Oral Combination Therapy Research Articles

Efficacy and safety of an oral combination therapy of niraparib and etoposide in platinum resistant/refractory ovarian cancer: a single arm, prospective, phase II study

ObjectiveNon-platinum chemotherapy is used in platinum resistant/refractory ovarian cancer patients but offers limited efficacy, especially in those who develop platinum resistance after ≤2 lines of platinum based chemotherapy. This phase...

Real-world evidence on pulmonary arterial hypertension: interim analysis from the Italian observational study INSPECTIO

Abstract Background Pulmonary arterial hypertension (PAH) is a rare, progressive disease leading to right-sided heart failure. The interest in risk assessment based on non-invasive parameters is growing, and insights from clinical practice are needed in this regard. INSPECTIO is an Italian observational study aimed at filling this knowledge gap. The results of an interim analysis at month 12 are presented below. Purpose The primary objective was to assess the change from baseline to month 12 in the number of the non-invasive low-risk parameters among World Health Organization functional class, 6-minutes walking distance, Brain Natriuretic Peptide (BNP) or N-terminal proBNP. Secondary objectives are the evaluation of echocardiographic and haemodynamic parameters, and the proportion of patients in which the therapy was optimized according to the guidelines. Methods Prospective, multicentre study on PAH patients at low/intermediate mortality risk treated with macitentan and/or selexipag as part of the oral combination therapy. Results Among 177 patients who were enrolled in 29 centres, 148 patients [median age 63.0 years (Q1/Q3: 53.5/73.0), 76.4% females] completed the 12-month follow up and were considered for this analysis. The median time from PAH diagnosis was 22.6 months (4.9/60.1). Sixty-four (43.2%) patients had idiopathic PAH; 4 (2.7%) heritable; 80 (54.1%) associated with other diseases [58 (72.5%) connective tissue disease, 11 (13.8%) congenital heart disease corrected for at least one year, 5 (6.3%) portal hypertension, 5 (6.3%) human immunodeficiency virus infection, 1 (1.3%) drug and toxins]. At baseline, 45.9% patients and 28.4% were in double and triple oral combination therapy, respectively. Primary objective: at month 12, the number of noninvasive low-risk parameters increased in 43 (29.1%) patients and remained stable in 80 (54.1%) patients [mean change 0.16 (p=0.017)]. The values at baseline, at month 12 and the change from baseline for each noninvasive parameter are shown in Table 1. Mean right atrial (RA) area (end-systole) and tricuspid annular plane systolic excursion (TAPSE) remained unchanged while a reduction of systolic pulmonary artery pressure (sPAP) was observed. Regarding the haemodynamic parameters, the mean pulmonary arterial pressure decreased [median change -4.5, (p=0.0346)], while cardiac index, pulmonary vascular resistance, and RA pressure remained stable (Table 2). The number of patients on triple therapy increased from 42 to 51 (+21.4%). Conclusions This study confirms that a noninvasive low-risk profile can be achieved with current combination PAH therapy. The modest or absent changes in echocardiographic and hemodynamic parameters suggest that treatment of PAH in real world is yet to be improved; on the other hand, the optimization of therapy in a significant portion of patients can possibly account for the improvement or stabilization observed.Noninvasive parametersEcho and hemodynamic parameters

Lenacapavir: Playing the Long Game in the New Era of Antiretrovirals.

