Variable Dosing Regimen Research Articles

Fixed- Versus Variable-Dose Prothrombin Complex Concentrate for the Emergent Reversal of Vitamin K Antagonists: A Systematic Review and Meta-Analysis.

Four-factor prothrombin complex concentrate (4-PCC) is recommended for rapid reversal of vitamin K antagonists (VKAs) such as warfarin, yet optimal dosing remains uncertain. A systematic review was conducted of PubMed, Embase, and Ovid MEDLINE (Wolters Kluwer) databases from January 2000 to August 2023 for clinical studies comparing fixed- vs. variable-dose 4-PCC for emergent VKA reversal with at least one reported clinical outcome. Abstracts and full texts were assessed independently and in duplicate by two reviewers. Data were extracted independently and in duplicate by two reviewers using predefined extraction forms. The analysis comprised three randomized trials and 16 cohort studies comprising a total of 323 participants in randomized trials (161 in fixed dosage and 162 in variable dosage) and 1912 patients in cohort studies (858 in fixed-dose and 1054 in variable dose). Extracranial bleeding was the predominant indication, while intracranial hemorrhage varied. Overall, a fixed-dose regimen may be associated with a lower dose of 4-PCC and results in a reduction in 4-PCC administration time compared with a variable-dose regimen. A fixed-dose regimen also likely results in increased clinical hemostasis. While there is no clear difference between the two regimens in terms of achieving a goal international normalized ratio (INR) less than 2, a fixed-dose regimen is less likely to achieve a goal INR less than 1.5. High certainty evidence indicates that the fixed-dose regimen reduces both mortality and the occurrence of thromboembolic events. Additional subgroup analyses provides exploratory data to guide future studies. A fixed-dose regimen for 4-PCC administration provides benefits over a variable-dose regimen in terms of dose reduction, faster administration time, improved clinical hemostasis, and reduced mortality and thromboembolic events. Further studies are warranted to better refine the optimal fixed-dose regimen.

Evaluation of Continuous Infusion Vancomycin in a Pediatric Hematology/Oncology Population.

Continuous infusion vancomycin (CIV) may benefit children who are unable to achieve therapeutic concentrations with intermittent vancomycin dosing and may facilitate outpatient administration by alleviating the burden of frequent dosing intervals. Previous studies have used variable dosing regimens and steady-state concentration goals. The purpose of this study was to evaluate the total daily dose (TDD) of CIV required to achieve therapeutic steady-state concentrations of 15-25 µg/mL in pediatric hematology/oncology patients. A single-center retrospective study was performed for patients treated with CIV from January 2017 to June 2019. The primary outcome was the TDD required to achieve therapeutic steady-state concentrations on CIV. Secondary outcomes included time to reach therapeutic steady-state concentrations, CIV indications and adverse events associated with CIV. Data were collected for 71 courses of CIV in 60 patients. Median patient age was 4 years (range: 0.4-20 years). The median TDD required to achieve initial therapeutic concentrations was 50.3 mg/kg/d (interquartile range: 38.8-59.2) and was further divided into age-based cohorts. TDD in mg/kg was significantly lower in the older cohort ( P < 0.001), but there was no statistically significant difference between age-based cohorts with TDD in mg/m 2 ( P = 0.97). Median time to achieve first therapeutic concentration was 19.3 hours (range: 8.6-72.3 hours). The most common indication for CIV was ease of outpatient administration (69.0%). Acute kidney injury incidence was minimal (4.2%). CIV is associated with rapid attainment of target concentrations in pediatric hematology/oncology patients and is safe and well tolerated.

Comparative Descriptive Analysis of Physician Versus Patient-Directed Gabapentin Usage In Chronic Pain – A Preliminary Report

