Archive for month: November, 2024

Harmful use of alcohol is a global burden both economically
and healthcare-wise. Psychological treatments are the main line of management
of this. However, pharmacological management can also be used to reduce the
harmful usage of alcohol. Research shows that Glucagon-like peptide-1 receptor
(GLP-1) agonists that are used to treat diabetes and obesity can also be used to
treat alcohol use disorder. Hence researchers conducted a study to investigate
the potential of GLP-1 agonists as a treatment for reducing alcohol-related
harms.

This observational cohort study used real-world data from
Swedish registries. The data was collected from registers of inpatient care,
specialized outpatient care, sickness absence, and disability pension.
Participants were all residents aged 16 to 64 with a diagnosis of AUD. A cohort
of 227 886 individuals were followed up from AUD diagnosis to death,
emigration, or end of data linkage. The main exposure was GLP-1 agonists, which
were exenatide, liraglutide, dulaglutide, and semaglutide. The secondary
exposure was the use of AUD medications. Hospitalization due to AUD was the
primary outcome of measurement while hospitalization due to substance use
disorder, somatic reasons, and suicide attempts was the secondary outcome of
measurement. Cox regression models with fixed effects were used to calculate
the within-individual risk of an outcome associated with use vs nonuse of
pharmacotherapies.

Findings:

• The cohort included 227 866 individuals with AUD
  of which 144 714 (63.5%) were male and the remaining (36.5%) were female.
• The cohort’s mean (SD) age was 40.0 (15.7)
  years, and the median (IQR) follow-up time was 8.8 (4.0-13.3) years.
• A total of 133 210 individuals (58.5%)
  experienced AUD hospitalization.
• Semaglutide (4321 users) and liraglutide (2509
  users) were associated with the lowest risk of both AUD and SUD
  hospitalization.
• AUD medications were associated with a modestly
  decreased risk.
• Semaglutide and liraglutide use were also
  associated with a decreased risk of somatic hospitalizations but not associated
  with suicide attempts.

Thus, the study concluded that semaglutide and liraglutide
were associated with a substantially decreased risk of hospitalization due to
AUD and can be effectively used in the management of alcohol use disorder.

Further reading: Lähteenvuo M, Tiihonen J, Solismaa
A, Tanskanen A, Mittendorfer-Rutz E, Taipale H. Repurposing
Semaglutide and Liraglutide for Alcohol Use Disorder. JAMA Psychiatry. Published
online November 13, 2024. doi:10.1001/jamapsychiatry.2024.3599

Recurrent corneal erosion
syndrome (RCES) is a painful eye condition frequently caused by mechanical
trauma and characterized by abnormal epithelial adhesion to the underlying
basal lamina. This condition leads to recurrent epithelial breakdown and
impairs vision causing severe pain. Conservative treatments include the use of topical
lubricants, topical hypertonic saline, and/or bandage contact lenses while
invasive approaches include mechanical debridement, alcohol delamination of the
epithelium, and excimer laser phototherapeutic keratectomy (PTK). As there is
ambiguity in the various treatment approaches for the management of RCES and
the use of phototherapeutic keratectomy (PTK), researchers conducted a retrospective
study to examine the long-term safety and efficacy of transepithelial PTK for
the management of RCES that is resistant to conservative management.

Findings:

• This study included 593 eyes of 555 patients
  (46.2% male; 50.9 ± 14.2 years old) who underwent TE-PTK.
• The leading identified causes of RCES were
  trauma (45.7%) and anterior basement membrane dystrophy (44.2%).
• The most common pre-PTK interventions were
  ocular lubricants (90.9%), hypertonic solutions (77.9%), and bandage contact
  lenses (50.9%).
• Thirty-six eyes had undergone surgical
  interventions such as stromal puncture, epithelial debridement, or diamond burr
  polishing.
• Post-PTK, 78% of patients did not require any
  subsequent therapies and 20% required ongoing drops.
• Six patients (1.1%) reported no symptom
  improvement and were required to repeat TE-PTK for ongoing RCES symptoms after the
  initial TE-PTK.
• All 6 eyes were successfully retreated with
  TE-PTK (average time to retreatment was 11.3 ± 14.9 months).
• There was no significant difference in best
  corrected visual acuity pre- vs. post-operatively. The mean postoperative
  follow-up was 60.5 months (range: 5–127 months).

Thus, the researchers concluded
that TE-PTK showed a high efficacy and safety profile and can be used as
a preferred treatment option for patients with RCES resistant to standard
treatments. The treatment showed a low recurrence rate and low rates of
retreatments. The researchers also suggested that TE-PTK can be considered for
broader application in resistant RCES based on cost-effectiveness and patient
satisfaction.

