Pfizer forecasts 2024 revenue below Wall Street expectations

New York: Pfizer on Wednesday forecast 2024 revenue that was below Wall Street expectations and raised its cost-cut target by $500 million.

The U.S. drugmaker expects its annual revenue to be in the range of $58.5 billion to $61.5 billion compared with analysts’ average estimate of $63.17 billion. It includes the contribution from sales of Seagen’s products.

Sales of Paxlovid and the vaccine Pfizer makes with German partner BioNTech had boosted revenue over the last two years, helping it generate more than $100 billion in 2022.

But a drop in annual vaccination rates and demand for the treatments have forced the company to launch a program in October to cut jobs and expenses to save as much as $3.5 billion.

The company, which employs roughly 83,000 employees globally, in November cut 500 jobs at its Sandwich, Kent site in the UK.

Read also: Pfizer Marstacimab regulatory submissions for treatment of Hemophilia A and B accepted by USFDA, EMA

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Linagliptin and Dapagliflozin: Therapeutic Applicability in T2DM with High CV Risk

Type 2 Diabetes Mellitus and Cardiovascular Disease

Type 2 diabetes mellitus (T2DM) prevalence has been increasing globally, particularly in India (1) T2DM in general increases the risk of CVD outcomes by a twofold and is independent of other risk factors. (1) The risk of coronary artery disease (CAD) in Indian T2DM patients is two to four times higher, and CAD occurs one to two decades earlier than in the West. (3) Impaired glucose metabolism, inflammation, and abnormal cell signaling all contribute to premature atherosclerosis, myocardial remodeling, and left ventricular fibrosis, which contribute to cardiovascular damage. (2)

Managing Cardiovascular Disease in Diabetes: Going Beyond HbA1c

The focus of CVD management in diabetes should extend beyond glycemic control and on antidiabetic drugs that alleviate the risk factors and improve CV outcomes. It is critical to identify pharmacological strategies that target cardiovascular inflammation, fibrosis; induce weight and blood pressure reduction; and provide renal and cardiovascular protection in managing CVD in T2DM.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a unique class of antidiabetic drugs. The primary advantage of SGLT2i is that they act independently of insulin, inhibiting proximal tubular glucose reabsorption and lowering plasma glucose levels and glucosuria. They also provide organ protection, including cardio-renal protection, lowering the risk of heart failure and cardiovascular mortality due to their direct and indirect pleiotropic effects. (2)

Dipeptidyl peptidase 4 (DPP4) inhibitors also reduce myocardial inflammation by inhibiting cytokine release, monocyte activation, and chemotaxis. Also, gliptins improve systolic and diastolic left ventricular dysfunction in CV diseases and support overall cardiovascular protection. (4)

Optimising Guideline Directed Medical Therapy in T2DM & High-Risk CVD

  • The RSSDI (Research Society for the Study of Diabetes in India) Clinical Practice Recommendations for the Management of Type 2 Diabetes: The RSSDI 2022 guidelines suggested the use of dual therapy to achieve glucose targets or to extend the time to treatment failure and also recommended using antidiabetic agents, including SGLT2 and DPP-4 inhibitors. The guideline further recommended SGLT2i for patients with established or high risk for ASCVD, heart failure, and in need of weight reduction. In elderly patients with an increased risk of hypoglycemia, the guideline suggested the use of DPP-4 inhibitors. (5)
  • American Association of Clinical Endocrinology (AACE) Consensus Statement for Management of Type 2 Diabetes Mellitus: The 2023 update for T2DM Management recommends using SGLT2 inhibitors to improve cardiorenal outcomes. AACE guidelines recommend SGLT2 inhibitors as first-line treatment for cardiorenal risk reduction regardless of background metformin use or HbA1c level within the complications-centric algorithm. (6)
  • ESC Guidelines for the Management of Cardiovascular Disease in Patients with Diabetes: The 2023 ESC Guideline for “Management of Cardiovascular Disease in Diabetes” recommend SGLT2i (Class I) to reduce CV risk independent of glucose control in T2DM with ASCVD. (7).
  • International Guidelines Expanding the Applicability of SGLT2-inhibitors: The ESC Guideline for ”Management of Cardiovascular Disease in Diabetes 2023 (7), the American Diabetes Association (ADA) “Standards of Care in Diabetes” 2023 (8), and the Kidney Disease Improving Global Outcomes (KDIGO) 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease (9) recommended the use of SGLT2i for patients with T2DM and CKD who have eGFR ≥20 mL/min/1.73 m2.