The mainstay of antiretroviral therapy (ART) has been combination oral therapy. While oral ART is highly effective, nonadherence remains a chief concern. Addressing this concern in recent years is the emergence of long-acting antiretrovirals for the treatment and prevention of HIV-1 infection. The most recently approved long-acting antiretroviral is the first-in-class capsid inhibitor lenacapavir (LEN) for heavily treatment-experienced adults with multidrug-resistant HIV-1 infection. Due to its biannual subcutaneous dosing scheme to inhibit the HIV-1 capsid, LEN exhibits unique pharmacokinetics and reinforces an evolving era of ART. In this review, we evaluate published and accepted research articles, conference proceedings, and clinical trial records to provide a comprehensive overview of LEN for treatment and preliminary data for the prevention of HIV-1 infection. These data include clinical trials outcomes, in vitro and in vivo resistance profiles, and preclinical data supporting downstream indications. We also discuss the unique clinical pharmacology of LEN with the goal of serving as a resource toward subsequent physiologically based, population-based, and other miscellaneous pharmacometric-focused analyses. Given the dynamic nature of the HIV treatment and prevention research fields, we also discuss ongoing studies related to LEN for treatment-naïve adults and for prevention. Lastly, we discuss important pharmacologic gaps in special populations, drug-drug interactions, and at the sites of action germane to HIV treatment and prevention. The information discussed in this review will provide knowledge and understanding of the unique pharmacologic properties of LEN to assist clinicians and researchers as they navigate the dynamic HIV research landscape.

Primary and secondary dysmenorrhea: symptoms, risk factors, diagnosis, and treatment – review

Dysmenorrhea, or painful uterine contractions during menstruation in women, is a common condition. It may affect up to 90% of patients in a doctor's office. Depending on the severity of symptoms, it may cause discomfort or prevent normal functioning in everyday life. Some women do not realize that this is not a normal symptom during menstruation. Unfortunately, lack of exercise, smoking, or drinking alcohol only increases the symptoms. A medical history and physical examination of the patient are important steps in finding the cause. Primary dysmenorrhea is primarily associated with the pathogenesis of prostaglandins and leukotrienes, which generate inflammation and pain. However, it has nothing to do with pelvic pathology. It usually first appears in young women during puberty, up to 24 months after their first period. If the history and physical examination are not clear about the primary cause of pain, a secondary cause should be considered. For this purpose, a transvaginal ultrasound examination should be performed. The most common secondary pathology is endometriosis. In the treatment of primary and secondary diseases, physical exercises and warm compresses are beneficial, which women are often unaware of. First-line pharmacological treatment may include NSAIDs or combined oral estrogen-progestogen hormonal therapy. The purpose of this review is to provide knowledge about the symptoms, risk factors, diagnosis, and treatment of dysmenorrhea.

Sex specific analysis of patients with and without reported statin intolerance referred to a specialized outpatient lipid clinic

BackgroundLowering LDL-cholesterol is a fundamental goal for both primary and secondary prevention of atherosclerotic cardiovascular diseases. Our study aims to analyse potential sex disparities regarding the tolerability and effectiveness of lipid-lowering therapy in patients with and without reported statin intolerance who are being treated at a lipid-outpatient clinic.MethodsFrom 2017 to 2022, n = 1062 patients (n = 612 men, n = 450 women) at high-risk were referred to our lipid-outpatient clinic because of difficulties in lipid control by primary healthcare providers. The main therapeutic objective was to optimize lipid-lowering therapy according to current treatment guidelines.ResultsPatients presented with high LDL-C baseline levels (4.97 ± 1.81 mmol/l (192 ± 70 mg/dL) in men and 5.46 ± 2.04 mmol/l (211 ± 79 mg/dL) in women). Intolerance towards statins was reported more frequently by women (48.2%) than by men (38.9%, p = 0.004). LDL-C continuously decreased with individual treatment adjustments across follow-up visits. In total, treatment goals (LDL < 1.4 mmol/l (< 55 mg/dl) or < 1.8 mmol/l (< 70 mg/dl)) were accomplished in 75.8% of men and 55.5% of women after the last follow-up visit (p < 0.0001). In men, these data are almost identical in subjects with statin intolerance. In contrast, treatment goals were reached less frequently in women with statin intolerance compared to women tolerant to statin therapy.ConclusionEven if treated in a specialized lipid clinic, women are less likely to reach their target LDL-C than men, particularly when statin intolerant. Nevertheless, many patients with statin intolerance can be successfully treated using oral combination and PCSK9 inhibitor therapy. However, ongoing follow-up care to monitor progress and to adjust treatment plans is necessary to reach this goal.