Further reading: Bizrah M,
Shunmugam M, Ching G, et al. Transepithelial phototherapeutic keratectomy for
treatment-resistant recurrent corneal erosion syndrome. Graefes Arch
Clin Exp Ophthalmol. 2024;262(10):3253-3260. doi:10.1007/s00417-024-06482-1

RDEB is a generalized form of EB, with delicate skin that blisters and heals with chronic wounds. Neuropathic pain and pruritus are often documented as severely impacting quality of life. Current treatments offer only incomplete relief, and scarce evidence has been available to guide the management of these disabling symptoms. Pregabalin is a drug already approved for neuropathic pain and may also prove helpful in this indication.

The objective of this study was to investigate the efficacy of oral pregabalin in the adjunctive treatment of neuropathic pain and itching in patients with RDEB. It was hypothesized that treatment with pregabalin would be significantly more effective at relieving symptoms than a placebo.

This is a randomized, double-blinded, crossover trial conducted at two sites, Toronto, Canada, and Santiago, Chile from January 2019 through December 2020. The participants should be aged 8 to 40 years with diagnosed RDEB experiencing neuropathic pain and itch. The inclusion criteria were having a score of 4 or greater on the Douleur Neuropathique 4 (DN4) questionnaire and scoring greater than 4 on the VAS for pain or itch. Patients with poorly controlled medical conditions or allergies to pregabalin were excluded.

Pre-therapy screening of all patients and then random allocation to two groups of thirty in each. Group 1 was treated first with pregabalin followed by a placebo, and group 2 was given a placebo first followed by pregabalin. The dose limit of pregabalin was 300 mg/day. The effectiveness of treatment was assessed in terms of VAS scores for pain and itch before and after therapy.

• Ten patients were recruited in the study with a mean age of around 26.6 years in both the groups.

• Pregabalin decreased mean pain scores by 1.9 points whereas in case of placebo, it decreased by 0.1 points.

• In comparison to the baseline, the decrease in mean was 0.9 points; on the other hand, the placebo group showed minimal reduction of 0.1 points.

• Generally, the tolerance of pregabalin by participants was good. No major adverse effects were encountered.

Pregabalin operates by the modulation of calcium channels within the central nervous system to block the release of certain neurotransmitters that cause pain. With RDEB, the antineuropathic pain property of pregabalin has made this drug a possible candidate for the management of chronic discomfort associated with this disease.

This study demonstrated that pregabalin considerably reduced pain and itch. The results provide renewed optimism for patients with RDEB, based on preliminary evidence that pregabalin may serve as a treatment for the neuropathic symptoms inherent to the disease; further investigation is necessary to formally confirm these results and ascertain long-term benefits of pregabalin in this patient population.

Reference:

Calvo, M., Tejos-Bravo, M., Passi-Solar, A., Espinoza, F., Fuentes, I., Lara-Corrales, I., & Pope, E. (2024). Pregabalin for neuropathic pain and itch in recessive dystrophic epidermolysis bullosa: A randomized crossover trial. JAMA Dermatology (Chicago, Ill.). https://doi.org/10.1001/jamadermatol.2024.3767

As per the notification in this regard, all the eligible Candidates included in the Kerala State Merit list who have applied for admission to PG Medical Courses 2024 in the State can register their options online through the CEE official website before 23 November 2024, 5.00 PM. To register the options, the candidate has to click on ‘PG Medical 2024-Candidate Portal’ available on the official website of CEE and enter their application number and password to access their home page. Candidates can register their options online by clicking on the menu ‘Options Registration’ available on the home page.

Meanwhile, a security deposit of Rs. 10,000/- will have to be paid at the time of option registration. For SC/ST/OEC and other candidates who are eligible for fee concession Rs.5000/- will have to be paid as a security deposit. The security deposit will be refunded to the eligible candidates after the completion of the entire counselling process.

Fee Structure

The list of Medical Colleges/Courses to which the Commissioner for Entrance Examinations makes allotment is provided on the Home page of the candidate. Candidates can give options as per their priority of the CourseCollege combinations in the option list. A candidate need only give options to a Course-College combination if he/she is sure to join the course and college, under the chosen quota, if allotted. Options registered online alone will be considered for allotment to the courses. Options sent to the Office of the Commissioner for Entrance Examinations via Post/Fax/E-mail will not be processed/considered for allotment to the courses.

Candidates who seek admission under the Minority/NRI quota in Self Financing Medical Colleges shall have to register options online to the desired courses/colleges in this first phase itself. Candidates who do not register options shall not be considered for allotment under the Minority/NRI quota even if they are included in the respective category lists.

Candidates are requested to go through the relevant clauses in the Prospectus with regard to the Centralised Allotment Process before registering options. The Eligible candidates, who are included in the Kerala State Merit List prepared by the CEE can register options in the first phase of counselling. The allotments will be strictly based on the options exercised, the rank obtained and the eligible reservations of the candidate. Candidates should register options only to those courses and colleges which they are sure to join on allotment.

