Safety and Efficacy of 25 mg/kg and 35 mg/kg vs 10 mg/kg Rifampicin in Pulmonary TB: A Phase IIb Randomized Controlled Trial.

Background: Globally, no trial data are available on head-to-head comparison between 10 mg/kg and 25/35 mg/kg rifampicin in treating pulmonary tuberculosis during study initiation. Methods: A multicentric, phase IIb randomized trial recruited 333 new culture-positive, drug-sensitive adult patients with pulmonary tuberculosis to compare safety and efficacy of high-dose rifampicin (R25/R35), against conventional dose (R10) given daily for 8 weeks followed by standard doses for 16 weeks. Main outcomes were treatment-emergent grade 3/4 adverse events (AEs) and time-to-culture conversion in liquid media, assessed by division of AIDS system for grading the severity of adverse events division of AIDS criteria and Kaplan-Meier methods. Results: In a modified intention-to-treat population of 323 patients (R10: 105/R25: 112/R35: 106), grade 3/4 AEs were reported in 34 patients (R10: 9.5% [10/105], R25: 9.8% [11/112], R35: 12.3% [13/106]) during the intensive phase. Among 23 patients (R10: 3.8% [4/105], R25: 6.3% [7/112], R35: 11.3% [12/106]) with grade 3/4 hepatotoxicity, 15 (R10: 1.9% [2/105], R25: 3.6% [4/112], R35: 8.5% [9/106]) had grade 3/4 hyperbilirubinemia and 9 patients (R10: 1.0% [1/105], R25: 0.9% [1/112], R35: 6.6% [7/106]) developed clinical jaundice. Significant differences observed only between R10 and R35 with hepatotoxicity (P = .039), hyperbilirubinemia (P = .031), clinical jaundice (P = .032), and treatment interruption (P = .039). Eighteen serious AEs and 6 deaths (R10: 3/R25: 1/R35: 2) occurred during study period. Time to stable culture conversion in liquid media was faster in R25 (adjusted hazard ratio, 1.71; 95% confidence interval [CI], 1.26-2.31 [solid: 1.97; 95% CI, 1.46-2.67]) and R35 (1.81; 95% CI, 1.33-2.48 [solid: 2.24; 95% CI, 1.64-3.06]), than R10 (34 vs 44 days). R25 had no failure/relapse. Conclusions: Hepatotoxicity, clinical jaundice, and treatment interruptions occurred significantly higher with R35 than R10. Because R25 was comparably safe as R10 and also highly efficacious than R10, it may be considered for implementation. Clinical Trials Registration. CTRI/2017/12/010951.

Effectiveness of Single-Tablet Combination Therapy in Improving Adherence and Persistence and the Relation to Clinical and Economic Outcomes.

Background: Single-tablet combination therapies (STCTs) combine multiple drugs into one formulation, making drug administration more convenient for patients. STCTs were developed to address concerns with treatment adherence and persistence, but the impact of STCT use is not fully understood across indications. Objectives: We conducted a systematic literature review (SLR) to examine STCT-associated outcomes across 4 evidence domains: clinical trials, real-world evidence (RWE), health-related quality of life (HRQoL) studies, and economic evaluations. Methods: Four SLRs were conducted across the aforementioned domains. Included studies compared STCTs as well as fixed-dose combinations ([FDCs] of non-tablet formulations) with the equivalent active compounds and doses in loose-dose combinations (LDCs). Original research articles were included; case reports, case series, and non-English-language sources were excluded. Databases searched included EconLit, Embase, and Ovid MEDLINE® ALL. Two independent reviewers assessed relevant studies and extracted data. Conflicts were resolved with a third reviewer or consensus-based discussion. Results: In all, 109 studies were identified; 27 studies were identified in more than one SLR. Treatment adherence was significantly higher in patients receiving FDCs vs LDCs in 12 of 13 RWE studies and 3 of 13 clinical trials. All 18 RWE studies reported higher persistence with FDCs. In RWE studies examining clinical outcomes (n = 17), 14 reported positive findings with FDCs, including a reduced need for add-on medication, blood pressure control, and improved hemoglobin A1C. HRQoL studies generally reported numerical improvements with STCTs or similarities between STCTs and LDCs. Economic outcomes favored STCT use. All 6 cost-effectiveness or cost-utility analyses found FDCs were less expensive and more efficacious than LDCs. Four budget impact models found that STCTs were associated with cost savings. Medical costs and healthcare resource use were generally lower with FDCs than with LDCs. Discussion: Evidence from RWE and economic studies strongly favored STCT use, while clinical trials and HRQoL studies primarily reported similarity between STCTs and LDCs. This may be due to clinical trial procedures aimed at maximizing adherence and HRQoL measures that are not designed to evaluate drug administration. Conclusions: Our findings highlight the value of STCTs for improving patient adherence, persistence, and clinical outcomes while also offering economic advantages.

