Oral health behavior of pregnant women in Nigeria: a scoping review.

BACKGROUND: Oral health care behaviors during pregnancy affects maternal and child health outcomes. This scoping review sought to map the existing literature on the oral healthcare behaviors of pregnant women in Nigeria. METHODS: PubMed, Science Direct, Web of Science, EBSCOHOST, Sabinet, African Index Medicus, and Scopus data based were searched in August 2023. Articles with reports on the oral health behavior of pregnant women in Nigeria, published in English in peer review were included in the review. Articles whose full lengths could not be accessed, and commentaries on studies, and letters to the editor were also excluded. Data on authors and year of publication of the study, study location, study objective, study design, methodological approach for data collection, and study outcomes were extracted and descriptively synthesized. RESULTS: The search yielded a total of 595 articles of which 573 were unique. Only 21 articles were left after titles and abstracts screening and only 18 articles met the eligibility criteria. The proportion of pregnant women had utilized dental services ranged from 4 to 62.9%, the use of toothbrush and toothpaste ranged from 59.6 to 99.3%, twice daily tooth brushing ranged from 5.2 to 66.9%, and the use of toothbrush among pregnant women in the studies varies from 70.9 to 100%. Chewing stick was used by 0.1-27.7% of study participants. Dental problems such as caries, pain, swollen gums, and excessive salivation were reasons for seeking dental care. We identified individual, structural, and behavioral factors, including myths as barriers for dental service utilization. CONCLUSION: This scoping review shows that dental service utilization by pregnant women in Nigeria is poor and mainly due to curative than preventive needs. Oral health behaviours also need to be improved through tailored oral health education accessible to pregnant women in Nigeria.

Is it preferable to administer a bronchodilator once- or twice-daily when treating COPD?

Nocturnal and early morning symptoms are common and uncomfortable in many patients with COPD, and are likely to affect their long-term outcomes. However, it is still debated whether it is better to give long-acting bronchodilators once- or twice-daily to symptomatic COPD patients. The functional link between circadian rhythms of autonomic tone and airway calibre explains why the timing of administration of bronchodilators in chronic airway diseases can induce different effects when taken at different biological (circadian) times. However, the timing also depends on the pharmacological characteristics of the bronchodilator to be used. Because the profile of bronchodilation produced by once-daily vs. twice-daily long-acting bronchodilators differs throughout 24 h, selecting long-acting bronchodilators may be customized to specific patient preferences based on the need for further bronchodilation in the evening. This is especially helpful for people who experience respiratory symptoms at night or early morning. Compared to placebo, evening bronchodilator administration is consistently linked with persistent overnight improvements in dynamic respiratory mechanics and inspiratory neural drive. The current evidence indicates that nocturnal and early morning symptoms control is best handled by a LAMA taken in the evening. In contrast, it seems preferable to use a LABA for daytime symptoms. Therefore, it can be speculated that combining a LAMA with a LABA can improve bronchodilation and control symptoms better. Both LAMA and LABA must be rapid in their onset of action. Aclidinium/formoterol, a twice-daily combination, is the most studies of the available LAMA/LABA combinations in terms of impact on daytime and nocturnal symptoms.

Efficacy and Tolerability of Twice-Daily Dosing Schedule of Deferasirox in Transfusion-Dependent Paediatric Beta-Thalassaemia Patients: A Randomized Controlled Study.

