Recently, the monkeypox incidence rates have greatly increased, prompting both the 

 to declare health emergencies for the virus. The former just declared in recent days, and allows for optimal mobilization of funding and resources to address the virus.

In July, the WHO stated the disease was a Public Health Emergency of International Concern (PHEIC). At that time, monkeypox infections have been reported in 68 countries where the virus is not endemic. Globally, there were just under 17,000 confirmed monkeypox infections.

The Centers for Disease Control and Prevention (CDC) discussed prioritizing specific high-risk groups for monkeypox clinical care and education in its latest Morbidity and Mortality Weekly Report (MMWR).

“Public health efforts should prioritize gay, bisexual, and other men who have sex with men, who are currently disproportionately affected, for prevention and testing, address equity, and minimize stigma, while maintaining vigilance for transmission in other populations,” MMWR reported. “Clinicians should test persons with rash consistent with monkeypox, regardless of whether the rash is disseminated or was preceded by prodrome.”

In the US, 2891 cases were reported from May-July 2022, in 43 states, Puerto Rico, and the District of Columbia. CDC received case report forms for 1195 (41%) cases as of July 27.

Among the report forms, the confirmed cases in the United States occurred in 99% of men, and “94% of whom reported recent male-to-male sexual or close intimate contact.”

Racial and minority groups are being disproportionately affected, as noticed by the report.

“Among the 88% of cases with available data, 41% were among non-Hispanic White (White) persons, 28% among Hispanic or Latino (Hispanic) persons, and 26% among non-Hispanic Black or African American (Black) persons.”

And the presentations are atypical with fewer persons experiencing prodrome and more experiencing genital rashes.

The WHO has been involved in both smallpox and monkeypox health campaigns and reported in May the vaccines developed for the former also protect against the latter.

“Vaccines used during the smallpox eradication program also provided protection against monkeypox. Newer vaccines have been developed of which one has been approved for prevention of monkeypox,” WHO wrote in a statement.

WHO is recommending people in high-risk groups—including men who have sex with men and health care workers—get vaccinated.

In the US, states have had a limited vaccine supply. Vaccines are only being provided for people who are close contacts of those with confirmed cases.

And with the recent increase in demand, there may be some shortages in some areas in the US. For example, The San Francisco Department of Public Health (SFDPH) initially requested 35,000 doses of the monkeypox vaccine, and within the last week, San Francisco had only received approximately 12,000 doses.

CDC and the Food and Drug Administration (FDA) have developed a process to help clinicians secure an antiviral therapy, tecovirimat (Tpoxx), for monkeypox treatment. This falls under the expanded access investigational new drug (EA-IND). Clinicians can begin the process to secure tecovirimat by going 

Tecovirimat is manufactured by SIGA Technologies, and is approved for smallpox and is being studied for monkeypox treatment. 

spoke with SIGA Technologies Chief Scientific Officer Dennis Hruby, PhD,

Articles

Latest monkeypox updates from CDC and WHO.

Latest Monkeypox Trends, Vaccines and Public Health Policy by CDC, WHO

Environmental factors such as bullying and substance use could play a factor in the etiological heterogeneity of 

A team, led by Mark J. Taylor, PhD, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, assessed etiological heterogeneity and exposure to environmental risks linked to psychotic experiences in adolescence patients using the twin design.

Genetic factors can play a role in the etiology of psychotic experiences in most individuals. 

However, there is not much known whether the risk factors of psychotic experiences interact with environmental risks for psychotic experiences.

In the twin study, the investigators examined 4855 twin pairs from a UK-based sample of twin pairs aged 16 years between December 1, 2014 and August 31, 2020 and evaluated the extent of genetic variance underlying psychotic experiences and the magnitude of the heritability of psychotic experience moderated by environmental factors.

The patient population included 1926 female same-sex pairs, 1397 male same-sex pairs, and 1532 opposite-sex pairs from the Twins Early Development Study (TEDS).

The analysis included 5 environmental factors—bullying, dependent life events, cannabis use, tobacco use, and low birth weight.

The team assessed psychotic experienced using 5 self-reported measures and 1 parent-reported measure and assessed patient exposure to environmental risks ages 12-16 years.