Improving efficacy and maintaining safety in the treatment of alopecia with low-dose oral minoxidil and spironolactone combination therapy: A retrospective review

Improving efficacy and maintaining safety in the treatment of alopecia with low-dose oral minoxidil and spironolactone combination therapy: A retrospective review

A Phase I Trial of Alpelisib Combined With Capecitabine in Patients With HER2-Negative Metastatic Breast Cancer

BackgroundAlpelisib is an oral α-specific class I PI3K inhibitor approved in combination with fulvestrant for the treatment of PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer. The tolerability of this drug with the oral chemotherapy capecitabine is unknown. Patients and MethodsThis phase I trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of alpelisib (250 mg or 300 mg daily for 3-weeks) with capecitabine (1000 mg/m2 twice daily for 2-weeks followed by a 1-week rest period) in patients with metastatic HER2-negative breast cancer, regardless of PIK3CA mutation status. ResultsEighteen patients were treated with alpelisib-capecitabine. Half of the patients had HR+ breast cancer, and 16 had prior systemic therapy for metastatic disease. The MTD of alpelisib was 250 mg daily in combination with capecitabine 1000 mg/m2 twice daily. DLTs included hyperglycemia, QTc prolongation, fatigue, and chest pain. The most common grade 3 adverse event (AE) was hyperglycemia (28%). No grade 4 AEs were observed. Three patients discontinued therapy due to an AE. One-third of patients required dose reduction of both alpelisib and capecitabine. Four patients experienced a partial response and 8 patients experienced stable disease. The median progression-free survival was 9.7 months (95% CI 2.8-13.5 months) and median overall survival was 18.2 months (95% CI 7.2-35.2 months). Twelve patients had PIK3CA mutation testing completed, of these 2 had known or likely deleterious PIK3CA mutation. ConclusionThis study provides safety data for an oral combination therapy of alpelisib-capecitabine and defines tolerable doses for further study.

Medical management of endometriosis.

While laparoscopic surgery plays a key role in the management of endometriosis, symptoms commonly recur, and repeat surgery comes with increased risk. Medical management, including hormonal and nonhormonal treatment, is vital in managing painful symptoms. This review summarizes recent evidence regarding various medical management options available to treat pelvic pain associated with endometriosis. Efficacy of dienogest vs. combined oral contraceptive on pain associated with endometriosis: randomized clinical trial.Once daily oral relugolix combination therapy vs. placebo in patients with endometriosis-associated pain: two replicate phase 3, randomised, double-blind, studies (SPIRIT 1 and 2).A randomized, double-blind, placebo-controlled pilot study of the comparative effects of dienogest and the combined oral contraceptive pill in women with endometriosis.Two-year efficacy and safety of relugolix combination therapy in women with endometriosis-associated pain: SPIRIT open-label extension study. All symptomatic women with suspected endometriosis who are not desiring immediate fertility can be offered suppressive treatment to control symptoms and slow the progression of disease. First-line treatments include the combined oral contraceptive pill and progestogens. Second-line treatments include gonadotropin-releasing hormone agonists and antagonists but current guidelines recommend that these should be reserved for people whose symptoms fail to be controlled by first-line agents. The use of complementary and alternative medicines is also increasing in both volume and number of agents used.

Four-Strata Risk Assessment in Patients with Pulmonary Arterial Hypertension Treated with Selexipag in Real-World Settings (EXPOSURE Study).