Background: Deferasirox has proved good efficacy and acceptable safety for the management of thalassaemia patients. However, some patients are unresponsive or intolerant to once-daily administration of deferasirox even at a high dose. The current study evaluated the effectiveness and tolerability of twice-daily dosing of deferasirox among transfusion-dependent paediatric beta-thalassaemia patients. Methods: This prospective randomized single-blinded parallel study included all transfusion-dependent paediatric beta-thalassaemia patients prescribed with deferasirox, who visit the study site for their regular blood transfusions and follow-up. The enrolled patients were randomized into intervention and control groups by using a simple block randomization method. In the intervention group, the once-daily dosing of deferasirox was changed to twice-daily dosing with the same total daily dose. Whereas, in the control group, the patients continued with the once-daily deferasirox dosing. The serum ferritin levels of both groups were determined on the enrolment day and after 6 months of follow-up. Results: Forty-one patients were included for analysis. A statistically significant mean decrease in serum ferritin levels was detected in the intervention group, while the serum ferritin levels of the control group significantly increased from baseline. The twice-daily dosing of deferasirox was better tolerated by the thalassaemia patients when compared to once-daily dosing. Conclusion: This study concludes that twice-daily dosing of deferasirox with the same total daily dose significantly enhances the iron chelation efficacy and tolerability among transfusion-dependent paediatric beta-thalassaemia patients when compared to once-daily regimen.

Adrenal Cushing's Syndrome Treated With Preoperative Osilodrostat and Adrenalectomy.

Background/Objective: Reducing severity of Cushing's syndrome caused by an adrenal adenoma (adrenal Cushing's syndrome [ACS]) might decrease morbidity and mortality risk in adrenalectomy. We used off-label osilodrostat, approved in the United States for pituitary Cushing's disease, to reduce cortisol levels and disease severity before adrenalectomy 3 weeks later. Case Report: A 48-year-old woman with a 6-year history of obesity, depression, and anxiety and 3-year history of diabetes and hypertension was admitted with vomiting and lumbar back pain. Facial plethora and hirsutism, posterior cervicothoracic fat pad, and truncal obesity coupled with morning serum cortisol >13 µg/dL after 1 mg oral dexamethasone suppression, urinary free cortisol 1324 µg/24hr (4.0-50.0 µg/24 h), and adrenocorticotropin <5 pg/mL (6-50 pg/mL) confirmed ACS. Computed tomography with contrast revealed a 3.4-cm right adrenal mass. Osilodrostat 2 mg twice daily initiated at discharge was increased to 4 mg twice daily on day 6. Three days later, she reported nausea, vomiting, and fatigue. Despite 7.2 µg/dL morning cortisol, adrenal insufficiency was suspected; osilodrostat was reduced to 2 mg twice daily and maintenance oral hydrocortisone 20 mg daily was added with symptom resolution. Prior to adrenalectomy, morning cortisol was 5.1 µg/dL, fasting glucose was 122 mg/dL, and she self-discontinued diabetes medications. Hypertension remained unchanged (149/100 vs 151/94 mmHg). Adrenalectomy revealed a 3.4-cm focally pigmented adrenocortical adenoma. Discussion: Three-week treatment of overt ACS with off-label osilodrostat reduced cortisol and glucose levels before curative adrenalectomy. Abrupt cortisol reduction led to suspected adrenal insufficiency managed with maintenance hydrocortisone. Conclusion: Osilodrostat might help reduce ACS severity before adrenalectomy. Adrenal insufficiency is a risk but can be safely managed with hydrocortisone.

Retrospective Comparison of Patients ≥ 80 Years With Atrial Fibrillation Prescribed Either an FDA-Approved Reduced or Full Dose Direct-Acting Oral Anticoagulant.

