A numerical study of spatio-temporal COVID-19 vaccine model via finite-difference operator-splitting and meshless techniques.

In this paper, a new spatio-temporal model is formulated to study the spread of coronavirus infection (COVID-19) in a spatially heterogeneous environment with the impact of vaccination. Initially, a detailed qualitative analysis of the spatio-temporal model is presented. The existence, uniqueness, positivity, and boundedness of the model solution are investigated. Local asymptotical stability of the diffusive COVID-19 model at steady state is carried out using well-known criteria. Moreover, a suitable nonlinear Lyapunov functional is constructed for the global asymptotical stability of the spatio-temporal model. Further, the model is solved numerically based on uniform and non-uniform initial conditions. Two different numerical schemes named: finite difference operator-splitting and mesh-free operator-splitting based on multi-quadratic radial basis functions are implemented in the numerical study. The impact of diffusion as well as some pharmaceutical and non-pharmaceutical control measures, i.e., reducing an effective contact causing infection transmission, vaccination rate and vaccine waning rate on the disease dynamics is presented in a spatially heterogeneous environment. Furthermore, the impact of the  aforementioned interventions is investigated with and without diffusion on the incidence of disease. The simulation results conclude that the random motion of individuals has a significant impact on the disease dynamics and helps in setting a better control strategy for disease eradication.

Two methodologies of the rendezvous procedure to establish ureteral continuity from a delayed ureteral leak following pelvic surgery.

BACKGROUND: Ureteral trauma recognized in the operating theater is managed, for the most part, at the same surgical procedure oftentimes with urologic consultation. A delayed urine leak presents unique problems in that direct access to the site of the leak is not possible except by a reoperative procedure. METHODS: In patients who develop delayed urine leakage following cancer surgery, the leakage may be controlled by the collaborative efforts of a urologist and interventional radiologist. Success depends on placement of a nephroureteral stent by the rendezvous procedure. RESULTS: The sequence of procedures to reestablish ureteral continuity following a delayed leak are important in the successful placement of a nephroureteral stent. In the first methodology, through a percutaneous nephrostomy, a guidewire is placed in the ureter and down to the ureteral defect. The guidewire is then recovered and advanced into the bladder using a ureteroscope and grasping forceps. A nephroureteral stent is placed over the guidewire to bridge the gap and stent the ureteral defect. In the second methodology, the urologist passed a guidewire into the distal ureter, out of the ureteral defect, and into the free peritoneal space. Under fluoroscopic control, the wire loop must snare the ureteral guidewire and pull it out at the percutaneous nephrostomy. The nephroureteral stent is passed over the ureteral wire into the bladder. CONCLUSIONS: Two different methodologies were described to complete the rendezvous procedure. It can be successful a large percentage of the time with a delayed ureteral leakage. Success requires a combined interventional radiology and urologic procedure.

Effect of intra-arterial vasodilator administration during radial artery access on systemic blood pressure in patients receiving moderate sedation.

PURPOSE: The hemodynamic effects of intra-arterial vasodilator administration for the prevention of radial artery spasm during transradial access have not been well characterized. This study evaluates the effect of intra-arterial Verapamil and Nitroglycerine administration on systemic blood pressure and its correlation with timing of moderate sedation administration. MATERIALS AND METHODS: Institutional review board approval was granted. Patients who underwent transradial access from 4/2018 to 4/2019 and received both intra-arterial vasodilators and moderate sedation were identified and their electronic medical records reviewed. Patients were divided into three cohorts based on the timing of sedation and intra-arterial vasodilator administration. Decrease in systolic blood pressure (SBP) was expressed as means with standard deviation which were then compared using Student's t-test. RESULTS: A total of 84 patients who met inclusion criteria demonstrated an overall mean decrease in SBP of 16.45 mmHg ± 15.45 mmHg. Patients receiving sedation and intra-arterial vasodilators within their expected peak SBP effect times had similar SBP change following the intra-arterial vasodilators as those in whom the interval was greater than 10 min (4.2 mmHg; 95% CI (-4.11 to 12.52), p = 0.3171). Two patients experienced asymptomatic hypotension. CONCLUSIONS: Patients undergoing transradial access for procedures utilizing moderate sedation can safely receive intra-arterial Verapamil and Nitroglycerine for prevention of radial artery spasm.

