Lettuce may be just as good as dock leaf for easing nettle sting symptoms: Study

Rubbing a lettuce leaf on a nettle sting to ease the associated discomfort may be just as good as using the age-old folk remedy of a dock leaf, suggest the results of a small comparative study, published online in Emergency Medicine Journal.

It may simply be the cooling and soothing effect of sap evaporating from a crushed leaf that brings relief, and doing nothing might work just as well, although possibly not if you’re a small child, suggest the researchers.

Nettles are a common native plant in the British Isles. Their stems and leaves are covered in stinging hairs, or trichomes, with a brittle tip that snaps off when touched, releasing a mini jet of chemicals (histamine, acetylcholine, and serotonin) into the skin.

Rubbing a dock leaf on the affected area to ease the ensuing discomfort is a well-known ancient folk remedy first mentioned 600 years ago by Geoffrey Chaucer in Troilus and Criseyde, point out the researchers.

This remedy may have been prompted by the cooling and soothing effect of sap evaporating from a crushed leaf, they say. “If so, any large, fresh and non-toxic leaf would do the job, and dock may have become the leaf of choice simply because it grows in similar habitats to nettle,” they suggest.

To find out if the remedy has any foundation in science, the researchers carried out the Nettle-induced Urticaria Treatment Study (NUTS), a randomised, double blind, active placebo-controlled trial involving 9 healthy emergency department doctors.

As the dummy treatment needed to mimic the physiological effect of the dock leaf, and be of similar size, shape, and texture, but contain no anti-inflammatory or toxic properties, a sweet gem lettuce was chosen.

Participants brushed the inside of a demarcated area of both forearms with two stems of freshly harvested nettle stem 10 times. They were then blindfolded.

After 60 seconds—to mimic the time it might take to find a dock leaf in real life-the participants rolled a die. If an odd number was rolled, 2 dock leaves were rubbed on the area for 60 seconds of their right arm and 2 lettuce leaves on their left for 60 seconds. For even numbers the application arms were reversed.

After each application participants were asked which arm they thought had been treated with dock and which with lettuce. And they rated the discomfort felt in each arm after 1–5, 10, 15 and 20 minutes on a scale of 0 (no discomfort) to 5 (the most discomfort possible from a nettle sting).

The term ‘discomfort’ incorporated the varied sensations provoked by nettle stings, to include burning, itching, and tingling. The score was tracked until resolution of symptoms, and named the Insult to Complete Healing (ITCH) score.

The total number of discrete wheals visible within the demarcated area at 5, 10, 15 and 20 minutes after stinging was also recorded and given as the Observable Urticaria/Count of Hives (OUCH) score.

Participants photographed their own forearms at these time points, and OUCH scores were counted subsequently by an observer unaware of the treatment arm to determine peak OUCH and time to peak OUCH.

The results showed that 3 participants correctly stated which arm had been treated with dock, 3 were incorrect, and 3 were completely unable to say which treatment had been applied.

The average absolute reduction in ITCH score at 5 minutes was 3 points for dock vs 2 points for lettuce-a difference of just 1 point, and not statistically significant.

And while there was a statistically significant fall in ITCH score over time for both interventions, there was no significant difference between dock and lettuce.

The average peak OUCH score was 27 for the dock treatment and 20 for the lettuce treatment, while the average time to peak OUCH was 5 minutes for both, neither of which was statistically significant.

The observed discomfort of nettle stings eased rapidly over 15–20 minutes with both dock and lettuce leaf applications, say the researchers. But “the effect was not significantly different between the two interventions.”

They add: “It is possible that the same relief would have occurred with no treatment at all, and our study design does not permit us to conclude that either dock or lettuce is better than simply doing nothing.”

And for children that probably isn’t an option, they suggest. “Patient/Public Involvement work from other studies suggests that children in particular do not consider doing nothing to be an acceptable option when they are in pain,and we feel this may well be applicable to nettle stings.”

They acknowledge the small sample size of the study, which precludes any firm conclusions from being drawn. And the trial was primarily carried out as part of a team building exercise and an exploration of the concepts involved in research.

