Catheter Exchange With Elongation of Tunnel (CEET) Procedure-A Novel Technique for Cuff Extrusion of Tunneled Dialysis Catheter: Surgical Experience and Early Outcomes.

BACKGROUND: Cuff extrusion of tunneled dialysis catheter (TDC) leads to catheter dysfunction, leading to loss of vascular access and the need for new catheter. Definitive management is to remove TDC and reinsert new catheter by new venous puncture and tunnel, which may not be possible in all cases. The study evaluated the surgical experience and early outcomes of a novel "Catheter Exchange with Elongation of Tunnel (CEET)" procedure for cuff extrusion. METHODS: The retrospective study included all cases of hemodialysis with TDC with partial or complete cuff extrusion and excluded complete catheter dislodgement, tunnel infection, or any catheter related infection. All patients also underwent the CEET procedure under fluoroscopy guidance, and the clinical details and outcomes were analyzed. RESULTS: Eleven cases of TDC cuff extrusion underwent the CEET procedure of which three (27.2%) had previous and four (36.4%) had partial cuff extrusion, and seven cases (63.6%) had short tunnel length, which likely predisposed to cuff extrusion. CEET procedure was successful in 10 cases (success rate 90.1%) with desired position of catheter tip and good blood flow. Study population was divided into early and late cuff extrusion (≥1 month). Short tunnel length was associated with late extrusion (p = 0.05), whereas premature removal of TDC anchor sutures was associated with early cuff extrusion (p = 0.04). CONCLUSION: CEET procedure is a successful alternative technique for correction of cuff extrusion of TDC with good success rate. Premature removal of anchor sutures was associated with early cuff extrusion, whereas short tunnel length was associated with late cuff extrusion.

An Improvised Cost-Effective Repair Technique for Management of Broken Luer Connections of Tunneled Dialysis Catheter and Salvage Existing Catheter.

Mechanical problems like break or crack in Luer connectors or hubs, clamps, and tubings are common non-infectious complications of tunneled dialysis catheters (TDC), which may lead to other TDC complications and the need to insert a new catheter. These can be tackled using TDC repair kits or spare parts, which are often not available, resulting in the insertion of a new TDC that increases morbidity, TDC-related procedures, and healthcare costs. We discuss two cases of broken Luer connections of TDC, which were managed by exchanging the broken Luer connector of TDC with the similar Luer connector of a temporary dialysis catheter. Both the repaired TDCs are thereafter functioning well. This improvised technique provides an easy, effective, long-lasting option that salvages the existing TDC and reduces the cost factor.

Practice of dialysis access interventional nephrology procedures in the Asia-Pacific region: Getting lay of the land.

AIM: This cross-sectional survey aimed to determine the prevalence of Interventional Nephrology (IN) practice amongst nephrologists in the Asia-Pacific Region (APR), specifically related to dialysis access (DA). METHODS: The Association of VA and intervenTionAl Renal physicians (AVATAR) Foundation from India conducted a multinational online survey amongst nephrologists from the Asia-Pacific to determine the practice of IN in the planning, creation, and management of dialysis access. The treatment modalities, manpower and equipment availability, monthly cost of treatment, specifics of dialysis access interventions, and challenges in the training and practice of IN by nephrologists were included in the survey. RESULTS: Twenty-one countries from the APR participated in the survey. Nephrologists from 18 (85.7%) countries reported performing at least one of the basic dialysis access-related IN procedures, primarily the placement of non-tunnelled central catheters (n-TCC; 71.5%). Only 10 countries (47.6%) reported having an average of <4% of nephrologists performing any of the advanced IN access procedures, the most common being the placement of a peritoneal dialysis (PD) catheter (20%). Lack of formal training (57.14%), time (42.8%), incentive (38%), institutional support (38%), medico-legal protection (28.6%), and prohibitive cost (23.8%) were the main challenges to practice IN. The primary obstacles to implementing the IN training were a lack of funding and skilled personnel. CONCLUSION: The practice of dialysis access-related IN in APR is inadequate, mostly due to a lack of training, backup support, and economic constraints, whereas training in access-related IN is constrained by a lack of a skilled workforce and finances.