Natural history and prognostic implications of left ventricular end-diastolic pressure in reperfused ST-segment elevation myocardial infarction: an analysis of the thrombolysis in myocardial infarction (TIMI) II randomized controlled trial.

BACKGROUND: The aim of the current study is to assess the natural history and prognostic value of elevated left ventricular end-diastolic pressure (LVEDP) in patients with ST-segment elevation myocardial infarction (STEMI) after reperfusion with thrombolysis; we utilize data from the Thrombolysis in Myocardial Infarction (TIMI) II study. METHODS: A total of 3339 patients were randomized to either an invasive (n = 1681) or a conservative (n = 1658) strategy in the TIMI II study following thrombolysis. To make the current cohort as relevant as possible to modern pharmaco-invasively managed cohorts, patients in the invasive arm with TIMI flow grade ≥ 2 (N = 1201) at initial catheterization are included in the analysis. Of these, 259 patients had a second catheterization prior to hospital discharge, and these were used to define the natural history of LVEDP in reperfused STEMI. RESULTS: The median LVEDP for the whole cohort was 18 mmHg (IQR: 12-23). Patients were divided into quartiles by LVEDP measured during the first cardiac catheterization. During a median follow up of 3 (IQR: 2.1-3.2) years, quartile 4 (highest LVEDP) had the highest incidence of mortality and heart failure admissions. In the cohort with paired catheterization data, the LVEDP dropped slightly from 18 mmHg (1QR: 12-22) to 15 mmHg (IQR: 10-20) (p = 0.01) from the first to the pre-hospital discharge catheterization. CONCLUSIONS: LVEDP remains largely stable during hospitalisation post-STEMI. Elevated LVEDP is a predictor of death and heart failure hospitalization in STEMI patients undergoing successful thrombolysis.

Evaluation and Treatment of Foot Drop Using Nerve Transfer Techniques.

Foot drop represents a complex pathologic condition, requiring a multidisciplinary approach for appropriate evaluation and treatment. Multiple etiologic factors require recognition before considering invasive/operative intervention. When considering surgical management for the treatment of foot drop, it is first and foremost imperative to establish the cause of the condition. Not all causes resulting in clinical foot drop have surgical options. Establishing a cause allows the provider to more appropriately curtail a multidisciplinary approach to working-up, and ultimately, treating the patient. The authors offer an algorithm for evaluating and treating foot drop conditions associated with lumbar spine radiculopathy and peripheral nerve lesions.

Rendezvous procedure to establish ureteral continuity from a delayed ureteral leak following pelvic surgery. A case report.

BACKGROUND: Iatrogenic damage to the ureter as a result of an abdominal or pelvic surgical procedure is unusual. However, it does occur and the surgeon must be prepared to deal knowledgeably with the injury. Leaks that are recognized within the operating theater are managed, for the most part, at the same surgical procedure oftentimes with urologic consultation. A delayed leak presents unique problems in that direct access to the site of the leak is not possible except by a reoperative procedure. Delayed leaks present a clinical situation involving the urologist, interventional radiologist, as well as the surgeon. METHODS: A patient who developed delayed urine leakage following a partial sacrectomy to remove recurrent mucinous appendiceal malignancy was studied. The leakage was controlled using a nephroureteral stent. Placement of the nephroureteral stent was made possible by the rendezvous procedure. RESULTS: The sequence of procedures to reestablish ureteral continuity following a delayed leak are important in the successful placement of a nephroureteral stent. After establishing the site of the injury a percutaneous nephrostomy must be placed. Then, through the nephrostomy, a guidewire is placed in the ureter to be recovered and advanced into the bladder using a ureteroscope and grasping forceps. A nephroureteral stent is placed over the guidewire to bridge the gap and stent the ureteral defect. CONCLUSIONS: The rendezvous procedure can be successful a large percentage of the time with a delayed ureteral leakage. Successful recovery of a guidewire in the ureter by ureteroscopy requires a combined interventional radiology and urologic procedure.

Skin Graft Techniques.

Management of extensive lower extremity soft tissue and skin loss can be a very difficult to achieve by any surgeon. There can be several associated comorbidities that need to be considered and addressed with these patients. The approach is multifactorial and requires commitment from both the surgeon as well as the patient. There are several protocols that have been formulated throughout the literature addressing soft tissue and skin coverage of the limbs. This article provides a review of the literature and describes the evaluation, harvesting, transplantation, and management of skin grafting techniques to the lower extremities.