But they write: “We conclude that dock leaf may work for nettle stings, [but] lettuce may be just as good, [and] relief comes quickly either way.”

Reference:

Nettle-induced Urticaria Treatment Study (NUTS): demonstrating the joy of research through a randomised, blinded, placebo-controlled trial, Emergency Medicine Journal (2024). DOI: 10.1136/emermed-2023-213915.

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Wearable single use subcutaneous Furosemide Delivery System Under Review for Use in CKD Patients

The US Food and Drug Administration (FDA) has accepted supplemental New Drug Application for review of a pH-neutral formulation of furosemide, a loop diuretic, designed for subcutaneous (SC) administration via a , single-use wearable, pre-programmed on-body infusor for outpatient self-administration. This will expand the approval of furosemide injection to include treatment of edema due to fluid overload in patients with chronic kidney disease.

Furoscix® is a formulation of furosemide, a loop diuretic, designed for subcutaneous (SC) administration and is supplied as a single-dose 80mg/10mL prefilled cartridge for SC infusion co-packaged with 1 on-body infusor. The product is not intended for chronic use and should be replaced with oral diuretics as soon as practical.

 The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of March 6, 2025.

In Type D meeting feedback provided by the FDA last year, the agency confirmed that no additional clinical studies would be needed to expand the indication, provided that the Company is able to demonstrate an adequate pharmacokinetic (PK) and pharmacodynamic (PD) bridge to the listed drug, furosemide injection, 10 mg/mL.

“The potential expansion of the FUROSCIX indication to include CKD could support a key long-term growth initiative for our Company, and an opportunity to improve the lives of CKD patients as CKD affects more than 1 in 7 U.S. adults and is characterized by frequent episodes of fluid overload.1” stated John Tucker, Chief Executive Officer of scPharmaceuticals. “We look forward to the review of our application by the FDA and are preparing to deploy additional commercial resources, if our sNDA is approved, to efficiently address what we estimate to be a $3 billion addressable market.”

FUROSCIX® (furosemide injection) 80 mg/10mL for subcutaneous use

FUROSCIX® is indicated for the treatment of congestion due to fluid overload in adult patients with New York Heart Association (NYHA) Class II and Class III chronic heart failure.

FUROSCIX is not indicated for use in emergency situations or in patients with acute pulmonary edema. The On-Body Infusor will deliver only an 80-mg dose of FUROSCIX.

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Childhood Respiratory Conditions Linked to Adult Chronic Rhinosinusitis, suggests study

The researchers have established respiratory conditions in childhood, with frequent head colds, tonsillitis, and asthma, as key independent predictors for the incidence of chronic rhinosinusitis in middle age. In this respect, a study published by Jennifer L. and colleagues in the journal Allergy has added important information on how respiratory problems in early life predispose toward Chronic rhinosinusitis (CRS) later in life and establishes the need for early intervention and careful monitoring.

CRS is a chronic inflammatory condition of the sinuses that significantly affects the quality of life of millions of individuals worldwide, generally with symptoms of nasal obstruction and facial pain. Although very common, the risk factors related to early life in the development of adult CRS are not so well understood. For example, the Tasmanian Longitudinal Health Study provides an exemplary cohort initiated in 1968 for investigating life course associations.

This study particularly examined the relationships between childhood conditions of respiratory infections and allergies and the incidence of CRS in middle age. It also took into consideration asthma and allergies during the course and their impact on the risk of CRS.

In this study, the included participants of the TAHS cohort were first studied in 1968 at age 6-7 years (n = 8583) and followed into middle age (n = 3609). At age 53, participants were categorized into CRS severity subtypes: no sinusitis/CRS, past doctor diagnosis only, current symptoms without doctor diagnosis, and doctor-diagnosed CRS with current symptoms. Using multinomial regression, it examined associations with childhood respiratory conditions and previously published asthma-allergy trajectories from ages 7 to 53 years.