Scientific Rationale for Considering Linagliptin & Dapagliflozin among T2DM Patients with High CV Risk

Linagliptin: The Gliptin Applicable in Wide Group of Type 2 Diabetes Patients Improving Macrovascular & Microvascular Complications: Linagliptin is a DPP-4 inhibitor with potent and durable DPP-4 inhibition. It is known to increase GLP-1(glucagon-like peptide-1) and GIP (gastric inhibitory polypeptide) levels, which may provide beneficial cardioprotection (10)

  • Linagliptin treatment benefits CV dysfunction associated with T2DM. It decreases cardiac hypertrophy and fibrosis and improves cardiac function (11)
  • Linagliptin treatment also provides renal protection by lowering albuminuria, and tubulo-interstitial fibrosis and preventing the progression of renal tissue injury.
  • It also decreases inflammation and pericytes and provides retinal capillary vaso-regression, thereby providing protection in retinopathy. (11)
  • Linagliptin also benefits neuropathy by suppressing arterial stiffening and vascular inflammation and improving vascular relaxation. (11)

Dapagliflozin: Durable Evidence with Robust Glycemic & CV-CKD Benefits

Dapagliflozin is a widely utilized SGLT2i in clinical settings. The mechanism of dapagliflozin in cardiovascular protection may involve improving ventricular loading conditions, improvement of cardiac metabolism and bioenergetics, Na+/H+ exchange, sugar and lipid metabolism & circulatory load. (12)

  • It improves cardiorenal outcomes through various pathways, including by reducing blood pressure, arterial stiffness, and endothelial dysfunction. (12)
  • Dapagliflozin treatment lowers the risk of hospitalization for heart failure, CV death, and all-cause mortality. (13)
  • It improves glomerular hemodynamics, resulting in long-term kidney function preservation. It provides renoprotective benefits regardless of diabetes status, age, cause of CKD, baseline albuminuria, and eGFR. (13)

Beneficial Impact of Linagliptin and Dapagliflozin on CV Outcomes- Clinical Evidence

Linagliptin Leads to CV Risk Reduction in Asian Type 2 Diabetes Patients: A real-world observational study evaluated the effect of linagliptin on CV risk reduction in Asian T2DM patients. The study enrolled 73 patients on Linagliptin and noted that the 12-month treatment with Linagliptin significantly reduced CV risk by 6.36% (P=0.17). It also reduces the atherosclerotic cardiovascular disease risk in patients with high ASCVD risk and the elderly population. These findings showed a promising effect of Linagliptin in cardiovascular risk reduction in Asian T2DM patients with higher baseline cardiovascular risk and older age. (14)

Linagliptin Improves Microalbuminuria in Diabetic Nephropathy: A double-blind, randomized, placebo-controlled trial analyzed the effect of linagliptin on microalbuminuria in patients with diabetic nephropathy (DN). The trial enrolled 92 patients with DN, divided into the intervention and control groups, who received linagliptin 5 mg and placebo for 24 weeks, respectively. Linagliptin significantly improved microalbuminuria (urine albumin creatinine ratio of < 30 mg/g) by 68.3% (p<0.001). This suggests that linagliptin therapy improves microalbuminuria in diabetic nephropathy patients. (15)

CARMELINA and CAROLINA: Linagliptin Reassures for CV Safety in Asian T2DM Patients:

The CARMELINA trial’s subgroup analysis explored Linagliptin’s CV safety in Asian T2DM (N=6979, 8.0% Asian). Linagliptin treatment reduced the risk of hospitalization for heart failure (HR 0.47; 95% CI 0.24–0.95; P=0.0368), the composite of hospitalization for heart failure or all-cause mortality (HR 0.55; 95% CI 0.32–0.95; P=0.2191), and all-cause hospitalization (HR 0.74; 95% CI 0.57–0.96; P=0.2182). This suggests the CV safety of linagliptin in Asian T2DM patients. (16)

Another subgroup analysis of the CAROLINA trial assessed the CV outcomes of linagliptin among Asian T2DM patients. Linagliptin reduced 3P-MACE (first occurrence of CV death, non-fatal MI, or non-fatal stroke events, HR 0.85), 4P-MACE (CV death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for unstable angina HR 0.86; 95% CI 0.59–1.26), all-cause mortality (HR 0.74; 95% CI 0.46–1.20) over a follow-up of 6.2 years. These findings suggest the CV safety of Linagliptin in Asian T2DM patients. (17)

