Background Surgery is the main modality of cure for solid cancers and was prioritised to continue during COVID-19 outbreaks. This study aimed to identify immediate areas for system strengthening by comparing the delivery of elective cancer surgery during the COVID-19 pandemic in periods of lockdown versus light restriction. Methods This international, prospective, cohort study enrolled 20 006 adult (≥18 years) patients from 466 hospitals in 61 countries with 15 cancer types, who had a decision for curative surgery during the COVID-19 pandemic and were followed up until the point of surgery or cessation of follow-up (Aug 31, 2020). Average national Oxford COVID-19 Stringency Index scores were calculated to define the government response to COVID-19 for each patient for the period they awaited surgery, and classified into light restrictions (index <20), moderate lockdowns (20–60), and full lockdowns (>60). The primary outcome was the non-operation rate (defined as the proportion of patients who did not undergo planned surgery). Cox proportional-hazards regression models were used to explore the associations between lockdowns and non-operation. Intervals from diagnosis to surgery were compared across COVID-19 government response index groups. This study was registered at ClinicalTrials.gov , NCT04384926 . Findings Of eligible patients awaiting surgery, 2003 (10·0%) of 20 006 did not receive surgery after a median follow-up of 23 weeks (IQR 16–30), all of whom had a COVID-19-related reason given for non-operation. Light restrictions were associated with a 0·6% non-operation rate (26 of 4521), moderate lockdowns with a 5·5% rate (201 of 3646; adjusted hazard ratio [HR] 0·81, 95% CI 0·77–0·84; p<0·0001), and full lockdowns with a 15·0% rate (1775 of 11 827; HR 0·51, 0·50–0·53; p<0·0001). In sensitivity analyses, including adjustment for SARS-CoV-2 case notification rates, moderate lockdowns (HR 0·84, 95% CI 0·80–0·88; p<0·001), and full lockdowns (0·57, 0·54–0·60; p<0·001), remained independently associated with non-operation. Surgery beyond 12 weeks from diagnosis in patients without neoadjuvant therapy increased during lockdowns (374 [9·1%] of 4521 in light restrictions, 317 [10·4%] of 3646 in moderate lockdowns, 2001 [23·8%] of 11 827 in full lockdowns), although there were no differences in resectability rates observed with longer delays. Interpretation Cancer surgery systems worldwide were fragile to lockdowns, with one in seven patients who were in regions with full lockdowns not undergoing planned surgery and experiencing longer preoperative delays. Although short-term oncological outcomes were not compromised in those selected for surgery, delays and non-operations might lead to long-term reductions in survival. During current and future periods of societal restriction, the resilience of elective surgery systems requires strengthening, which might include...

Furosemide-loaded alginate microspheres were prepared by the ionic cross-linking technique using CaCl2, Al2(SO4)3 and BaCl2. The process induced the formation of microspheres with the incorporation efficiency of 65% to 93%. The effect of sodium alginate concentration, cross-linking agents and drying conditions was evaluated with respect to entrapment efficiency, particle size, surface characteristics and in vitro release behaviors. Infrared spectroscopic study confirmed the absence of any drug-polymer interaction. Differential scanning calorimetric analysis revealed that the drug was molecularly dispersed in the alginate microspheres matrices showing rough surface, which was confirmed by scanning electron microscopy study. The mean particle size and entrapment efficiency were found to be varied by changing various formulation parameters. The in vitro release profile could be altered significantly by changing various formulation parameters to give a sustained release of drug from the microspheres. The kinetic modeling of the release data indicate that furosemide release from the alginate microspheres follow anomalous transport mechanism after an initial lag period when the drug release mechanism was found to be fickian diffusion controlled.

NeuroAIDS (Neuro Acquired Immunodeficiency Syndrome) or HIV (Human Immunodeficiency Virus) associated neuronal abnormality is continuing to be a significant health issue among AIDS patients even under the treatment of combined antiretroviral therapy (cART). Injury and damage to neurons of the brain are the prime causes of neuroAIDS, which happens due to the ingress of HIV by direct permeation across the blood-brain barrier (BBB) or else via peripherally infected macrophage into the central nervous system (CNS). The BBB performs as a stringent barricade for the delivery of therapeutics drugs. The intranasal route of drug administration exhibits as a non-invasive technique to bypass the BBB for the delivery of antiretroviral drugs and other active pharmaceutical ingredients inside the brain and CNS. This method is fruitful for the drugs that are unable to invade the BBB to show its action in the CNS and thus erase the demand of systemic delivery and thereby shrink systemic side effects. Drug delivery from the nose to the brain/CNS takes very less time through both olfactory and trigeminal nerves. Intranasal delivery does not require the involvement of any receptor as it occurs by an extracellular route. Nose to brain delivery also involves nasal associated lymphatic tissues (NALT) and deep cervical lymph nodes. However, very little research has been done to explore the utility of nose to brain delivery of antiretroviral drugs in the treatment of neuroAIDS. This review focuses on the potential of nasal route for the effective delivery of antiretroviral nanoformulations directly from nose to the brain.