In middle age, 5.8% of participants reported current CRS symptoms, with 2.5% having a doctor diagnosis. Significant childhood conditions associated with symptomatic doctor-diagnosed CRS included:

• Frequent head colds: mOR = 2.04 (95% CI: 1.24, 3.37)

• Frequent tonsillitis: mOR = 1.61 (95% CI: 1.00, 2.59)

• Current childhood asthma: mOR = 2.23 (95% CI: 1.25, 3.98)

Life course trajectories with late-onset or persistent asthma and allergies were associated with all CRS subtypes in middle age. Notably, early-onset persistent asthma and allergies had a significant association with symptomatic doctor-diagnosed CRS:

• Early-onset persistent asthma and allergies: mOR = 6.74 (95% CI: 2.76, 16.4)

• Late-onset asthma allergies: mOR = 15.9 (95% CI: 8.06, 31.4)

• Late-onset hayfever: mOR = 3.02 (95% CI: 1.51, 6.06)

These findings indicate that children who have frequent respiratory infections and asthma run a higher risk of contacting CRS at middle age. The research puts forth the importance of very early and active management of respiratory conditions in childhood, which probably would reduce the risk of CRS at old age. Persistent and late-onset asthma and allergies are robust predictors for adult CRS, underpinning their interrelationship across the life course.

The current asthma, frequent head colds, and tonsillitis at age 7 are indicators of a higher risk for CRS in mid-adult life. These results call for close follow-up and early interventions on childhood respiratory morbidity in order to reduce long-term risks. Concomitant asthma and allergy are treatable traits whose management in childhood may lighten the burden of CRS in adulthood.

Reference:

Perret, J. L., Idrose, N. S., Walters, E. H., Bui, D. S., Lowe, A. J., Lodge, C. J., Fernandez, A. R., Yao, V., Feather, I., Zeng, X.-W., Thompson, B. R., Erbas, B., Abramson, M. J., & Dharmage, S. C. (2024). Childhood infections, asthma and allergy trajectories, and chronic rhinosinusitis in middle age: A prospective cohort study across six decades. Allergy. https://doi.org/10.1111/all.16184

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Poor neighbourhood may predict severe skin lesions in discoid lupus erythematosus: JAMA

Researchers have found that socioeconomic and behavioral factors are of prime importance in the severity of discoid lupus erythematosus among the residents of Philadelphia. A recent study by Katharina S. Shaw, MD, and colleagues from the University of Pennsylvania added that people living in areas marked by poverty tended to have greater severity in manifestations of DLE; however, associations with racial identity were relatively weak after adjustment for socioeconomic factors. This study was published in JAMA Dermatology.

This study reviewed data on 154 adult DLE patients seen at the University of Pennsylvania’s rheumatology-dermatology specialty clinic from 2007 to 2024. This was a cross-sectional analysis in which SES disadvantage was measured via the area deprivation index. ADI combines 17 neighborhood-level data points measuring education, employment, housing quality, and indicators of wealth into one index value from 1 to 10, with greater values indicating greater socioeconomic disadvantage.

Key Findings

  • Among the 154 patients, 64% were Black, and 30% were white. At their first clinic visit, about one-quarter had moderate-to-severe disease activity, and three-quarters had moderate-to-severe damage.

  • The mean ADI rating for Black patients was 6.8, compared to 2.7 for white patients.

  • The odds of showing moderate to severe skin damage (CLASI-D ≥6) were roughly quadrupled among residents of census blocks with an ADI score greater than 5 compared with blocks rated at 5 or less (OR 3.90, 95% CI 1.27-12.69).

  • Odds of high CLASI scores for disease activity (CLASI-A ≥10) were strongly associated with ADI values greater than 5 (OR 3.31, 95% CI 1.27-9.44).

  • Initially, 87% of Black patients were characterized as having moderate-to-severe disease compared with 52% of white patients (P<0.001).

  • After adjusting for ADI and other confounders, race was not significantly associated with higher CLASI-D severity (OR 2.78, 95% CI 0.95-8.44).