Clinical Trials for Oral, Inhaled and Intravenous Drug Delivery System for Lung Cancer and Emerging Nanomedicine-Based Approaches.

Lung cancer is one of the most common malignant tumors worldwide and is characterized by high morbidity and mortality rates and a poor prognosis. It is the leading cause of cancer-related death in the United States and worldwide. Most patients with lung cancer are treated with chemotherapy, radiotherapy, or surgery; however, effective treatment options remain limited. In this review, we aim to provide an overview of clinical trials, ranging from Phase I to III, conducted on drug delivery systems for lung cancer treatment. The trials included oral, inhaled, and intravenous administration of therapeutics. Furthermore, the study also talks about the evolving paradigm of targeted therapy and immunotherapy providing promising directions for personalized treatment. In addition, we summarize the best results and limitations of these drug delivery systems and discuss the potential capacity of nanomedicine.

Copper iodide nanoparticles (CuI NPs): an efficient catalyst for the synthesis of alkynyl esters.

An environmentally benign protocol for the synthesis of alkynyl esters, by the cross-coupling of diazoacetate with various substituted alkynes under neat reaction conditions, has been described. Copper iodide nanoparticles (CuI NPs) were found to promote the Sonogashira-type coupling to afford the corresponding alkynyl esters in good yields. The CuI nanoparticles were characterized by PXRD, FESEM, EDAX, and Raman techniques. The developed methodology has several advantages such as a broad substrate scope, less reaction time, atom economy, avoidance of an additive/base/solvent, and enhanced values of green chemistry. The catalyst was recycled up to threefold without the loss of its catalytic activity.

Unveiling the Three-Component Phosphonylation on Alkynylaldehydes: Toolbox toward Fluorescent Molecules.

A regioselective tandem approach for annulated napthyridines/isoquinolines embedded with the phosphine oxide group under mild reaction conditions has been achieved in good to excellent yields. The designed strategy involves the triflate-induced formation of new C sp3-P and C sp2-N bond formation in one pot. This protocol was also well tolerated for the construction of densely functionalized organo-phosphorylated chromenes in good yields. Further, phosphino-derived sulfamethazine and sulfamethoxazole drugs were also successfully synthesized in good yields. The mechanistic studies revealed that the ionic pathway and the formation of regioselective 6-endo dig cyclized products were confirmed through X-ray crystallographic studies. Interestingly, photophysical studies of selectivity selected compounds revealed their stimulating fluorescence properties.

Enhanced Gas Sensing Performance of ZnO/Ti3C2Tx MXene Nanocomposite.

A representative of titanium carbide MXene, Ti3C2Tx is a promising candidate for high performance gas sensing and has attracted significant attention. However, MXene naturally has a multilayer structure with low porosity, which prevents its gas-sensing activity. Zinc oxide (ZnO) has long been utilized as a gas detector. Despite its good response to multiple gases, high operation temperature has limited its widespread use as a gas-sensing material. In this study, a room-temperature toxic gas sensor was prepared from ZnO/Ti3C2Tx MXene nanocomposite consisting of 2D few-layered MXene and 1D ZnO nanoparticles. A simple technique for synthesizing the nanocomposite was established. The physicochemical properties of the nanocomposite were fine-controlled with more active sites and higher porosity. The sensitivity and gas-selectivity of the sensing material were closely examined. The nanocomposite showed enhanced response and recovery behaviors to toxic gases, which outperformed pure Ti3C2Tx MXene and pure ZnO. This study offers a practical strategy by which to increase the gas-sensing performance of Ti3C2Tx MXene, and expands comprehensive understanding of the gas-sensing process of ZnO/Ti3C2Tx p-n heterostructure.

