Significant decreases in prescription days, doses, refill requests, with few patient complaints
A restrictive postoperative opioid prescribing policy for patients with cancer led to a 50% reduction in opioid prescription days and an even larger decrease in the rate of conversion to chronic opioid use, a prospective cohort study showed.
Mean opioid prescription days decreased from 3.9 days before policy implementation to 1.9 days in the first 6 months afterward, accompanied by a 45% decrease in prescribed opioids after surgery. Patient requests for new opioid prescriptions also declined significantly.
Conversion to chronic opioid use occurred in 11.3% of patients prior to the policy versus 4.5% afterward, reported Emese Zsiros, MD, PhD, of Roswell Park Comprehensive Cancer Center in Buffalo, New York, and co-authors in JAMA Oncologyopens in a new tab or window. The findings set the stage for future investigations of opioids’ impact on cancer outcomes.
“We really don’t know what is the effect of opioids on cancer outcomes,” Zsiros told MedPage Today. “There are some data suggesting that opioids can fuel cancer progression, can lead to premature death. Many of our patients are long-term survivors, so this is really a big concern [whether] a patient becomes a chronic opioid user because they had surgery at the beginning of their cancer treatment. Are we really shortening their life expectancy by giving them too much and converting them to chronic users?”
“I think our future research is really going to focus on the impact of opioids on cancer outcomes, really trying to look at what is happening to those patients who are chronically using opioids compared to an opioid-naive cohort,” she added.
Patient-reported outcomes will be described in a future publication, but Zsiros said patients treated before and after implementation of the prescribing policy reported similar levels of satisfaction with their care.
The findings came from an analysis involving 4,068 patients with cancer treated surgically at Roswell Park from Aug. 1, 2018 to July 31, 2019. The study represented an expansion of a previously reportedopens in a new tab or window pilot investigation limited to patients who had surgery for gynecologic cancers. The pilot study showed an 89% reduction in postoperative opioid prescriptions and few complaints from patients.
The current study involved all surgical services at the cancer center. The restrictive protocol limited postoperative opioid prescriptions to a maximum of 3 days after discharge. The policy included standardized patient education about opioids and opioid prescribing. The primary outcome was compliance with the protocol in each surgical service, mean number of prescription days and refill requests, type of opioid prescribed, and rate of conversion to chronic opioid use (determined by a state-run opioid prescription program).
The study population comprised 2,017 patients treated in the 6 months prior to implementation of the prescription policy (Aug. 1, 2018 to Jan. 31, 2019) and 2,051 treated after the policy went into effect (Feb. 1 to July 31, 2019). Mean patient age was 61, and women accounted for 62.1% of the total.
The most common procedures in both cohorts involved breast, gastrointestinal, head and neck, and thoracic cancers (>80%). Two-thirds of operations were open procedures, and surgical complexity had fairly even distribution between major and minor. Length of stay averaged 2.5 days during both study periods, and 81-82% of patients in both groups had cancer diagnoses confirmed by surgery.
Overall, compliance with the prescription protocol was 95%. The decrease in prescription days achieved statistical significance (P<0.001), and the magnitude of decrease was similar across the different surgical services. Continued follow-up into the fourth quarter of 2020 showed that the change in opioid prescribing practices remained stable after 6 months.
Mean prescribed opioids after surgery (in morphine milligram equivalents [MME]) decreased from 157 prior to the policy to 83.54 after implementation (P<0.001). Mean MME continued to decline in the post-study period, reaching a low of 43.01 during the subsequent year. The proportion of patients requesting refills decreased from 20.9% to 17.9% (P=0.02), despite the fact that the post-policy cohort received fewer opioids after surgery.
About 20% of patients with cancer diagnoses in the pre-policy cohort met criteria for opioid exposure prior to surgery, as did 16.5% of the patients in the post-policy period. About 15-16% of patients with noncancer diagnoses also had prior opioid exposure. Zsiros said patients with prior exposure to opioids were more likely to convert to chronic opioid use after surgery, and the trend was evident in patients with and without cancer diagnoses.
Zsiros emphasized the study focused only on patients undergoing surgery for cancer, not patients at end of life with terminal cancer.
“Every time we have published on opioids, I have learned that it is a bit of a controversial topic,” she said. “I anticipate that we are going to get a little bit of negative media as a result. In the manuscript I think we spend a lot of time in the discussion section saying that if someone needs end-of-life care or needs opioids, our priority is to make sure that they have it.”