Continuous Ambulatory Peritoneal Dialysis Peritonitis Guidelines - Consensus Statement of Peritoneal Dialysis Society of India - 2020.

Continuous ambulatory peritoneal dialysis (CAPD) related peritonitis is a major cause of technique failure, morbidity, and mortality in patients on CAPD. Its prevention and management is key to success of CAPD program. Due to variability in practice, microbiological trends and sensitivity towards antibiotics, there is a need for customized guidelines for management of CAPD related peritonitis (CAPDRP) in India. With this need, Peritoneal Dialysis Society of India (PDSI) organized a structured meeting to discuss various aspects of management of CAPDRP and formulated a consensus agreement which will help in management of patients with CAPDRP.

Tenofovir induced Fanconi syndrome: A rare cause of hypokalemic paralysis.

We report a 55-year-old female who presented to the emergency department with acute onset quadriparesis. She was diagnosed to have acquired immunodeficiency syndrome 7 years ago and was on tenofovir based anti-retroviral therapy for past 10 months. As the patient also had hypophosphatemia, glucosuria and proteinuria Fanconi syndrome (FS) was suspected. She improved dramatically over next 12 h to regain normal power and also her renal functions improved over next few days. Tenofovir induced FS presenting as hypokalemic paralysis is very rare complication and is the first case reported from India.

Design of a novel bilayered gastric mucoadhesive system for localized and unidirectional release of lamotrigine.

Lamotrigine is a BCS class II drug with pH dependent solubility. The bilayered gastric mucoadhesive tablets of lamotrigine were designed such that the drug and controlled release polymers were incorporated in the upper layer and the lower layer had the mucoadhesive polymers. The major ingredients selected for the upper layer were the drug and control release polymer (either HPMC K15M or polyox) while the lower MA layer predominantly comprised of Carbopol 974P. A 2(3) full factorial design was constructed for this study and the tablets were optimized for parameters like tablet size, shape, ex vivo mucoadhesive properties and unidirectional drug release. Oval tablets with an average size of 14 mm diameter were set optimum. Maximum mucoadhesive bond strength of 79.3 ± 0.91 * 10(3) dyn/cm(2) was achieved with carbopol when used in combination with a synergistic resin polymer. All the tested formulations presented a mucoadhesion time of greater than 12 h. The incorporation of methacrylic polymers in the lower layer ensured unidirectional drug release from the bilayered tablets. The unidirectional drug release was confirmed after comparing the dissolution results of paddle method with those of a modified basket method. Model independent similarity and dissimilarity factor methods were used for the comparison of dissolution results. Controlled drug release profiles with zero order kinetics were obtained with polyox and HPMC K15M which reported t 90% at 6th and 12th hours, respectively. The "n" value with polyox was 0.992 and that with HPMC K15M was 0.946 indicating an approximate case II transport. These two formulations showed the potential for oral administration of lamotrigine as bilayered gastric mucoadhesive tablets by yielding highest similarity factor values, 96.06 and 92.47, respectively, between the paddle and modified basket method dissolution release profiles apart from reporting the best tablet physical properties and maximum mucoadhesive strength.

Newer approaches for optimal bioavailability of ocularly delivered drugs: review.