Spontaneous subcapsular renal haematoma in a diabetic patient with acute pyelonephritis.

Spontaneous renal subcapsular haematoma is not a common clinical condition. It is mainly caused by renal tumours, vascular diseases, trauma, anticoagulation, and urological interventions. Patients present with sudden onset abdominal pain mainly in the flank region, haematuria, and abdominal tenderness. We report a case of 42-year-old diabetic patient who presented with a history of fever and left flank pain with clinical signs of pyelonephritis, on whom abdominal ultrasound and computed tomography demonstrated a subcapsular renal haematoma which was confirmed by percutaneous aspiration. Management with antibiotics and percutaneous nephrostomy proved successful.

P016 Impact of Non-Remission on Health-Related Quality of Life and Patient Reported Outcomes in Patients With Crohn's Disease: Targeted Literature Review.

BACKGROUND: Crohn's disease (CD) leads to chronic inflammation of the gastrointestinal tract that significantly impacts patients over an entire lifetime. The decrease in health-related quality of life (HRQoL) may have an impact on patient's level of functioning, work productivity, and other activities. The goal of treatment for CD is clinical remission based on clinical, endoscopic, and biological parameters. There has been introduction of new treatments in recent years. A review was conducted to assess the impact of non-remission on HRQoL and patient reported outcomes (PROs) in patients with CD. METHODS: Literature search of English language publications from 2015-2021 was conducted in Embase® and MEDLINE®. Real world studies meeting predefined criteria (adult CD patients in non-remission presenting data for HRQoL or PROs) were included in the review. Data on study characteristics, disease characteristics, HRQoL and PROs were extracted from the included studies. RESULTS: The review retrieved 1384 records from which only 10 studies presented data for HRQoL and/or PROs. The definition of remission varied across the included studies. In most studies (90%), remission was defined using Harvey-Bradshaw Index and/or Crohn's disease activity index. Different tools were used to assess HRQoL and sleep quality. In a study, no normalization of long-term HRQoL was observed in patients who did not achieve clinical remission. A negative correlation was found between utility indexes & disease activity in a study (ρ = -0.586, p < 0.001). A significant correlation was also observed in a study between HRQoL and disease activity where HRQoL in patients with active disease was poor compared to patients in remission. The HRQoL domains of anxiety, depression and pain were impacted in non-remitters. The mean IBDQ score was 189 ± 16.1 in remitters and 145 ± 15.9 in non-remitters (p < 0.001). A strong negative correlation between IBDQ and disease activity was reported by a study. In a study, work productivity was moderately but significantly correlated with disease activity indicating reduction in work productivity of patients with active disease (mild, moderate, and severe) compared to remitters. In another study, severe disease activity was significantly associated with an increased amount of fragmented sleep. Patients with moderate to severe disease had a significantly longer time awake after falling asleep compared to patients in remission or with mild disease activity (65.8 minutes, 44.3 minutes, 49.1 minutes, respectively). Patients with active disease also reported poor sleep quality and suffered from excessive daytime sleepiness. There was a significant difference in the median sleep efficiency for patients with moderate to severe disease compared to patients with remission. CONCLUSION: This targeted review found in general that not being able to achieve/maintain remission had an impact on the HRQoL of patients with CD. Patients not achieving remission were associated with decreased work productivity, poor sleep quality, lower sleep efficiency, daytime sleepiness and poor HRQoL. However, studies assessing HRQoL and PROs in the real-world are scarce, with discrepancies based on remission status. Further research is warranted, and health care providers and payers should consider the impact of therapies on the improvement in HRQoL of patients with CD.

P025 The Impact of Non-Remission on Costs and Resource Use In Patients With Crohn's Disease: Targeted Literature Review.