Risk assessment can aid management of pulmonary arterial hypertension (PAH) and clinical decision-making. This analysis describes characteristics, treatment patterns and outcomes of patients with PAH, categorised by risk status at time of treatment escalation with selexipag in clinical settings. Patients initiating selexipag in the ongoing multicentre, prospective EXPOSURE (EUPAS19085) study were grouped as low, intermediate-low, intermediate-high or high risk of 1-year mortality according to the ESC/ERS 4-strata method. As of November 2022, 77% (535/698) of patients initiating selexipag had data allowing for risk calculation; 14% (N = 76) were low, 31% (N = 168) intermediate-low, 34% (N = 182) intermediate-high and 20% (N = 109) high risk of 1-year mortality. Overall, patients were predominantly female (71%), with idiopathic/heritable PAH (56%) or PAH associated with connective tissue disease (CTD-PAH; 27%), median age of 60years and prevalent (2years) disease. From low to high risk, proportion of CTD-PAH and age increased (from 12%-40% and 46-68years, respectively); time from diagnosis decreased and presence of cardiovascular risk factors increased. Most patients across risk groups (74-81%) initiated selexipag as part of triple oral combination therapy. Overall median (Q1, Q3) selexipag exposure duration was 10.1 (3.5, 24.1) months. Proportions of hospitalised patients increased with increasing risk group (16-42% from low to high, respectively); more hospitalisations were PAH-related for the high risk (71%) versus other risk groups (47-54%). Kaplan-Meier survival estimates were 98%, 98%, 93% and 80% at 1-year and 98%, 92%, 81% and 67% at 2-years, from low to high risk, respectively. In clinical settings, selexipag is initiated across all risk groups, predominantly as triple therapy. Only 45% of patients being at low/intermediate-low risk at selexipag initiation suggests an opportunity for more frequent patient monitoring and earlier treatment escalation, given that 4-strata risk assessment was prognostic for hospitalisations and survival in this contemporary PAH cohort. A graphical abstract is available with this article.

Risk factors for breast cancer subtypes by race and ethnicity: A scoping review.

Breast cancer is comprised of distinct molecular subtypes. Studies have reported differences in risk factor associations with breast cancer subtypes, especially by tumor estrogen receptor (ER) status, but their consistency across racial and ethnic populations has not been comprehensively evaluated. We conducted a qualitative, scoping literature review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis, extension for Scoping Reviews to investigate consistencies in associations between 18 breast cancer risk factors (reproductive, anthropometric, lifestyle, and medical history) and risk of ER-defined subtypes in women who self-identify as Asian, Black or African American, Hispanic or Latina, or White. We reviewed publications between January 1, 1990 and July 1, 2022. Etiologic heterogeneity evidence (convincing, suggestive, none, or inconclusive) was determined by expert consensus. Publications per risk factor ranged from 14 (benign breast disease history) to 66 (parity). Publications were most abundant for White women, followed by Asian, Black or African American, and Hispanic or Latina women. Etiologic heterogeneity evidence was strongest for parity, followed by age at first birth, post-menopausal BMI, oral contraceptive use, and estrogen-only and combined menopausal hormone therapy. Evidence was limited for other risk factors. Findings were consistent across racial and ethnic groups, although the strength of evidence varied. The literature supports etiologic heterogeneity by ER for some established risk factors that are consistent across race and ethnicity groups. However, in non-White populations evidence is limited. Larger, more comparable data in diverse populations is needed to better characterize breast cancer etiologic heterogeneity.

Intravenous methylprednisolone in patients with episodic cluster headache non-responders to oral steroids: results from an observational, interventional, single-center study

Background: Verapamil is the drug of choice in the prophylaxis of episodic cluster headache (ECH), and oral corticosteroids are frequently prescribed as concurrent bridging therapy. Approximately 25% of the patients do not respond to oral treatment. The aim of this study was to assess safety and efficacy of high dose intravenous methylprednisolone (MPD) in ECH patients who had not responded to combined oral therapy with prednisone and verapamil. Methods: Forty-four ECH patients – non responders to oral therapy – were treated with intravenous MPD (500 mg/day for 5 days) and verapamil during cluster headache active periods. No serious adverse event was reported. Results: After 5 days of intravenous therapy, the 24-hour frequency of cluster headache attacks significantly decreased. Sixty-eight percent of patients became headache-free, and 25% experienced a reduction of more than 50% in daily attacks. No clinical benefit was reported in the remaining three patients. Conclusions: Our study shows that intravenous MPD is a safe, effective, and reproducible treatment for ECH patients not responding to oral therapy.