Targeting elevated left ventricular end-diastolic pressure following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction - a phase one safety and feasibility study.

INTRODUCTION: Elevated left ventricular end diastolic pressure (LVEDP) is an independent predictor of mortality and heart failure in patients with ST-segment elevation myocardial infarction (STEMI). Whether lowering elevated LVEDP improves outcomes remains unknown. METHODS: This non-randomized, single blinded study with prospective enrolment and sequential group allocation recruited patients undergoing primary percutaneous coronary intervention for STEMI with LVEDP ⩾ 20 mmHg measured immediately after primary percutaneous coronary intervention. The intervention arm (n=10) received furosemide 40 mg intravenous bolus plus escalating doses of glyceryl trinitrate (100 µg per min to a maximum of 1000 µg) during simultaneous measurement of LVEDP. The control group (n=10) received corresponding normal saline boluses with simultaneous measurement of LVEDP (10 readings over 10 min). Efficacy endpoints were final LVEDP achieved, and the dose of glyceryl trinitrate needed to reduce LVEDP by ⩾ 20%. Safety endpoint was symptomatic hypotension (systolic blood pressure < 90 mmHg). RESULTS: From 1 April 2017 to 23 August 2017 we enrolled 20 patients (age: 64±9 years, males: 60%, n=12, anterior STEMI: 65%, n=13). The mean LVEDP for the whole cohort (n=20) was 29±4 mmHg (intervention group: 28±3 mmHg vs. control group: 31±5 mmHg; p=0.1). The LVEDP dropped from 28±3 to 16±2 mmHg in the glyceryl trinitrate + furosemide group (p <0.01) but remained unchanged in the control group. The median dose of glyceryl trinitrate required to produce ⩾ 20% reduction in LVEDP in the intervention group was 200 µg (range: 100-800). One patient experienced asymptomatic decline in systolic blood pressure to below 90 mmHg. There was no correlation between LVEDP and left ventricular ejection fraction. CONCLUSION: The administration of glyceryl trinitrate plus furosemide in patients with elevated LVEDP following primary percutaneous coronary intervention for STEMI safely reduces LVEDP.

Pre-hospital thrombolysis for ST-segment elevation myocardial infarction in regional Australia: long-term follow up.

BACKGROUND: Delivering reperfusion therapy to patients with ST-segment elevation myocardial infarction (STEMI) in regional areas without access to tertiary cardiology care remains challenging. The systems of care in Hunter New England Health, New South Wales, Australia (area covered = 130 000 km2 ) to provide reperfusion to patients with STEMI involve a 12-lead electrocardiogram in the ambulance, discussion between cardiologist and paramedic, followed by pre-hospital thrombolysis (PHT) delivered in ambulance to appropriate patients >60 min from the cardiac catheterisation laboratories. Patients who can access the cardiac catheterisation laboratories within 60 min are treated with primary percutaneous coronary intervention (PCI). AIMS: We have previously reported excellent 12-month outcomes for patients receiving PHT and the aim of the current analysis is to look at the long term outcomes. METHODS: We assessed long-term all-cause mortality and major adverse cardiovascular events of STEMI patients undergoing PHT in our health district from August 2008 to August 2013 and compared with the primary PCI group. RESULTS: One hundred and fifty (mean age: 62 ± 13 years, males: 76%, n = 114) patients were administered PHT and 334 patients (mean age: 65 ± 13 years, males: 75%, n = 251) underwent primary PCI during the study period. During a median follow up of 6.2 years (interquartile range: 4.8-7.4 years) all-cause mortality was 16% and 19% in the PHT and primary PCI groups respectively (P = 0.4). CONCLUSION: Our real-world experience shows that PHT followed by early transfer to a primary PCI-capable centre is an effective reperfusion strategy, with comparable results to primary PCI, and mortality benefits are sustained to more than 6 years.

Ibrutinib-related atrial fibrillation: A single center Australian experience.