Eye diseases can cause discomfort and anxiety in patients, with the ultimate fear of loss of vision and facial disfigurement. Many regions of the eye are relatively inaccessible to systemically administered drugs and, as a result, topical drug delivery remains the preferred route in most cases. Drugs may be delivered to treat the precorneal region for conjunctivitis and blepharitis, or to provide intraocular diseases such as glaucoma, uveitis, and cytomegalovirus retinitis. Most of the ophthalmic formulation strategies aim at maximizing ocular drug permeability through prolongation of the drug residence time in the cornea and conjunctival sac, as well as minimizing precorneal drug loss. The conventional topical ocular drug delivery systems show drawbacks such as increased precorneal elimination and high variability in efficacy. Attempts have been made to overcome these problems and enhance ocular bioavailability by the development of newer drug delivery systems. This review is concerned with classification, recent findings and applications and biocompatibility of newer drug delivery systems for the treatment of ocular diseases.

Solid state interaction of raloxifene HCl with different hydrophilic carriers during co-grinding and its effect on dissolution rate.

This study investigated the effects of different classes of hydrophilic carriers (poly vinyl pyrrolidones [PVPs] [Plasdone K-25 and Plasdone S-630], cellulosic polymers [hydroxypropyl methyl cellulose and hydroxy propyl cellulose], and Sodium Alginate) on the solid state and dissolution rate of Raloxifene hydrochloride (R-HCl). Solid state characterizations of co-ground mixtures and physical mixtures in 1:1 and 1:2 ratios of drug to polymer were performed by employing laser diffractometer for particle size and differential scanning calorimetry (DSC) for solid state interactions. The results of particle size studies showed that only co-grinding with PVPs was more effective in the reduction of particle size than the milling of drug alone. DSC study indicated that the crystalline nature of the drug was reduced after co-grinding with PVPs when compared with their corresponding physical mixtures. The hydrophilic carriers other than PVPs did not reduce the crystalline nature of the drug significantly. X-ray diffraction and scanning electron microscopy were carried out for selected batches to confirm DSC results. Significant enhancement in dissolution rate and extent was observed with co-ground mixtures of drug and PVPs. Plasdone S-630 was found to be a better carrier for R-HCl in terms of achieving improvement in dissolution. In vitro dissolution data can be described by Hixson-Crowell model, indicating the drug release mechanism predominated by erosion.

Studies on Indomethacin Intraocular Implants Using Different in vitro Release Methods.

Intra ocular implants of sodium alginate alone and in combination with hydroxypropylmethylcellulose with or without calcium chloride were formulated with indomethacin as a model drug. The drug release from the implants was evaluated using static method, continuous flow through apparatus (developed in house), USP dissolution and agar diffusion. Except in the static method, indomethacin particle size did not impart any effect on the drug release. In agar diffusion method, an increase in agar concentration from 1 to 2% resulted in a significant decrease (P< 0.005) in the amount of drug released. Inclusion of hydroxypropylmethylcellulose (33.3, 41.6 and 50% w/w), resulted in decrease of indomethacin release irrespective of the method of dissolution study. The agar diffusion method and the continuous flow through methods seem to simulate to a certain extent the in vivo conditions as far as the placement of the device and the hydrodynamic diffusion layer around the intra ocular implant is concerned. The static method and USP method affected the hydrodynamic diffusion layer either too slowly or too fast.

Gastroretentive drug delivery system of metoclopramide hydrochloride: formulation and in vitro evaluation.

The present investigation concerns the development of floating matrix tablets of metoclopramide hydrochloride (MHCl) for improving its bioavailability by prolonging gastric residence time. Floating matrix tablets (FMT) of MHCl were prepared using the polymers guar gum (GG), karaya gum (KG), HPMC E15 (HE) alone and in combination with HPMC K15M (HK) and gas generating agents such as calcium carbonate and citric acid. The fabricated tablets were evaluated for their physical characteristics such as hardness, drug content, buoyancy, swelling properties and in vitro release studies in 0.1N HCl. The tablets without gas generating agents and HK did not float at all whereas tablets with gas generating agents and without HK floated for 2.33-5.48 h then eroded completely and exhibited faster drug release. Tablets with gas generating agents and HK floated for 24 h without complete erosion and showed slower drug release. This indicates that gas generating agents contributes towards the initial floating of tablets and faster drug release and HK for maintaining the integrity of the FMT and sustaining the drug release. The increase in the concentration of HK in FMT from 10 mg to 40 mg resulted in decrease in release rate of drug. The possibility of drug polymer interaction was determined by differential scanning calorimetry (DSC) and fourier transform infrared (FTIR) spectrometer, and confirmed no interaction between drug and polymers. The release pattern of prepared tablets followed Higuchi kinetics which confirms release mechanism by diffusion.