BACKGROUND: The incidence of Crohn's disease (CD) has been rising globally. Patients with CD are at an increased risk of mortality compared to general population. The goal of treatment for CD is clinical remission based on clinical, endoscopic, and biological parameters. There has been introduction of new treatments in recent years. A review was conducted to assess the impact of non-remission on cost and resource use in patients with CD. METHODS: Literature search of English language publications from 2015-2021 was conducted in Embase® and MEDLINE®. Real world studies meeting predefined review criteria were included and data were extracted in pre-defined extraction form. RESULTS: The review retrieved 1384 records; 24 fulfilled eligibility criteria. The definition of remission varied across the included studies. In most studies (66.67%), remission was defined using Crohn's disease activity index and/or Harvey-Bradshaw Index. Among included evidence, 21 studies reported proportion of non-remitters undergoing surgery, 11 studies reported the data for hospitalizations and 2 studies reported cost of treatment for non-remitters. Proportion of non-remitters requiring hospitalizations ranged from 6.7% to 30.6%. Univariate analysis suggested that deep remission was significantly associated with lower hazards for being hospitalized (HR: 0.18 [95%CI: 0.08, 0.25]); suggesting a significantly higher risk of hospitalization in non-remitters. In a study, the mean duration of cumulative hospital stays was significantly higher in patients with a pathological MRI (19.7 ± 7.4 days) compared to patients in deep remission (0.75 ± 0.52 days, p < 0.05). The proportion of non-remitters undergoing surgery ranged from 1.5% to 57%. The proportion of patients undergoing surgery were high in non-remitters compared to remitters. Hematopoietic stem cell transplantation was needed in 4.1% non-remitters and repeat surgery in 3.5% non-remitters. In a study, surgery was required by 11.6% patients with no healing (due to refractory strictures, penetrating complications, and severe refractory disease) and 11.5% patients presenting with mucosal healing (due to structuring and penetrating complications), while no patient with transmural healing required surgery. Non-remission led to higher total costs, especially in patients undergoing surgery or dependent on in-hospital administrated drugs. The costs were 4 to 6 times higher in patients in an active period and 19 times higher for patients requiring surgery compared to patients in remission. Adjusted total indirect cost among participants with disease remission was reduced by 60% compared to patients with active disease (€243.44 per patient per month, p < 0.001). The number of consultations in the last month, monthly consultation cost, current treatment cost, amount of benefits from public organisations, and self-reported expenses on all categories were significantly higher in non-remitters compared to patients in remission. CONCLUSION: This targeted review found in general that not being able to achieve/maintain remission has an impact on the economic outcomes of patients with CD. Non-remission in patients with CD was associated with an increased number of hospitalizations and surgeries. The cost of treatment for non-remitters was significantly higher than patients in remission. None of the studies presented data for patients who respond to treatment but are not able to achieve remission. Further research is warranted in these patients.

Plant-derived utility products: knowledge comparison across gender, age and education from a tribal landscape of western Himalaya.

BACKGROUND: Plant-derived utility products (PDPs) play an important role in sustaining humans, especially tribal communities. Despite this, knowledge on PDPs is declining. METHODS: The present study was therefore carried to document the PDPs used by Bhangalis, a tribal community of western Himalaya, through door-to-door surveys (n=420) and detailed questionnaire recordings (n=240). In addition to taxonomic richness, frequency of species used; use value (UV), use diversity (UD), and cultural importance index (CI) were also analysed. Knowledge comparison between genders, four identified age groups (group 1: 16-32 years, group 2: 33-49 years, group 3: 50-66 years, group 4: >66 years), and level of education of the respondents was also carried out using multiple regression in SPSS. RESULTS: Bhangalis reported 55 PDPs under five use categories namely tools (34), artefacts (7), construction and storage (6 each), and miscellaneous (2). For making these PDPs, 20 plant species representing 12 families were used. Picea smithiana (16.54%), Cedrus deodara (14.96%), Cotoneaster bacillaris (12.60%) and Quercus semecarpifolia (11.02%) reported the highest use frequency. On an average 15.13±0.25 PDPs per respondent was noted. Similarly, Picea smithiana (UV=0.088) and Cedrus deodara (UV= 0.079) reported the highest UV when compared to other species. Amongst all the species, maximum UD was revealed for Juglans regia in the tool category (0.91). On the other hand, maximum CI was also recorded for Picea smithiana (CITotal=2.91). With respect to gender, males were found to be more knowledgeable than females (B=6.370, p=0.001). Amongst the four age groups, respondents in group 1 (B=-13.302, p=0.001) and group 2 (B=-5.867, p=0.001) were less knowledgeable in comparison to respondents in the third and fourth age groups. Similarly, education also had a significant negative coefficient (B=-0.275, p=0.037), with educated respondents having lesser knowledge. It was observed that alternates available in the market seem to be limiting the use of PDPs. CONCLUSIONS: Bhangalis still use PDPs that have a crucial role in their lifestyle. However, their use is declining. A multipronged strategy that not only focusses on socio-economic characteristics but also on awareness especially at school levels is desired.