No antagonism or cross-resistance and a high barrier to the emergence of resistance in vitro for the combination of islatravir and lenacapavir.

Islatravir (ISL) is a deoxyadenosine analog that inhibits HIV-1 reverse transcription by multiple mechanisms. Lenacapavir (LEN) is a novel capsid inhibitor that inhibits HIV-1 at multiple stages throughout the viral life cycle. ISL and LEN are being investigated as once-weekly combination oral therapy for the treatment of HIV-1. Here, we characterized ISL and LEN in vitro to assess combinatorial antiviral activity, cytotoxicity, and the potential for interactions between the two compounds. Bliss analysis revealed ISL with LEN demonstrated additive inhibition of HIV-1 replication, with no evidence of antagonism across the range of concentrations tested. ISL exhibited potent antiviral activity against variants encoding known LEN resistance-associated mutations (RAMs) with or without the presence of M184V, an ISL RAM in reverse transcriptase (RT) . Static resistance selection experiments were conducted with ISL and LEN alone and in combination, initiating with either wild-type virus or virus containing the M184I RAM in RT to further assess their barrier to the emergence of resistance. The combination of ISL with LEN more effectively suppressed viral breakthrough at lower multiples of the compounds' IC50 (half-maximal inhibitory concentration) values and fewer mutations emerged with the combination compared to either compound on its own. The known pathways for development of resistance with ISL and LEN were not altered, and no novel single mutations emerged that substantially reduced susceptibility to either compound. The lack of antagonism and cross-resistance between ISL and LEN support the ongoing evaluation of the combination for treatment of HIV-1.

Comparative Brain Microanatomical and Neurochemical Alterations Following the Administration of Seven Oral Artemisinin-Based Combination Therapies in Swiss Mice

Over a decade after artemisinin-based combination therapy (ACT) approval as the most preferred anti-malarial drug. Seven ACTs can be sourced as over-the-counter medications in most African pharmacies without prescription. A comparative neurotoxicity of these ACTs was investigated in an in vivo experimental model. Swiss mice numbering 40, weighing 18 - 26 g were allotted to eight groups (n = 5). Group 1 (normal control [NC]), received distilled water 10 mL, while groups 2 to 8 were administered (5.71 mg artesunate+amodiaquine [AA]); (19.29 mg artesunate+mefloquine [AM]); (10.36 mg artesunate+sulfadoxine+pyrimethamine [ASP]); (19.29 mg artesunate+pyronaridine [APy]); (12.5 mg artemisinin+piperaquine [AP]); (15.42 mg dihydroartemisinin+piperaquine [DP]); and (8 mg artemether+lumefantrine [AL]) per kg body weights, respectively orally for 3 days, but for 2 days in group 6. Animals were sacrificed 24 hrs after last administration under ketamine anaesthesia (100 mg/kg, i.p), and excised brains were evaluated for neurochemical and neurohistological alterations. Oxidative stress markers: malondialdehyde and reduced glutathione significantly (p &lt; 0.05) increased as well as antioxidant enzymes glutathione peroxidase, catalase, superoxide dismutase in ACT-administered groups compared to NC. Neurohistology of hippocampal cornu ammonis 1 (CA1) and cerebellum demonstrated vacuolations, neuronal hypertrophy and atrophy pyramidal, and Purkinje neurons. Immunohistochemistry with glial fibrillary acidic protein antibody demonstrated mild to mostly severe astrogliosis in the ACT-administered groups. In conclusion, oxidative stress markers and antioxidants were elevated in the order DP&gt;APy&gt;AP&gt;ASP&gt;AA&gt;AL&gt;AM. Together with the neurohistology, neurotoxicity were in the order DP&gt;ASP&gt;APy&gt;AP&gt;AL&gt;AA&gt;AM particularly in the hippocampus compared to the cerebellum. KEYWORDS: Artemisinin-based combination therapies, Cerebellum, CA1 region of the hippocampus, Neurodegeneration, Oxidative stress.