This study shows that SES and behavioral risk factors more strongly relate to poor health status in those with DLE than does racial identity. The bottom line for social policy implications is that already-recognized inequities at the structural level need to be addressed, and a more sophisticated approach—one which embeds a sense of socioeconomic context within which racial disparities are observed—taken toward understanding these issues.

In addition to socioeconomic factors, smoking status and SLE diagnosis were associated with higher disease activity and damage. Odds ratios for moderate-to-severe damage were 3.15 for current smoking and 3.63 for SLE; the odds ratios for moderate-to-severe disease activity were 2.20 and 1.97, respectively, where the latter did not reach statistical significance.

This suggests that smoking cessation programs should be available to all patients with DLE, more importantly in deprived areas. Second, neighborhood deprivation is potentially modifiable. Strategies that may influence this include increasing transportation, such as better access to health facilities, medical trust within the community, better education of patients, and medications should be afforded and easily accessible.

This study makes an explanation of the relationships between the socioeconomic factors and DLE severity, which is rather complex. Racial disparities in severity exist but these could be partially explained by socioeconomic deprivation. Further studies with larger sample sizes are required to further elucidate the association between the components of the ADI and DLE disease severity.

Reference:

Faden, D. F., Xie, L., Stone, C., Lopes Almeida Gomes, L., Le, T., Ezeh, N., Buckingham, W. R., Kind, A., Vleugels, R. A., Werth, V. P., Arkin, L., & Shaw, K. S. (2024). Area deprivation and disease severity in adult patients with discoid lupus erythematosus. JAMA Dermatology (Chicago, Ill.). https://doi.org/10.1001/jamadermatol.2024.2355

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Novel Surgical Technique beneficial for Lateral Patellofemoral Ligament Reconstruction Using Bone Tunnels: Study

Medial patellar instability (lateral patellofemoral ligament tear) is a rare condition which is commonly associated with lateral release for lateral patellar instability. LPFL is a lateral stabilizer of the patellofemoral joint. Reconstruction of LPFL is necessary to provide stability to the patella-femoral joint in patients with instability.

Arora et al describe a novel technique of trans-osseous reconstruction of LPFL to gain stability and have better graft incorporation. This is an easy, novel, and reproducible technique which can be used to reconstruct LPFL.

The patient is laid in a supine position and the ipsilateral peroneus longus tendon is harvested and doubled to create an LPFL graft. A 4-cm incision is made over the lateral epicondyle of the femur and dissected till the bony prominence. The insertion of the LPFL is confirmed with a guide wire on the image intensifier. The insertion point is 5 mm distal to and anterior to the tip of the lateral epicondyle. The guide wire is advanced from the lateral to the medial aspect of the femur, taking care to avoid inter-notch placement. It is then subsequently over-reamed with a reamer corresponding to graft size. A 2-cm incision is marked on the middle one-third of the lateral aspect of the patella. Careful dissection is done to expose the lateral aspect of the patella without exposing the joint. The mid-point of the patellar bone is identified under visualization. If necessary, with fluoroscopic guidance, its position is marked with a guide wire and drilled from the lateral to the anteromedial direction to prevent joint violation and subchondral damage. This ensures the final endo button resting position to be subcutaneous, on the anteromedial surface of the patella. Then, an endo button reamer of 4.5 mm is passed over the guide wire through and through the patella. The graft-sized tunnel reamer is then drilled for a distance of 10 mm medially to allow 10 mm of graft in the final tunnel. The prepared graft is passed into the patellar tunnel with an adjustable loop endo button and flipped on the patella’s anteromedial aspect, following the shuttle sutures. Then, the graft is passed in the extra synovial layer to avoid intra-articular placement to come out in the incision made for the femoral tunnel. This is followed by cycling of 10 repetitions to allow graft elongation and prevent future creep. The graft is then shuttled into the femoral tunnel and fixed with an interference screw 1–2 sizes larger than the graft diameter.

The authors commented – ‘The novelty of this technique is using bone tunnels and peroneus longus as graft choices for LPFL reconstruction. While the bone tunnel provides better graft ft and incorporation, peroneus longus gives adequate stability without compromising knee function, including surgical site morbidity associated with hamstrings.’