Photon-Induced Superior Antibacterial Activity of Palladium-Decorated, Magnetically Separable Fe3O4/Pd/mpg-C3N4 Nanocomposites.

Three-component nanocomposites (Fe3O4/Pd/mpg-C3N4) have been systematically synthesized using a three-step solution method for the photocatalytic bacterial decontamination. The mesoporous g-C3N4 nanosheets (mpg-C3N4), which were prepared by the acid treatment, showed a great improvement in photocatalytic performance. The photoluminescence intensity of the mpg-C3N4 nanosheets was disclosed to drop about 60% from the value of normal g-C3N4 nanosheets. Decoration of mpg-C3N4 with palladium (Pd) nanoparticles led to the effective suppression of carrier recombination and the carrier migration to Fe3O4 nanoparticles. It was revealed that the three-component nanocomposites degraded 99.9% of E. coli and 99.8% of S. aureus bacterial strains within 2 h of solar light irradiation at a 100 µg/mL concentration, demonstrating their superb photocatalytic antibacterial activity. In addition, the nanocomposites could be easily separated from the bacterial cells and repeatedly used for photocatalytic bacterial degradation with good recyclability. The strong photon-induced antibacterial activity and good recyclability of the three-component nanocomposites may represent their potential as a promising antibacterial photocatalyst.

The Synergistic Effect of Zinc Ferrite Nanoparticles Uniformly Deposited on Silver Nanowires for the Biofilm Inhibition of Candida albicans.

Near-monodisperse zinc ferrite nanoparticles (ZnFe2O4 NPs) are synthesized by a co-precipitation method and deposited on the surface of silver nanowires (AgNWs), employing a stepwise solution method. The resulting hybrid nanostructures (ZnFe2O4@AgNWs) show a thin and uniform layer of ZnFe2O4 NPs at an optimum weight ratio of 1:6 between the two component nanostructures. The hybrid nanostructures retain the high crystal quality and phase purity of their constituents. It is demonstrated that the ZnFe2O4@AgNWs hybrid nanostructures are effective at inhibiting the biofilm formation of Candida albicans cells. The biofilm inhibition activity of the hybrid nanostructures is estimated to be more than 50% at a low concentration of 100 µg/mL from both crystal violet assay and XTT assay, which are more than 8-fold higher than those of pure AgNWs and ZnFe2O4 NPs. This greatly enhanced biofilm inhibition activity is attributed to the ZnFe2O4 NPs-carrying membrane penetration by AgNWs and the subsequent interaction between Candida cells and ZnFe2O4 NPs. These results indicate that the ZnFe2O4@AgNWs hybrid nanostructures have great potential as a new type of novel antibiofilm agent.

Why they eat, what they eat: patterns of wild edible plants consumption in a tribal area of Western Himalaya.

BACKGROUND: From time immemorial, wild plants have been used for edible purposes. They still continue to be a major source of nutrition for tribal people. However, unfortunately, their use is now declining. This has implications in food security, narrowing genetic base, and future leads. The present study was, therefore, carried out in Chhota Bhangal region of Western Himalaya to analyze uses of wild edible plants (WEP) and the motivations behind their use or abandonment. METHODS: Field surveys were conducted to the study area from January 2016 to March 2017. Household surveys, group discussions, free listing, and structured questionnaires were used to elicit information on WEP. WEP use was categorized into six categories (vegetables, fruits, chutney, flavoring food, raw food, and local brew). Trends of use (continuing, decreasing, increasing, and not used) and motivations (environmental, economic, sociocultural, agriculture and land use practices, and human-wildlife conflict) behind their use were analyzed. RESULTS: Fifty plant species were used by the local people for edible purposes under six WEP categories. Mean and median of WEP used per respondent was 22.3 and 21, respectively. Highest number of these were used as vegetable (mean 8.9) while lowest were used as brew (mean 0.4). Out of the 50 WEP used, 20 were prioritized for motivation analyses. Though plant use is still maintained in the area, changes are evident. Almost 50% of the respondents revealed that they still continue the use of WEP while 36% reported trends of declining use as compared to 5-10 years back. Close to 10% respondents have stopped consuming WEP now and ~ 3% reported an increase in the use of WEP. Among the WEP categories, use of chutney showed an increasing trend. Sociocultural motivations were found to play a prime role, both, in limiting and promoting WEP use. Taste and aroma were the major sociocultural reasons behind using WEP while modernization and changing lifestyle were the main reasons behind declining use of WEP. CONCLUSIONS: The study concludes that though use of WEP is still maintained in the area, changes in consumption trends are evident. Sociocultural motivations guided use of WEP in the area.