Dapagliflozin for CV risk reduction-Insights from DECLARE TIMI 58 Trial: The DECLARE TIMI 58 trial assessed the effect of Dapagliflozin; enrolling 17160 patients with T2DM; 6974 had known ASCVD, of whom 3584 had a history of MI, with a median duration of 5.4 years from their last event. The trial randomized the participants to receive dapagliflozin (10mg once daily) or a placebo. Dapagliflozin significantly reduced MACE by 16% (hazard ratio [HR], 0.84; 95% CI, 0.72–0.99; P=0.039) in those with a history of prior MI. The efficacy result based on ejection fraction showed that in T2DM with Heart Failure with reduced Ejection Fraction (HFrEF), dapagliflozin treatment reduced CV death by 45%, hospitalization for HF by 36%, and all-cause mortality by 41%. Among HF without reduced EF, the treatment reduced CV death by 12% and hospitalization for HF by 24%. These findings suggest the CV benefit & safety of dapagliflozin in T2DM patients. (18)

Dapagliflozin Improves Cardio-Renal Outcomes in DAPA CKD Trial: The Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial, designed in a randomized, double-blind, placebo-controlled, multicenter design, assessed the long-term efficacy and safety of the SGLT2 inhibitor dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes. The trial enrolled 4304 subjects with an eGFR of 25-75 ml/minute/1.73 m2. Treatment with dapagliflozin has a lower hazard ratio for the composite of a sustained decline in the eGFR of at least 50%, end-stage kidney disease, or death from renal causes was by 35% (95% CI, 0.45 to 0.68; P<0.001), reduced the chance of composite of death from cardiovascular causes or hospitalization for heart failure by 41% (95% CI, 0.55 to 0.92; P=0.009). The study’s findings highlight Dapagliflozin’s renal safety and benefit in T2DM patients with CKD. (19)

Robust Clinical Benefits of Linagliptin & Dapagliflozin in High CV Risk Patients

  • Linagliptin therapy provides beneficial cardiorenal protection, and its use is guideline-directed owing to its CV safety profile. (7,11)
  • Linagliptin treatment improves microalbuminuria (urine albumin creatinine ratio of < 30 mg/g) by 68.3% among patients with diabetic nephropathy(DN). (15)
  • Dapagliflozin is a glucose-lowering agent with CV benefits and provides cardio-protection and renal protection in T2DM patients. (12,13)
  • Dapagliflozin treatment reduces seated SBP by 10.4 mmHg (21), 24-hour ambulatory BP by 9.6 mmHg (21), weight by 4.27 kgs (22), BMI by 1.53 kg/m2 (22), and left ventricular mass by 2.82g (22).
  • Dapagliflozin reduces CV death by 45%, hospitalization for HF by 36%, and all-cause mortality by 41%. (18)
  • Dapagliflozin reduces albuminuria by 33% and reduces death from renal causes in T2DM patients. (19)

Clinical Takeaways:

  • Managing CVD in patients with T2DM is a rapidly evolving scientific field, and using antidiabetic agents with proven CV safety is important in this patient population.
  • Linagliptin provides cardioprotection benefits, and dapagliflozin improves ventricular loading conditions, cardiac metabolism, and bioenergetics.
  • Linagliptin treatment improves the progression of CKD and reduces microalbuminuria in diabetic nephropathy.
  • Dapagliflozin improves cardiorenal outcomes through various pathways, including reducing blood pressure, arterial stiffness, and endothelial dysfunction.
  • Dapagliflozin treatment led to a reduction in heart failure hospitalization, CV death, and all-cause mortality in patients with diabetes and high CV risk. Treatment with dapagliflozin prevents CKD progression, ESKD, and death from renal causes.

Linagliptin and dapagliflozin seem effective in achieving glycemic control, alleviating CV risk factors and improving CV-CKD outcomes; potentially allowing these agents to be an ‘evergreen duo’ in the management of the Type 2 Diabetes continuum.

References:

1. Unnikrishnan AG, Sahay RK, Phadke U, Sharma SK, Shah P, Shukla R, Viswanathan V, Wangnoo SK, Singhal S, John M, Kumar A, Dharmalingam M, Jain S, Shaikh S, Verberk WJ. Cardiovascular risk in newly diagnosed type 2 diabetes patients in India. PLoS One. 2022 Mar 31;17(3):e0263619. doi: 10.1371/journal.pone.0263619.

2. Hodrea J, Saeed A, Molnar A, Fintha A, Barczi A, Wagner LJ, Szabo AJ, Fekete A, Balogh DB. SGLT2 inhibitor dapagliflozin prevents atherosclerotic and cardiac complications in experimental type 1 diabetes. PLoS One. 2022 Feb 17;17(2):e0263285. doi: 10.1371/journal.pone.0263285.

