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

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.

Download Full-text

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

Download Full-text

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.

Download Full-text

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.

Download Full-text

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.

Download Full-text

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.

Download Full-text

First-line treatment with a cyclin-dependent kinase 4/6 inhibitor combined with an aromatase inhibitor for hormone receptor-positive, human epidermal growth factor receptor-2 negative metastatic breast cancer: Population-based outcomes for patients treated in Alberta, Canada.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e13020 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e13020-e13020

Author(s):

Carla Pires Amaro ◽

Atul Batra ◽

Sasha M. Lupichuk

Keyword(s):

Hormonal Therapy ◽

Growth Factor Receptor ◽

Metastatic Breast ◽

Population Based ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Hormone Receptor Positive ◽

Targeted Agent ◽

First Line Treatment

e13020 Background: Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) in combination with an aromatase inhibitor (AI) has emerged as the standard first line treatment in patients with hormone receptor positive, human epidermal growth factor receptor-2 (HER-2) negative metastatic breast cancer (MBC). In this analysis, we describe population-based outcomes for first-line treatment with a CDK4/6i combined with an AI. Methods: All patients who were prescribed CDK4/6i + AI from January 2016 through June 2019 in a large Canadian province were included. Descriptive statistics were used to summarize patient demographics, tumor and treatment characteristics. Survival distributions were estimated using the Kaplan-Meier method. Multivariate analysis (MVA) using a Cox proportional hazards model was constructed to examine associations between potentially prognostic clinical variables and progression free survival (PFS). Results: A total of 316 patients were included. Median age was 61 years (interquartile range, 53-70 years), 82% were postmenopausal women, 39% had de novo MBC, and 48% had non-visceral disease. Palbociclib was prescribed in 94% of patients and the remaining patients received ribociclib. The CDK4/6i was dose-reduced upfront or during treatment in 47%. While 70% of the patients discontinued treatment due to progression, 30% stopped due to toxicity/patient preference/physician recommendation. With a median follow-up of 28.1 months, the median PFS was 37.9 months (95% CI, 26.7-NR). In the MVA, PR-negative tumour (HR, 2.37; 95% CI, 1.45-3.88; P = 0.001) and dose reduction of the CDK4/6i (HR, 1.51; 95% CI, 1.06-2.16; P = 0.022) predicted worse PFS. Median overall survival (OS) was not reached. The 30-month and 36-month OS rates were 74% and 68%, respectively. Of patients who progressed (n = 131), 89% received second-line treatment (chemotherapy in 46%, single agent hormonal therapy in 35%, hormonal therapy plus a targeted agent in 15%, and other in 4%). Median time to progression on second line chemotherapy was 9.0 (5.8-17.6) months and second line hormonal therapy +/- targeted agent was 4.0 (3.4-8.6) months (P = 0.012). Conclusions: The real-world outcomes of first-line use of CDK4/6i and AI are encouraging. PR negative tumors and dose reduction appear to be negative prognostic markers. CDK4/6i + AI as first-line treatment for HR-positive, HER2-negative MBC in Alberta is justified based on favorable PFS and early OS outcomes.

Download Full-text

Stent-over-sponge (SOS): a novel technique complementing endosponge therapy for foregut leaks and perforations

Endoscopy ◽

10.1055/s-0043-120442 ◽

2017 ◽

Vol 50 (02) ◽

pp. 148-153 ◽

Cited By ~ 10

Author(s):

Piero Valli ◽

Joachim Mertens ◽

Arne Kröger ◽

Christoph Gubler ◽

Christian Gutschow ◽

...

Keyword(s):

Adverse Events ◽

Success Rate ◽

Vacuum Therapy ◽

Line Treatment ◽

Second Line ◽

Metal Stent ◽

First Line ◽

Novel Technique ◽

Upper Gastrointestinal ◽

First Line Treatment

Abstract Background and study aims Endoluminal vacuum therapy (EVT) has evolved as a promising option for endoscopic treatment of foregut wall injuries in addition to the classic closure techniques using clips or stents. To improve vacuum force and maintain esophageal passage, we combined endosponge treatment with a partially covered self-expandable metal stent (stent-over-sponge; SOS). Patients and methods Twelve patients with infected upper gastrointestinal wall defects were treated with the SOS technique. Results Indications for SOS were anastomotic leakage after surgery (n = 11) and chronic foregut fistula (n = 1). SOS treatment was used as a first-line treatment in seven patients with a success rate of 71.4 % (5/7) and as a second-line treatment after failed previous EVT treatment in five patients (success rate 80 %; 4/5). Overall, SOS treatment was successful in 75 % of patients (9/12). No severe adverse events occurred. Conclusion SOS is an effective method to treat severely infected foregut wall defects in patients where EVT has failed, and also as a first-line treatment. Comparative prospective studies are needed to confirm our preliminary results.

Download Full-text