Further reading:

Surgical Technique for Lateral Patellofemoral Ligament Reconstruction Using Bone Tunnels: A New Method

Arora et al

Indian Journal of Orthopaedics (2024) 58:330–337

https://doi.org/10.1007/s43465-023-01091-2

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Higher levels of MUFA and PUFA closely associated with psoriasis severity

A recent study published in the journal of Nutrients found that higher levels of monounsaturated and saturated fatty acids could be associated with more severe psoriasis. This is a complicated systemic illness that presents with joint problems and inflammatory skin lesions. The comorbidities include cardiovascular problems like hypertension and/or coronary heart disease, as well as metabolic disorders like diabetes and obesity. The etiology of psoriasis is often divided into two phases as the maintenance of the pathogenic condition and the beginning/triggering of the illness. In the start phase, external triggers including stress, damage to the skin, or infections combine with a genetic propensity to cause psoriasis. During the maintenance phase, immune cells such as dendritic cells, keratinocytes, and T-cells initiate a persistent inflammatory response that perpetuates the illness through an intricate web of cytokines and signaling pathways.

Omega-3 fatty acids reduce inflammation by decreasing IL-1β, TNF-α, and IL-6, whereas omega-6 fatty acids promote inflammation. Mariola Marchlewicz and colleagues undertook this study to analyze the fatty acid composition in erythrocyte membranes of psoriasis patients in relation to body mass index and disease severity

For this study, 58 adult psoriasis patients from the Pomeranian Medical University in Szczecin’s Department of Skin and Venereal Diseases were eligible. The patients received a physical examination and an interview where the severity of their psoriasis was determined. To determine their body mass index, the weight and height of each patient were assessed (BMI). The biochemical parameters ( AST, ALT, total cholesterol) and inflammatory markers (CRP) in the blood were measured three months into the therapy. The fatty acid (PUFA, SFA, and MUFA) extraction from erythrocyte membranes was done, and a gas chromatograph was used to perform a qualitative and quantitative profile analysis.

The erythrocyte membranes of patients with severe psoriasis who needed systemic treatment had a different fatty acid profile than those of patients with less severe psoriasis who were receiving topical treatment. Specifically, there was a significantly reduced amount of polyunsaturated fatty acids (omega-3), which have an anti-inflammatory effect; a substantially greater amount of saturated fatty acids; and a decreased concentration of oleic acid (omega-9). Pro-inflammatory arachidonic acid was detected in erythrocyte membranes at considerably greater quantities and blood AST and ALT values in psoriasis patients with a BMI of at least 25. Overall, the erythrocyte membranes have a different fatty acid composition, including decreased levels of PUFAs. This study found that high levels of SFA and low levels of oleic acid (n-9) may be associated with a more severe form of psoriasis.

Source:

Marchlewicz, M., Polakowska, Z., Maciejewska-Markiewicz, D., Stachowska, E., Jakubiak, N., Kiedrowicz, M., Rak-Załuska, A., Duchnik, M., Wajs-Syrenicz, A., & Duchnik, E. (2024). Fatty Acid Profile of Erythrocyte Membranes in Patients with Psoriasis. In Nutrients (Vol. 16, Issue 12, p. 1799). MDPI AG. https://doi.org/10.3390/nu16121799

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Trisomic conceptions associated with subsequent diagnoses of infertility, reveals research

Researchers in a recent study found that women who had trisomic pregnancies were at a higher risk of being diagnosed with infertility in the later years. A study was published by Satu W. and colleagues in the International Journal of Obstetrics and Gynecology. The authors carried out a nationwide cohort study in Finland to determine any linkage with gynecologic or reproductive disorders with regard to trisomic conceptions. The data sources were obtained from the Registry of Congenital Malformations and the Finnish Maternity Cohort.

