Comparison of the efficacy, safety, and tolerability of the FDC of telmisartan + bisoprolol with telmisartan + metoprolol succinate ER combination therapy for stage 1 and stage 2 hypertension: A double-blind, multicentric, phase-III clinical study.

AIM: The present study compared the safety, efficacy, and tolerability of the new fixed-dose combination (FDC) of telmisartan 40 mg + bisoprolol 5 mg (TBP) tablets with the existing comparator FDC telmisartan 40 mg + metoprolol succinate ER 50 mg (TMS) tablets in patients with stage 1 and stage 2 hypertension. METHODOLOGY: The multicentric, double-blind, parallel-group, comparative, prospective, phase-III clinical study involved 264 subjects with stage 1 and stage 2 hypertension from 10 centres across India. The selected subjects were randomized into two groups: group A received the TMS and group B received the new FDC TBP. The primary endpoint was the mean change in seated systolic blood pressure (SeSBP) and seated diastolic blood pressure (SeDBP) from baseline to week 12 in both the control and study arms. The secondary endpoint was achieving the target of SeSBP <140 mmHg and SeDBP <90 mmHg from baseline to week 12 in both groups. Safety and tolerability parameters were evaluated in both groups based on adverse effects (AEs) reported by the patients and the physician. RESULTS: Both treatment groups exhibited a reduction in BP after 2 weeks of treatment, which was sustained until 12 weeks. The mean change in SeSBP and SeDBP at weeks 2, 6, and 12 compared to the previous visit showed statistical significance (p < 0.001) in all cases for both groups A and B. The mean changes in SeSBP and SeDBP from baseline to study end were numerically higher in group B than in group A. The mean difference in SeSBP from baseline to study end was significantly higher in group B compared to group A (p = 0.029). By week 12, 88.28 % and 89.84 % of subjects in group B achieved SeSBP <140 mmHg and SeDBP <90 mmHg respectively, while 86.71 % and 91.40 % of subjects in group A achieved the same targets. Reported AEs were mostly mild to moderate in both treatment groups, and no serious AEs or deaths were reported. Tolerability was rated as 'excellent' by 93.75 % of subjects in group B and 91.40 % of subjects in group A. CONCLUSION: Both the new FDC TBP and the existing comparator TMS combination therapy have comparable efficacy, tolerability, and safety for the management of stage 1 and stage 2 hypertension. TRIAL REGISTRY NAME: Clinical Trials Registry of India (CTRI) TRIAL REGISTRATION NO: CTRI/2021/11/037,926 PROTOCOL NO: MLBTL/05/2021 PROTOCOL URL: https://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=62069&EncHid=&userName=bisoprolol.

Fixed-Dose Combination of Canagliflozin and Metformin as an Adjunct to Diet and Exercise in Indian Adults with Type 2 Diabetes Mellitus: Results from a Multicentric, Open-Label, Single-Arm, Phase IV Study.

BACKGROUND: Canagliflozin and metformin fixed-dose combination (CANA/MET FDC), an approved treatment for type 2 diabetes mellitus (T2DM) in India, effectively lowers glycated hemoglobin (HbA1c), promotes weight loss, and improves patient adherence. As a regulatory requirement, we aimed to evaluate the safety and efficacy of CANA/MET FDC in Indian patients with T2DM. RESEARCH DESIGN AND METHODS: This prospective, multicenter, open-label, single-arm, phase IV study included Indian patients with T2DM (aged 18-65 years) inadequately controlled on diet and exercise. Patients received CANA/MET (50/500 and 50/1000 mg) immediate-release (IR) FDC twice daily for 24 weeks. The primary endpoint was safety assessment, including adverse events (AEs) and serious AEs (SAEs). The secondary endpoint included a change in HbA1c from baseline to weeks 12 and 24. Descriptive statistics were used for all continuous safety variables and efficacy parameters. RESULTS: Of the 310 patients screened, 276 were enrolled. 114/274 (41.6%) patients had ≥1 treatment-emergent AE [treatment-emergent AEs (TEAEs), among which 29 (10.6%) were related to study intervention]. The most common TEAEs were dyslipidemia (4.7%), pyrexia (4.7%), genital infections (3.3%), hypoglycemia (3.3%), and urinary tract infections (2.6%). Three (1.1%) patients had serious TEAEs, and all cases were resolved. No deaths were reported. The mean change in HbA1c from baseline was -0.92 and -0.93% at weeks 12 and 24, respectively. CONCLUSION: The study demonstrates the safety and efficacy of CANA/MET FDC in Indian patients with T2DM, presenting a safe therapeutic option for diabetes management in India.