They used structural equation models to assess differences in the variance in and heritability of psychotic experiences across the exposures, while also controlling for gene-environment correlation effects and also repeated the analyses in an independent Swedish sample, which included 6435 twin pairs, including 2358 female same-sex pairs, 1861 male same-sex pairs, and 2216 opposite-sex pairs from the Child and Adolescent Twin Study in Sweden (CATSS).

The investigators sought primary outcome measures of exposure to environmental factors measured by a composite score and psychotic experiences.

The mean age of twins in the UK-sample was 16.5 years and the mean age of twins in the Swedish-sample was 18.6 years.

The results show more exposure to environmental risk factors is linked to having more psychotic experiences, while the relative contribution of genetic influences to psychotic experiences was lower with increasing environmental exposure for paranoia (44%; 95% CI, 33-53% to 38%; 95% CI, 14-58%), cognitive disorganization (47%; 95% CI, 38-51% to 32%; 95% CI, 11-45%), grandiosity (41%; 95% CI, 29-52% to 32%; 95% CI, 9-48%), and anhedonia (49%; 95% CI, 42-53% to 37%; 95% CI, 15-54%).

The investigators found the pattern replicated in the Swedish cohort.

They also found the heritability of hallucinations and parent-related negative symptoms was relatively consistent.

“Findings of this twin study suggest that environmental factors play a greater role in the etiology of psychotic experiences than genetic factors,” the authors wrote. “The relative importance of environmental factors is even higher among individuals exposed to environmental risks for psychotic experiences, highlighting the importance of a diathesis-stress or bioecological framework for understanding adolescent psychotic experiences.”

Heritability of Psychotic Experiences in Adolescents and Interaction With Environmental Risk

The relative contribution of genetic influences to psychotic experiences was lower with increasing environmental exposure for paranoia, cognitive disorganization, grandiosity, and anhedonia.

Environmental Factors Play a Role in Psychotic Experiences for Adolescent Twins

 by eating early in the day (eTRE) was more effective for weight loss than eating over a window of 12 or more hours in adults with obesity.

Relative to the control eating group, the eTRE plus energy restriction trial group lost an additional 2.3 kg, an approximate 50% improvement in weight loss.

Study author Courtney M. Peterson, PhD, University of Alabama at Birmingham and colleagues noted that eTRE is both feasible, with participants averaging 6.0 days per week on average and may lead to greater improvements in mood, which may benefit adherence.

“It also improves mood by decreasing fatigue and feelings of depression-dejection and increasing vigor, and those who can stick with eTRE lose more body fat and trunk fat,” Peterson wrote. “However, eTRE did not affect most fasting cardiometabolic risk factors in the main intention-to-treat analysis.”

To determine the efficacy of eTRE on weight loss and cardiometabolic health, investigators conducted the 14-week, parallel-arm trial between August 2018 - April 2020. They included new patients with obesity at the Weight Loss Medicine Clinic of the University of Alabama at Birmingham (UAB) Hospital. Eligible patients were 25 - 75 years old, had a body mass index (BMI) between 30.0 and 60.0, and were not diabetic or had a severe or unstable chronic medical condition.

They were randomized to follow low eTRE with an 8-hour eating window between 7:00 and 15:00 or a control eating schedule with a self-selected ≥12-hour window designed to mimic US median meal filming habits, noted the investigators. All received weight-loss treatment with energy restriction.

The study enrolled 90 participants (72 [80%] female), with a mean BMI of 39.6 and mean age of 43 years. The findings suggest the eTRE + ER group adhered to a mean of 6.0 days per week, which was lower than the control + ER group (6.3 days per week; 

Both study groups achieved clinically meaningful weight loss (-6.3 kg vs -4.0 kg), but the eTRE + ER intervention was more effective for weight loss, losing an additional 2.3 kg (95% confidence interval [CI], -3.7 to -0.9 kg; 

However, investigators noted there was no statistically significant differences in absolute fat loss (-1.4 kg; 95% CI, -2.9 to 0.2 kg; 

 = .09) or the ratio of fat loss to weight loss (n = 41; -4.2%; 95% CI, -14.9 to 6.5%; 

Moreover, the eTRE+ER intervention lowered diastolic blood pressure by an additional 4 mm Hg (95% CI, -8 to 0 mm Hg; 

 = .04) relative to CON+ER. The effects of eTRE+ER were equivalent to reducing calorie intake by an additional 214 kcal/d.

The intervention was additionally more effective at improving total mood disturbances, including fatigue-inertia, depression-dejection, and vigor-activity. All other cardiometabolic risk factors, food intake, physical activity, and sleep outcomes were similar between groups, reported the investigators.