Immune modulation of the liver metastatic colorectal cancer microenvironment via the oral CAPOX-mediated cGAS-STING pathway

We evaluated modulation of the immunosuppressive tumor microenvironment in both local and liver metastatic colorectal cancer (LMCC), focusing on tumor-associated macrophages, which are the predominant immunosuppressive cells in LMCC. We developed an orally administered metronomic chemotherapy regimen, oral CAPOX. This regimen combines capecitabine and a nano-micelle encapsulated, lysine-linked deoxycholate and oxaliplatin complex (OPt/LDC-NM). The treatment effectively modulated immune cells within the tumor microenvironment by activating the cGAS-STING pathway and inducing immunogenic cell death. This therapy modulated immune cells more effectively than did capecitabine monotherapy, the current standard maintenance chemotherapy for colorectal cancer. The macrophage-modifying effect of oral CAPOX was mediated via the cGAS-STING pathway. This is a newly identified mode of immune cell activation induced by metronomic chemotherapy. Moreover, oral CAPOX synergized with anti-PD-1 antibody (αPD-1) to enhance the T-cell–mediated antitumor immune response. In the CT26. CL25 subcutaneous model, combination therapy achieved a 91 % complete response rate with a confirmed memory effect against the tumor. This combination also altered the immunosuppressive tumor microenvironment in LMCC, which αPD-1 monotherapy could not achieve. Oral CAPOX and αPD-1 combination therapy outperformed the maximum tolerated dose for treating LMCC, suggesting metronomic therapy as a promising strategy.

Efficacy of Oral Acetazolamide as Add-on Diuretic Therapy in Decongestion in Patients with Heart Failure: A Study Protocol for a Randomized Controlled Trial

Background: Acute heart failure is a common clinical syndrome leading to hospital admission, with few evidence-based therapies for managing congestion. This trial aims to assess the efficacy of acetazolamide combined with loop diuretics in achieving decongestion among patients who fail to respond to oral diuretics and progress to acute decompensated heart failure in the absence of injectable furosemide. Methods: This single-center, double-blind randomized controlled trial with a 1:1 allocation ratio aims to evaluate 130 patients admitted to the infusion ward. Participants will receive standard furosemide treatment and be randomized to either oral acetazolamide (250 mg twice daily) or placebo for 3 consecutive days. The primary objective is to assess the efficacy of combined oral acetazolamide and furosemide therapy in achieving decongestion. The prespecified secondary outcomes include the following: N-terminal pro-B-type natriuretic peptide levels on day 30, readmission rates within 3 months, health-related quality of life as assessed by the Heart Failure Quality of Life Questionnaire at 3 months, and changes in weight, creatinine levels, urinary sodium excretion, potassium levels, and hematological indices from the complete blood count on day 3 of the trial. Conclusion: Diuretic resistance commonly occurs in patients with heart failure, underscoring the urgent need for innovative interventions that can effectively address the limitations of current diuretics, including diuretic resistance and electrolyte imbalances, while enhancing their efficacy in this patient population.

Is Itraconazole Plus Clofazimine an Effective Treatment for Cutaneous Leishmaniasis?