Management of diacapitular mandibular condyle fracture using a single lag screw fixation: case report / Manejo de fractura de cóndilo mandibular diacapitular mediante fijación con tornillo de tracción único: reporte de caso

Introduction: Mandibular fractures are the most common facial fractures affecting various anatomical sites of the mandible. Among the various mandibular fractures, management of condylar fractures remains a challenging task for surgeons. Case Report: We report the case of a 28 year old male patient who presented with pain in the chin and restricted mouth opening. Computed tomography revealed a sagittal fracture of the right condylar head with medial displacement of the fractured fragments. Management of diacapitular fractures includes open reduction and internal fixation of the right condyle using a single lag-screw. Results: The postoperative outcomes were favorable, where normal mandibular movements, desired dental occlusion and exact positioning of the condyle with rigid fixation were established thereby maintaining the shape of the condyle. Conclusion: Use of single lag screw fixation is highly recommended as it greatly supports the stabilized fracture fragments and also aid in prevention of fracture fragment rotation medially.

Introducción: Las fracturas mandibulares son las fracturas faciales más comunes que afectan a diversos sitios anatómicos de la mandíbula. Entre las diversas fracturas mandibulares, el manejo de las fracturas condilares sigue siendo una tarea desafiante para los cirujanos. Reporte del Caso: Presentamos el caso de un paciente masculino de 28 años que consultó por dolor en el mentón y restricción de la apertura de la boca. La tomografía computarizada reveló una fractura sagital de la cabeza condilar derecha con desplazamiento medial de los fragmentos fracturados. El tratamiento de las fracturas diacapitulares incluye la reducción abierta y la fijación interna del cóndilo derecho con un solo tirafondo. Resultados: Los resultados postoperatorios fueron favorables, donde se establecieron los movimientos mandibulares normales, la oclusión dentaria deseada y el posicionamiento exacto del cóndilo con fijación rígida manteniendo así la forma del cóndilo. Conclusión: Se recomienda encarecidamente el uso de una fijación con un solo tornillo de tracción, ya que soporta en gran medida los fragmentos de fractura estabilizados y también ayuda a prevenir la rotación medial de los fragmentos de fractura.

Comparison of dexamethasone administration through sublingual and intramuscular routes for evaluation of pain, swelling, and trismus after impacted mandibular third molar surgery-a prospective randomized controlled study.

PURPOSE: To compare the efficacy of dexamethasone when administered preoperatively through sublingual and intramuscular routes for evaluating the reduction in pain, swelling, and trismus after removal of impacted mandibular third molar. METHODS: The study was conducted on patients who required surgical removal of impacted mandibular third molars under local anesthesia. A total of 150 patients were considered for the study who were divided into two groups of 75 patients each. Patients in the sublingual group were administered with 2 ml of dexamethasone 8 mg along with 2 ml of normal saline through sublingual route and patients in the intramuscular group were administered with 2 ml of dexamethasone 8 mg through intramuscular route 1 h before the commencement of mandibular third molar surgery. The subjects of all two groups were evaluated for pain, swelling, and trismus on 1st, 3rd, and 7th postoperative days. RESULTS: Patients in the sublingual group had significantly less pain and increased mouth opening on 1st, 3rd, and 7th postoperative days when compared to patients in the intramuscular group (P < 0.05), while the amount of swelling in the sublingual group was significantly less only on the 3rd and 7th postoperative days when compared to patients in the intramuscular group (P < 0.05). Four patients in the sublingual group consumed one dose of paracetamol 500 mg as a rescue drug on the day of surgery. In the intramuscular group, 9 patients consumed one dose of the same rescue drug on the day of surgery and 11 patients consumed one dose of rescue drug both on the day of surgery and on the 1st postoperative day. CONCLUSION: This study concludes that preoperative administration of dexamethasone 8 mg through sublingual route had better efficacy than intramuscular route in controlling pain, swelling and trismus after mandibular third molar surgery.