In invited commentary, Shalender Bhasin, MB, BS, Harvard Medical School, noted the limitations of this study’s findings, including a lack of clarity on whether TRE late in the day is deleterious and a lack of generalization to those with cardiometabolic disorders.

“Substantially larger randomized clinical trials of longer duration are needed to comprehensively evaluate the hypothesized benefits and risks of long-term TRE of calorically restricted diets in adults,” Bhasin said. “For now, TRE is a promising idea in need of stronger clinical trial evidence to support its benefits and long-term safety.”

Effectiveness of Early Time-Restricted Eating for Weight Loss, Fat Loss, and Cardiometabolic Health in Adults With Obesity: A Randomized Clinical Trial

Early time-restricted eating was more effective for losing weight than eating over a window of ≥12 hours, but did not affect body fat. 

Early Time-Restricted Eating Effective for Weight Loss in Patients with Obesity 

 was found to have become less common in Finland over 4 decades, in a national population study which attributes the trend to improved diagnostic tools, earlier diagnoses, and new therapy options.

Petri Purola, MS, SILK, of the department of opthalmology and faculty of medicine and health technology at Tampere University in Finland, and colleagues found that there have been few studies which have evaluated the prevalence of AMD and its relation to visual impairment and new therapies.Those few, they noted, had the limitations of using single site populations, and/or were clinical trials with short follow-up periods, or had restricted the cohort to those with legal blindness due to AMD.

"Hence, there is a need for a comprehensive, population-based evaluation of trends in VI due ot AMD and the impact of new treatment options on the VI of AMD patients," Purola and colleagues wrote.

To fill in what they characterize as a "gap in knowledge", the investigators conducted a population study with over 30,000 visually impaired persons with AMD as the main diagnosis for visual impairment, drawn from the Finnish Register of visual impairment data from 1980 - 2019. The number of persons treated with intravitreal injections was obtained from hospital data at the Finnish Institute for Health and Welfare.

Purola and colleagues reported that although there had been a doubling of the incidence of reported visual impairment between the 1980s and the 2010s, the rate then plateaued, and has trended lower since 2012. The investigators also found a trend of decreasing severity of reported visual impairment over the studied time period; while that the mean age of onset had increased. The declining prevalence of visual impairment from AMD was apparent in all age groups except those 85 years and older; and the prognosis of VI had improved over the 4 decades.

"What was most remarkable, however, was the stagnation of the incidence and prevalence in the 2010s; in fact, even some decline was observed in younger age groups," Purola and colleagues remarked.

The prevalence of reported visual impairment was significantly higher in females than males, however, across decades and with age-adjustment. The investigators found no significant differences in visual impairment grades between sexes; and, after considering effect of longer life expectancy of females and looking for, but not finding undertreatment of exudative AMD among females, they concluded that females are at greater risk for visual impairment due to AMD.

Purola and colleagues attribute the overall favorable trend of reduced prevalence of visual impairment from AMD to several factors, including that the number of patients treated with intravitreal injections increased 40-fold during the period of 2005 - 2019.

"Today, we can say that exudative AMD treatment has been revolutionized by the introduction of intravitreal anti-VEGF drugs," Puola and colleagues enthused; but with a caveat. "Despite this development, undertreatment is frequent and the availability of treatment and protocols differs between clinics."

In addition to pharmacotherapeutic progress,the investigators cite other studies which have suggested that healthier lifestyles have contributed to the favorable trend. They also noted that many public campaigns have likely succeeded in making persons more aware of the symptoms, and prompted them to seek diagnosis and treatment.

Purola and colleagues pointed out that non-exudative AMD remains without effective treatment options, and is a significant cause for visual impairment in developed countries. "Therefore, it is important to evaluate the amount and burden of VI caused by the disease in order to improve health care and treatment," they concluded.

Visual impairment due to age-related macular degeneration during 40 years in Finland and the impact of novel therapies

Finnish population study attributes reduction in visual impairment from AMD to improved diagnostic tools, earlier diagnoses, and new therapies.

Less Visual Impairment From AMD Found in Population Study

One of the most persistent burdens surrounding 

 is the frequently delay in diagnosis by clinicians and initiated care for affected patients. It’s critical for caregivers and at-risk persons alike to identify the telling signs and symptoms of apnea risk—and the initial steps necessary to begin managing the chronic disease.