Background: Leishmaniasis is endemic in 88 countries and has a worldwide prevalence of 12 million. Cutaneous leishmaniasis (CL) cases deserve the highest attention due to their magnitude and risk of causing scars in humans. Although several studies have been performed on novel therapies, treatment failure and drug resistance are still common, and most systemic treatments are parenteral. Thus, in this study, it was attempted to find an effective combination oral therapy for this disease. Case Series: Six patients (between 35 and 64 years old) with confirmed CL were treated with a combination of clofazimine (CLZ, 200 mg/d) and itraconazole (ITN, 300 mg/d) for 4 weeks. Then, ITZ 300 mg/d was given for another 4 weeks. All patients were followed up to assess the efficacy and side effects of this treatment regimen. Every single lesion in the patients was remarkably smaller after the course of the treatment (P=0.001), and skin smears became negative. Conclusion: The combination of CLZ and ITN could be a helpful treatment modality in the treatment of CL. However, more and larger studies should be conducted to assess the efficacy and side effects of this combination therapy.

Risk factors for breast cancer subtypes by race and ethnicity: A scoping review of the literature.

Breast cancer is comprised of distinct molecular subtypes. Studies have reported differences in risk factor associations with breast cancer subtypes, especially by tumor estrogen receptor (ER) status, but their consistency across racial and ethnic populations has not been comprehensively evaluated. We conducted a qualitative, scoping literature review using the Preferred Reporting Items for Systematic Reviews and Meta-analysis, extension for Scoping Reviews to investigate consistencies in associations between 18 breast cancer risk factors (reproductive, anthropometric, lifestyle, and medical history) and risk of ER-defined subtypes in women who self-identify as Asian, Black or African American, Hispanic or Latina, or White. We reviewed publications between January 1, 1990 and July 1, 2022. Etiologic heterogeneity evidence (convincing, suggestive, none, or inconclusive) was determined by expert consensus. Publications per risk factor ranged from 14 (benign breast disease history) to 66 (parity). Publications were most abundant for White women, followed by Asian, Black or African American, and Hispanic or Latina women. Etiologic heterogeneity evidence was strongest for parity, followed by age at first birth, post-menopausal BMI, oral contraceptive use, and estrogen-only and combined menopausal hormone therapy. Evidence was limited for other risk factors. Findings were consistent across racial and ethnic groups, although the strength of evidence varied. The literature supports etiologic heterogeneity by ER for some established risk factors that are consistent across race and ethnicity groups. However, in non-White populations evidence is limited. Larger, more comparable data in diverse populations is needed to better characterize breast cancer etiologic heterogeneity.

Malaria Diagnosis at the Pediatric Emergency Unit of a Teaching Hospital in Makurdi, North Central Nigeria.

Globally, there were 241 million cases of malaria in 2020, with an estimated 627,000 deaths with Nigeria accounting for 27% of the global malaria cases. In sub-Saharan Africa, testing is low with only 28% of children with a fever receiving medical advice or a rapid diagnostic test in 2021. In Nigeria, there are documented reports of over-diagnosis and over-treatment of malaria in children. Therefore, this study examined the diagnosis of malaria at the Benue State University Teaching Hospital, Makurdi. A 5-year (2018-2022) retrospective study was carried out at the Emergency Pediatric Unit (EPU). Records of all children presenting to the EPU with an assessment of malaria were retrieved and reviewed. Data was analyzed using SPSS 23. Out of 206 children reviewed, 128 (62.1%) were tested using either malaria RDT or microscopy while 78(37.9%) were not tested. Out of the number tested, 59(46.1%) were negative while 69(53.9%) tested positive, of which 14(20.3%) had uncomplicated malaria while 55(79.7%) had severe malaria. However, while 97.1% (n=67) of the positive cases were treated with IV artesunate, 69.5% (n=41) of those who tested negative and 88.5% (69) of those who were not tested also received IV artesunate. Moreover, while 85.5% (n=59) of those who tested positive received oral artemisinin-based combination therapy (ACT), 72.9% (n=43) of those who tested negative and 67.9% (53) of those who were not tested also received oral ACT. There was over-diagnosis of malaria, and subsequently, over-treatment. Hence continued emphasis on parasitological confirmation of malaria before treatment is recommended.