“Medical Journeys” is a set of clinical resources reviewed by physicians, meant for the medical team as well as the patients they serve. Each episode of this 12-part journey through a disease state contains both a physician guide and a downloadable/printable patient resource. “Medical Journeys” chart a path each step of the way for physicians and patients and provides continual resources and support, as the caregiver team navigates the course of a disease.
Urothelial cancer is the most common form of bladder canceropens in a new tab or window, but the term also encompasses cancers of the urethra, ureters, and renal pelvis. Rarer types of bladder cancer (representing less than 5% of bladder cancers) include squamous cell carcinoma, adenocarcinoma, small cell carcinoma, and sarcoma.
Urothelial cancer is also sometimes called transitional cell cancer, but both terms are typically used interchangeably with bladder cancer.
About 80,000 new cases of bladder cancer and 17,000 deaths attributable to the disease were expected in the U.S. in 2022, according to American Cancer Society statisticsopens in a new tab or window. Approximately three to four times as many men as women develop bladder cancer — mostly in those older than 55. Whites are more likely to be diagnosed with bladder cancer than Blacks or Hispanic Americans. In 2019, there were an estimated 712,644 people living with bladder cancer in the U.S., according to the National Cancer Instituteopens in a new tab or window.
Approximately 75% of bladder cancers are detected before they invade the detrusor muscle of the bladder, and are referred to as nonmuscle-invasive bladder cancer (NMIBC).
“The presence of microscopic or gross hematuria is often the first sign of bladder cancer,” Paras Shah, MD, of the Mayo Clinic in Rochester, Minnesota, told MedPage Today. “Other early signs and symptoms include frequency, urgency, or pain with urination. In advanced stages of disease, obstruction of the ureters may occur where they drain into the bladder, resulting in lower back pain or flank pain localized to the side of the blockage.”
The most common methods to evaluate for the presence of bladder cancer involve office-based procedures such as cystoscopy and urine cytology, as well as computed tomography (CT)-based imaging of the abdomen and pelvis. “Cystoscopy is the most sensitive and specific method for identification of bladder malignancies, but it is somewhat invasive and thus carries a slight risk for complications such as bleeding, infection, and pain,” Shah noted. “These procedures are often prompted by the presence of blood in the urine or persistent irritative voiding symptoms in the absence of infection.”
A formal diagnosis of bladder cancer is made only after biopsy is performed of suspicious masses noted within the bladder on cystoscopy or CT scan or if there is concern based on urine cytology.
Biopsy of the bladder tumor is performed endoscopically through the urethra by transurethral resection of bladder tumor (TURBT). Although other urinary biomarker tests exist, such as fluorescence in situ hybridization (FISH), and tumor marker tests such as bladder tumor-associated antigen — also called complement factor H-related protein (CFHrp) — ImmunoCyt/uCyt+, and NMP22 BladderChek, these tests lack sensitivity and specificity and thus have limited value.
What is the Value of Urine Cytology?
Urine cytology is typically part of the initial workup when a patient has visible blood in the urine, given its sensitivity for high-grade bladder cancer. In this instance, cytopathologic analysis of the sample under the microscope may reveal shedding of tumor cells from the bladder epithelium due to the dyscohesive nature of high-grade malignancy.
Results are reported as:
Negative for high-grade urothelial carcinoma
Atypical
Suspicious for high-grade urothelial carcinoma
Positive for high-grade urothelial carcinoma
Shah noted that interpretation of urine cytology can be highly variable, leading to heterogeneity in the way it’s reported, which may limit its value. “For example, to one pathologist, the cells may be atypical, but to another the cells may look suspicious. There is a very broad spectrum of characterization,” Shah said.
Moreover, the utility of cytology is primarily in the context of high-grade cancers due to their dyscohesive nature and propensity for shedding. This, however, is not a feature of slower-growing cancer. “The report may say negative for high-grade urothelial carcinoma, but that doesn’t mean it’s negative for bladder cancer,” Shah said. “A low-grade bladder cancer is still a possibility.”
Bladder cancer may also manifest itself in the form of microscopic hematuria, or blood that is not visible to the naked eye but is appreciated only under microscopic analysis. However, microscopic hematuria is a relatively common condition that may be a sign of a wide spectrum of urologic issues, both benign and malignant, and thus the ensuing urologic work-up is controversial, he explained.
The American Urological Association (AUA) defines microscopic hematuria as three or more red blood cells per high power field on microscopic evaluation of a single specimen. Anthony Corcoran, MD, of NYU Langone Perlmutter Cancer Center in New York City, noted that AUA recently endorsed a personalized risk-based strategy for evaluationopens in a new tab or window based on factors including age, sex, smoking, and other urothelial cancer risk factors, and degree and persistence of microhematuria.