Microencapsulation of ß-Carotene Based on Casein/Guar Gum Blend Using Zeta Potential-Yield Stress Phenomenon: an Approach to Enhance Photo-stability and Retention of Functionality.

ß-Carotene, abundant majorly in carrot, pink guava yams, spinach, kale, sweet potato, and palm oil, is an important nutrient for human health due to its scavenging action upon reactive free radicals wherever produced in the body. Inclusion of liposoluble ß-carotene in foods and food ingredients is a challenging aspect due to its labile nature and low absorption from natural sources. This fact has led to the application of encapsulation of ß-carotene to improve stability and bioavailability. The present work was aimed to fabricate microcapsules (MCs) of ß-carotene oily dispersion using the complex coacervation technique with casein (CA) and guar gum (GG) blend. The ratio of CA:GG was found to be 1:0.5 (w/v) when optimized on the basis of zeta potential-yield stress phenomenon. These possessed a higher percentage yield (71.34 ± 0.55%), lower particle size (176.47 ± 4.65 µm), higher encapsulation efficiency (65.95 ± 5.33%), and in general, a uniform surface morphology was observed with particles showing optimized release behavior. Prepared MCs manifested effective and controlled release (up to 98%) following zero-order kinetics which was adequately explained by the Korseymer-Peppas model. The stability of the freeze-dried MCs was established in simulated gastrointestinal fluids (SGF, SIF) for 8 h. Antioxidant activity of the MCs was studied and revealed the retention of the functional architecture of ß-carotene in freeze-dried MCs. Minimal photolytic degradation upon encapsulation of ß-carotene addressed the challenge regarding photo-stability of ß-carotene as confirmed via mass spectroscopy.

Formation and functional attributes of electrostatic complexes involving casein and anionic polysaccharides: An approach to enhance oral absorption of lycopene in rats in vivo.

The current work entails a novel strategy of formulating the microparticles of lycopene solely using rational blends of biopolymers without using equipment-intensive techniques. The study is intended to enhance oral bioavailability of lycopene by controlling its release from micro-formulation and facilitating its absorption though lymphatic pathways. Considering the minimum particle size, maximum entrapment efficiency and loading capacity, the amounts of casein (i.e., protein) and gum tragacanth (i.e., polysaccharide) were selected as the critical factors for formulation of microparticles. Complex formation and electrostatic interaction was confirmed by Fourier transform infra red (FTIR) spectra. Size and surface properties of microparticles were studied using scanning electron microscopy (SEM). The optimized formulation (mean particle size: ∼130µm; % entrapment efficiency: ∼67% and loading capacity: ∼71%) designated noticeable improvement in lycopene release profile (over 80% in 24h). Increment in the values of Cmax (2.22-fold) and AUC (1.97-fold) further indicated noteworthy augmentation in the rate and extent of bioavailability by the microparticles formulation compared to plain lycopene. The resulting formulation was found to be quite stable all through two months of study episode. The resultant microparticles formulation was evaluated for antioxidant activity and tested for their effectiveness in self life enhancement of vegetable oil by calculating peroxide value under temperature and storage condition. Encapsulation strongly increased the stability of micronutrients. The current investigations, therefore, report the successful development of biopolymeric microparticles with improved bioavailability potential of lycopene.

Characterization of microcapsulated ß-carotene formed by complex coacervation using casein and gum tragacanth.