Direct-acting oral anticoagulants (DOACs) represent the standard for preventing stroke and systemic embolization (SSE) in patients with atrial fibrillation (AF). There is limited information for patients ≥ 80 years. We report a retrospective analysis of AF patients ≥ 80 years prescribed either a US Food and Drug Administration (FDA)-approved reduced (n = 514) or full dose (n = 199) DOAC (Dabigatran, Rivaroxaban, or Apixaban) between January 1st, 2011 (first DOAC commercially available) and May 31st, 2017. The following multivariable differences in baseline characteristics were identified: patients prescribed a reduced dose DOAC were older (p < 0.001), had worse renal function (p = 0.001), were more often prescribed aspirin (p = 0.004) or aspirin and clopidogrel (p < 0.001), and more often had new-onset AF (p = 0.001). SSE and central nervous system (CNS) bleed rates were low and not different (1.02 vs 0 %/yr and 1.45 vs 0.44 %/yr) for the reduced and full dose groups, respectively. For non-CNS bleeds, rates were 10.89 vs 4.15 %/yr (p < 0.001, univariable) for the reduced and full doses, respectively. The mortality rate was 6.24 vs 1.75 %/yr (p = 0.001, univariable) for the reduced and full doses. Unlike the non-CNS bleed rate, mortality rate differences remained significant when adjusted for baseline characteristics. Thus, DOACs in patients ≥ 80 with AF effectively reduce SSE with a low risk of CNS bleeding, independent of DOAC dose. The higher non-CNS bleed rate and not the mortality rate is explained by the higher risk baseline characteristics in the reduced DOAC dose group. Further investigation of the etiology of non-CNS bleeds and mortality is warranted.

Once versus twice daily direct oral anticoagulants in patients with recent stroke and atrial fibrillation.

Background: Data on the safety and effectiveness of once-daily (QD) versus twice-daily (BID) direct oral anticoagulants (DOAC) in comparison to vitamin K antagonists (VKA) and to one another in patients with atrial fibrillation (AF) and recent stroke are scarce. Patients and methods: Based on prospectively obtained data from the observational registry Novel-Oral-Anticoagulants-in-Ischemic-Stroke-Patients(NOACISP)-LONGTERM (NCT03826927) from Basel, Switzerland, we compared the occurrence of the primary outcome - the composite of recurrent ischemic stroke, major bleeding, and all-cause death - among consecutive AF patients treated with either VKA, QD DOAC, or BID DOAC following a recent stroke using Cox proportional hazards regression including adjustment for potential confounders. Results: We analyzed 956 patients (median age 80 years, 46% female), of whom 128 received VKA (13.4%), 264 QD DOAC (27.6%), and 564 BID DOAC (59%). Over a total follow-up of 1596 patient-years, both QD DOAC and BID DOAC showed a lower hazard for the composite outcome compared to VKA (adjusted HR [95% CI] 0.69 [0.48, 1.01] and 0.66 [0.47, 0.91], respectively). Upon direct comparison, the hazard for the composite outcome did not differ between patients treated with QD versus BID DOAC (adjusted HR [95% CI] 0.94 [0.70, 1.26]). Secondary analyses focusing on the individual components of the composite outcome revealed no clear differences in the risk-benefit profile of QD versus BID DOAC. Discussion and conclusion: The overall benefit of DOAC over VKA seems to apply to both QD and BID DOAC in AF patients with a recent stroke, without clear evidence that one DOAC dosing regimen is more advantageous than the other.

Sequential Hypofractionated versus Concurrent Twice-Daily Radiotherapy for Limited-Stage Small-Cell Lung Cancer: A Propensity Score-Matched Analysis.

Background: As there are no randomized trials comparing twice-daily with sequential hypofractionated (sequential hypo) radiotherapy regimens for limited-stage small-cell lung cancer (LS-SCLC). This study aimed to compare these two regimens for LS-SCLC by propensity score-matched analysis (PSM). Methods: We retrospectively analyzed 108 LS-SCLC patients between January 2015 and July 2019. All patients received concurrent twice-daily or sequential hypo radiotherapy. The survival, failure patterns, and toxicities were evaluated before and after PSM. Results: Before PSM, multivariate analysis showed that patients treated with sequential hypo had a significantly better overall survival (OS) and distant metastasis-free survival (DMFS) (HR = 0.353, p = 0.009; HR = 0.483, p = 0.039, respectively). Total radiotherapy time ≥ 24 days and stage III (HR = 2.454, p = 0.004; HR = 2.310, p = 0.004, respectively) were poor prognostic indicators for OS. Patients with a total radiotherapy time ≥ 24 days and N2−3 were more likely to recur than others (HR = 1.774, p = 0.048; HR = 2.369, p = 0.047, respectively). N2−3 (HR = 3.032, p = 0.011) was a poor prognostic indicator for DMFS. After PSM, being aged ≥65 years was associated with poorer OS, relapse-free survival (RFS) and DMFS (p < 0.05). A total radiotherapy time of ≥24 days was a poor prognostic indicator for OS and RFS (HR = 2.671, p = 0.046; HR = 2.370, p = 0.054, respectively). Although there was no significant difference, the patients in the sequential hypo group had a trend towards a better OS. The failure pattern between the two groups showed no difference. More patients had grade 1−2 esophagitis in the twice-daily group (p = 0.001). Conclusions: After propensity matching, no difference was shown in survival and failure. The sequential hypo schedule was associated with comparable survival and less toxicity and may be used as an alternative to concurrent twice-daily regimens.

