Conjugated and Entrapped HPMA-PLA Nano-Polymeric Micelles Based Dual Delivery of First Line Anti TB Drugs: Improved and Safe Drug Delivery against Sensitive and Resistant <Emphasis Type="Italic">Mycobacterium Tuberculosis</Emphasis>

Purpose

First line antiTB drugs have several physical and toxic manifestations which limit their applications. RIF is a hydrophobic drug and has low water solubility and INH is hepatotoxic. The main objective of the study was to synthesize, characterize HPMA-PLA co-polymeric micelles for the effective dual delivery of INH and RIF.

Methods

HPMA-PLA co-polymer and HPMA-PLA-INH (HPI) conjugates were synthesized and characterized by FT-IR and ¹H–NMR spectroscopy. Later on RIF loaded HPMA-PLA-INH co-polymeric micelles (PMRI) were formulated and characterized for size, zeta potential and surface morphology (SEM, TEM) as well as critical micellar concentration. The safety was assessed through RBC’s interaction study. The prepared PMRI were evaluated through MABA assay against sensitive and resistant strains of M. Tuberculosis.

Results

Size, zeta and entrapment efficiency for RIF loaded HPMA-PLA-INH polymeric micelles (PMRI) was 87.64 ± 1.98 nm, ?19 ± 1.93 mV and 97.2 ± 1.56%, respectively. In vitro release followed controlled and sustained delivery pattern. Sustained release was also supported by release kinetics. Haemolytic toxicity of HPI and PMRI was 8.57 and 7.05% (p < 0.01, INH Vs PMRI; p < 0.0001, RIF Vs PMRI), respectively. MABA assay (cytotoxicity) based MIC values of PMRI formulation was observed as ≥0.0625 and ≥0.50 μg/mL (for sensitive and resistant strain). The microscopic analysis further confirmed that the delivery approach was effective than pure drugs.

Conclusions

RIF loaded and INH conjugated HPMA-PLA polymeric micelles (PMRI) were more effective against sensitive and resistant M tuberculosis. The developed approach can lead to improved patient compliance and reduced dosing in future, offering improved treatment of tuberculosis.

     

Intravitreal dexamethasone in exogenous bacterial endophthalmitis: results of a prospective randomised study

AIM: To evaluate the efficacy of intravitreal dexamethasone co-administered with intravitreal antibiotics along with vitrectomy in the management of exogenous bacterial endophthalmitis. METHODS: In a prospective randomised clinical trial, 63 patients (63 eyes) with suspected bacterial endophthalmitis (postoperative and post-traumatic) were treated with vitrectomy and intravitreal antibiotics and randomised to intravitreal dexamethasone (IOAB with = 29 eyes) and no dexamethasone (IOAB without = 34 eyes). Inflammation score (IS) and visual acuity were measured by two masked observers before surgery, and at 1, 4, and 12 weeks after surgery in both the groups. RESULTS: There was significant reduction (p <0.0001) in IS at 1, 4, and 12 weeks after the surgery in the "IOAB with" group; there was temporary but significant increase (p <0.01) in IS at 1 week in the "IOAB without" group, before decline (p <0.001) of IS at 4 and 12 weeks. The magnitude and relative percentage change in IS between the two groups were found to be significant at 1 (p <0.0001), and 4 (p <0.01) weeks, and not at 12 weeks. The visual acuity at 12 weeks was comparable in both the IOAB with and IOAB without groups. CONCLUSION: Intravitreal dexamethasone helps in early reduction of inflammation in exogenous bacterial endophthalmitis, but has no independent influence on the visual outcome. In selected patients with endophthalmitis where oral corticosteroids cannot be given for medical reasons intravitreal corticosteroids could be beneficial; in other situations they could be complementary to oral corticosteroid therapy.     

Effect of Personalized Messages Sent by a Health System’s Patient Portal on Influenza Vaccination Rates: a Randomized Clinical Trial

BackgroundAdult influenza vaccination rates are low. Tailored patient reminders might raise rates.ObjectiveEvaluate impact of a health system’s patient portal reminders: (1) tailored to patient characteristics and (2) incorporating behavioral science strategies, on influenza vaccination rates among adults.DesignPragmatic 6-arm randomized trial across a health system during the 2019–2020 influenza vaccination season. The setting was one large health system—53 adult primary care practices.ParticipantsAll adult patients who used the patient portal within 12 months, stratified by the following: young adults (18–64 years, without diabetes), older adults (≥65 years, without diabetes), and those with diabetes (≥18 years).InterventionsPatients were randomized within strata to either (1) pre-commitment reminder alone (1 message, mid-October), (2) pre-commitment + loss frame messages, (3) pre-commitment + gain frame messages, (4) loss frame messages alone, (5) gain frame messages alone, or (6) standard of care control. Patients in the pre-commitment group were sent a message in mid-October, asking if they planned on getting an influenza vaccination. Patients in loss or gain frame groups were sent up to 3 portal reminders (late October, November, and December, if no documented influenza vaccination in the EHR) about importance and safety of influenza vaccine.Main MeasuresReceipt of 1 influenza vaccine from 10/01/2019 to 03/31/2020.Key Results196,486 patients (145,166 young adults, 29,795 older adults, 21,525 adults with diabetes) were randomized. Influenza vaccination rates were as follows: for young adults 36.8%, for older adults 55.6%, and for diabetics 60.6%. On unadjusted and adjusted (for age, gender, insurance, race, ethnicity, and prior influenza vaccine history) analyses, influenza vaccination rates were not statistically different for any study group versus control.ConclusionsPatient reminders sent by a health system’s patient portal that were tailored to patient demographics (young adults, older adults, diabetes) and that incorporated two behavioral economic messaging strategies (pre-commitment and loss/gain framing) were not effective in raising influenza vaccination rates.Trial RegistrationThis trial was registered with ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT04110314","term_id":"NCT04110314"}}NCT04110314).Supplementary InformationThe online version contains supplementary material available at 10.1007/s11606-021-07023-w.     

Surgical reconstruction of semilunar valves in the growing child: Should we mimic the venous valve? A simulation study

Objectives

Neither heart valve repair methods nor current prostheses can accommodate patient growth. Normal aortic and pulmonary valves have 3 leaflets, and the goal of valve repair and replacement is typically to restore normal 3-leaflet morphology. However, mammalian venous valves have bileaflet morphology and open and close effectively over a wide range of vessel sizes. We propose that they might serve as a model for pediatric heart valve reconstruction and replacement valve design. We explore this concept using computer simulation.