3. Mohan V, Venkatraman JV, Pradeepa R. Epidemiology of cardiovascular disease in type 2 diabetes: the Indian scenario. J Diabetes Sci Technol. 2010;4(1):158-170. Published 2010 Jan 1. doi:10.1177/193229681000400121

4. Zakaria EM, Tawfeek WM, Hassanin MH, Hassaballah MY. Cardiovascular protection by DPP-4 inhibitors in preclinical studies: an updated review of molecular mechanisms. Naunyn Schmiedebergs Arch Pharmacol. 2022;395(11):1357-1372. doi:10.1007/s00210-022-02279-3

5. Kumar V, Agarwal S, Saboo B, Makkar B. RSSDI Guidelines for the management of hypertension in patients with diabetes mellitus [published online ahead of print, 2022 Dec 15]. Int J Diabetes Dev Ctries. 2022;42(Suppl 1):1-30. doi:10.1007/s13410-022-01143-7

6. Samson SL, Vellanki P, Blonde L, Christofides EA, Galindo RJ, Hirsch IB, Isaacs SD, Izuora KE, Low Wang CC, Twining CL, Umpierrez GE, Valencia WM. American Association of Clinical Endocrinology Consensus Statement: Comprehensive Type 2 Diabetes Management Algorithm – 2023 Update. Endocr Pract. 2023 May;29(5):305-340. doi: 10.1016/j.eprac.2023.02.001. Erratum in: Endocr Pract. 2023 Sep;29(9):746.

7. Marx N, Federici M, Schütt K, Müller-Wieland D, Ajjan RA, Antunes MJ, Christodorescu RM, Crawford C, Di Angelantonio E, Eliasson B, Espinola-Klein C, Fauchier L, Halle M, Herrington WG, Kautzky-Willer A, Lambrinou E, Lesiak M, Lettino M, McGuire DK, Mullens W, Rocca B, Sattar N; ESC Scientific Document Group. 2023 ESC Guidelines for the management of cardiovascular disease in patients with diabetes. Eur Heart J. 2023 Oct 14;44(39):4043-4140. doi: 10.1093/eurheartj/ehad192.

8. ElSayed NA, Aleppo G, Aroda VR, et al. 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes-2023. Diabetes Care. 2023;46(Suppl 1):S191-S202. doi:10.2337/dc23-S011

9. Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022 Nov;102(5S):S1-S127. doi: 10.1016/j.kint.2022.06.008.

10. Johansen, O.E., Neubacher, D., von Eynatten, M. et al. Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme. Cardiovasc Diabetol 11, 3 (2012). https://doi.org/10.1186/1475-2840-11-3

11. Aroor AR, Manrique-Acevedo C, DeMarco VG. The role of dipeptidylpeptidase-4 inhibitors in management of cardiovascular disease in diabetes; focus on linagliptin. Cardiovasc Diabetol. 2018 Apr 18;17(1):59. doi: 10.1186/s12933-018-0704-1.

12. Zhai M, Du X, Liu C, Xu H. The Effects of Dapagliflozin in Patients With Heart Failure Complicated With Type 2 Diabetes: A Meta-Analysis of Placebo-Controlled Randomized Trials. Front Clin Diabetes Healthc. 2021 Jun 30;2:703937. doi: 10.3389/fcdhc.2021.703937.

13. Bell, DSH, McGill, JB, Jerkins, T. Management of the ‘wicked’ combination of heart failure and chronic kidney disease in the patient with diabetes. Diabetes Obes Metab. 2023; 25(10): 2795-2804. doi:10.1111/dom.15181

14. Poonchuay N, Wattana K, Uitrakul S. Efficacy of linagliptin on cardiovascular risk and cardiometabolic parameters in Thai patients with type 2 diabetes mellitus: A real-world observational study. Diabetes Metab Syndr. 2022 May;16(5):102498. doi: 10.1016/j.dsx.2022.102498. Epub 2022 May 13.

15. Karimifar, M., Afsar, J., Amini, M. et al. The effect of linagliptin on microalbuminuria in patients with diabetic nephropathy: a randomized, double-blinded clinical trial. Sci Rep 13, 3479 (2023). https://doi.org/10.1038/s41598-023-30643-7

16. Inagaki N, Yang W, Watada H, et al. Linagliptin and cardiorenal outcomes in Asians with type 2 diabetes mellitus and established cardiovascular and/or kidney disease: subgroup analysis of the randomized CARMELINA® trial. Diabetol Int. 2019;11(2):129-141. Published 2019 Oct 22. doi:10.1007/s13340-019-00412-x

17. Kadowaki T, Wang G, Rosenstock J, et al. Effect of linagliptin, a dipeptidyl peptidase-4 inhibitor, compared with the sulfonylurea glimepiride on cardiovascular outcomes in Asians with type 2 diabetes: subgroup analysis of the randomized CAROLINA® trial. Diabetol Int. 2020;12(1):87-100. Published 2020 Jun 27. doi:10.1007/s13340-020-00447-5

18. Verma S, McMurray JJV. The Serendipitous Story of SGLT2 Inhibitors in Heart Failure. Circulation. 2019 May 28;139(22):2537-2541. doi: 10.1161/CIRCULATIONAHA.119.040514. Epub 2019 Mar 18.