BACKGROUND: Gabapentin is one of the most common medications employed in Pain Medicine, specifically targeting the management of neuropathic pain. We are most familiar with the incremental dosing strategy where a ceiling dose is eventually attained guided by efficacy and patient tolerance, after which a fixed dosing regimen is prescribed. We propose that autonomous short-term dose variations per patient could have rapid clinically significant effects in the management of chronic pain. OBJECTIVES: This study examines the frequency at which patients take gabapentin on a fixed vs variable schedule and how the pattern of gabapentin use correlates with efficacy, side effects, and patient satisfaction. STUDY DESIGN: Single institution, cross-sectional observational survey study with data collection performed over 2 phases as a pilot for proof of concept. SETTING: Remote contact via telephone with researchers calling from a quiet, private location within the hospital complex conducive for confidential conversation. METHODS: Patients recently prescribed gabapentin were queried on the patterns of use and self-perceived efficacy, satisfaction, and side effects in accordance to a standardized oral script. Patients selected met the criteria of being new patients freshly prescribed gabapentin who have been consistently on the medication for at least a month, while having chronic pain symptoms for over 3 months. Responses were collected in the form of a 5-point Likert scale. Statistical analyses were performed using GraphPad Prism. RESULTS: Of the 222 patients, 92 patients agreed to participate in the survey for a response rate of 41.4. Of these, 51% had terminated the medication for various reasons. Of the patients still taking gabapentin, 73% were on a fixed schedule, while 27% were on a variable dosing schedule. Variable dosing cohort reported better efficacy (P = 0.027) and satisfaction (P = 0.036), while the side-effect profile between the 2 groups was similar. LIMITATIONS: The study is limited by its nature of being a pilot, single-institution study performed on a relatively small sample size. None of the patients we surveyed had been given the autonomy to adjust gabapentin doses by their providers and this could significantly reduce the proportion of patients who would be encouraged to run a variable dosing regimen. CONCLUSIONS: This pilot study suggests that a significant portion of patients choose to administer variable doses of gabapentin and associate this with better efficacy and satisfaction. A larger study is needed to confirm this supposition. Based upon this pilot study, the variable dosing option may be an option for improved therapeutic efficacy or as an alternative to those whose lifestyles do not allow for fixed dosing regimens. Discussion of the risks of gabapentin, including respiratory depression, and clear dosage parameters of use, would need to be outlined when considering a variable dose regimen. KEY WORDS: Gabapentin, chronic pain, physician directed, patient directed

Targeted Metabolomics of Organophosphate Pesticides and Chemical Warfare Nerve Agent Simulants Using High- and Low-Dose Exposure in Human Liver Microsomes.

Our current understanding of organophosphorus agent (pesticides and chemical warfare nerve agents) metabolism in humans is limited to the general transformation by cytochrome P450 enzymes and, to some extent, by esterases and paraoxonases. The role of compound concentrations on the rate of clearance is not well established and is further explored in the current study. We discuss the metabolism of 56 diverse organophosphorus compounds (both pesticides and chemical warfare nerve agent simulants), many of which were explored at two variable dose regimens (high and low), determining their clearance rates (Clint) in human liver microsomes. For compounds that were soluble at high concentrations, 1D-NMR, 31P, and MRM LC-MS/MS were used to calculate the Clint and the identity of certain metabolites. The determined Clint rates ranged from 0.001 to 2245.52 µL/min/mg of protein in the lower dose regimen and from 0.002 to 98.57 µL/min/mg of protein in the high dose regimen. Though direct equivalency between the two regimens was absent, we observed (1) both mono- and bi-phasic metabolism of the OPs and simulants in the microsomes. Compounds such as aspon and formothion exhibited biphasic decay at both high and low doses, suggesting either the involvement of multiple enzymes with different KM or substrate/metabolite effects on the metabolism. (2) A second observation was that while some compounds, such as dibrom and merphos, demonstrated a biphasic decay curve at the lower concentrations, they exhibited only monophasic metabolism at the higher concentration, likely indicative of saturation of some metabolic enzymes. (3) Isomeric differences in metabolism (between Z- and E- isomers) were also observed. (4) Lastly, structural comparisons using examples of the oxon group over the original phosphorothioate OP are also discussed, along with the identification of some metabolites. This study provides initial data for the development of in silico metabolism models for OPs with broad applications.

Drug reactions with eosinophilia and systemic symptoms induced by immune checkpoint inhibitors: an international cohort of 13 cases.