Sodium alginate microspheres of metformin HCl: formulation and in vitro evaluation.

Metformin microspheres with sodium alginate alone and in combination with gellan were prepared using an emulsion-cross linking method. The prepared microspheres were evaluated for their physico-chemical characteristics like particle size, morphology using SEM, incorporation efficiency, equilibrium water content (swelling) and in vitro drug release. The effect of various formulation variables like polymer concentration (sodium alginate; and proportion of gellan in microspheres prepared by a combination of sodium alginate and gellan), drug loading, crosslinking agent concentration and cross-linking time on the in vitro dissolution of the prepared microspheres were evaluated. The results showed that both the particle size and the incorporation efficiency were proportional to the polymer concentration. In case of microspheres containing both sodium alginate and gellan, the mean diameter and the incorporation efficiency were higher than the corresponding microspheres containing only alginate, both increasing with an increase in proportion of gellan. The prepared microspheres were found to be discrete and spherical in shape and were successful in sustaining the drug release for 8 hours. Incorporation of gellan caused a significant decrease in drug release. The release followed a biphasic profile, in all cases, characterized by an initial phase of moderate drug release followed by a phase of higher release. Further, the kinetic treatment of the dissolution data revealed the prevalence of matrix diffusion kinetics.

Development and evaluation of a novel floating in situ gelling system of amoxicillin for eradication of Helicobacter pylori.

The aim of this study was to develop a new intra-gastric floating in situ gelling system for controlled delivery of amoxicillin for the treatment of peptic ulcer disease caused by Helicobacter pylori (H. pylori). Gellan based amoxicillin floating in situ gelling systems (AFIG) were prepared by dissolving varying concentrations of gellan gum in deionized water containing sodium citrate, to which varying concentrations of drug and calcium carbonate, as gas-forming agent, was added and dissolved by stirring. The formulation variables like concentration of gellan gum and calcium carbonate significantly affected the in vitro drug release from the prepared AFIG. The in vivo H. pylori clearance efficacy of prepared AFIG in reference to amoxicillin suspension following repeated oral administration to H. pylori infected Mongolian gerbils was examined by polymerase chain reaction (PCR) technique and by a microbial culture method. AFIG showed a significant anti-H. pylori effect in the in vivo gerbil model. It was noted that the required amount of amoxicillin for eradication of H. pylori was 10 times less in AFIG than from the corresponding amoxicillin suspension. The results further substantiated that the prepared AFIG has feasibility of forming rigid gels in the gastric environment and eradicated H. pylori from the gastrointestinal tract more effectively than amoxicillin suspension because of the prolonged gastrointestinal residence time of the formulation.

Niridazole biodegradable inserts for local long-term treatment of periodontitis: possible new life for an orphan drug.

Periodontal pocket inserts of niridazole (NZ) made with Resomer(R) (grades RG 503H and RG858, designated as RH and RG, respectively) were studied. Various formulation variables were evaluated to obtain a biodegradable delivery systems showing device degradation and drug depletion parallel to each other in vitro. Drug release from the prepared inserts was evaluated using a static dissolution setup (for 1 month). Incorporation of 3 parts of RG in 1 part of RH inserts caused a 50% decrease in the initial release rate. The RH-NZ inserts showed a spurt in release around the 10th day of the study, which coincided with the decrease in device weight, suggesting onset of device degradation. Pilot-scale clinical trials in 12 patients indicated improvements in clinical indices from the baseline values. The average pocket depth was reduced significantly (alpha = 0.05) from 6.34 +/- 1.86 mm at baseline to 5.94 +/- 0.28 mm after 28 days of treatment.