153Sm, an attractive therapeutic radionuclide, was produced by neutron activation of both natural Sm2O3 and 98% enriched 152Sm2O3 targets. The production logistics and radionuclidic purity aspects of 153Sm obtained using both these targets are discussed with respect to the intended end use for metastatic bone pain palliation (MBPP) in terminal cancer patients and radiation synovectomy (RS) of medium size joints. The specific activity of 153Sm obtained was around 11 GBq x mg(-1) (approximately 300 mCi x mg(-1)) and 44 GBq x mg(-1) (approx. 1200 mCi x mg(-1)) from natural and enriched targets, respectively. The level of the long-lived radionuclidic impurity burden in 153Sm obtained from the natural Sm2O3 targets, namely, due to 154Eu (5 Bq x MBq(-1) 153Sm (5 nCi x mCi(-1) 153Sm)) and 155Eu (75 Bq x MBq(-1) 153Sm (75 nCi x mCi(-1) 153Sm)), appears low enough not to pose a problem, both in the palliative treatment of terminal cancer patients (at 1.85-2.22 GBq (50-60 mCi) dose) as well as in RS (at 74 MBq (2 mCi) dose). The 154Eu content in 153Sm from the enriched target was comparable, while, as expected, the level of 155Eu was nearly two orders of magnitude lower. There is a notable overall advantage of 153Sm over the use of 186Re, the other radionuclide of interest for the same purposes.

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The main objective of the present study was to improve bioavailability of diltiazem hydrochloride and decrease the frequency of dosage form administration by increasing the encapsulation efficiency of the drug, residence time of the dosage form at the site of absorption and sustained release of the drug from the delivery system. Alginate microspheres containing diltiazem hydrochloride were prepared by the emulsification-internal gelation method by using barium carbonate as a cross-linking agent with improved encapsulation efficiency. The effect of various factors (concentration of alginate and barium chloride) on the drug loading efficiency and in vitro release were investigated. Fourier transform infrared spectroscopy (FT-IR) analysis confirmed the absence of any drug polymer interaction. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) pattern showed that the crystallinity of the drug was decreased in the dosage forms. The in vitro drug release mechanism was non-Fickian type controlled by swelling and relaxation of polymer. The stability studies of drug-loaded microspheres showed that the drug was stable at different storage conditions.

The aim of our study was to investigate the enhancing effect of several essential oils in the percutaneous absorption of trazodone hydrochloride (TZN). For this purpose, fennel oil, eucalyptus oil, citronella oil, and mentha oil were applied on the skin membrane in three different ways: included in the transdermal device, as a pretreatment, or both. To investigate the effect of penetration enhancers used in this study on the percutaneous absorption of TZN through mouse epidermis, Keshary-Chien diffusion cells were employed. The receptor phase was constantly stirring saline phosphate buffer of pH 7.4 at 37 +/- 1 degrees C. Results showed that pretreatment of skin with essential oils increases the flux values of TZN compared with the values obtained when the same essential oils were included in the transdermal devices. The percutaneous penetration flux for TZN was increased with skin pretreatment by 10% essential oils in the following order: fennel oil > eucalyptus oil > citronella oil > mentha oil. The amount of TZN retained in the skin after pretreatment with essential oils was found to be very similar in all cases and much higher than in the experiments without skin pretreatment.

The aim of this study was to formulate and evaluate microencapsulated controlled release preparations of zidovudine using ethyl cellulose as the retardant material with high entrapment efficiency and extended release. Microspheres were prepared by water-in-oil-in-oil (w/o/o) double emulsion solvent diffusion method. A mixed solvent system (MSS) consisting of acetonitrile and dichloromethane in a 1:1 ratio and light liquid paraffin were chosen as primary and secondary oil phases, respectively. Span 80 was used as the surfactant for stabilizing the secondary oil phase. The prepared microspheres were white, free flowing and spherical in shape and characterized by drug loading, infrared spectroscopy (IR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release studies were performed using PH 7.4 phosphate buffer. The drug loaded microspheres showed 41-55% of entrapment and release was extended up to 18-20 h. The infrared spectra and DSC and DTA thermograms showed stable character of zidovudine in the drug loaded microspheres and revealed the absence of drug-polymer interactions. SEM studies showed that the microspheres are spherical and porous in nature. Data obtained from in vitro release were fitted to various kinetic models and high correlation was obtained in the Higuchi model. The drug release was found to be diffusion controlled.