19. Heerspink HJL, Stefánsson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjöström CD, Toto RD, Langkilde AM, Wheeler DC; DAPA-CKD Trial Committees and Investigators. Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. doi: 10.1056/NEJMoa2024816. Epub 2020 Sep 24.

20. McGill JB. Linagliptin for type 2 diabetes mellitus: a review of the pivotal clinical trials. Ther Adv Endocrinol Metab. 2012;3(4):113-124. doi:10.1177/2042018812449406

21. Weber MA, Mansfield TA, Alessi F, Iqbal N, Parikh S, Ptaszynska A. Effects of dapagliflozin on blood pressure in hypertensive diabetic patients on renin-angiotensin system blockade. Blood Press. 2016;25(2):93-103. doi: 10.3109/08037051.2015.1116258. Epub 2015 Dec 1. Erratum in: Blood Press. 2016 Aug;25(4):x.

22. Brown AJM, Gandy S, McCrimmon R, Houston JG, Struthers AD, Lang CC. A randomized controlled trial of dapagliflozin on left ventricular hypertrophy in people with type two diabetes: the DAPA-LVH trial. Eur Heart J. 2020 Sep 21;41(36):3421-3432. doi: 10.1093/eurheartj/ehaa419.

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Prophylactic Oropharyngeal Surfactant at birth fails to reduce Intubation Rates among preterm newborns

A recent study published in Journal of American Medical Association suggests that administration of prophylactic oropharyngeal surfactant to newborns born before 29 weeks of gestational age does not reduce the need for intubation during the critical first 120 hours of life.

This clinical trial included 251 newborns born before 29 weeks of gestation without severe congenital anomalies. This study from December 2017 to September 2020 was conducted in Prophylactic Oropharyngeal Surfactant for Preterm Infants (POPART) trial across nine tertiary NICU. The infants were either assigned to receive oropharyngeal surfactant at birth in addition to continuous positive airway pressure (CPAP) or CPAP alone. The primary outcome measured was the need for intubation within 120 hours of birth due to bradycardia, apnea, or respiratory failure.

The outcomes found that, among the participants, the rate of intubation within the specified time frame did not significantly differ between the oropharyngeal surfactant group and the control group. 

63.5% of infants in the oropharyngeal surfactant group and 64.8% in the control group required intubation (relative risk, 0.98 [95% CI, 0.81-1.18]).

However, this study indicate that more newborns in the oropharyngeal surfactant group were diagnosed with and treated for pneumothorax compared to the control group (16.6% vs. 6.4%, P = .04).

The randomized clinical trial concluded that the prophylactic administration of oropharyngeal surfactant to newborns born before 29 weeks of gestation did not result in a reduced rate of intubation in the first 120 hours of life. These findings challenge the routine use of surfactant administration into the oropharynx immediately after birth in addition to CPAP for preterm infants and this prompts a reevaluation of existing protocols in neonatal intensive care units.

Reference:

Murphy, M. C., Miletin, J., Klingenberg, C., Guthe, H. J., Rigo, V., Plavka, R., Bohlin, K., Barroso Pereira, A., Juren, T., Alih, E., Galligan, M., & O’Donnell, C. P. F. (2023). Prophylactic Oropharyngeal Surfactant for preterm newborns at birth: A randomized clinical trial. JAMA Pediatrics. https://doi.org/10.1001/jamapediatrics.2023.5082

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Both digital and conventional fabrication of complete dentures yield comparable clinical outcome

Both digital and conventional fabrication of complete dentures yield comparable clinical outcome suggests a new study published in the Journal of Prosthetic Dentistry.

Reports on digitally fabricated complete dentures are increasing. However, comprehensive evidence-based research on their cost-efficiency and patient-reported outcome measures (PROMs) is lacking.

The purpose of this systematic review was to compare the cost-effectiveness and PROMs between digitally and conventionally fabricated complete dentures.

Material and methods

An electronic search of publications from 2011 to mid-2023 was established using PubMed/Medline, EBSCOhost, and Google Scholar. Retrospective, prospective, randomized controlled, and randomized crossover clinical studies on at least 10 participants were included. A total of 540 articles were identified and assessed at the title, abstract, and full article level, resulting in the inclusion of 14 articles. Data on cost, number of visits, patient satisfaction, and oral health-related quality of life were examined and reported.