Gellan-based scleral implants of indomethacin: in vitro and in vivo evaluation.

Film-type scleral implants of indomethacin with gellan gum were prepared by solvent casting and evaluated for uniformities of thickness, weight, drug content, and surface pH. The effect of plasticizers like glycerol, propylene glycol (PG), and polyethylene glycol 200, and 400 on the void volume of free gellan films (placebo) was calculated from the water content of the films. The drug release from the prepared implants was determined using a static dissolution set-up developed and optimized in our laboratory. Based on the results of the void volume and initial drug release studies, glycerol and PG were selected as the plasticizers for the gellan-based implants. The morphology of the drug-free films (containing 10% and 40% of PG) and the drug-loaded films (before and after dissolution and crosslinked) was studied using scanning electron microscopy. Further, the effect of plasticizer concentration, gellan concentration, effect of crosslinking technique, and duration of crosslinking using calcium chloride on in vitro drug release characteristics were evaluated. Selected batches of the implants were subjected to pharmacodynamic studies, after scleral placement, in uveitis-induced (intravitreal injection of bovine serum albumin 50 microg/ml) rabbit eyes. The release of indomethacin from the prepared implants followed matrix diffusion kinetics with diffusion co-efficient (n) values ranging between 0.358 to 0.708 and seemed to depend on both gellan and plasticizer concentration. Surface crosslinking with 10% calcium chloride for 8 hr retarded drug release (1.42 times less than noncrosslinked implant) and was optimum. The pharmacodynamic studies showed a marked improvement in the various clinical parameters (congestion, keratitis, flare, clot, aqueous cells, and synechias) in the implanted eye compared with the control eye in the rabbits. The scleral implants survived up to 3 weeks in vivo.

In vitro and in vivo characterization of scleral implant of indomethacin: role of plasticizer and cross-linking time.

Film-type scleral implants of indomethacin using sodium alginate and PEG 400 and 600 (3, 5, 8, and 10% w/w w.r.t. sodium alginate) as plasticizers were fabricated by solvent casting. The prepared implants were cross-linked by treatment with calcium chloride 10, 20, and 30% w/v solution, for periods between 1 to 24 hr. Uniformity of thickness, weight, and drug content and surface pH of the implants were evaluated. The influence of plasticizer type/concentration and crosslinking time/concentration of calcium chloride on indomethacin release was studied on a static dissolution setup developed by us. Selected batches of the implants were subjected to pharmacodynamic studies, after scleral placement, in uveitis-induced (intravitreal injection of bovine serum albumin 50 microg/ml) rabbit eyes. The release of indomethacin from the implants was influenced by the concentration and nature of plasticizers used. Chemical cross-linking with calcium chloride was successful in retarding the drug release. The pharmacodynamic studies showed a marked improvement in the various clinical parameters (congestion, keratitis, flare, clot, aqueous cells, and synechias) in the implanted eye when compared with the control eye in the rabbits. The implants survived for 2 weeks in vivo.

Ion-activated in situ gelling systems for sustained ophthalmic delivery of ciprofloxacin hydrochloride.

The poor bioavailability and therapeutic response exhibited by the conventional ophthalmic solutions due to precorneal elimination of the drug may be overcome by the use of in situ gel forming systems that are instilled as drops into the eye and undergo a sol-gel transition in the cul-de-sac. Our present work describes the formulation and evaluation of an ophthalmic delivery system of an antibacterial agent, CPH, based on the concept of ion-activated in situ gelation. Gelrite gellan gum, a novel ophthalmic vehicle that gels in the presence of mono or divalent cations, present in the lacrimal fluid was used alone and in combinations with sodium alginate as the gelling agent. The developed formulations were therapeutically efficacious and provided sustained release of the drug over an 8-hr period in vitro.