BACKGROUND: Ibrutinib increases the risk of atrial fibrillation (AF) and is associated with bleeding tendencies. Reported rates of arrhythmia are variable in different studies. The aim of the current analysis was to evaluate the incidence of AF in a single-center cohort of patients. METHODS: This analysis was conducted at Hunter New England Local Health District, Australia between April 1, 2015 and June 30, 2017. We included all consecutive patients commenced on ibrutinib for hematological malignancies. Patients with a history of paroxysmal AF were excluded. The primary end point was incidence of AF. Time to diagnosis and management were secondary outcomes of interest. RESULTS: A total of 24 patients (age 73 ± 9 years, males n = 16 [67%]) were commenced on ibrutinib treatment during the study period with chronic lymphocytic leukemia (n = 21, 88%) as the main indication. During a median follow-up of 12 months, four (17%) patients were diagnosed with AF with increasing age, duration of ibrutinib treatment as associations. The median time to AF diagnosis was 9 (interquartile range [IQR]: 7-18) months. All patients were managed with a rate control strategy with beta blockers as the preferred agents. Three (75%) patients were commenced on anticoagulation for stroke prevention. During a follow-up of 18 (IQR: 17-23) months following AF onset, one patient required hospitalization for AF. There were no bleeding complications reported. CONCLUSIONS: In conclusion, this series noted a higher incidence of AF than previously reported. Oncologists and cardiologists need to be aware of the increased risk of AF in patients receiving ibrutinib.

Outcomes following heart failure hospitalization in a regional Australian setting between 2005 and 2014.

AIMS: The aim of the current study is to examine 10 year trends in mortality and readmission following heart failure (HF) hospitalization in metropolitan and regional Australian settings. METHODS AND RESULTS: We identified all index HF hospitalizations in the Hunter New England region from 2005 to 2014, using a 10 year 'look back' period. The primary endpoint was a composite of all-cause mortality or all-cause readmission at 1 year. Secondary endpoints included all-cause mortality, all-cause readmission, and HF readmission at 30 days and 1 year. We used logistic regression to explore the predictors of the composite outcome of either all-cause death or readmission at 1 year. There were 12 114 patients admitted with a first episode of HF between 2005 and 2014, followed up until death or the end of 2015. The mean age was 78 ± 12 years and 49% (n = 5906) were male. A total of 4831 (40%) resided in regional areas and the remainder in metropolitan areas. One hundred sixty-eight patients (1.4%) were Aboriginal. Approximately 69% of patients had either died or been readmitted for any cause within 12 months of their index event. The 30 day and 1 year all-cause mortality rates were 13% and 32%, respectively, with no change in the trend over the study period. Age, socio-economic disadvantage, ischaemic heart disease, renal failure, and chronic lower respiratory disease were predictors of the primary endpoint. CONCLUSIONS: Heart failure hospitalizations are followed by high rates of death or readmission. There was no change in this composite endpoint over the 10 year study period.

Increasing mortality from ischaemic heart disease in China from 2004 to 2010: disproportionate rise in rural areas and elderly subjects. 438 million person-years follow-up.

Aims: We sought to ascertain the changes in mortality from ischaemic heart disease (IHD) from 2004 to 2010 in China as the sheer size of China's population makes disease patterns relevant globally. Methods and results: Data on IHD mortality were obtained from the Chinese Centre for Disease Control and Prevention National Disease Surveillance Point System, which includes 161 counties and a population of over 73 million-a representative sample of over 6% of the entire population of China. Both crude and World Health Organization (WHO)-standardized IHD mortality increased, in both men and women and in both urban and rural locations, during the study period, demonstrating the effect of urbanization, economic growth, and epidemiological transition on cardiovascular health. WHO-standardized IHD mortality increased for rural males by 9.2% per year (95% CI: 6.7-11.7%; P < 0.0001), and the trend was statistically significantly higher (P = 0.0001) than in urban males by 6.4% per year (95% CI: 3-10%; P = 0.02). WHO-standardized IHD mortality rate increased for rural females by 7.0% per year (95% CI: 4.6-9.4%; P < 0.0001); this was statistically significantly higher than urban females by 4.3% per year (95% CI: 1-8%; P = 0.02). The age group over 80 years showed the greatest increase in IHD mortality. Conclusions: Mortality from IHD is increasing in China, in contrast to decreasing in other countries. This is largely driven by increasing IHD mortality in rural areas and subjects over 80 years old. This needs urgent attention by public health workers and policymakers.

Clozapine and incidence of myocarditis and sudden death - Long term Australian experience.