In this large study, cases comprised all women with a pregnancy trisomy between 1987 and 2018, while the respective trisomies were T13 (n=351), T18 (n=1065), and T21 (n=4369), each matched with population controls based on age, residence, and timing of pregnancy.These cases were cross-linked to ICD-10 diagnoses from the National Care Registry for Health Care, covering the period 1996–2019. The research was restricted both to inflammatory disorders, ICD-10: N70–N77, and non-inflammatory disorders of the genital tract, ICD-10: N80–N98. Crude odds ratios with 95% confidence intervals were calculated to estimate the associations of such diagnoses with trisomic conception.

The key findings of the study were:

  • The study revealed that a diagnosis of female infertility (ICD-10: N97) was associated with trisomic conceptions (OR: 1.19, 95% CI: 1.08–1.32).

  • This association was particularly notable for T18 (OR: 1.29, 95% CI: 1.03–1.61) and T21 (OR: 1.17, 95% CI: 1.04–1.32), but not for T13 (OR: 1.15, 95% CI: 0.75–1.72).

  • When considering the timing of the infertility diagnosis, an elevated OR was observed only after the index pregnancy (OR: 1.81, 95% CI: 1.56–2.09).

  • Increased odds of infertility following trisomic conceptions were noted both in women under 35 years (T18 OR: 1.91, 95% CI: 1.21–3.00; T21 OR: 1.68, 95% CI: 1.31–2.14) and in women 35 years or older (T18 OR: 2.17, 95% CI: 1.40–3.33; T21 OR: 1.87, 95% CI: 1.47–2.39), with no significant association found after T13 conceptions.

These findings provide evidence for a possible link between trisomic conceptions and subsequent diagnoses of infertility. In this study, associations were seen that suggest some common underlying mechanisms predisposing a woman to trisomy and infertility, irrespective of advanced maternal age. This study, however, does not allow for inference of causality.

Observational data suggest that trisomic conceptions are related to subsequent diagnoses of infertility, raising the possibility of partially shared mechanisms that might predispose to both. The association with the presence of trisomic conception draws attention to the need for data on reproductive history in the management of infertility.

Reference:

Wedenoja, S., Pihlajamäki, M., Gissler, M., Wedenoja, J., Öhman, H., Heinonen, S., Kere, J., Kääriäinen, H., & Tanner, L. (2024). Infertility following trisomic pregnancies: A nationwide cohort study. International Journal of Gynaecology and Obstetrics: The Official Organ of the International Federation of Gynaecology and Obstetrics. https://doi.org/10.1002/ijgo.15828

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Higher axial length variation between two eyes tied to inter-eye glaucoma severity with quicker progression: Study

A new study published in the recent issue of Ophthalmology journal found that the glaucoma in the longer eyes tend to be more severe and to advance more quickly when there was an axial length variation of more than 1.0 mm, the findings of this study were .

Elevated intraocular pressure (IOP) can compress retinal ganglion cell axons at the lamina cribrosa, resulting in death and interrupting axonal transport. Long axial length (AL) is also independently linked to an elevated the risk of normotensive primary open angle glaucoma (OAG), and myopia is another well-known risk factor for glaucoma. Thus, Min Gu Huh and team sought out to determine if individuals with asymmetric axial length had a different inter-eye glaucoma development and severity.

The long-term observational research included patients over the age of 20 who were diagnosed with glaucoma at Seoul National University Hospital in Seoul, Korea, between 2010 and 2020. The patients who had an axial length difference of more than 1.0 mm and bilateral glaucoma were included. The paired test was used to compare baseline and follow-up clinical data after each individual’s eyes and were classified as “longer eye” or “shorter eye.” The main finding of this study was that those with asymmetric axial length had varied clinical characteristics.

The study comprised of a total of 190 eyes with unequal axial length from 95 glaucoma patients. The mean follow-up duration was 10.1 ± 3.9 years, and the mean age of these patients were 51.2 ± 12.3 years. The central corneal thickness (CCT) and baseline intraocular pressure (IOP) of longer and shorter eyes were the same. The ovality index, beta- and gamma-zone parapapillary atrophy (PPA) region, and other baseline disc characteristics were all higher in the longer eyes.