Among dermatologic adverse events induced by immune checkpoint inhibitors (ICI), drug reactions with eosinophilia and systemic symptoms (DRESS) have been very rarely reported. The objective of this study is to better define the clinical and histologic features, treatment and prognosis of ICI-related DRESS. This retrospective case series was conducted between 01 January 2015 and 31 December 2021 by the dermatology departments of five international networks involved in drug reactions. Inclusion criteria were age ≥18 years old, DRESS with Regiscar score ≥4 (probable or certain) and ICI as a suspect drug. Clinical, biologic and follow-up data were extracted from the medical charts. Thirteen patients were included. The median time to onset was 22 days (3-11). No patients had a high-risk drug introduced in the past 3 months. A majority of patients presented fever (92%), diffuse exanthema (77%) and facial edema (69%). Biologic features included hypereosinophilia in eight patients (61.5%), hyperlymphocytosis in 3 (23%), elevated liver function tests in 11 (85%, grade 1 or 2 in most cases) and renal involvement in 5 (38%). Two patients (15%) had lung involvement. PCR evidence of viral replication was detected in five patients (38.5%). Treatment involved discontinuation of the suspect ICI and systemic steroids with variable dose and duration regimens. Among the four patients in which ipilimumab + nivolumab combination therapy was initially suspected, one was rechallenged with nivolumab monotherapy with good tolerance. Five patients were switched to another anti-PD-1 plus low-dose systemic steroids, with good tolerance in four cases. No patient died because of DRESS. DRESS induced by ICI are rare and of moderate severity. A consensus for management is still pending.

A data-informed approach using individualised dispensing patterns to estimate medicine exposure periods and dose from pharmaceutical claims data.

Pharmaceutical claims data are often used as the primary information source to define medicine exposure periods in pharmacoepidemiological studies. However, often critical information on directions for use and the intended duration of medicine supply are not available. In the absence of this information, alternative approaches are needed to support the assignment of exposure periods. This study summarises the key methods commonly used to estimate medicine exposure periods and dose from pharmaceutical claims data; and describes a method using individualised dispensing patterns to define time-dependent estimates of medicine exposure and dose. This method extends on important features of existing methods and also accounts for recent changes in an individual's medicine use. Specifically, this method constructs medicine exposure periods and estimates the dose used by considering characteristics from an individual's prior dispensings, accounting for the time between prior dispensings and the amount supplied at prior dispensings. Guidance on the practical applications of this method is also provided. Although developed primarily for application to databases, which do not contain duration of supply or dose information, use of this method may also facilitate investigations when such information is available and there is a need to consider individualised and/or changing dosing regimens. By shifting the reliance on prescribed duration and dose to determine exposure and dose estimates, individualised dispensing information is used to estimate patterns of exposure and dose for an individual. Reflecting real-world individualised use of medicines with complex and variable dosing regimens, this method offers a pragmatic approach that can be applied to all medicine classes.

Dalbavancin in the treatment of acute bacterial skin and skin structure and other infections: a safety evaluation

ABSTRACT Introduction Dalbavancin is a second-generation lipoglycopeptide approved since 2014 to treat acute bacterial skin and skin-structure infections (ABSSSI). Dalbavancin is characterized by Gram-positive activity and novel pharmacokinetic properties allowing prolonged terminal half-life andonce weekly dosing . A good safety profile was reported in clinical trials . Areas covered Dalbavancin safety and tolerability from trials and post-marketing studies were reviewed. While most reports included predominantly ABSSSI, two clinical trials and recent observational studies have explored the use of dalbavancin for off-label indications, mainly including bloodstream and osteoarticular infections. Expert opinion The occurrence of drug-related adverse effects (AE) was similar between dalbavancin and comparators in clinical trials enrolling patients with ABSSSI. Most common AE included gastrointestinal symptoms, infusion reaction, and hypersensitivity. Low rates of drug discontinuation and serious AE were reported across studies. In the past 5 years, several observational studies have reported safety data on the use of dalbavancin, confirming its favorable safety profile. Nevertheless, data from dalbavancin off-label use, often derived from prolonged (>2 weeks) treatments with variable dosing regimens, were mainly retrospective and lacked comparators. Further research is required to allow a reliable analysis of short- and long-term dalbavancin-related AE in non-ABSSSI.