Jagat and Bala intraocular lens supporting system: An artificial platform for intraocular lens implantation in an aphakic patient with inadequate capsular support.

We describe a novel device, Jagat and Bala Intraocular lens Supporting System (JBISS), an artificial Intraocular lens (IOL) platform that facilitates IOL fixation in an aphakic patient with poor capsular support and also facilitates IOL exchange in case of myopic shift or refractive surprise. Implantation of JBISS along with IOL was carried out in four patients and results are promising without any adverse events.

Alternate iris bypass technique of iridodialysis repair.

We describe a novel technique "alternate iris bypass technique" of iridodialysis repair in four patients experiencing traumatic iridodialysis along with cataract. In these cases, we have combined iridodialysis repair with phacoemulsification and intraocular lens implantation. The main advantage of this technique is that edges of the iridodialysis can be visible till the end of the repair by bypassing the iris tissue in alternate bites which helps in minimizing the corectopia of the pupil and localized iris clumping.

Efficacy and Safety of Remogliflozin Etabonate, a New Sodium Glucose Co-Transporter-2 Inhibitor, in Patients with Type 2 Diabetes Mellitus: A 24-Week, Randomized, Double-Blind, Active-Controlled Trial.

BACKGROUND: Metformin is the first-line treatment for type 2 diabetes mellitus (T2DM), but many patients either cannot tolerate it or cannot achieve glycemic control with metformin alone, so treatment with other glucose-lowering agents in combination with metformin is frequently required. Remogliflozin etabonate, a novel agent, is an orally bioavailable prodrug of remogliflozin, which is a potent and selective sodium-glucose co-transporter-2 inhibitor. OBJECTIVE: Our objective was to evaluate the efficacy and safety of remogliflozin etabonate compared with dapagliflozin in subjects with T2DM in whom a stable dose of metformin as monotherapy was providing inadequate glycemic control. METHODS: A 24-week randomized, double-blind, double-dummy, active-controlled, three-arm, parallel-group, multicenter, phase III study was conducted in India. Patients aged ≥ 18 and ≤ 65 years diagnosed with T2DM, receiving metformin ≥ 1500 mg/day, and with glycated hemoglobin (HbA1c) levels ≥ 7 to ≤ 10% at screening were randomized into three groups. Every patient received metformin ≥ 1500 mg and either remogliflozin etabonate 100 mg twice daily (BID) (group 1, n = 225) or remogliflozin etabonate 250 mg BID (group 2, n = 241) or dapagliflozin 10 mg once daily (QD) in the morning and placebo QD in the evening (group 3, n = 146). The patients were followed-up at weeks 1 and 4 and at 4-week intervals thereafter until week 24. The endpoints included mean change in HbA1c (primary endpoint, noninferiority margin = 0.35), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), bodyweight, blood pressure, and fasting lipids. Treatment-emergent adverse events (TEAEs), safety laboratory values, electrocardiogram, and vital signs were evaluated. RESULTS: Of 612 randomized patients, 167 (group 1), 175 (group 2), and 103 (group 3) patients with comparable baseline characteristics completed the study. Mean change ± standard error (SE) in HbA1c from baseline to week 24 was - 0.72 ± 0.09, - 0.77 ± 0.09, and - 0.58 ± 0.12% in groups 1, 2, and 3, respectively. The difference in mean HbA1c of group 1 versus group 3 (- 0.14%, 90% confidence interval [CI] - 0.38 to 0.10) and group 2 versus group 3 (- 0.19%; 90% CI - 0.42 to 0.05) was noninferior to that in group 3 (p < 0.001). No significant difference was found between group 1 or group 2 and group 3 in change in FPG, PPG, and bodyweight. The overall incidence of TEAEs was comparable across study groups (group 1 = 32.6%, group 2 = 34.4%, group 3 = 29.5%), including adverse events (AEs) of special interest (hypoglycemic events, urinary tract infection, genital fungal infection). Most TEAEs were mild to moderate in intensity, and no severe AEs were reported. CONCLUSION: This study demonstrated the noninferiority of remogliflozin etabonate 100 and 250 mg compared with dapagliflozin, from the first analysis of an initial 612 patients. Remogliflozin etabonate therefore may be considered an effective and well-tolerated alternative treatment option for glycemic control in T2DM. TRIAL REGISTRATION: CTRI/2017/07/009121.