Understanding and modifying Fabry disease: Rationale and design of a pivotal Phase 3 study and results from a patient-reported outcome validation study.

The use of available treatments for Fabry disease (FD) (including enzyme replacement therapy [ERT]) may be restricted by their limited symptom improvement and mode of administration. Lucerastat is currently being investigated in the MODIFY study as oral substrate reduction therapy for the treatment of FD. By reducing the net globotriaosylceramide (Gb3) load in tissues, lucerastat has disease-modifying potential to improve symptoms and delay disease progression. MODIFY is a multicenter, double-blind, randomized, placebo-controlled, parallel-group Phase 3 study (ClinicalTrial.gov: NCT03425539); here we present the rationale and design of this study. Eligible adults with a genetically confirmed diagnosis of FD and FD-specific neuropathic pain entered screening. Patients were randomized (2:1) to receive either oral lucerastat twice daily or placebo for 6 months; treatment allocation was stratified according to sex and ERT treatment status. The main objectives of MODIFY are to assess the effects of lucerastat on neuropathic pain, gastrointestinal (GI) symptoms, FD biomarkers, and determine its safety and tolerability. Neuropathic pain and GI symptoms are key features of FD that have a significant impact on quality of life. Despite various tools available to assess pain and GI symptoms, there are currently limited tools available to assess neuropathic and GI symptoms in FD, validated according to health authority guidelines. Based on FDA recommendations, we undertook a patient-reported outcome (PRO) validation study, using a novel eDiary-based PRO tool to assess the validity of evaluating neuropathic pain as a primary efficacy endpoint in MODIFY. Results from the PRO validation study are included. To date, MODIFY is the largest Phase 3 clinical study conducted in patients with FD. Enrollment to MODIFY is now complete, with 118 patients randomized. Results will be presented in a separate publication. Long-term effects of lucerastat are being assessed in the ongoing open-label extension study (NCT03737214).

Thoracic Radiotherapy in Limited-Stage SCLC-a Population-Based Study of Patterns of Care in Norway From 2000 Until 2018.

INTRODUCTION: Twice-daily (BID) thoracic radiotherapy (TRT) of 45 Gy per 30 fractions is recommended for limited-stage (LS) SCLC, but most patients are treated with once-daily (OD) schedules owing to toxicity concerns and logistic challenges. An alternative is hypofractionated OD TRT of 40 to 42 Gy per 15 fractions. A randomized trial by our group indicated that TRT of 45 Gy per 30 fractions is more effective than TRT of 42 Gy per 15 fractions, and because it was not more toxic, 45 BID replaced 42 OD as the recommended schedule in Norway. The aims of this study were to evaluate to what extent BID TRT has been implemented in Norway and whether this practice change has led to improved survival. METHODS: Data on all patients diagnosed with LS SCLC from 2000 until 2018 were collected from the Cancer Registry of Norway, containing nearly complete data on cancer diagnosis, radiotherapy, and survival. RESULTS: A total of 2222 patients were identified; median age was 69 years, 51.8% were women, and 87.1% had stage II to III disease. Overall, 64.6% received TRT. The use of BID TRT increased from 1.8% (2000-2004) to 83.2% (2015-2018). Median overall survival among patients receiving curative TRT improved significantly during the study period (2000-2004: 17.9 mo, 2015-2018: 25.0 mo, p = 0.0023), and patients receiving 45 BID had significantly longer median overall survival than patients receiving 42 OD (BID: 26.2 mo, OD: 19.6 mo, p = 0.0015). CONCLUSIONS: BID TRT has replaced hypofractionated OD TRT as the standard treatment of LS SCLC in Norway which has led to a significant (p = 0.0023) and clinically relevant survival improvement.