Obstructive sleep apnea mouth breathing phenotype response to combination oral appliance therapy

IntroductionObstructive sleep apnea (OSA) is a multisystem physiological disorder of breathing during sleep that may contribute to systemic physiological imbalances and can also be exacerbated by the use of some commonly prescribed medications.MethodsIn a randomized parallel design trial, we included phenotypic mild to severe OSA mouth-breathing subjects (n = 36) confirmed by home polygraphy, to evaluate the efficacy of oral appliance plus mouth shield and oral appliance only during sleep on night 1 (T1) after 4 weeks (T2), and after 8 weeks (T3) of oral appliance therapy. Respiratory dynamics data were collected. Primary outcomes were respiratory event index and mouth breathing. Anamnesis on medication intake was collected at enrollment.ResultsThe respiratory event index and the hypopnea index did not statistically differ between groups at T3. Oral appliance plus mouth shield and oral appliance only significantly reduced mouth breathing at T2 (p = 0.012) and T3 (p ≤ 0.001) compared with baseline. Exploratory analyses showed oral appliance plus mouth shield supine respiratory rate at T3 (p = 0.039) was marginally decreased compared with oral appliance only. The snore percentage did not differ statistically between groups at T3. Oral appliance only showed a marginal oxygen saturation increase (p = 0.019) at T3 compared with oral appliance plus mouth shield. At T3, medication users had persistent respiratory events, mouth breathing, and snoring compared with non-medication users. Logistic regression showed medication use may increase the odds of mouth breathing (OR = 1.148; p = 0.015) and snoring (OR = 1.036; p = 0.049).DiscussionIn our OSA-mouth breathing cohort, oral appliance only was similar to oral appliance plus mouth shield in attenuating the respiratory event index, hypopnea index, and mouth breathing after 8 weeks. Oral appliance only increased oxygen saturation at T3, while oral appliance plus mouth shield maintained a relatively narrow oxygen saturation range from T1–3. Oral appliance plus mouth shield marginally lowered the supine respiratory rate at T3 compared with oral appliance only. Persistent respiratory events, mouth breathing, and snoring were observed in medication users at T3.

A Challenging case of essensial iris atrophy ICE Syndrome with secondary angle closure glaucoma at Pasar Rebo General Hospital : A Case Report

Introduction : ICE syndrome is a unique ophthalmic disorder that involves an iris atrophy, irregular corneal oedema, and secondary angle-closure mainly occurs unilaterally in young and middle-aged women, with no family history. Approximately 50% of ICE syndrome patients will later develop secondary angle closure glaucoma. The following case report presents a patient with essential iris atrophy and secondary angle closure glaucoma.&#x0D; Case Illustration : A 50 year old woman presented with painful and redness of the right eye (RE) since 1 week. Her visual acuity was 6/40 of RE and 6/30 of left eye (LE). Her intraocular pressure (IOP) was 61,3 mmHg and 19 mmHg for the RE and LE. On the slit lamp, we had a proper RE finding, the iris atrophy with deformity in the direction from 12 to 6 hours, with minimal corneal edema. We performed gonioscopy, fundus photographs and papillary optical coherence tomography. The patient was diagnosed with ICE syndrome with essential iris atrophy type and secondary angle closure glaucoma then was given anti glaucoma agents.DiscussionICE syndrome treatments focus on managing the corneal edema and secondary glaucoma. We treated our patient with maximal oral and topical combination therapy such as carbonic anhydrase inhibitors, beta blockers, cholinergic, prostaglandin analogs for 6 months the IOP and corneal oedema were well maintained. However, maintaining long term success can be challenging, surgical therapy with a filtering procedure can be considered if the IOP is uncontrolled.&#x0D; Conclusion : We confirmed the diagnosis of essential iris atrophy based on its clinical findings and abnormalities in complementary exams.