First study of extended half-life rFVIIIFc in previously untreated patients with hemophilia A: PUPs A-LONG final results

AbstractPUPs A-LONG evaluated the safety and efficacy of recombinant factor VIII Fc fusion protein (rFVIIIFc) in previously untreated patients (PUPs) with hemophilia A. This open-label, phase 3 study enrolled male PUPs (<6 years) with severe hemophilia A to receive rFVIIIFc. The primary endpoint was the occurrence of inhibitor development. Secondary endpoints included annualized bleed rate (ABR). Of 103 subjects receiving ≥1 dose of rFVIIIFc, 80 (78%) were aged <1 year at the study start, 20 (19%) had a family history of inhibitors, and 82 (80%) had high-risk F8 mutations. Twenty subjects began on prophylaxis, while 81 began an on-demand regimen (69 later switched to prophylaxis). Eighty-seven (81%) subjects completed the study. Inhibitor incidence was 31.1% (95% confidence interval [CI], 21.8% to 41.7%) in subjects with ≥10 exposure days (or inhibitor); high-titer inhibitor incidence was 15.6% (95% CI, 8.8% to 24.7%). The median (range) time to high-titer inhibitor development was 9 (4-14) exposure days. Twenty-eight (27%) subjects experienced 32 rFVIIIFc treatment-related adverse events; most were inhibitor development. There was 1 nontreatment-related death due to intracranial hemorrhage (onset before the first rFVIIIFc dose). The overall median (interquartile range [IQR]) ABR was 1.49 (0.00-4.40) for subjects on variable prophylaxis dosing regimens. In this study of rFVIIIFc in pediatric PUPs with severe hemophilia A, overall inhibitor development was within the expected range, although high-titer inhibitor development was on the low end of the range reported in the literature. rFVIIIFc was well-tolerated and effective for prophylaxis and treatment of bleeds. This trial is registered at www.clinicaltrials.gov (NCT02234323).

2-Year Real-World Outcomes with Intravitreal Aflibercept in Neovascular Age-Related Macular Degeneration: Literature Review and Meta-analysis of Patient-Relevant Outcomes.

BackgroundThe 96 weeks’ assessment from the VIEW studies provided insights into the long-term efficacy of intravitreal aflibercept (IVT-AFL) in neovascular age-related macular degeneration (nAMD) and demonstrated that it was possible to maintain long-term outcomes while moving from a fixed bimonthly regimen in Year 1 to a variable dosing regimen in Year 2. The aim of this analysis was to perform a literature review and meta-analysis assessing the use of IVT-AFL and real-world outcomes in treatment-naïve patients with nAMD treated with IVT-AFL for 2 years, as per label.MethodsA literature review and meta-analysis were performed to provide an overview of the baseline characteristics of the population, the 2-year outcomes, the associated treatment burden, and safety.ResultsEleven publications providing data from patients with nAMD who had treatment initiated with IVT-AFL between 2012 and 2016 were identified. The mean baseline age of patients was 78.62 years, with a baseline best-corrected visual acuity (BCVA) of 57.73 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Patients reported a mean BCVA at 2 years of 62.55 ETDRS letters, with 47.39% of patients having a BCVA ≥ 70 ETDRS letters. Mean gain in BCVA versus baseline was + 4.49 ETDRS letters for the combined population (+ 5.91 letters for patients treated with a treat-and-extend regimen). Over the 2 years of the study, patients received an average of 12.34 injections, with a reduction in injections in Year 2 versus Year 1. The qualitative assessment of the safety data suggested that no new safety signals were identified.ConclusionPatients treated with IVT-AFL reported significant gains in visual acuity versus baseline after 2 years. The evidence identified indicates that the visual gains achieved during the first year of treatment are maintained through the second year and that these were achieved with a reduction in the mean number of IVT-AFL injections administered in Year 2 of treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40123-021-00350-5.

Modified version of the American College of Cardiology's recommendation for low-dose prothrombin complex concentrate is effective for warfarin reversal

BackgroundDosing of four factor prothrombin complex concentrate (4PCC) for warfarin reversal remains controversial. Recently, the American College of Cardiology (ACC) recommended a low-dose PCC regimen as an option for warfarin reversal in acute major bleeding. We performed a retrospective study evaluating if a modified version of the ACC guideline recommendations was effective for warfarin reversal in acute major bleeds when compared to traditional variable dosing. MethodsThis was a retrospective cohort study of patients who received 4PCC for warfarin reversal in a 12 month period. We included patients that were ≥18 years of age, received 4PCC for warfarin reversal, and had an initial International Normalized Ratio (INR) of >2. Our primary outcome was the number of patients who had a post-4PCC infusion INR of <1.6. ResultsA total of 60 patients were included in the final analysis with 30 patients stratified to the traditional dosing and low-dose groups, respectively. Patient demographics were similar between both groups. We found no difference in the number of patients who had a post-4PCC infusion INR <1.6 between the traditional dosing and low dosing group (90.0% vs. 86.7%; p = 0.68). Additionally, we found no difference between post-infusion median INRs in each group (1.35 vs. 1.30; p = 0.16). Approximately 1000 units per patient were spared when utilizing the low-dose regimen. ConclusionA modified version of the ACC's low-dose 4PCC option for warfarin reversal achieves similar outcomes for lowering INR values compared to traditional variable dosing regimens.

