Influvac Tetra: clinical experience on safety, efficacy, and immunogenicity.

INTRODUCTION: This paper summarizes the safety and immunogenicity data of Influvac Tetra across all age groups starting from 6 months of age, obtained during its clinical development program. AREAS COVERED: The article covers the clinical development program of Influvac Tetra based on five registration studies that included different age groups, different comparators, and participants from Europe and Asia. Safety and immunogenicity were assessed in all studies and in one study, the efficacy of Influvac Tetra was assessed. EXPERT OPINION: Seasonal influenza is a vaccine-preventable disease that can cause serious complications. Several types of influenza vaccines are available, including egg-based (standard dose, high dose, and adjuvanted), cell-based, and recombinant. The COVID-19 pandemic has stimulated innovation in the development such as mRNA vaccines. However, these vaccines are still in development and the true value still has to be proven. Regardless of the type of vaccine, it is also important to increase overall vaccination coverage. ECDC recommends that EU Member States implement action plans and policies aimed at reaching 75% coverage in at-risk groups and healthcare workers. Even so, vaccine coverage is still far from recommended.

Reply letter to "Vaccine effectiveness of recombinant and standard dose influenza vaccines against outpatient illness during 2018-2019 and 2019-2020 calculated using a retrospective test-negative design".

A recent study by Zimmerman et al. (2023) reported non-significant higher relative vaccine effectiveness of recombinant (RIV4) over the standard-dose influenza vaccines (SDIV) against outpatient illness during the 2018-19 and 2019-20 vaccination seasons. We agree with the authors' conclusions and would like to emphasize minimal difference between RIV4 and SDIV using Number Needed to Vaccinate (NNV). The NNV analysis showed 8.9 for the RIV4 and 10 for the SDIV in the 50-64 age group. In the 65+ age group, the NNV was 10.6 for the RIV4 and 11.4 for the SDIV. This indicates a minimal difference between both vaccines and hence they both can be used in immunization programs to improve vaccine coverage.

Equipping providers to offer novel MPTs: Developing counseling messages for the Dual Prevention Pill in clinical studies and beyond.

Introduction: The pipeline for multi-purpose prevention technologies includes products that simultaneously prevent HIV, pregnancy and/or other sexually transmitted infections. Among these, the Dual Prevention Pill (DPP) is a daily pill co-formulating oral pre-exposure prophylaxis (PrEP), and combined oral contraception (COC). Clinical cross-over acceptability studies for the DPP require training providers to counsel on a combined product. From February 2021-April 2022, a working group of eight HIV and FP experts with clinical and implementation expertise developed counseling recommendations for the DPP based on existing PrEP/COC guidance. Assessment of policy/guidelines options and implications: The working group conducted a mapping of counseling messages from COC and oral PrEP guidance and provider training materials. Six topics were prioritized: uptake, missed pills, side effects, discontinuation and switching, drug interactions and monitoring. Additional evidence and experts were consulted to answer outstanding questions and counseling recommendations for the DPP were developed. Missed pills was the topic with the most complexity, raising questions about whether women could "double up" on missed pills or skip the last week of the pack to recover protection faster. Uptake required aligning the time to reach protective levels for both DPP components and explaining the need to take DPP pills during week 4 of the pack. The potential intensity of DPP side effects, given the combination of oral PrEP with COC, was an important consideration. Discontinuation and switching looked at managing risk of HIV and unintended pregnancy when stopping or switching from the DPP. Guidance on drug interactions contended with differing contraindications for COC and PrEP. Monitoring required balancing clinical requirements with potential user burden. Actionable recommendations: The working group developed counseling recommendations for the DPP to be tested in clinical acceptability studies. Uptake: Take one pill every day for the DPP until the pack is empty. Days 1-21 contain COC and oral PrEP. Days 22-28 do not contain COC to allow for monthly bleeding, but do contain oral PrEP and pills should be taken to maintain HIV protection. Take the DPP for 7 consecutive days to reach protective levels against pregnancy and HIV. Missed pills: If you miss 1 pill multiple times in a month or 2+ consecutive pills, take the DPP as soon as you remember. Do not take more than 2 pills in a day. If 2+ consecutive pills are missed, only take the last missed pill and discard the other missed pills. Side effects: You may experience side effects when you start using the DPP, including changes to monthly bleeding. Side effects are typically mild and go away without treatment. Discontinuation/switching: If you decide to discontinue use of the DPP, but want to be protected from HIV and/or unintended pregnancy, in most cases, you can begin using PrEP or another contraceptive method right away. Drug interactions: There are no drug-drug interactions from combining oral PrEP and COC in the DPP. Certain medications are not recommended due to their contraindication with oral PrEP or COC. Monitoring: You will need to get an HIV test prior to initiating or restarting the DPP, and every 3 months during DPP use. Your provider may recommend other screening or testing. Discussion: Developing recommendations for the DPP as a novel MPT posed unique challenges, with implications for efficacy, cost, and user and provider comprehension and burden. Incorporating counseling recommendations into clinical cross-over acceptability studies allows for real-time feedback from providers and users. Supporting women with information to use the DPP correctly and confidently is critically important for eventual scale and commercialization.