, Reena Mehra, MD, MS, director of sleep disorders research at the Cleveland Clinic, spoke with American Lung Association (ALA) chief medical officer Albert Rizzo, MD, on the most common or undercooked symptoms in obstructive sleep apnea. She noted how often patients present to her clinic with symptoms of excessive daytime sleepiness and general fatigue.

“That is by far and away the most common symptoms of obstructive sleep apnea, and it’s by virtue of the disruptive sleep that’s introduced from these repetitive episodes of stopped breathing—and probably some other pathways by which hypoxia may alter certain areas of the brain and lead to that sleepiness as well,” Mehra said.

Mehra additionally highlighted the importance of identifying persistent snoring, drowsing driving—an “important one” to quickly address—altered mood, or even nocturia as signs of untreated sleep apnea.

Rizzo and Mehra additionally discussed the misconception that obesity is a direct correlation with sleep apnea, highlighting the risk persons with unique airway anatomy and tissue accumulation face with the disease.

“It’s not everyone who is obese has sleep apnea, and not everyone who has sleep apnea is obese,” Mehra said.

Lastly, the pair reviewed differences in use of at-home and in-lab testing for sleep apnea.

“There’s a lot that’s monitored during an in-lab, attended polysomnogram,” Mehra said. ”It’s great from the standpoint of being able to collect a lot of helpful, important information about the degree of severity of sleep apnea…it allows us to more carefully and in a detailed way characterize the sleep-disordered breathing.”

“There can be some underestimation of the true degree of sleep apnea with home sleep apnea tests, so it’s important to recognize if you have high test probability, you’re doing the home sleep apnea test but it’s not conclusive nor revealing of a diagnosis, then one should pursue in-lab diagnostic testing to really confirm if there’s presence of sleep apnea,” she added.

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Reena Mehra, MD, MS, reviews telling signs, the role of obesity, and the importance of proper testing for sleep apnea.

Obstructive Sleep Apnea: Common Symptoms and Misconceptions

The US Food and Drug Administration (FDA) 

 the combination therapy relugolix, estradiol, and norethindrone acetate (Myfembree) for the management of moderate to severe pain associated with 

Endometriosis is often accompanied by debilitating symptoms. The condition is characterized by the presence of uterine tissue outside of the uterine cavity leading to disruptive symptoms including painful periods, lower back and abdomen pain, heavy menstrual pain, and painful intercourse. 

While there are prescription and over-the-counter medications available, as well as surgical options to remove the cysts, these approaches don't work for all patients. Additionally, it's a difficult condition to diagnose with some women going 4-11 years before receiving a diagnosis. 

“Approximately 7.5 million premenopausal women in the US have endometriosis and 75-80% of them are symptomatic,” Juan Camilo Arjona Ferreira, MD, Chief Medical Officer of Myovant Sciences, said in a 

 underscore the value relugolix combination therapy may provide as a potential new treatment option for women with endometriosis-associated pain.” 

 from the phase 3 SPIRIT 1 and SPIRIT 2 studies, which supported the FDA decision. The agency requested supplemental data and an update throughout the review process.

Most recently, Myovant Sciences and Pfizer Inc. announced that they 

 the medication's supplemental New Drug Application (sNDA), which was already undergoing review by the FDA. The agency had notified the companies of deficiencies it identified, halting the discussion of labeling and post-marketing requirements until they were addressed. 

Within a week of the notice, the companies were able to submit an update. The drug is a once-daily oral treatment consisting of relugolix 40 mg, estradiol 1 mg and norethindrone acetate 0.5 mg. 

“The data from the SPIRIT studies showed the clinical benefit that relugolix combination therapy can have on moderate to severe pain associated with endometriosis and how it can impact patients,” Linda Giudice, MD, PhD, Distinguished Professor, University of California, San Francisco (UCSF), Chair, SPIRIT Program Steering Committee said in a 

“This newly approved option for patients with pain from endometriosis offers the convenience of one pill taken once daily with a mean change in bone mineral density of <1% that did not appear to worsen at 12 months of treatment; however, monitoring is recommended.”

Myfembree Clinical Trials for Endometriosis

Both studies demonstrated clinically meaningful reductions of 75% in dysmenorrhea (menstrual pain) and non-menstrual pelvic pain, compared with 27% and 30% in the placebo groups, achieving their co-primary endpoints. The 2 replicate, phase 3, multicenter, randomized, double-blind, placebo-controlled trials spanned 219 community and hospital research centers across the globe. 