Results

The systematic review included 572 digitally fabricated complete dentures and 939 conventionally fabricated complete dentures inserted in 1300 patients. Digitally fabricated complete dentures require less clinical time with a lower total cost, despite higher material costs compared with the conventional fabrication technique. Digitally and conventionally fabricated complete dentures were found to have significant effects on mastication efficiency, comfort, retention, stability, ease of cleaning, phonetics, and overall patient satisfaction, as well as social disability, functional limitation, psychological discomfort, physical pain, and handicap.

Digitally fabricated complete dentures are more cost-effective than conventionally fabricated dentures. There are various impacts of conventionally and digitally fabricated complete dentures on PROMs, and they are not better than one another.

To read this article in full you will need to make a payment

Reference:

Digitally versus conventionally fabricated complete dentures: A systematic review on cost-efficiency analysis and patient-reported outcome measures (PROMs)

In Meei Tew, Suet Yeo Soo, Edmond Ho Nang Pow. Published:November 23, 2023DOI:https://doi.org/10.1016/j.prosdent.2023.10.028

Keywords:

Both, digital, conventional, fabrication, complete, dentures, yield, comparable, clinical outcome, In Meei Tew, Suet Yeo Soo, Edmond Ho Nang Pow,Journal of Prosthetic Dentistry

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Patients undergoing bariatric surgery for GERD may very often require revision surgery

Gastroesophageal reflux disease (GERD) is a recognized possible outcome of bariatric surgery and may necessitate revisional surgery.

In a recent study published in Surgical Endoscopy, researchers said GERD is the second most common reason for revisional surgery after bariatric surgery, primarily affecting sleeve gastrectomy (SG) patients who mainly underwent Roux-en-Y gastric bypass (RYGB) revision. They mentioned further investigation is needed to optimize these patients’ pre-operative approaches and surgical strategies.

Our understanding of the population needing revision needs to be improved. This study aims to characterize GERD patients requiring revisional surgery, understand their perioperative risks, and identify strategies for improved outcomes.

In 2020, a retrospective cohort of GERD patients needing revisional surgery was identified using the MBSAQIP registry. Multivariable logistic regression was used to examine correlations between baseline characteristics and morbidity.

Key findings from this study are:

· 4412 patients required revisional surgery for GERD, encompassing 24% of all conversion procedures.

· Most patients underwent SG as their original surgery, constituting 80.1%.

· The revisional surgery for most patients was RYGB, constituting 84.4%.

· 527 patients experienced major complications.

· Ten patients died within 30 days of revisional surgery.

· Major complications included anastomotic leak (0.70%) and gastrointestinal bleeding (0.86%).

· Operative length, pre-operative antacid use, and RYGB were predictors of major complications.

This study is the largest to date on patients undergoing revisional surgery for GERD. The pathophysiology of GERD in bariatric surgery patients is still debated, but a better understanding could reduce the need for revisional procedures. They said that novel endoscopic techniques raise new questions as potential alternatives for primary and revisional bariatric procedures.

Reference:

MacVicar, S., Mocanu, V., Jogiat, U. et al. Revisional bariatric surgery for gastroesophageal reflux disease: characterizing patient and procedural factors and 30-day outcomes for a retrospective cohort of 4412 patients. Surg Endosc (2023). https://doi.org/10.1007/s00464-023-10500-4

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Single administration of travoprost intraocular implant may effectively lower IOP over 3 years

Single administration of travoprost intraocular implant may effectively lower IOP over course of 3 years suggests a new study published in the Drugs.

A travoprost intraocular implant may effectively lower intraocular pressure (IOP) over the course of 36 months after a single administration, according to new findings, substantially diminishing the necessity of topical IOP-lowering medications and helping to lessen problems with adherence and side effects.

These findings on the implant’s sustained-release drug delivery system were the results of a phase 2 trial conducted to look at the long-term safety and the effectiveness of travoprost intraocular implant. The investigators noted prior to their research that IOP is the only known modifiable risk factor for glaucoma, with many studies pointing to the essential role of IOP lowering in the practice of decreasing glaucoma development.

The overall goal of the investigators was to find a way to reduce treatment burden for patients and to improve adherence to IOP-lowering treatments, and this particular system was assessed in this analysis. The research into this implant for IOP was authored by Tomas Navratil, from the Glaukos Corporation in Aliso Viejo, California.

“The objective of the current study was to report on the 3 year safety of the implant, and percentage of patients who reduced or maintained their topical IOP-lowering medication burden relative to pre-study medications,” Navratil and colleagues wrote.

The team sought to examine the safety and efficacy of 2 travoprost intraocular implants that each used different elution rates compared to timolol eye drops (Timolol Maleate Ophthalmic Solution, USP, 0.5%) for those with OAG or OHT who were already on 0–3 topical medications that were IOP-lowering.