Patient-reported health-related quality of life from a randomized phase II trial comparing standard-dose with high-dose twice daily thoracic radiotherapy in limited stage small-cell lung cancer.

OBJECTIVES: In a randomized phase II trial, twice daily (BID) thoracic radiotherapy (TRT) of 60 Gy/40 fractions improved survival compared with 45 Gy/30 fractions in limited stage small-cell lung cancer (LS SCLC). Notably, the higher dose did not cause more toxicity. Here we present health related quality of life (HRQoL) reported by the trial participants during the first 2 years. MATERIALS AND METHODS: 170 patients were randomized 1:1 to TRT of 45 Gy or 60 Gy concurrently with cisplatin/etoposide chemotherapy. The 150 patients who commenced TRT and completed a minimum of one HRQoL-questionnaire were included in the present study. Patients reported HRQoL on the European Organization for Research and Treatment of Cancer Core 30 and Lung Cancer 13 Quality of Life Questionnaires. Questionnaires were completed weeks 0, 4 (before TRT), 8 (end of TRT), 12 (response evaluation after chemoradiotherapy) and 16 (end of prophylactic cranial irradiation), then every 10 weeks year one, and every 3 months year two. Primary HRQoL endpoints were dysphagia and dyspnea. A difference in mean score of ≥10 was defined as clinically significant. RESULTS: Maximum dysphagia was reported on week 8, with no significant difference between treatment arms (mean scores 45 Gy: 44.2, 60 Gy: 51.1). The 60 Gy arm had more dysphagia in the convalescence period, but dysphagia scores returned to baseline levels at week 16 in both arms. For dyspnea there were no significant changes, or differences between treatment arms, at any timepoint. There were no significant differences between treatment arms for any other HRQoL-scales. CONCLUSION: TRT of 60 Gy did not cause significantly higher maximum dysphagia, though patients on the 60 Gy arm reported more dysphagia the first 8 weeks of convalescence. The higher dose was well tolerated and is an attractive alternative to current TRT schedules in LS SCLC. Trial reg Clinicaltrials.gov NCT0204184.

Considerations for prenatal and postpartum management of a female patient with ornithine transcarbamylase deficiency.

We report on pregnancy management and outcomes in a 27-year-old female patient with ornithine transcarbamylase (OTC) deficiency, the most common inherited enzyme deficiency in the urea cycle. Our patient was diagnosed during childhood after hyperammonemia associated with surgery and steroid treatment and was well-controlled with nitrogen scavenger treatment, low-protein diet, and L-citrulline supplementation. OTC gene sequencing identified a variant of unknown significance that has more recently been classified as likely pathogenic. Women with OTC deficiency are at increased risk of hyperammonemia during pregnancy and the postpartum period, therefore monthly follow up and laboratory assessments are critical in management decision making. Our patient was maintained on glycerol phenylbutyrate, L-citrulline and essential amino acid supplements, along with restricted protein intake during pregnancy. A multidisciplinary approach with the obstetrics, prenatal genetics, high risk obstetric, and anesthesia teams was also necessary for optimal management during pregnancy, throughout labor and delivery, and during the postpartum period. After successful childbirth and discharge, our patient experienced a hyperammonemic crisis related to poor enteral nutrition, and acute management protocols were implemented to stabilize her. For her newborn son, acute hyperammonemia protocols were on standby, and newborn screening and laboratory testing were expedited to assess his risk. He was healthy and did not experience symptoms of concern. In this case report, we emphasize the importance of close collaboration with maternal-fetal medicine team members during and immediately after pregnancy to ensure successful management of a female patient with OTC deficiency and her newborn.

