effective Therapeutic Option ◽

Line Setting ◽

First Line Treatment

AbstractColorectal cancer is the second leading cause of cancer-related death worldwide. For metastatic colorectal cancer (mCRC) patients, it is recommended, as first-line treatment, chemotherapy (CT) based on doublet cytotoxic combinations of fluorouracil, leucovorin, and irinotecan (FOLFIRI) and fluorouracil, leucovorin, and oxaliplatin (FOLFOX). In addition to CT, biological (targeted agents) are indicated in the first-line treatment, unless contraindicated. In this context, most of mCRC patients are likely to progress and to change from first line to second line treatment when they develop resistance to first-line treatment options. It is in this second line setting where Aflibercept offers an alternative and effective therapeutic option, thought its specific mechanism of action for different patient’s profile: RAS mutant, RAS wild-type (wt), BRAF mutant, potentially resectable and elderly patients. In this paper, a panel of experienced oncologists specialized in the management of mCRC experts have reviewed and selected scientific evidence focused on Aflibercept as an alternative treatment.

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Evidence-Based Second-Line Treatment in RAS Wild-Type/Mutated Metastatic Colorectal Cancer in the Precision Medicine Era

International Journal of Molecular Sciences ◽

10.3390/ijms22147717 ◽

2021 ◽

Vol 22 (14) ◽

pp. 7717

Author(s):

Guido Giordano ◽

Pietro Parcesepe ◽

Giuseppina Bruno ◽

Annamaria Piscazzi ◽

Vincenzo Lizzi ◽

...

Keyword(s):

Colorectal Cancer ◽

Metastatic Colorectal Cancer ◽

Checkpoint Inhibitors ◽

Line Treatment ◽

Second Line ◽

Wild Type ◽

First Line ◽

Braf Mutations ◽

Mutational Status ◽

First Line Treatment

Target-oriented agents improve metastatic colorectal cancer (mCRC) survival in combination with chemotherapy. However, the majority of patients experience disease progression after first-line treatment and are eligible for second-line approaches. In such a context, antiangiogenic and anti-Epidermal Growth Factor Receptor (EGFR) agents as well as immune checkpoint inhibitors have been approved as second-line options, and RAS and BRAF mutations and microsatellite status represent the molecular drivers that guide therapeutic choices. Patients harboring K- and N-RAS mutations are not eligible for anti-EGFR treatments, and bevacizumab is the only antiangiogenic agent that improves survival in combination with chemotherapy in first-line, regardless of RAS mutational status. Thus, the choice of an appropriate therapy after the progression to a bevacizumab or an EGFR-based first-line treatment should be evaluated according to the patient and disease characteristics and treatment aims. The continuation of bevacizumab beyond progression or its substitution with another anti-angiogenic agents has been shown to increase survival, whereas anti-EGFR monoclonals represent an option in RAS wild-type patients. In addition, specific molecular subgroups, such as BRAF-mutated and Microsatellite Instability-High (MSI-H) mCRCs represent aggressive malignancies that are poorly responsive to standard therapies and deserve targeted approaches. This review provides a critical overview about the state of the art in mCRC second-line treatment and discusses sequential strategies according to key molecular biomarkers.

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Immune Checkpoint Inhibition in Oesophago-Gastric Carcinoma

Pharmaceuticals ◽

10.3390/ph14020151 ◽

2021 ◽

Vol 14 (2) ◽

pp. 151

Author(s):

Anica Högner ◽

Peter Thuss-Patience

Keyword(s):