The use of tranexamic acid in adult spinal deformity: is there an optimal dosing strategy?

BACKGROUND CONTEXTASD (Adult spinal deformity) surgery often entails complex osteotomies and realignment procedures, particularly in the setting of rigid deformities. Although previous studies have established the efficacy of tranexamic acid (TXA), data evaluating the widely variable dosing regimens remains sparse. PURPOSETo improve understanding of blood loss and transfusion requirements for low-dose and high-dose TXA regimens for adult spinal deformity (ASD) surgery. STUDY DESIGN/SETTINGThis is a retrospective cohort study of 318 ASD patients who received TXA. Outcome measures include estimated blood loss (EBL), perioperative transfusion requirement, and complications. METHODSA retrospective review was conducted on 318 ASD patients: 258 patients received a low-dose regimen of TXA (10 or 20 mg/kg loading dose with a 1 or 2 mg/kg/h maintenance dose) and 60 patients received a high-dose regimen of TXA (40 mg/kg loading dose with a 1 mg/kg/h maintenance dose, 30 mg/kg loading dose with a 10 mg/kg/h maintenance dose, or 50 mg/kg loading dose with a 5 mg/kg/h maintenance dose). RESULTSCompared with the low-dose TXA group, the high-dose TXA group had significantly decreased EBL (1402 vs. 1793 mL, p=.009), blood volume lost (30.3 vs. 39.4%, p=.01), intraoperative packed red blood cell (pRBC) transfusion (0.9 vs. 1.6 U, p<.0001), and intraoperative platelet transfusion (0 vs. 0.1 U, p<.0001). High-dose TXA was predictive of 515 cc less EBL (p=.002), 11.4% less blood volume lost (p=.004), and 1 U pRBC less transfused intraoperatively (p<.0001) than the low-dose TXA group. The high-dose TXA group had a higher incidence of postop atrial fibrillation (5 vs. 0%, p<.0001) and myocardial infarction (1.7 vs. 0%, p=.04). CONCLUSIONSVarying dosing regimens of TXA are utilized for ASD surgery, with a prevailing theme of dosing ambiguity. These data demonstrate that high-dose TXA is more effective than low-dose TXA in reducing blood loss and blood product transfusion requirement in ASD surgery. Importantly, rates of MI and postop AF were higher in the high-dose TXA group.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

Anti-vascular endothelial growth factor for neovascular age-related macular degeneration.

Oral Vancomycin for Secondary Prophylaxis of Clostridium difficile Infection.

To summarize and critically appraise the evidence regarding oral vancomycin prophylaxis (OVP) to prevent recurrent Clostridium difficile infections (RCDIs), identify potential consequences of this emerging practice, and highlight future directions of study. A MEDLINE literature search of English-language publications from 1947 through September 2018 was performed using the search terms vancomycin and C difficile and prophylaxis. Clinical trials were identified on the National Library of Medicine clinical trials registry. All clinical studies (n = 3) assessing oral vancomycin for secondary prophylaxis of C difficile infection (CDI) were evaluated by all authors. Other search results and references in selected publications were used for background and discussion. OVP reduced the risk of RCDI in high-risk patients taking systemic antibiotics. Variable dosing regimens and lack of safety data are limitations. OVP may have an adverse impact on the gastrointestinal microbiome, but this was not examined in the clinical studies. Relevance to Patient Care and Clinical Practice: Although current studies are limited by methodological concerns, clinicians can consider vancomycin 125 mg orally once or twice daily in high-risk patients receiving broad-spectrum antibacterial agents. Results of ongoing trials will define the most appropriate regimen and its impact on outcomes, including collateral damage. OVP reduces the risk of RCDIs and should be considered on a case-by-case basis. Caution is warranted before routine use is implemented because the impact on long-term outcomes has not been assessed and the optimal regimen has not been defined.

Factors influencing macular atrophy growth rates in neovascular age-related macular degeneration treated with ranibizumab or aflibercept according to an observe-and-plan regimen

Background/aimsTo investigate the factors associated with macular atrophy (MA) growth rates in neovascular age-related macular degeneration treated with either ranibizumab or aflibercept.MethodsWe obtained data from two identical prospective studies using...