The down regulation of PTP1B expression and attenuation of disturbed glucose and lipid metabolism using Borassus flabellifer (L) fruit methanol extract in high fat diet and streptozotocin induced diabetic rats.

Borassus flabellifer L. is a tall palm traditionally used for its stimulating, diuretic and anti-inflammatory activities; it is rich in fibers and various pharmacologically important secondary metabolites. This study was undertaken to evaluate the antidiabetic effects of Borassus flabellifer fruit methanol extract (BF-M) on diabetic rats induced with High Fat Diet (HFD)/streptozotocin (STZ). When BF-M (100 or 200 mg/kg) was administered for 21 days orally it led to a sharp decline in triglycerides, total cholesterol, free unsaturated fat, glucose-6-phosphate, fasting blood glucose and fructose 1,6 bisphosphatase in contrast to diabetic control. BF-M also downregulated Protein Tyrosine Phosphatase 1B. In vitro study showed the IC50 value to be 23.98 µg/mL. BF-M significantly increased serum insulin, glycogen content, and body weight. Western blot analysis exhibited significant inhibition of PTP1B in pancreatic tissue which was confirmed by histology and immunohistological studies. GC-MS analysis revelaled that the presence of major compounds such as 5-hydroxymethylfurfural (47.56%), Guanosine (21.01%) and n-hecxadeconoic acid (25.14%) in BF-M. In short, BF-M exerted antidiabetic property by down regulating PTP1B expression, and eventually enhancing glucose stimulated insulin release; it also exhibited favorable effects in diabetes and its secondary complications.

A Novel Modification of the Sagittal Split Osteotomy as an Access Osteotomy.

Pathologies present in the central zone of the mandible are difficult to access, primarily because of the presence of the inferior alveolar nerve (IAN) and the need to remove a large corticocancellous component to reach the area of interest. Many times, this bony window is replaced as a free graft and there is complete resorption in the long term or even rejection of the graft causing a bony defect which can weaken the mandible. Furthermore, the damage to the IAN is profound. To try and avoid these comorbidities the traditional sagittal split osteotomy was modified to access a central osteoma impinging on the IAN and the successful removal of the same without any comorbidities such as paraesthesia or loss of bone structure. We believe that this modification can be used for other scenarios such as benign cysts and difficult presentations of impacted teeth.

Comparison of primary and secondary closure with a buccal mucosal-advancement flap on postoperative course after mandibular impacted third molar surgery.

PURPOSE: The purpose of this study was to compare primary and secondary wound closure with a buccal mucosal-advancement flap technique on the postoperative course after mandibular impacted third molar surgery. METHODS: The study was conducted on 150 patients who required surgical removal of impacted mandibular third molars under local anesthesia. The study subjects were divided into three groups of 50 patients each, based on the type of closure over the third molar socket. Patients in group I underwent primary closure of the socket with hermetic suturing of the flap, including the vertical release. In group II, a secondary closure was performed, leaving the socket communicating with the oral cavity. In group III, a buccal mucosal-advancement flap technique was employed to achieve primary closure of the flap over the socket while leaving the anterior vertical release, generously patent. All the patients were assessed for pain using the visual analogue scale (VAS), swelling, and mouth opening at postoperative intervals of 2, 4, and 7 days. The wound healing was assessed on day 7. RESULTS: Patients in the buccal mucosal-advancement flap group had significantly less pain and swelling and increased mouth opening compared with primary and secondary closure. Wound dehiscence was seen in 18 patients and alveolar osteitis in 4 patients in primary closure. Delayed wound healing with food accumulation was seen in 6 patients in secondary closure. No complications of flap dehiscence or breakdown were observed in the buccal mucosal-advancement flap group. CONCLUSION: This study concludes that the buccal mucosal-advancement flap technique was a superior closure technique with less pain, swelling, trismus, and satisfactory wound healing compared with both primary and secondary closure after mandibular third molar surgery.