A patient case demonstrating the efficacy of benralizumab in uncontrolled severe eosinophilic asthma refractory to omalizumab and mepolizumab treatment.

Severe eosinophilic asthma is associated with a heavy burden and impact on daily living in patients experiencing uncontrolled symptoms, exacerbations, and treatment side effects. This case study reports a 49-year-old woman who presented to the severe asthma center with uncontrolled severe asthma despite multiple maintenance medications and omalizumab treatment. On presentation, the patient had experienced two to three hospitalizations per year, frequent asthma exacerbations requiring courses of oral corticosteroids, and symptoms that impacted her quality of life. Omalizumab was previously discontinued, and bronchial thermoplasty was also unsuccessful. The patient stabilized on injectable steroids and commenced mepolizumab once available on prescription. Owing to continued exacerbations and an inability to reduce steroid treatment without exacerbating, mepolizumab was discontinued and the patient commenced benralizumab (30 mg subcutaneously every 4 weeks for the first three doses, every 8 weeks thereafter) under the sole care of the severe asthma center. Benralizumab treatment resulted in a reduction in steroid treatment, zero asthma exacerbations, improved asthma control and lung function, and a marked improvement in activity levels that allowed the patient to participate in a long-distance running event. Additionally, 7 months following the initiation of benralizumab treatment, her blood eosinophils were completely depleted. These findings support the use of benralizumab in patients with refractory uncontrolled severe eosinophilic asthma despite previous biologic treatment with omalizumab and mepolizumab, as improvements in clinical and patient outcomes, including quality of life, can be achieved in difficult-to-treat cases.

Once- Versus Twice-Daily Angiotensin-Converting Enzyme Inhibitors for Blood Pressure Control in Adult Patients With Hypertension.

This review aimed to assess the efficacy and safety of once- versus twice-daily administration of angiotensin-converting enzyme (ACE) inhibitors for the management of hypertension. A literature search on PubMed and Google Scholar was performed (January 1980 to June 2020) using the following search terms: ACE inhibitors, lisinopril, enalapril, fosinopril, trandolapril, ramipril, perindopril, captopril, benazepril, ambulatory blood pressure, hypertension, twice-daily dosing, once-daily dosing. Reference lists from retrieved articles were examined for additional reports. Relevant English-language studies or those conducted in humans were considered. Overall, six studies were included that compared the efficacy of once-daily to twice-daily dosing of ACE inhibitors. Similar blood pressure-lowering effects, and, in some studies, greater blood pressure lowering has been noted in the twice-daily administration arm than once-daily administration of ACE inhibitors. ACE inhibitors' pharmacokinetic and pharmacodynamic properties play an integral role in determining the expected blood pressure-lowering outcome. It is noteworthy that adherence issues may arise when transitioning from a once-daily regimen to a twice-daily regimen. There appear to be no added safety concerns between twice-daily and once-daily administration of ACE inhibitors regarding safety outcomes. After reviewing the available literature, twice-daily dosing of ACE inhibitors may promote added blood pressure-lowering effects, with the advantages of reducing cost, reducing the risk of drug-drug interactions, reducing polypharmacy, and reducing patient confusion about their medications. Recommendations for twice-daily administration of ACE -inhibitors should be made via shared decision-making with the patient, and clinician judgment, to drive treatment selection.

Uninterrupted Direct Oral Anticoagulants Without a Change in Regimen for Catheter Ablation for Atrial Fibrillation Is an Acceptable Protocol.