Antidepressant medication and ocular factors in association with the need for anti-VEGF retreatment in neovascular age-related macular degeneration

Background/AimsVascular endothelial growth factor (VEGF) is a key player in the pathogenesis of neovascular age-related macular degeneration (nAMD) and is also involved in the final common pathway of antidepressant medication....

MACULAR ATROPHY INCIDENCE IN ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR-TREATED NEOVASCULAR AGE-RELATED MACULAR DEGENERATION: Risk Factor Evaluation for Individualized Treatment Need of Ranibizumab or Aflibercept According to an Observe-and-Plan Regimen.

To investigate factors associated with macular atrophy (MA) incidence in neovascular age-related macular degeneration treated with either ranibizumab or aflibercept in an Observe-and-Plan variable dosing regimen. Information was obtained from two identical prospective treatment protocols using ranibizumab or aflibercept in a variable dosing regimen termed "Observe and Plan." Eyes without MA at baseline were included. New atrophy at the final 2-year visit was investigated with univariate and multivariate analysis to identify associated risk factors, focusing on treatment factors. De novo MA developed in 63 (42%) of 149 eyes/patients (mean age 79.0 years), in 70 eyes treated using aflibercept and 79 eyes using ranibizumab. The univariate analysis showed multiple associations of MA with baseline factors, of which the following were confirmed as independent risk factors after multivariate stepwise logistic regression: lower number of anti-vascular endothelial growth factors injections (P = 0.011), depigmentation (P = 0.0004), reticular pseudodrusen (P = 0.0005), lower baseline visual acuity (P = 0.0006), and retinal angiomatous proliferation (P = 0.001). The drug type showed no significant association with MA incidence (P = 0.21). Within the variable dosing regimen, MA incidence was higher when fewer injections were required. More injections, if required by disease activity, did not increase the risk for MA.

Two-year outcome of an observe-and-plan regimen for neovascular age-related macular degeneration treated with Aflibercept

PurposeThe purpose of our study was to investigate the two-year outcome of Aflibercept treatment for neovascular age-related macular degeneration (nAMD), using the Observe-and-Plan regimen, an individually planned treatment regimen, based on the predictability of an individual’s need for retreatment, aiming to reduce the clinical burden.MethodsOur prospective study used the Observe-and-Plan regimen with Aflibercept to treat nAMD: Three loading doses, followed by monthly observation visits until the disease-recurrence interval was determined, which then was shortened by 2 weeks in a treatment plan for the next three injections without intermediate monitoring visits. The subsequent treatment plans were adjusted according to periodically assessed disease activity. The primary outcome measures were visual acuity changes, number of injections, and number of monitoring visits.ResultsThe study included 112 eyes of 102 patients with a mean age of 80.7 years (SD 7.6). Mean visual acuity (VA) improved from 61.8 ETDRS letters (20/60+2) at baseline, by 8.5, 8.0, and 6.2 letters at months 3, 12 and 24, respectively. Mean central retinal thickness was 438um at baseline, and reduced by 152um, 155um, and 150um at months 3, 12 and 24, respectively. The mean number of injections was 8.7 and 6.5 in the first and second year, respectively. The mean number of monitoring visits after baseline was 3.8 and 2.8 during the first and second year, respectively.ConclusionsThe Observe-and-Plan regimen significantly improved VA, while fewer monitoring visits were needed as compared to other variable dosing regimens, thus reducing the workload for chronic care management of nAMD.

Beliefs and practices in using misoprostol for induction of labour among obstetricians in Zimbabwe