BACKGROUND: Clozapine is the cornerstone of therapy for refractory schizophrenia; however, the potential for cardiotoxicity is an important limitation in its use. In the current analysis we sought to evaluate the long term cardiac outcomes of clozapine therapy. METHODS: All-cause mortality, incidence of sudden death and time to myocarditis were assessed in a cohort of patients maintained on clozapine between January 2009 and December 2015. All patients had regular electrocardiograms, complete blood count, clozapine levels and echocardiography as part of a formal protocol. RESULTS: A total of 503 patients with treatment-resistant schizophrenia were maintained on clozapine during the study period of which 93 patients (18%) discontinued therapy with 29 (6%) deaths. The incidence of sudden death and myocarditis were 2% (n=10) and 3% (n=14) respectively. Amongst patients with sudden death, 7 out of 10 (70%) were documented to have used illicit drugs prior to death, with a tendency to weight gain also noted. The mean time to myocarditis post clozapine commencement was 15±7days. The reduction in left ventricular ejection fraction in those with myocarditis was 11±2%. CONCLUSION: Myocarditis and sudden cardiac death are uncommon but clinically important complications in a cohort of patients followed while maintained on clozapine undergoing regular cardiac assessment. Further studies are required to document the role of preventive measures for left ventricular dysfunction and sudden cardiac death in this population.

Echocardiographic assessment of pulmonary artery systolic pressure following treadmill stress testing.

AIMS: The use of treadmill stress echocardiography (SE) for the diagnosis of nascent pulmonary hypertension (PH) has been hampered by a lack of well-defined, post-exercise pulmonary artery systolic pressure (PASP) values across representative age groups in a normal cohort. METHODS AND RESULTS: Five hundred and eleven subjects (mean age: 53 ±14, 68% female) with normal resting PASP were included in the study. All participants performed treadmill exercise using the Bruce protocol to a high level of perceived exertion. PASP was calculated before and immediately after exercise using Doppler assessment of tricuspid regurgitation. For the cohort, post-exercise PASP was 39 ± 7 mmHg (range: 23-64 mmHg) representing an increase of 11 ± 6 mmHg (44%) from resting values (P < 0.001). The 95th centile values for post-exercise PASP were calculated for the following age cohorts: <30 years; 46 mmHg, 31-50 years; 50 mmHg, 51-70 years; 52 mmHg, >70 years; 53 mmHg. There was a modest independent correlation between post-exercise PASP and (i) increasing age and (ii) resting PASP (r2 = 0.35 and 0.49, respectively, P = 0.01). CONCLUSION: An increase of post-exercise PASP was seen in all patients undergoing SE in this study. Age was directly correlated with post-exercise PASP. Using normative data from healthy controls, treadmill SE-derived post-exercise PASP may be a useful adjunct in the diagnosis of PH.

Heart Failure Hospitalisations in the Hunter New England Area Over 10 years. A Changing Trend.

BACKGROUND: Heart failure carries a major burden on our health system, mainly related to the high rate of hospital admission. An understanding of the recent trends in heart failure hospitalisation is essential to the future allocation of health resources. Our aim is to analyse the temporal trends in heart failure hospitalisation. METHODS: We extracted all separations in the Hunter New England Local Health District between 2005-2014 (n=40,119) with an ICD 10 code for heart failure (I-50) in the first four diagnoses on discharge. The numbers of hospitalisations were age-standardised to the 2001 Australian population and compared based on gender and remoteness. RESULTS: There was a decline in the age-standardised hospitalisation. However, there was a clear inflection point between 2009-2010, after which the decline levelled off. The absolute number of hospitalisations increased between 2010 and 2014. Heart failure hospitalisation was higher in males compared to females and rural compared to metropolitan inhabitants. CONCLUSION: The gains in heart failure treatment noted in recent years seem to have come to an end. Patients aged 75 years and older are contributing the majority of age-standardised hospitalisations.

Incidence, time of occurrence and response to heart failure therapy in patients with anthracycline cardiotoxicity.