Background: In patients undergoing catheter ablation (CA) for atrial fibrillation (AF), the use of uninterrupted direct oral anticoagulants (DOACs) is the current protocol. This study evaluated bleeding complications following the uninterrupted use of 4 DOACs in patients undergoing CA for AF without any change in the dosing regimen. Moreover, we assessed differences between once- and twice-daily DOAC dosing in patients undergoing CA for AF who continued on DOACs without any change in the dosing regimen. Methods and Results: This study was a retrospective single-center cohort study of consecutive patients. All patients continued DOACs without interruption or changes to the dosing schedule, even in the case of morning procedures. The primary endpoint was the incidence of major bleeding events within the first 30 days after CA. In all, 710 consecutive patients were included in the study. Bleeding complications were less frequent in the uninterrupted twice- than once-daily DOACs group. However, the incidence of cardiac tamponade across all DOACs was low (0.98%; 7/710), suggesting that uninterrupted DOACs without changes to the dosing regimen may be an acceptable strategy. The rate of total bleeding events, including minor bleeding (12/710; 1.6%), was also satisfactory. Conclusions: Uninterrupted DOACs without any change in dosing regimen for patients undergoing CA for AF is acceptable. Bleeding complications may be less frequent in patients receiving DOACs twice rather than once daily.

Sepsis Following Liver Biopsy in a Liver Transplant Recipient: Case Report and Review of Literature.

Percutaneous liver biopsy is a relatively safe procedure with low complication rates. Infections following liver biopsy are uncommon and can lead to a poor outcome. There are limited data on liver biopsy-related infections among liver transplant (LT) recipients. Also, there is a paucity of data regarding the use of prophylactic antibiotics in LT patients undergoing percutaneous liver biopsy. We report a case of systemic sepsis following percutaneous liver biopsy in a LT recipient with choledochojejunal anastomosis. This was followed by severe rejection and deterioration of liver function and recurrence of primary sclerosing cholangitis (PSC) to the extent that he has been listed for retransplantation. This case report emphasizes the potential risk of sepsis in LT recipients with bilioenteric anastomosis undergoing percutaneous liver biopsy. This increased risk may warrant periprocedural broad spectrum antibiotic prophylaxis, in this subgroup of patients.

Comparative study of the usefulness of a novel insulin therapy in Japanese patients with Type 2 diabetes for concomitant use of an oral antidiabetic agent with twice-daily dosing either of insulin aspart, biphasic insulin aspart-30, or insulin detemir: Two times Insulin injection Combined with oral therapy Efficacy Study (TWICE study).

OBJECTIVES: It is common to treat type 2 diabetes by regular injections of insulin. We compared the efficacy and safety of twice-daily administration of short-acting, premixed, and long-acting insulins. METHODS: This was a multi-center, randomized, open-label, 52-week study. Patients were randomized to administer twice daily short-acting analog insulin (Aspart) plus a sulfonylurea (SU), premixed 70/30 analog insulin (Mix), or long-acting insulin (Detemir) plus a glinide derivative. RESULTS: Twelve (mean baseline HbA1c 9.86±1.71%), eight (9.24±1.14%), and eight (11.26±1.81%) patients were treated with Aspart, Mix, or Detemir, respectively, for 52 weeks. After 12 weeks, the reductions in HbA1c were similar in the groups. A further significant reduction in HbA1c occurred between weeks 12 and 52 in the Detemir, but not the Aspart or Mix groups. After 52 weeks, the target of an HbA1c <7.4% was achieved in 16.7% of the Aspart group, 37.5% of the Mix group, and 12.5% of the Detemir group (no significant differences among the three groups by χ2 analysis). The mean changes from baseline in blood glucose concentration measured after breakfast, and before and after dinner, were also similar in each group. CONCLUSIONS: Early and meaningful reductions in HbA1c were achieved by twice-daily administration of a premix, aspart plus an SU, and detemir plus a glinide, without severe hypoglycemia or an increase in body mass. However, the target HbA1c was achieved in relatively few participants, perhaps due to an insufficient dose of insulin or the small study size.

Elective Nodal Irradiation for Non-small Cell Lung Cancer Complicated With Chronic Obstructive Pulmonary Disease Affects Immunotherapy Αfter Definitive Chemoradiotherapy.