Background . Misoprostol is commonly used for induction of labour in term pregnancy. There are different routes and dosing schedules for administering the drug. Objectives . To describe the prescribing pattern (dose, route, duration), beliefs and factors affecting use of misoprostol for inducing term pregnancy among practising obstetricians in Zimbabwe. Methods . A cross-sectional descriptive survey was undertaken among practising obstetricians in Zimbabwe. A questionnaire was sent as an email, WhatsApp or short message service (SMS, or text) web link to all practising obstetricians in Zimbabwe using the SurveyMonkey online tool. All consenting practitioners were requested to respond online. The responses were analysed using the SurveyMonkey software. Results . There were 52 responses from the 63 questionnaires, a response rate of 82.5%. Seventy-six percent preferred oral misoprostol for induction of labour. The most common indication for induction was prolonged pregnancy accounting for 58% of respondents. The largest group of the practitioners who responded (36%) learnt their misoprostol dosing regimen from WHO/FIGO/NICE guidelines. A composite of highly variable dose regimens referred to as ‘other regimens’ was the dosing regimen preferred by 34% of respondents. Fiftyeight percent of practitioners used two cycles of misoprostol dosing before concluding that induction had failed and 52% would resort to caesarean section immediately if induction failed. Conclusion. The results show marked heterogeneity in the dosing schedules employed by obstetricians for induction of labour with the majority not following standard misoprostol guidelines for labour induction.

Effect of intravenous phenylephrine infusion on dose requirement of intrathecal plain levobupivacaine for cesarean section: A placebo-controlled preliminary study

Background:Phenylephrine infusion has been shown to decrease rostral spread of plain and hyperbaric local anesthetic (LA) when compared to ephedrine infusion. However, it does not result in higher dose requirement of hyperbaric LA for cesarean section. There is no trial evaluating the effect of phenylephrine infusion on ED50 of a plain intrathecal LA.Methods:Pregnant patients with term uncomplicated singleton pregnancy undergoing elective cesarean section were given combined spinal-epidural anesthesia. They received intrathecal plain levobupivacaine 0.5% in a dose decided by up-and-down sequential allocation method along with 25 μg fentanyl. Intravenous infusion of phenylephrine (100 μg/ml) or normal saline was initiated immediately after intrathecal injection. Systolic arterial pressure ≤0.8 times baseline was treated using rescue boluses of phenylephrine 50 μg.Results:Demographic, other patient and surgical characteristics were similar in the two groups. ED50 of intrathecal plain levobupivacaine was significantly greater in phenylephrine group (5.5 mg [95% confidence interval (CI): 5.1–5.9 mg]) compared to saline group (4.2 mg [95% CI: 3.4–5.1 mg]) (P = 0.01). Maximum sensory level, time to achieve adequate block, Apgar scores, and umbilical artery pH were similar in both groups. Total phenylephrine dose and patients having significant bradycardia were lesser in the saline group.Conclusions:Intrathecal dose requirement of plain levobupivacaine is greater using phenylephrine infusion as compared to saline infusion with rescue phenylephrine boluses. When using phenylephrine as a variable dose regimen titrated to maintain blood pressure within 20% of baseline, the ED50 of plain levobupivacaine is 5.5 mg (95% CI: 5.1–5.9 mg).

Ranibizumab in neovascular age-related macular degeneration: a 5-year follow-up.

PurposeOur aim was to evaluate an optical coherence tomography (OCT) and visual acuity (VA)-guided, variable-dosing regimen with intravitreal ranibizumab injection for treating patients with neovascular age-related macular degeneration (AMD) from 2007 to 2012.DesignThis was a retrospective clinical study of 5 years follow-up in a tertiary eye center.Patients and methodsIn this study, 66 patients with neovascular AMD (mean age of 74 years, SD 8.7 years) were included. We investigated the development of best-corrected visual acuity (BCVA), the number of intravitreal injections, and the central retinal thickness measured with OCT (OCT Spectralis) over 5 years of intravitreal treatment.ResultsThe mean number of intravitreal ranibizumab injections over 5 years was 8.8. The mean BCVA before therapy was 0.4 logarithm of the minimum angle of resolution (logMAR). After 5 years of therapy, the mean BCVA was 0.6 logMAR. In all, 16% of treated patients had stable VA over 5 years and 10% of study eyes approved their VA. The mean OCT-measured central retinal thickness at the beginning of this study was 295 µm; after 5 years of treatment, the mean central retinal thickness was 315 µm. There was an increase in central retinal thickness in 47.5% of examined eyes.ConclusionOther studies showed VA improvement in OCT-guided variable-dosing regimens. Our study revealed a moderate decrease in VA after a total mean injection number as low as 8.8 injections over 5 years. In OCT, an increase in central retinal thickness over 5 years could be observed. Probably, this is due to deficient treatment when comparing the total injection number to other treatment regimens. Anti-VEGF therapy helps to keep the VA stable for a period of time, but cannot totally stop the progression of the disease completely. Patients with late stages of neovascular AMD can maintain VA even if they are relatively undertreated.