Dissolution, bioavailability and ulcerogenic studies on piroxicam-nicotinamide solid dispersion formulations.

Solid dispersions with different ratios of Piroxicam and Nicotinamide (as a carrier) were prepared by fusion method. Drug-carrier interactions in the solid state were ascertained using phase-diagram, X-ray diffraction (XRD) and Differential scanning colorimetry (DSC). Select ratios of the formed piroxicam-nicotinamide solid dispersions and their corresponding physical mixtures were formulated into tablets and capsules. The dissolution characteristics of the formed solid dispersions, physical mixtures and their formulations were compared with pure piroxicam in 900 ml of 0.1 N HCl (pH 1.2) at 37 +/- 0.5 degrees C, 50 rpm using USP XXI paddle apparatus. Solid dispersion capsule PNC1 (containing 1:5--drug-carrier ratio solid dispersion) and the corresponding physical mixture capsule PNC1A were used for bioavailability studies in healthy human volunteers. Further, ulcer indices of the prepared solid dispersion and their corresponding physical mixture were compared with pure piroxicam in rats. The DSC, XRD and phase diagram indicated the formation of solid dispersed system. The prepared dispersion showed better dissolution than the corresponding physical mixture and pure drug. The fabricated formulation complied with the pharmacopoeial limits for physico-chemical properties and the solid dispersion capsules PNC1 and PNC2 (containing 1:9 ratio of drug to carrier solid dispersion) showed 3 and 6.6 fold increase and 3.2 and 8 fold increases in dissolution rate compared to the corresponding physical mixture capsules (PNC1A and PNC2A), respectively. The solid dispersion capsule PNC1 showed significantly higher absorption and dissolution and consequently better bioavailability than the corresponding physical mixture capsule (PNC1A) in healthy human volunteers. The ulcer indices of the prepared dispersions were significantly lower than the corresponding physical mixture and pure drug.

Bioavailability studies on fast release formulations of indomethacin.

Indomethacin-nicotinamide solid dispersions were prepared by fusion method. Drug-carrier interaction in the liquid and solid states were studied using phase solubility data and differential scanning colorimetry (DSC). DSC revealed the formation of an eutectic mixture of indomethacin and nicotinamide. Tablets and capsules, formulated from the solid dispersions showed significantly better dissolution and enhanced absorption rate in human volunteers, compared to commercial capsule of indomethacin.

Novel therapeutic approaches for uveitis and retinitis.

A virtual increase in the number of patients undergoing immunosuppressant therapy and those suffering from AIDS has created a unique class of population suffering from virulent uveitis and retinopathies. A very common pathogen implicated in retinopathy in such patients is the cytomegalovirus (CMV).

In vitro and in vivo characterization of scleral implants of indomethacin.

Scleral implants of indomethacin with sodium alginate as carrier were fabricated and evaluated for various physico-chemical properties such as uniformity of thickness, weight, drug content, surface pH, percent dissolution and water up-take capacity (swelling index). The effect of drug particle size, polymer concentration, drug loading, plasticizer concentration, and effects of physical reinforcement (freeze-thawing for 3 and 6 cycles) and chemical cross-linking with calcium chloride, on the in vitro drug release characteristics were evaluated. Selected batches of the implants were subjected to pharmacodynamic studies, after scleral placement, in uveitis induced (intravitreal injection of Bovine Serum Albumin (BSA)-50 micrograms/ml) rabbit eyes. The release of indomethacin from the prepared implants followed predominantly matrix diffusion kinetics. Swelling and moisture absorption/loss studies correlated well with the in vitro release studies. The pharmacodynamic studies showed a marked improvement in the various clinical parameters (congestion, keratitis, flare, clot, aqueous cells and synechias), in the implanted eye when compared to the control eye in the rabbits.