The studies also met their secondary endpoints. SPIRIT 1 achieved 7 key secondary endpoints and SPIRIT 2 met 6. The evaluation included changes in mean dysmenorrhea, non-menstrual pelvic pain, overall pelvic pain, impact of pain on daily activities as measured by the Endometriosis Health Profile-30 (EHP-30) pain domain, the proportion of women not using opioids, the proportion of women not using analgesics, and change in mean dyspareunia (painful intercourse). 

As for the seventh endpoint of SPIRIT 2, reduction in analgesic use (based on pill count), it did not achieve statistical significance. However, investigators speculated that could be due to the low number of average pills per day and variability in day-to-day pill consumption. 

In a post-hoc analysis of SPIRIT 2,  the percentage of patients who were analgesic-free at end of treatment was greater among patients in the combination therapy group as opposed to those in placebo.

The most common adverse events reported in both groups were headache, nasopharyngitis, and hot flushes. 

Prior to this decision, relugolix, estradiol, and norethindrone acetate combination therapy was indicated for managing heavy bleeding associated with uterine leiomyomas (fibroids) in premenopausal women, with a limitation of 24 months. 

FDA approved combination therapy relugolix, estradiol, and norethindrone acetate (Myfembree) for the management of moderate to severe pain associated with endometriosis. 

Combination Therapy Receives FDA Approval for Endometriosis

 often have higher levels of oxidative stress-induced nucleic acid damage from oxidative stress (NA-OXS) compared to the general population.

A team, led by Anders Jorgensen, MD, PhD, Psychiatric Center Copenhagen, Mental Health Services Copenhagen, analyzed data on nucleic acid damage from oxidative stress across the psychiatric disorder diagnostic spectrum.

Research shows nucleic acid damage from oxidative stress could be a molecular mechanism leading to increased morbidity and mortality from somatic causes in adult patients with psychiatric disorders.

“The predefined hypothesis was that individuals with psychiatric disorders have increased NA-OXS levels,” the authors wrote.

In the study, the investigators searched various databases from inception to November 16, 2021, while also conducting a hand search of reference lists of relevant articles. Participants in the study were adults with measurements of any marker of DNA or RNA damage from oxidative stress, and either a cross-sectional design comparing patients with any diagnosis of psychiatric disorders with a control group or a prospective intervention.

The investigators synthesized data with random-effects and multi-level meta-analyses.

The team sought main outcomes of the standardized mean differences among patients and controls in nucleic acid oxidation markers compared across different diagnostic groups.

The analyses were divided into combinations of biological matrices and nucleic acids.

Overall, there were 82 studies included in the analyses, with a total of 205 patient vs control group comparisons, as well as 10,151 patient and 10,532 control observations.

The analysis found patients with psychiatric disorders had higher NA-OXS levels compared to the control patients across matrices and molecules.

They also found pooled effect sizes ranged from moderate for urinary DNA markers (SMD , 0.44; 95% CI, 0.20-0.68; 

 < .001) to very large for blood cell DNA markers (SMD , 1.12; 95% CI, 0.69-1.55; 

Patients with dementias also had higher levels of NA-OXS, as did psychotic and bipolar disorders.

After conducting a sensitivity analyses excluding low-quality studies, the investigators observed the results were not materially altered.

Also, intervention studies were few and too heterogenous for meaningful meta-analysis.

“The results of this meta-analysis suggest that there is an association with increased NA-OXS levels in individuals across the psychiatric disorder diagnostic spectrum,” the authors wrote. “NA-OXS may play a role in the somatic morbidity and mortality observed among individuals with psychiatric disorders.”

Association of Oxidative Stress–Induced Nucleic Acid Damage With Psychiatric Disorders in Adults

Patients with dementias also had higher levels of NA-OXS, as did psychotic and bipolar disorders. 

Psychiatric Disorders Linked to Higher NA-OXS Levels

A new diagnosis code for reporting cases of activated phosphoinositide 3-kinase delta syndrome (APDS) will be included in the International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) by the US Centers for Disease Control and Prevention (CDC), according to a 

Beginning on October 1, 2022, the diagnosis code D81.82 will be activated and designated for the disease. Upon activation, this code will enable physicians and payers to add the diagnosis to patient charts for the first time in the US. 