The ganglion cell-inner plexiform layer (GCIPL) and retinal nerve fiber layer (RNFL) thicknesses in the baseline OCT data were both thinner in the longer eyes. A baseline visual field (VF) test revealed that the longer eyes had considerably lower mean deviation (MD) and visual field index (VFI) values. The longer eyes had higher rates of change in superior GCIPL (-0.65 μm/yr, shorter eyes: -0.40 μm/yr), MD (-0.40 dB/yr, shorter eyes: -0.21 dB/yr), and VFI (-0.92%/yr, shorter eyes: -0.46%/yr) during glaucoma development. 

The rate of change of RNFL and GCIPL rises when the mean IOP and beta-zone PPA area vary between eyes. Also, the difference in rate of change between MD and VFI grew with the IOP fluctuation difference. When the axial length difference was more than 1.0 mm, glaucoma was more severe and progressed quicker in longer eyes. The inter-eye variation in glaucoma progression rate is proportional to both mean IOP and IOP fluctuations.

Reference:

Huh, M. G., Jeong, Y., Shin, Y. I., Kim, Y. K., Jeoung, J. W., & Park, K. H. (2024). Assessing Glaucoma Severity and Progression in Individuals with Asymmetric Axial Length: An Intra-Patient Comparative Study. In Ophthalmology. Elsevier BV. https://doi.org/10.1016/j.ophtha.2024.07.013

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FDA approves long acting extended-release injection for treating Schizophrenia

The US Food and Drug Administration has approved a new long acting monthly paliperidone palmitate (Erzofri) extended-release injectable suspension for treating schizophrenia in adults.

Paliperidone palmitate is an atypical antipsychotic indicated for schizoaffective disorder in adults, as monotherapy or adjunct to mood stabilizers or antidepressants.

Both schizophrenia and schizoaffective disorder are severe, chronic psychiatric disorders characterized by recurring relapses. Antipsychotic medications play an important role in treating and controlling symptoms of schizophrenia and schizoaffective disorder, but patient adherence to antipsychotics is generally poor. Using long-acting injectable (LAI) antipsychotics is effective in improving patient adherence, as they can reduce the dosing frequency and can also reduce the risk of patients not adhering to their dosing regimen without the knowledge of their healthcare providers.

ERZOFRI, administered once a month, is the first patented paliperidone palmitate long-acting injection developed in China to get approved in the U.S. The product was granted a U.S. patent (Patent No.11,666,573) in 2023, which will expire in 2039. ERZOFRI is approved as a new drug under the 505(b) (2) pathway in the U.S.

According to publicly available information, the sales of paliperidone palmitate LAIs were $2.897 billion across the U.S. in 20233. ERZOFRI will provide patients with a new treatment option after its launch.

ABOUT ERZOFRI®

What is ERZOFRI (paliperidone palmitate) extended-release injectable suspension?

ERZOFRI is an atypical antipsychotic indicated for:

• The treatment of schizophrenia in adults.

• The treatment of schizoaffective disorder in adults as monotherapy and as an adjunct to mood stabilizers or antidepressants.

About the Clinical Trial

The U.S. FDA approval of ERZOFRI is based on the results of an open-label, randomized, multiple-dose, parallel-group study that enrolled 281 patients (ages 18-65) with schizophrenia or schizoaffective disorder (NCT04922593), designed to evaluate the PK profile of ERZOFRI and its relative bioavailability compared with the listed drug INVEGA SUSTENNA®. ERZOFRI was demonstrated to be bioequivalent to the listed drug at steady state after multiple injections. Compared with the listed drug, the initial dosing was optimized for ERZOFRI by omitting the injection on Day 8 after the first injection, resulting in a comparable total drug exposure.

The safety profile of ERZOFRI was consistent with the known safety profile of the listed drug. 

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Low-Dose Ketamine, Lignocaine, and Dexmedetomidine Combo effectively controls hemodynamics and pain for laparoscopic nephrectomies: Study

Notable numbers of drugs, alone or in combinations, have been tested with variable results in the quest for opioid-free anesthesia. Recently published randomized, single-blind pilot study that compared the analgesic and recovery profiles of a low-dose combination of ketamine, lignocaine, and dexmedetomidine (KeLiDex) versus fentanyl-based anesthesia in patients undergoing laparoscopic nephrectomies. The primary aim was to compare hemodynamic variation as a surrogate marker of adequate analgesia under standardized and controlled balanced anesthesia.