BACKGROUND/AIM: The aim of this retrospective study was to detect the frequency, reasons, and significant factors for not receiving immunotherapy after chemoradiotherapy in non-small cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: Thirty-four patients with NSCLC received definitive chemoradiotherapy. The endpoint of this study was receiving durvalumab within 45 days after chemoradiotherapy for NSCLC. RESULTS: Twenty-five of 34 (73%) patients received immunotherapy within 45 days after chemoradiotherapy. The reasons for not receiving immunotherapy were radiation pneumonitis (50%), radiation esophagitis (10%), and four other reasons (40%). Univariate analysis showed that significant factors for not receiving immunotherapy were elective nodal irradiation (ENI)+ and chronic obstructive pulmonary disease (COPD)+. The rate of immunotherapy was 100% (17/17 cases) in the COPD- and ENI- group, and 16% (1/6 cases) in the COPD+ and ENI+ group. CONCLUSION: ENI for NSCLC complicated with COPD decreased the rate of immunotherapy after definitive chemoradiotherapy.

Biphasic human insulin 30 thrice daily, is it reasonable?

OBJECTIVE: To evaluate the efficacy and safety of thrice daily Biphasic Human Insulin 30 (BHI 30) versus the traditional twice-daily regimen in type 2 diabetes mellitus (T2DM) patients. It's a cross over single clinical study. Twenty-two diabetic patients who were already using BHI 30 in twice or thrice daily regimens with or without metformin were included. At the 1st interval; patients continued on their usual insulin regimen as twice or thrice daily injections with adjustment of insulin doses guided by their glucose readings. On the 2nd interval; patients were switched to the other regimen with the same total daily insulin dose redistributed. RESULTS: There was a significant decrease in HbA1c level (p < 0.05) at the end of the first 3 months of trial regardless on which regimen the patient started, but there was no significant difference in the mean HbA1c reduction in patients when they were on twice daily insulin injections (1.1 ± 1.3) versus the time they were on thrice daily insulin injections (0.8 ± 1.71), p > 0.05. On the other hand, patients had lower average blood glucose readings (mg/dl) when they were on thrice daily insulin injections (161.4 ± 62.7) compared to twice daily regimen (166.0 ± 69.5), p < 0.05.

RIVAroxaban TWICE daily for lysis of thrombus in the left atrial appendage in patients with non-valvular atrial fibrillation: the RIVA-TWICE study.

INTRODUCTION: Rivaroxaban is a direct factor Xa inhibitor used once a day for prevention of thrombotic events in patients with atrial fibrillation (AF). However, in a small proportion of subjects thrombus in the left atrial appendage (LAA) is present despite this treatment. The aim of this study was assess the efficacy of increased dose of rivaroxaban (15 mg twice daily) treatment for lysis of thrombus in the LAA. MATERIAL AND METHODS: In the RIVA-TWICE prospective, open label study, with non-blinded patients and blinded outcome assessors, rivaroxaban 15 mg twice daily for 8 weeks was administered in patients with AF who had LAA thrombus despite standard 20 mg once a day therapy. Transesophageal echocardiography was performed at baseline and after 8 weeks. Blood samples were taken to measure the activity of the anti-Xa factor. RESULTS: Fifteen patients (9 males, mean age: 63 ±10 years) were enrolled. Following 8 weeks of rivaroxaban 15 mg twice daily, complete resolution of thrombus in the LAA was observed in 7 (46.7%) patients. The mean activity of anti-Xa factor was significantly higher during rivaroxaban twice daily therapy compared with the standard dose. However, there were no significant differences between effectively and non-effectively treated patients. CONCLUSIONS: Rivaroxaban 15 mg twice daily seems to be safe and may dissolve LAA thrombus when standard rivaroxaban therapy is ineffective. Lower CHA2DS2-VASc and HAS-BLED as well as preserved LAA emptying function identified responders.