Knowledge and perception regarding effectiveness in influenza vaccines among General Practitioners in Germany: A national survey.

Objectives: To understand physicians' knowledge and perception regarding the effectiveness of influenza vaccines and to communicate the importance of understanding the differences in terms of vaccine efficacy and vaccine effectiveness. Methodology: This cross-sectional quantitative online survey was conducted using a questionnaire comprising 20 questions, between September 11 and 19, 2021. The survey was conducted across 14 cities in Germany, including physicians actively involved in influenza vaccine purchasing decisions. Descriptive statistics were used to summarize the data and paired t-test was performed to compare the physicians' understanding of efficacy and effectiveness. Results: Eighty physicians (21%) completed the survey. Physicians defined the terms vaccine efficacy and effectiveness similarly, with only minimal distinctions. Forty-one percent agreed that both terms can be used interchangeably in clinical practice. A higher proportion used the phrase "observational study" for vaccine efficacy and 21% associated "controlled environment" with effectiveness. The majority of physicians indicated that antigen match to circulating strain plays a large role in overall effectiveness and vaccine coverage strongly influences overall influenza case prevention. Vaccine performance in observational studies under so-called "real-world conditions" and (vaccine independent) strain match were the most important factors to assess vaccine performance and vaccine choice. Conclusion: These findings show that physicians in Germany use the terms vaccine efficacy and vaccine effectiveness interchangeably. A better knowledge of the differences between these terms will help to make informed decisions on the choice of influenza vaccine for its population. Finally, and most important, increasing the annual flu vaccine uptake rates will have more and the greatest beneficial impact on reducing flu-related disease and public health, regardless of the expression of the benefits for different vaccine types.

Reply letter to "Immunogenicity and safety of a quadrivalent high-dose inactivated influenza vaccine compared with a standard-dose quadrivalent influenza vaccine in healthy people aged 60 years or older: a randomized Phase III trial".

A recent study reported that the high-dose quadrivalent influenza vaccine provided superior immunogenicity and efficacy versus the standard-dose quadrivalent vaccine in the elderly. However, we need to view these results in terms of public health benefits as well. The Number Needed to Vaccinate (NNV) is an important tool to measure the benefit of a given vaccine. Further, NNV evaluates the benefits of a vaccine in preventing and controlling communicable diseases. Considering the target of vaccination and coverage of 75% not met in the elderly in Europe, it is important not to prioritize one vaccine over the other, but rather to increase the vaccine coverage with all the available vaccines.

A Prospective Study of the Clinical and Demographic Profile of Type 2 Diabetes Mellitus Patients Receiving Antidiabetic Drug Combinations.