Cell Death ◽

Gastric Carcinoma ◽

Programmed Cell Death ◽

Immune Checkpoint ◽

Disease Free Survival ◽

Line Treatment ◽

Second Line ◽

First Line ◽

The Usa ◽

First Line Treatment

Immune checkpoint inhibitors enrich the therapeutic landscape in oesophago-gastric carcinoma. With regard to oesophageal squamous cell carcinoma (ESCC), the selective PD-1 (programmed cell death receptor 1)-inhibitor nivolumab improves disease-free survival in the adjuvant therapy setting (CHECKMATE-577). In first-line treatment, ESCC patients (pts) benefit in overall survival (OS) from the PD-1-inhibitor pembrolizumab in combination with chemotherapy (KEYNOTE-590). In the second-line setting, nivolumab (ATTRACTION-03) and pembrolizumab (KEYNOTE-181) demonstrate a benefit in OS compared with chemotherapy. These data resulted in the approval of nivolumab for the second-line treatment of advanced ESCC pts regardless of PD-L1 (programmed cell death ligand 1) status in Europe, Asia, and the USA, and pembrolizumab for pts with PD-L1 CPS (combined positivity score) ≥ 10 in Asia and the USA. Further approvals can be expected. In gastro-oesophageal junction and gastric cancer, the addition of nivolumab to chemotherapy in first-line treatment improves OS in pts with advanced disease with PD-L1 CPS ≥ 5 (CHECKMATE-649). Additionally, pembrolizumab was non-inferior to chemotherapy for OS in PD-L1 CPS ≥ 1 pts (KEYNOTE-062). In third-line treatment, nivolumab shows benefits in OS regardless of PD-L1 expression (ATTRACTION-02) with approval in Asia, and pembrolizumab prolonged the duration of response in PD-L1 positive pts (KEYNOTE-059) with approval in the USA. We discuss the recent results of the completed phase II and III clinical trials.

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Trends in access to anti‐malarial treatment in the formal private sector in Uganda: an assessment of availability and affordability of first‐line anti‐malarials and diagnostics between 2007 and 2018

Malaria Journal ◽

10.1186/s12936-021-03680-8 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Denis Kibira ◽

Anthony Ssebagereka ◽

Hendrika A. van den Ham ◽

Jimmy Opigo ◽

Henry Katamba ◽

...

Keyword(s):

Private Sector ◽

Diagnostic Tests ◽

Malaria Treatment ◽

World Health ◽

First Line ◽

Cross Sectional ◽

Malaria Rapid Diagnostic Tests ◽

Retail Outlets ◽

Health Action ◽

Health Organization

Abstract Background Malaria is the single largest cause of illness in Uganda. Since the year 2008, the Global Fund has rolled out several funding streams for malaria control in Uganda. Among these are mechanisms aimed at increasing the availability and affordability of artemisinin-based combination therapy (ACT). This paper examines the availability and affordability of first-line malaria treatment and diagnostics in the private sector, which is the preferred first point of contact for 61% of households in Uganda between 2007 and 2018. Methods Cross-sectional surveys were conducted between 2007 and 2018, based on a standardized World Health Organization/Health Action International (WHO/HAI) methodology adapted to assess availability, patient prices, and affordability of ACT medicines in private retail outlets. A minimum of 30 outlets were surveyed per year as prescribed by the standardized methodology co-developed by the WHO and Health Action International. Availability, patient prices, and affordability of malaria rapid diagnostic tests (RDTs) was also tracked from 2012 following the rollout of the test and treat policy in 2010. The median patient prices for the artemisinin-based combinations and RDTs was calculated in US dollars (USD). Affordability was assessed by computing the number of days’ wages the lowest-paid government worker (LPGW) had to pay to purchase a treatment course for acute malaria. Results Availability of artemether/lumefantrine (A/L), the first-line ACT medicine, increased from 85 to100% in the private sector facilities during the study period. However, there was low availability of diagnostic tests in private sector facilities ranging between 13% (2012) and 37% (2018). There was a large reduction in patient prices for an adult treatment course of A/L from USD 8.8 in 2007 to USD 1.1 in 2018, while the price of diagnostics remained mostly stagnant at USD 0.5. The affordability of ACT medicines and RDTs was below one day’s wages for LPGW. Conclusions Availability of ACT medicines in the private sector medicines retail outlets increased to 100% while the availability of diagnostics remained low. Although malaria treatment was affordable, the price of diagnostics remained stagnant and increased the cumulative cost of malaria management. Malaria stakeholders should consolidate the gains made and consider the inclusion of diagnostic kits in the subsidy programme.

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