Click chemistry-assisted, bis-cholesteryl-appended, isosorbide-based, dual-responsive organogelators and their self-assemblies.

A new series of symmetric, bis-cholesteryl-appended, isosorbide derivatives (BCIE, BCIC2 and BCIC4) were designed as gelators to respond to changes in their environment and were synthesized successfully. Among these derivatives, BCIE can gel a wide variety of organic solvents (23 solvents), suggesting that BCIE acts as a more versatile gelator than BCIC2 and BCIC4. The CGC of the gels varies from 1.53 mM in 1-hexanol to 23 mM in pyridine. The results of the gelation ability in different solvents revealed that changing the linking group (ester/carbamate) attached to the cholesteryl units can produce a dramatic change in the gelation behavior of the compounds. The morphology of the as-formed organogels can be regulated by changing the types of organic solvents. The results from electron microscopy studies revealed that the gelator molecule self-assembled into different aggregates, from wrinkled fibers to dense fibers, with the change of solvents. The gels of BCIE in 1-hexanol and 1-octanol exhibited strong CD (circular dichroism) signals, indicating that the gelation induced supramolecular chirality in these gel systems. Secondary forces of van der Waals and π-π stacking (from both 1,2,3-triazole and aromatic units) played important roles in the aggregation of compounds in the solvents according to FTIR and variable temperature (1)H-NMR analysis, and a mechanism for the gel formation was proposed. The gel-to-sol phase transition can be triggered by the addition of trifluoroacetic acid (TFA), and the gel state was obtained slowly (after 1 day) when neutralizing with triethyl amine (TEA), which indicated that the sol ⇄ gel phase transitions are tunable by pH, which is further supported by (1)H-NMR and SEM analysis. In addition, the gel stability of BCIE was investigated using Cu(2+), Cd(2+), Ag(2+), Fe(3+), Hg(2+), Mg(2+), Pd(2+), Al(3+) and Zn(2+), and the results showed that the gel-to-sol phase transition process could be selectively controlled by interaction with Pd(2+) and Zn(2+) because complexation with 1,2,3-triazoles destroyed the interactions between the triazoles, collapsing the gel, which was further evidenced by (1)H-NMR and SEM analysis. However, the gel stability of BCIE was enhanced by the addition of Pd(2+) and Zn(2+) in the presence of pyridine, whereas the gel collapsed in other solvents, which may be due to the chelating effect of the pyridine moiety. Another interesting feature of this gel is that when using the gelator as a stabilizer, stable water in oil (W/O) gel-emulsions were created, in which styrene can be used as the continuous phase and water as the dispersed phase with the stabilizer in the continuous phase of only 2% (w/v). Gel-emulsions were observed with any ratio of water to styrene.

Non-centralised service for palliative stenting of malignant gastric outlet obstruction.

INTRODUCTION: Malignant gastric outlet obstruction (GOO) is a common, debilitating and frequently pre-terminal symptom of intra-abdominal malignancies. Traditional 'gold standard' treatment has been palliative surgical gastro-enterostomy. Over the past two decades, use of self-expanding metallic stents (SEMSs) to relieve malignant GOO has become first-line treatment. We present the results from a single district general hospital in the UK in which malignant GOO was treated with SEMSs over a six-year period. METHODS: All patients who underwent palliative stenting for malignant gastro-duodenal tumours in our centre for six years up to January 2013 were assessed retrospectively. Outcomes were assessed with regard to: technical and clinical success; return to oral nutrition; prevalence of complications and re-intervention; and overall survival. RESULTS: Thirty-two stents were implanted in 29 patients. Technical success was 100%. Clinical success and return to oral nutrition were both 91%. The prevalence of complications was 16%. The prevalence of re-intervention was 13%. Mean survival was 91 (range, 5-392) days. Median wait from decision to implant a stent to stent implantation was 1 (range, 0-14) day. Overall, 25 covered and nine uncovered stents were implanted. CONCLUSION: Stent implantation for GOO in this patient group is an established and preferable alternative to surgical intervention. Much of the treatment for malignancies of the upper gastrointestinal tract has now been centralised. Our data showed comparable results with published data for these procedures, with a high prevalence of success and low prevalence of major complications. It is of considerable benefit to these patients not to have to travel to a regional centre for stent implantation.