BACKGROUND: The specific treatment recommendations for type 2 diabetes mellitus (T2DM) differ based on a particular guideline. The goal of pharmacotherapy is to achieve the target HbA1c and fasting and postprandial blood glucose levels to avoid disease complications. OBJECTIVE: To evaluate the profile of T2DM patients on different antidiabetic treatment regimens and the factors leading to dose escalation in these patients. METHODS: A prospective descriptive study was conducted at Kasturba Medical College Hospital, Mangalore, a tertiary care teaching hospital, over a period of one year. The study population comprised of patients with T2DM for ≥5 years. The demographic and clinical data were collected during the baseline and follow-up visits. RESULTS: Of the 119 patients studied, 59.7% were males; 32.8% were ≥65 years of age. A significant decrease in the fasting blood glucose (FBG) on follow-up was seen (p = 0.028) in patients on sulfonylurea and metformin combination. A significant decrease in the glycated haemoglobin (HbA1c) was seen in patients on sulfonylurea with metformin and pioglitazone (p = 0.011); sulfonylurea with metformin, pioglitazone, and sitagliptin (p = 0.026); and metformin with insulin (p = 0.001). Patients who received dose escalation had a longer duration of the disease (p = 0.042), higher FBG (p = 0.039) and HbA1c (p = 0.05). CONCLUSION: A combination of metformin with sulfonylurea was the preferred first-line treatment; insulin was added when HbA1c was >9. Patients who received dose escalation had a longer duration of the disease and higher FBG and HbA1c.

Asian consensus recommendations on optimizing the diagnosis and initiation of treatment of hepatitis B virus infection in resource-limited settings.

Asia has an intermediate-to-high prevalence of and high morbidity and mortality from hepatitis B virus (HBV) infection. Optimization of diagnosis and initiation of treatment is one of the crucial strategies for lowering disease burden in this region. Therefore, a panel of 24 experts from 10 Asian countries convened, and reviewed the literature, to develop consensus guidance on diagnosis and initiation of treatment of HBV infection in resource-limited Asian settings. The panel proposed 11 recommendations related to diagnosis, pre-treatment assessment, and indications of therapy of HBV infection, and management of HBV-infected patients with co-infections. In resource-limited Asian settings, testing for hepatitis B surface antigen may be considered as the primary test for diagnosis of HBV infection. Pre-treatment assessments should include tests for complete blood count, liver and renal function, hepatitis B e-antigen (HBeAg), anti-HBe, HBV DNA, co-infection markers and assessment of severity of liver disease. Noninvasive tests such as AST-to-platelet ratio index, fibrosis score 4 or transient elastography may be used as alternatives to liver biopsy for assessing disease severity. Considering the high burden of HBV infection in Asia, the panel adopted an aggressive approach, and recommended initiation of antiviral therapy in all HBV-infected, compensated or decompensated cirrhotic individuals with detectable HBV DNA levels, regardless of HBeAg status or alanine transaminase levels. The panel also developed a simple algorithm for guiding the initiation of treatment in noncirrhotic, HBV-infected individuals. The recommendations proposed herein, may help guide clinicians, to optimize the diagnosis and improvise the treatment rates for HBV infection in Asia.

Consensus on management of hepatitis C virus infection in resource-limited Ukraine and Commonwealth of Independent States regions.