BACKGROUND: Anthracyclines are commonly used chemotherapeutic medications. AIM: In the current analysis, we evaluated all-cause mortality and incidence, timing and response to medical therapy of anthracycline cardiotoxicity. METHODS: Left ventricular ejection fraction (LVEF) was serially assessed using gated heart pool scan/echocardiography in patients receiving anthracycline-based chemotherapy from January 2009 to December 2014. RESULTS: A total of 1204 patients was administered anthracyclines during the study period. During a median follow up of 32 (interquartile range: 15-58) months, all-cause mortality was 38% (n = 463), with the incidence of cardiotoxicity 10.2% (n = 123). Only 15.4% (n = 19) patients required heart failure hospitalisation, with 48% (n = 59) of patients commenced on beta blockade therapy and/or angiotensin-converting enzyme inhibitors. The majority of patients (73.2%, n = 90) experienced cardiotoxicity within 1 year of anthracycline initiation. The proportion of patients with complete, partial and no LVEF recovery were 16.3% (n = 20), 29.3% (n = 36) and 54.4% (n = 67) respectively. Mortality was higher in the cardiotoxicity group (49% vs 37%, P < 0.01). History of coronary artery disease, leukaemia, idarubicin use and high cumulative anthracycline dose were predictors of cardiotoxicity. CONCLUSIONS: Cardiotoxicity after anthracycline use predictably occurs within the first year of therapy and is dose-related, with variable degrees of recovery. While the need for hospitalisation for heart failure was uncommon, medical therapy appears underutilised, suggesting there may be a role for improved surveillance and early initiation of treatment.

Pre-hospital thrombolysis in ST-segment elevation myocardial infarction: a regional Australian experience.

OBJECTIVE: The system of care in the Hunter New England Local Health District for patients with ST-segment elevation myocardial infarction (STEMI) foresees pre-hospital thrombolysis (PHT) administered by paramedics to patients more than 60 minutes from the cardiac catheterisation laboratory (CCL), and primary percutaneous coronary intervention (PCI) at the CCL for others. We assessed the safety and effectiveness of the pre-hospital diagnosis strategy, which allocates patients to PHT or primary PCI according to travel time to the CCL. DESIGN, SETTING AND PARTICIPANTS: Prospective, non-randomised, consecutive, single-centre case series of STEMI patients diagnosed on the basis of a pre-hospital electrocardiogram (ECG), from August 2008 to August 2013. All patients were treated at the tertiary referral hospital (John Hunter Hospital, Newcastle). MAIN OUTCOME MEASURES: The primary efficacy endpoint was all-cause mortality at 12 months; the primary safety endpoint was bleeding. RESULTS: STEMI was diagnosed in 484 patients on the basis of pre-hospital ECG; 150 were administered PHT and 334 underwent primary PCI. The median time from first medical contact (FMC) to PHT was 35 minutes (IQR, 28-43 min) and to balloon inflation 130 minutes (IQR, 100-150 min). In the PHT group, 37 patients (27%) needed rescue PCI (median time, 4 h; IQR, 3-5 h). The 12-month all-cause mortality rate was 7.0% (PHT, 6.7%; PCI, 7.2%). The incidence of major bleeding (TIMI criteria) in the PHT group was 1.3%; no patients in the primary PCI group experienced major bleeding. CONCLUSION: PHT can be delivered safely by paramedical staff in regional and rural Australia with good clinical outcomes.

Ethosomal nanocarriers: the impact of constituents and formulation techniques on ethosomal properties, in vivo studies, and clinical trials.

Ethosomal systems are novel lipid vesicular carriers containing a relatively high percentage of ethanol. These nanocarriers are especially designed for the efficient delivery of therapeutic agents with different physicochemical properties into deep skin layers and across the skin. Ethosomes have undergone extensive research since they were invented in 1996; new compounds were added to their initial formula, which led to the production of new types of ethosomal systems. Different preparation techniques are used in the preparation of these novel carriers. For ease of application and stability, ethosomal dispersions are incorporated into gels, patches, and creams. Highly diverse in vivo models are used to evaluate their efficacy in dermal/transdermal delivery, in addition to clinical trials. This article provides a detailed review of the ethosomal systems and categorizes them on the basis of their constituents to classical ethosomes, binary ethosomes, and transethosomes. The differences among these systems are discussed from several perspectives, including the formulation, size, ζ-potential (zeta potential), entrapment efficiency, skin-permeation properties, and stability. This paper gives a detailed review on the effects of ethosomal system constituents, preparation methods, and their significant roles in determining the final properties of these nanocarriers. Furthermore, the novel pharmaceutical dosage forms of ethosomal gels, patches, and creams are highlighted. The article also provides detailed information regarding the in vivo studies and clinical trials conducted for the evaluation of these vesicular systems.