Complex coacervation in casein/gum tragacanth (CAS/GT) mixtures was studied as a function of pH, initial protein to polysaccharide mixing ratio (Pr:Ps), total biopolymer concentration, core material load and ionic strength. This study is aimed at understanding how these parameters influence the coacervation kinetics, the coacervate yield, and entrapment efficiency. At a Pr:Ps=2:1, an optimum pH of complex coacervation was found 4.35, at which the intensity of electrostatic interaction was maximum. At these conditions, the phase separation occurred the fastest and the final coacervate yield and entrapment efficiency were the largest. Moreover, the developed ß-carotene loaded microcapsules formulation was found to have particle size 159.71±2.16µm, coacervates yield 82.51±0.412%, entrapment efficiency 79.36±0.541%. Varying the Pr:Ps shifted the value of optimum pH. Electrostatic interaction and formation of coacervates was confirmed by Fourier Transform Infra Red (FTIR) spectra. Size and surface properties of coacervates were studied using Scanning Electron Microscopy (SEM). Entrapment of core material within the coacervates was confirmed by Confocal Laser Scanning Microscope (CLSM). The resultant formulation was evaluated for release study and antioxidant activity. Stability of encapsulated ß-carotene was evaluated under three levels of temperature (5, 25 and 40°C) for 3 months. Encapsulation strongly increased the stability of micronutrients. Our results advocate potential of microcapsules as a novel carrier for the safeguard and sustained release of micronutrient.

Systematic review of humanistic and economic burden of symptomatic chronic obstructive pulmonary disease.

BACKGROUND: An understanding of the humanistic and economic burden of individuals with symptomatic chronic obstructive pulmonary disease (COPD) is required to inform payers and healthcare professionals about the disease burden. OBJECTIVES: The aim of this systematic review was to identify and present humanistic [health-related quality of life (HRQoL)] and economic burdens of symptomatic COPD. METHODS: A comprehensive search of online databases (reimbursement or claims databases/other databases), abstracts from conference proceedings, published literature, clinical trials, medical records, health ministries, financial reports, registries, and other sources was conducted. Adult patients of any race or gender with symptomatic COPD were included. Humanistic and economic burdens included studies evaluating HRQoL and cost and resource use, respectively, associated with symptomatic COPD. RESULTS: Thirty-two studies reporting humanistic burden and 74 economic studies were identified. Symptomatic COPD led to impairment in the health state of patients, as assessed by HRQoL instruments. It was also associated with high economic burden across all countries. The overall, direct, and indirect costs per patient increased with an increase in symptoms, dyspnoea severity, and duration of disease. Across countries, the annual societal costs associated with symptomatic COPD were higher among patients with comorbidities. CONCLUSIONS: Symptomatic COPD is associated with a substantial economic burden. The HRQoL of patients with symptomatic COPD is, in general, low and influenced by dyspnoea.

Impact of prolonged-release oxycodone/naloxone on outcomes affecting patients' daily functioning in comparison with extended-release tapentadol: a systematic review.

PURPOSE: The objective of this systematic review was to assess the clinical efficacy, safety, tolerability, and health-related quality of life outcomes associated with management of moderate-to-severe chronic pain with oxycodone/naloxone and tapentadol, focusing on the effect of these treatments on patients' daily functioning. METHODS: Literature from a wide range of sources, including Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register of Controlled Trials, was searched to identify randomized controlled trials investigating tapentadol or oxycodone/naloxone for the treatment of patients with chronic pain. A network meta-analysis was conducted to determine the relative efficacy and safety profiles of these treatments. FINDINGS: Oxycodone/naloxone was significantly better than tapentadol with respect to the Patient Assessment of Constipation Symptoms total score (risk ratio = -3.60; 95% credible interval, -5.36 to -2.11) and revealed a significantly lower risk of dizziness (risk ratio = 0.72; 95% credible interval, 0.42-0.98). Oxycodone/naloxone was directionally favored, although not significantly superior to tapentadol for headache, fatigue, dry mouth, dyspepsia, and withdrawals due to lack of efficacy. For the AE outcomes of constipation, nausea, and vomiting, as well as pain efficacy and all-cause withdrawals from studies, tapentadol was directionally favored without any statistical difference from oxycodone/naloxone. However, the two treatments were not wholly comparable for the evaluation of pain efficacy because of differences in on-study rescue medication and a higher baseline pain severity in the tapentadol studies. IMPLICATIONS: Oxycodone/naloxone offers significant improvements in Patient Assessment of Constipation Symptoms total score and dizziness and was directionally favored for fatigue and headache compared with extended-release tapentadol, which may translate to improved patient daily functioning and health-related quality of life.