Individuals who had been diagnosed with open-angle glaucoma or with ocular hypertension were assigned to be placed into 1 of 3 groups:

A fast-eluting implant (FE implant, n = 51) and twice-daily (BID) placebo eye drops

A slow-eluting implant (SE implant, n = 54) and BID placebo eye drops

A sham surgical procedure with BID timolol 0.5% (n = 49)

IOP measurements were done at several different intervals up to 36 months. The investigators looked at efficacy by assessing the mean change from the 8:00 AM unmedicated baseline IOP throughout the total study period.

The research team also looked into the percentage of subjects using the same or fewer topical IOP-lowering treatments as they had at screening. They evaluated safety data by monitoring the reported adverse events and using different ophthalmic parameters.

The intraocular implant was shown to have strong efficacy in its reduction of IOP, with the investigators finding major decreases in subjects’ need for topical medications designed for IOP-lowering. This decrease lasted for a duration of up to 36 months following a single administration.

“These results suggest that the travoprost intraocular implant may represent a meaningful addition to the interventional glaucoma armamentarium, demonstrating safe and well-tolerated IOP lowering for up to 36 months after a single administration and addressing the key shortcomings of topical IOP-lowering medications defined by low adherence and adverse impact on ocular surface health,” they wrote.

Refrence:

Berdahl, J.P., Sarkisian, S.R., Ang, R.E. et al. Efficacy and Safety of the Travoprost Intraocular Implant in Reducing Topical IOP-Lowering Medication Burden in Patients with Open-Angle Glaucoma or Ocular Hypertension. Drugs (2023). https://doi.org/10.1007/s40265-023-01973-7.

Keywords:

Single, administration, travoprost, intraocular, implant, may, effectively, lower, IOP, over, course, 3 years, Berdahl, J.P., Sarkisian, S.R., Ang, R.E, Drugs

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Roche Gets CDSCO Panel Nod to Study anti-cancer Drug Inavolisib

New Delhi: The drug major Roche has got approval from the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) to conduct the trial of anti-cancer drug Inavolisib.

This came the drug major Roche presented Phase III Clinical Study Protocol no. WO44263. The study is to evaluate the efficacy and safety of Inavolisib in combination with Phesgo versus placebo in combination with Phesgo in participants with PIK3CA-Mutated HER2-Positive locally advanced or metastatic breast cancer.

Inavolisib is an oral therapy with high in vitro potency and selectivity for PI3Kα inhibition and the ability to specifically trigger the breakdown of mutant PI3Kα protein. With this unique dual mechanism of action, inavolisib may provide well-tolerated, durable disease control and potentially improved outcomes for people with HR-positive/HER2-negative, PIK3CA-mutated advanced breast cancer. PIK3CA mutations can lead to mutated PI3Kα protein which contributes to uncontrolled tumor growth, disease progression, and resistance to endocrine-based treatment.
Inavolisib is currently being investigated in three Phase III clinical studies in people with PIK3CA-mutated metastatic breast cancer (INAVO120, INAVO121, INAVO122) in various combinations.
At the recent SEC meeting for Oncology and Hematology held on 29th and 30th November 2023, the expert panel reviewed the Phase III clinical study protocol of the anti-cancer drug Inavolisib presented by drug major Roche.
After detailed deliberation, the committee recommended a grant of permission to conduct the trial as presented by the firm.

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Does Drinking Adequate Water Improve Your Sugar Levels? – Dr Kaushik Hazra

Water is vital for the living, especially humans. Water makes up most
of your body and is essential for many everyday critical bodily functions,
including regulating your body temperature, aiding your brain function,
eliminating waste, and carrying nutrients and oxygen across your body.

Every
person needs to consume a certain amount of water to ensure the smooth and
efficient functioning of the body. However, an alarming number of Indians are
constantly dehydrated, which affects their health.

When your water intake is lower than your body needs, it affects your
brain, kidneys, digestive and urinary systems and most importantly, your blood.

When you do not drink enough water, your blood will be more concentrated,
affecting your sugar levels and overall health. And if you have diabetes, the
concentrated blood will report a higher amount of glucose per deciliter of
blood when measured.

Now let us see how dehydration affects your blood sugar levels:

Mild Dehydration causes a quick but minor increase in
your blood sugar levels. However, even this spike negatively affects your
overall diabetes health.

Sudden Dehydration causes a significant spike in your blood
sugar levels that instantly affects your ketone levels, causing an increase in
diabetes.

Severe Dehydration causes a gradual increase in your blood
sugar levels, escalating your ketone levels and may lead to diabetic
ketoacidosis.