In the second phase of counselling, there is no facility for fresh option registration for the candidates. Only option confirmation/deletion/rearrangement of the existing options in phase 2 is possible. Option confirmation is compulsory to participate in phase 2. Option registration will be available only to those courses which are newly added to the list at the second stage. If a candidate is allotted a seat in the first phase and joins the allotted seat, his/her higher options will be retained and all those options listed below the allotted option will automatically be deleted thus enabling only upgradation/retention in the same seat. If a candidate joined in a seat in phase 1 does not confirm option in phase 2 he will not be considered for upgradation in phase 2, but the seat joined in phase 1, if any, will be retained. So if a candidate joined in round 1 does not want upgradation in phase 2, he/she may not confirm options or delete all options registered.

After the 2nd Phase allotment, vacancies that exist or arise shall be filled in the 3rd round allotment. There is a facility for fresh option registration in 3rd round.

After the 3rd Phase allotment, if any vacancies exist or arise, those vacancies shall be filled through Stray vacancy allotment.

When a seat is allotted in a particular phase based on the valid options registered by the candidate, previous admission, if any, will stand cancelled irrespective of whether the new allotment is going to be accepted or not accepted by the candidate.

IMPORTANT POINTS

1 The allotment to Colleges/Courses will be subject to recognition of All India Regulatory Bodies/Affiliation from the Universities concerned.

2 Seat matrix will be published when the Government approves the same.

3 Those candidates whose positions in the Merit List have been withheld due to various reasons can also register their online options for allotment. But the options submitted by such candidates be considered for allotment only if they rectify or clear the defects before 4.00 PM on 23 November 2024 and otherwise eligible.

To view the notification, click the link below

https://medicaldialogues.in/pdf_upload/cee-261379.pdf

“It’s been 10 years since a new treatment for platinum-resistant ovarian cancer was approved in the EU, and now oncologists have an effective, new, targeted treatment option for these patients,” said Toon Van Gorp, Professor of Gynaecological Oncology at the University of Leuven.

Ovarian cancer is one of the leading causes of death from gynecological cancers worldwide.i Most patients present with late-stage disease and will typically undergo surgery followed by platinum-based chemotherapy. Unfortunately, most patients eventually develop platinum-resistant disease. Historically, treatment options for patients with platinum-resistant ovarian cancer (PROC) have been limited, and those available often result in adverse events which can negatively impact quality of life.

“Ovarian cancer can be devastating, taking women away from precious moments with their family, disrupting careers and the many other important contributions that women make to society,” said Clara Mackay, CEO, World Ovarian Cancer Coalition. “In Europe, ovarian cancer is three times more deadly than breast cancer, and having new innovative options allows us to work toward a world where everyone living with ovarian cancer has the best chance of survival and the best quality of life possible, no matter where they live.”

In approximately one third of people living with ovarian cancer, the folate-receptor alpha (FRα) biomarker is highly expressediv (≥75% of tumor cells with ≥2+ membrane staining intensity). To determine biomarker status, patients can be tested with Roche’s VENTANA FOLR1 (FOLR1-2.1) RxDx Assay at diagnosis or at the first sign of resistance to platinum-based chemotherapy. AbbVie collaborated with Roche Diagnostics on the newly approved immunohistochemistry (IHC) companion diagnostic test to identify patients who may be eligible for ELAHERE.

“The approval of ELAHERE by the European Commission provides a much needed clinically meaningful option for patients who receive the heartbreaking news their ovarian cancer has returned, fearing what’s next in their treatment journey after they’ve developed platinum-resistance,” said Roopal Thakkar, M.D., executive vice president, research and development, chief scientific officer, AbbVie.

The marketing authorization of ELAHERE is supported by data from MIRASOL: a global, Phase 3 open-label, randomized, controlled trial.

• Trial participants were 18 years of age or older with disease that had progressed while on or after one to three lines of previous therapy. Patient tumors had to express high levels of FRɑ (≥75% of tumor cells with ≥2+ membrane intensity), assessed using the VENTANA FOLR1 (FOLR1-2.1) RxDx Assay. The primary endpoint was investigator-assessed progression-free survival (PFS). Key secondary endpoints included objective response rate (ORR) and overall survival (OS).
• Results presented at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated a 35% reduction in the risk of tumor progression or death in patients treated in the ELAHERE arm compared with the investigator’s choice (IC) chemotherapy arm, which represented an improvement in PFS [HR 0.65 (95% CI: 0.52, 0.81; p<0.0001)].
• ELAHERE also demonstrated improvement in OS compared with IC chemotherapy, representing a 33% reduction in the risk of death in the ELAHERE arm in comparison to the IC chemotherapy arm [HR 0.67 (95% CI: 0.50, 0.89; p=0.0046)].
• The most common adverse reactions with ELAHERE were blurred vision, nausea, diarrhea, fatigue, abdominal pain, keratopathy, dry eye, constipation, vomiting, decreased appetite, peripheral neuropathy, headache, asthenia, increased aspartate aminotransferase and arthralgia. The most commonly reported serious adverse reaction was pneumonitis.
• Data from the Phase 3 MIRASOL Trial were also published in the New England Journal of Medicine (NEJM).