Additionally, this can aid in facilitating better connection between individuals and investigators who are studying the course and prevalence of the disease. Beyond this, the code may emphasize the medical necessity and improve patient access to relevant care options through US health insurance plans.

“By assigning this ICD-10-CM code, the CDC is formally recognizing APDS as a discrete immunological disease, and that will make a life-altering difference for people affected by the condition," Anurag Relan, Chief Medical Officer of Pharming said in a 

Activated Phosphoinositide 3-Kinase Delta Syndrome (APDS)

 affecting 1-2 people per million. Variants in either the PIK3CD or PIK3RI gene lead to the condition by hyperactivating the phosphoinositide 3-kinase delta (PI3K) pathway. These genes regulate the maturation of white blood cells and without balanced signaling in the PI3K pathway physiological immune functioning is disrupted.

Individuals living with APDS experience severe, recurrent sinopulmonary infections, lymphoproliferation, autoimmunity, and enteropathy. Because this progressive disease is often misdiagnosed, a delayed diagnosis can lead to an array of irreversible organ damage including lung damage and lymphoma.

"By using the unique diagnostic code to identify both established and new patients with APDS, physicians will increase care options for affected individuals while helping to boost the world’s understanding of the prevalence, mechanisms, and outcomes of this progressively debilitating disease," Relan continued. "For healthcare practitioners, this milestone marks an opportunity to make a big difference by taking a simple action.”

Primary Immunodeficiency Treatment & Awareness

Supportive care is the primary treatment for APDS, incorporating the administration of antibiotics and immunoglobulin replacement therapy. Efforts have been made by physician and patient advocacy groups to raise awareness of the rare disease. 

Vicki and Fred Modell co-founded the Jeffrey Modell Foundation (JMF) in honor of their son who passed at the age of 15 from primary immunodeficiency (PI) complications. The nonprofit organization is dedicated to early diagnosis, meaningful treatments, and cures for these diseases through research, physician education, public awarenss, advocacy, patient support, newborn screening, and genetic sequencing. 

“We are excited that US regulatory authorities have assigned APDS an ICD-10-CM code. As a foundation dedicated to early diagnosis, meaningful treatments, and cures for primary immunodeficiency, we are aware of the physical and emotional challenges people with APDS face due to misdiagnosis of their disease," Vicki and Fred Modell stated. 

"By increasing recognition of the condition, we expect the new diagnostic code to help ensure that every patient is included when it comes to the delivery of appropriate and meaningful treatments for APDS.”

In October, a new ICD-10-CM diagnosis code will be activated for APDS, a rare primary immunodeficiency disease, which will enable physicians and payers to add the diagnosis to patient charts for the first time in the US. 

CDC will Include New ICD-10-CM Diagnosis Code for a Rare Disease in Fall

New findings from year 2 of the RECOVERY trial suggest treatment with monthly or quarterly intravitreal 2 mg aflibercept in patients with 

 led to significant increases in retinal nonperfusion (RNP)

However, the study reported a majority of subjects demonstrated improvement in Diabetic Retinopathy Severity Scale (DRSS) levels from baseline.

“Despite the expansion of the RNP area in nearly all subjects, 82% of subjects demonstrated an improvement in DRSS levels from baseline, with no subjects experiencing worsening in DRSS scores,” wrote study author Charles C. Wycoff, MD, PhD, Retina Consultants of Texas.

As an important biomarker for diabetic retinopathy, the development of retinal nonperfusion may be slowed by consistent anti-VEGF pharmacotherapy. THE RECOVERY trial evaluated the impact of aflibercept on RNP among eyes with proliferative diabetic retinopathy (PDR).

The prospectively, randomized clinical trial had treatment crossover in the second year. At baseline, the study individuals were randomized 1:1 to monthly (arm 1) or quarterly (arm 2) intravitreal 2 mg aflibercept.

When the second year of study began, the treatment arms were then crossed over. The monthly-dosed subjects then received quarterly dosing and the quarterly-dosed subjects received monthly dosing.

The main outcomes were considered the change in total RNP area (mm2) through year 2. The secondary outcomes included Diabetic Retinopathy Severity Scale (DRSS) scores, best-corrected visual acuity, central subfield thickness, additional measures of RNP, including ischemic index (ISI), and adverse event incidence. Investigators calculated means and 95% confidence intervals (CI).