Unfortunately, not many of you know that sipping coffee and having
beverages does not add to your overall water intake, even though it may seem
so, as the caffeine content in coffee is known to increase insulin resistance.

At the same time, beverages are loaded with chemicals that also affect insulin
resistance. On the contrary, unsweetened traditional beverages are a great way
to stay hydrated. However, nothing beats the good-old hydrating option – water.

As a healthcare practitioner, I come across many patients with
ill-formed water-drinking habits. So, I recommend they inculcate certain
must-dos in their daily routines and learn to rehydrate themselves.

Set Water Routine

According to Ayurveda, drinking a glass of warm water upon waking up
and before sleeping aids digestion and sleep while keeping you active during
the day.

Energize Your Water

As some of you feel water is too bland, make your water more
interesting; add sliced lemon, fruit pieces and herbs to infuse it with flavor
and minerals.

Schedule Hydration Breaks

Just as you take tea or bathroom breaks, you must schedule hydration
breaks to drink some water mindfully for a few minutes.

Carry a Reusable Bottle

Keeping a reusable and measurable water bottle with you throughout the
day is a visual reminder to drink water and helps track your water intake.

Think Beyond Water

Water hydrates; however, many other drinks hydrate equally well.
Alternating milk, coconut water, and tea to increase fluid intake is a good
idea.

Include Water-Rich Food

It is effortless to include greens, vegetables, and fruits high in
water in your diet through salads and smoothies to keep you hydrated.

So, the real crux is that adequate water intake is essential to good
health. So, talk to your doctor to understand how much water you should drink.
Once you know this, prioritize water to improve your blood sugar levels and
overall health.

Disclaimer: The views expressed in this article are of the author and not of Medical Dialogues. The Editorial/Content team of Medical Dialogues has not contributed to the writing/editing/packaging of this article.

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NMC sets deadline for FMGs to avail benefits of Academic Mobility Programme

The National Medical Commission (NMC) has now set a deadline for Foreign Medical Graduates to avail the benefits of the Academic Mobility Programme.

Issuing a Public Notice on 07.12.2023, the Undergraduate Medical Education Board (UGMEB) of the National Medical Commission (NMC) mentioned that medical students abroad are allowed to migrate to other countries to complete their medical education till 07.03.2024.

For more details, check out the link given below:

All FMGs Who Returned Till 31.03.2022 Can Avail Academic Mobility Programme Till Mach 7, 2024: NMC

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Bangalore Cancer Hospital files police case against staff for selling cancer medicines at discounted price to indoor patients

Bangalore: Taking action against its employees who were providing cancer medicines to the indoor admitted patients from other sources than the hospital dispensary, a Bengauluru hospital has now filed a police complaint against its 3 employees. 

Based on the complaint filed by the managing trustee of Dr BS Srinath of Sri Shankara Cancer Hospital and Research Center , a case has been registered under IPC sections 427 (mischief causing damage amounting to fifty rupees), 406 (criminal breach of trust) and 120B (criminal conspiracy)

It was alleged in the complaint that some employees of the cancer hospital were caught on charges of selling medicines to patients illegally. Despite the same medicine being available in the hospital dispensary, the staff was purchasing it from outside and allegedly giving it to the cancer patients at lower prices than what was being charged at the hospital dispensary.

as part of the ongoing investigation, the police will also issue a notice to those accused to appear for questioning.

Also Read: Karnataka High Court allows elected body of Karnataka Medical Council 2020 to assume charges of office

The matter came to light on Thursday 7 December 2023, when the hospital management checked all the reports. It is suspected that this act has  going on for almost a year. The managing trustee of the hospital, Dr BS Srinath, has filed a complaint against Demappa Hannavar and Satish R, former employee Chandrappa BM and other employees. Dr Srinath has accused these employees of selling illegally purchased medicines, which has caused loss to the hospital. He also told the police that the patients undergoing hospital treatment and surgery are issued medicines from the hospital dispensary.

A senior police officer told Times of India, that the investigating officer is going to issue notices to the accused persons to appear for questioning, and necessary action will also be taken after the investigation. “We’re going to ask the hospital to provide details of the total loss caused and for how long the illegal sale was taking place,” a senior police officer said.

During the verification of documents, Demappa was caught red-handed with medicines which were imported from outside. Then when he was interrogated about this matter, he confessed that “the medicines were from outside and sold to patients at a lower price than what the hospital charged”. He further added “The medicines were sourced based on the instructions given by Satish, HOD of the outpatient (OP) pharmacy”. 

He confirmed that he was purchasing the medicines from one Chandrappa, an ex-employee of the hospital, who had opened his own medical store after quitting his job at the hospital in 2022.

Also Read: Proposal to eliminate compulsory rural service for medical graduates moved in Karnataka Assembly

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