Anesthesia Administration and Comparison

Twenty patients were randomly assigned to receive either the KeLiDex infusion or fentanyl infusion as the analgesic component for balanced general anesthesia. All patients also received paracetamol and a quadratus lumborum block. Intraoperative hemodynamics, time to extubation after reversal (T-tEAR), post-anesthesia care unit (PACU) discharge readiness, sedation, postoperative pain, and rescue analgesia consumption were compared between the two groups.

Comparison of Hemodynamics

The results showed that the KeLiDex group had a significantly lower heart rate between 45-90 minutes and at the time of reversal compared to the fentanyl group. Mean arterial pressure only differed significantly at the 60-minute interval, with the KeLiDex group having lower values. The change in heart rate and mean arterial pressure over time within each group was not statistically significant.

Time to Extubation and Recovery

The mean T-tEAR was 6.37 minutes in the KeLiDex group and 8.18 minutes in the fentanyl group, which was not significantly different. Sedation scores, modified Aldrete scores, pain scores, and rescue analgesic requirements were also comparable between the two groups.

Pain Control and Anesthesia Recovery

This study demonstrates that the KeLiDex combination could effectively control hemodynamics and pain, both at rest and with movement, to a similar degree as fentanyl-based anesthesia for laparoscopic nephrectomies. Recovery from anesthesia, sedation, and PACU discharge readiness were also comparable between the two groups.

Implications and Need for Further Research

The findings suggest that the KeLiDex combination may be an effective opioid-free anesthetic regimen that can replace fentanyl-based anesthesia without compromising analgesic efficacy or recovery profiles. This is an important implication given the increasing focus on opioid-sparing techniques to avoid the adverse effects of opioids. However, the authors note that this was a pilot study with a small sample size, and larger, well-powered studies are needed to further evaluate the efficacy and safety of the KeLiDex combination compared to opioid-based anesthesia.

Key Points

Here are the 6 key points from the research paper: 1. This was a randomized, single-blind pilot study that compared the analgesic and recovery profiles of a low-dose combination of ketamine, lignocaine, and dexmedetomidine (KeLiDex) versus fentanyl-based anesthesia in patients undergoing laparoscopic nephrectomies. 2. The KeLiDex group had a significantly lower heart rate between 45-90 minutes and at the time of reversal compared to the fentanyl group. Mean arterial pressure only differed significantly at the 60-minute interval, with the KeLiDex group having lower values. 3. The mean time to extubation after reversal (T-tEAR) was 6.37 minutes in the KeLiDex group and 8.18 minutes in the fentanyl group, which was not significantly different. Sedation scores, modified Aldrete scores, pain scores, and rescue analgesic requirements were also comparable between the two groups. 4. The study demonstrates that the KeLiDex combination could effectively control hemodynamics and pain, both at rest and with movement, to a similar degree as fentanyl-based anesthesia for laparoscopic nephrectomies. Recovery from anesthesia, sedation, and PACU discharge readiness were also comparable between the two groups. 5. The findings suggest that the KeLiDex combination may be an effective opioid-free anesthetic regimen that can replace fentanyl-based anesthesia without compromising analgesic efficacy or recovery profiles. 6. The authors note that this was a pilot study with a small sample size, and larger, well-powered studies are needed to further evaluate the efficacy and safety of the KeLiDex combination compared to opioid-based anesthesia.

Reference –

Arun T, Karim H R, Singha S K, et al. (June 28, 2024) A Comparison of Analgesic and Recovery Profiles of Ketamine, Lignocaine, and Dexmedetomidine (KeLiDex) Versus Fentanyl-Based Anesthesia in Laparoscopic Nephrectomies: A Randomized, Single-Blind, Pilot Study. Cureus 16(6): e63380. DOI 10.7759/cureus.63380

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