In all study participants from baseline to year 2, investigators found the mean RNP increased from 235 mm2 to 402 mm2 (

 <.0001) and the ISI increased from 25.8% to 50.4% (

Moreover, data show increases in the mean RNP (

 <.0001) were also observed from year 1 to year 2. Additionally, the mean total RNP increased from 264 mm2 at baseline to 386 mm2 (

 <.0001) at year 2 in arm 1 and increased from 207 mm2 at baseline to 421 mm2 (

Investigators noted the increases in mean RNP for both treatment arms (

 <.0001) were specifically observed within year 2 as well (

 = .32; arm 1 vs arm 2). In comparison to baseline, the DRSS scores at the end of year 2 improved in 82% (n = 27) of subjects and remained stable in 18% (n = 6), with none experiencing worsening.

At the 2-year mark, the DRSS scores improved by 2 or more steps in 65% (n = 11) and 81% (n = 13) of subjects in arms 1 and 2, respectively.

Final Outcomes from the Randomized RECOVERY Trial of Aflibercept for Retinal Nonperfusion in Proliferative Diabetic Retinopathy

However, 82% of patients with proliferative diabetic retinopathy at year 2 of the RECOVERY trial demonstrated an improvement in DRSS levels from baseline. 

Monthly, Quarterly Aflibercept Linked to Increases in Retinal Nonperfusion

While the majority of research of colorectal cancer in patients with 

 (IBD) has focused on a younger population, new research is looking at elderly-onset IBD and whether or not it is related to an increased incidence and mortality rate of colorectal cancer.

A team, led by Asa H. Everhov, Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, estimatated the risk of incident colorectal cancer and mortality in elderly onset IBD.

There is previous research showing an increased relative risk of colorectal cancer in IBD, but this is limited to young-onset IBD.

“The risk of [colorectal cancer] is higher in IBD patients with extensive disease, a family history of [colorectal cancer], primary sclerosing cholangitis (PSC), and long disease duration,” the authors wrote.

Currently, endoscopic surveillance programs recommend varied colonoscopy intervals according to the presence of risk factors.

In addition, approximately 4-21% of patients with Crohn’s disease and 11-25% of patients with ulcerative colitis are diagnosed after the age of 60 years. And the highest risk of colorectal cancer is reported for patients diagnosed with IBD aged younger than 30 years.

The study included patients diagnosed with IBD aged 60 years and older between 1969-2017 identified using Danish and Swedish National Patient Registers and histopathology data.

The investigators linked data to the Cancer and Causes of Death Registers. They also estimated hazard ratios for colorectal cancer diagnosis and mortality compared to a control group matched by sex, age, and region of IBD-free individuals using Cox regression.

Overall, the team identified 7869 patients with Crohn’s disease that were followed for 54,220 person-years and 21,224 patients with ulcerative colitis followed for 142,635 person-years.

Of this group, 2.10% of patients with Crohn’s disease and 1.90% of patients with ulcerative colitis were diagnosed with colorectal cancer, compared to 2.26% and 2.34% of reference individuals (median follow-up 6 and 7 years).

In addition, the cancer incidence was elevated during the first year following an IBD diagnosis. The data show an incidence rate of 4.36 (95% CI, 3.33-5.71) in Crohn’s disease and 2.48 (95% CI, 2.03-3.02) in ulcerative colitis. However, this decreased after the first year of follow-up to 0.69 (95% CI, 0.56-0.86) for Crohn’s disease and 0.78 (95% CI, 0.69-0.88) for ulcerative colitis.

Following a colorectal cancer diagnosis, mortality was similar between patients with IBD and the general population.

“The excess risk of [colorectal cancer] in elderly-onset IBD was probably due to bias and not observed beyond the first year,” the authors wrote. “From 2010, the HR for [colorectal cancer] diagnosis more than 1 year after initial IBD diagnosis was lower than in the largely unscreened reference population, supporting the benefit of endoscopic screening and surveillance in patients with IBD.”

Colorectal cancer in elderly-onset inflammatory bowel disease: A 1969–2017 Scandinavian register-based cohort study

In the study, 2.10% of patients with Crohn’s disease and 1.90% of patients with ulcerative colitis were diagnosed with colorectal cancer.

No Evidence of Heightened Colorectal Cancer Risk in Patients With Elderly-Onset IBD

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