Globally, 69.6 million individuals were infected with hepatitis C virus (HCV) infection in 2016. Of the six major HCV genotypes (GT), the most predominant one is GT1, worldwide. The prevalence of HCV in Central Asia, which includes most of the Commonwealth of Independent States (CIS), has been estimated to be 5.8% of the total global burden. The predominant genotype in the CIS and Ukraine regions has been reported to be GT1, followed by GT3. Inadequate HCV epidemiological data, multiple socio-economic barriers, and the lack of region-specific guidelines have impeded the optimal management of HCV infection in this region. In this regard, a panel of regional experts in the field of hepatology convened to discuss and provide recommendations on the diagnosis, treatment, and pre-, on-, and posttreatment assessment of chronic HCV infection and to ensure the optimal use of cost-effective antiviral regimens in the region. A comprehensive evaluation of the literature along with expert recommendations for the management of GT1-GT6 HCV infection with the antiviral agents available in the region has been provided in this review. This consensus document will help guide clinical decision-making during the management of HCV infection, further optimizing treatment outcomes in these regions.

Evaluation of Adverse Drug Reaction Profile of Drugs Used as First-Line Antiretroviral Therapy.

BACKGROUND AND OBJECTIVES: The objective was to study the adverse drug reaction (ADR) profile in HIV patients receiving first-line antiretroviral therapy. METHODS: This was a prospective, observational study that included 171 HIV patients with a follow-up at six months. Demographic details, medical history, details of HIV infection including most recent CD4 count, details of antiretroviral therapy, and other concomitant medication were recorded. Adverse drug reactions were elicited by reviewing patient records and also by interviewing the patient/attendants directly. RESULTS: 171 patients completed the study out of which 88 (51.5%) were males and 83 (48.5%) were females. The study subjects included HIV-positive, treatment naïve patients who were started on treatment regimens recommended by the NACO guidelines. The ADRs observed were a fall in haemoglobin or absolute anaemia in response to zidovudine, nonspecific symptoms like headache, and a nonspecific feeling of being unwell in response to tenofovir, stavudine, and efavirenz; dyslipidaemia, pancreatitis, peripheral neuropathy, and lactic acidosis in response to stavudine; generalised rash in response to nevirapine and one case of nephrotoxicity to efavirenz. Majority of the ADRs satisfied the 'probable' category (60.1%), and the rest were "possible". ADRs to zidovudine and nevirapine superseded all others. INTERPRETATION AND CONCLUSION: Gastrointestinal effects were the most commonly observed group of ADRs, with nausea being the most common ADR, the others being gastritis and diarrhoea. The other ADRs included rash, hepatotoxicity, blood dyscrasias like anaemia, neutropenia, and thrombocytopenia, and fatigue. Few cases of lactic acidosis, peripheral neuropathy, headache, lipoatrophy, and pancreatitis were reported.

Can Metabotropic Glutamate Receptor 7 (mGluR 7) be a Novel Target for Analgesia?

INTRODUCTION: The present study was carried out to study the role of metabotropic glutamate receptor 7 (mGluR7) using its agonist, N,N'-bis(diphenylmethyl)-1,-ethanediamine (AMN082) for nociceptive stimuli, in animal models. By conducting this research, we aim to introduce a novel target for acute pain management. OBJECTIVE: To study the role of metabotropic glutamate receptor 7 (mGluR7), in analgesia, using mGluR7 agonist AMN082 in animal models. MATERIALS AND METHODS: Swiss albino mice of either sex, weighing 20-30gm were used for the study. The animals were divided into 3 groups with 6 mice in each group: Control or Normal group received 0.5% methylcellulose in normal saline; Standard group received the drug tramadol HCl at 40mg/kg; and test group received drug AMN 082 at 5mg/kg. All the drugs were administered by intraperitoneal route. Hot plate test and Tail flick test were done to evaluate the analgesic effect of the drug. Reaction time for the end points in both the models were noted before drug administration at 0 min and after drug administration at 15, 30,60,90 and 120 min. Statistical analysis was done using One-Way-ANOVA followed by Tukeys post hoc test. p-value was considered significant at ≤ 0.05. RESULTS: The group that received AMN082 showed significantly lesser reaction time compared to normal and standard groups in both the analgesia models. CONCLUSION: The mGluR 7 stimulation by an agonist AMN082, did not show analgesic effect but induced hyperalgesia in response to thermal nociceptive stimuli.