“It used to be that everyone with microscopic hematuria got a cystoscopy, but now the AUA is supporting risk stratification for cystoscopy based on these risk factors if the patient has 20 or fewer red blood cells per high power field,” said Corcoran, who is also director of Urologic Oncology at NYU Langone Hospital – Long Island.
Urine cytology has little diagnostic value when a patient presents with microscopic hematuria, especially given that the yield for low-grade cancer is low. “Cytology is not going to catch the low-grade tumor,” Shah said. “Urine cytology is collected in the setting of microscopic hematuria mainly when patients persistently have microscopic amounts of blood in the urine and have otherwise undergone an exhaustive negative work-up, which includes imaging and cystoscopy. The likelihood of high-grade malignancy even in this setting generally remains low — in part because of the absence of gross hematuria.”
Beyond Urine Cytology: Imaging
For patients with microscopic hematuria, AUA recommends personalizing the diagnostic evaluation according to patient risk and involving shared decision-making. The evaluation generally involves cystoscopy and upper tract imaging in the form of either renal ultrasound (low-risk and intermediate-risk) or CT of the abdomen and pelvis (i.e., CT urogram) among high-risk patients.
For low-risk patients, Corcoran said, the choice of cystoscopy and renal ultrasound or repeat urinalysis in 6 months is discussed with the patient. Low-risk patients include those who are young, nonsmokers, have no family history of bladder cancer, and no occupational exposure to environmental carcinogens.
“In higher-risk patients [i.e., those who are male, have had prior radiation, are older, and have more severe urinary symptoms], I would encourage a CT scan and cystoscopy with the cytology, and for patients in the middle, I would typically do cystoscopy and an ultrasound,” Corcoran said. The overwhelming majority of patients tolerate cystoscopy well, “and I think that patients would rather have peace of mind than something hanging over their heads.”
For patients who present with gross hematuria, upfront urine cytology is often pursued as part of the evaluation, in addition to cystoscopy and imaging. The preferential imaging technique is a CT urogram as this offers a more comprehensive search for the source of bleeding, whether from the kidney, ureter, or bladder. Of note, although CT urography may demonstrate the presence of a bladder mass, cystoscopy is still generally performed to visually confirm its presence and better characterize the tumor.
Several imaging findings on CT urography for hematuria strongly suggest the presence of malignancy within the bladder. Features such as a discrete soft tissue mass within the bladder, filling defect within the bladder lumen on delayed phase imaging (i.e., an area within the bladder that is devoid of contrast), focal hyperenhancement of the bladder urothelium, urothelial thickening, or nodularity are all suggestive of a malignant process within the bladder and may represent the source of bleeding.
These findings are often still confirmed by subsequent cystoscopy. A visible tumor in the bladder prompts TURBT to establish a tissue diagnosis, assess the grade of the tumor, and evaluate the extent of disease — specifically, the depth of invasion or the stage (which will be covered in a subsequent installment in this series).
These factors will ultimately influence treatment selection, since the majority of NMIBCs can be managed conservatively with intravesical instillations of chemotherapy or immunotherapy agents, whereas muscle-invasive tumors require more radical treatment such as bladder removal or radiation.
Other sites of disease may also cause gross hematuria, such as tumors of the kidney or the collecting system. Tumors within the kidney are most often identified by upper tract imaging, such as renal ultrasound or CT scan.
Similarly, tumors within the urinary collecting system, referred to as upper tract urothelial carcinoma, are also most often identified on upper tract imaging, particularly CT urography. These tumors may appear as filling defects on delayed phase imaging of the CT urogram, soft tissue masses within the ureter, or thickening of the ureteral lining with enhancement.
In many cases, swelling of the ureter (i.e., hydroureteronephrosis) upstream from the site of concern may also be present. Upper tract urothelial cancers, particularly those that are high grade, may also cause a positive urine cytology associated with the shedding of cancer cells into the urine.
Similar to the situation for bladder tumors, visualization and biopsy is typically necessary to confirm the diagnosis. This most often involves placement of a cystoscope through the urethra into the bladder and the subsequent insertion of a guide wire through the cystoscope into the ureter. A longer version of the cystocope, referred to as a ureteroscope, is inserted over the guide wire into the ureter and permits both visualization of the ureteral tumor and biopsy of the area of concern.
CT urogram will also provide partial staging information when a tumor is discovered in the bladder, ureter, or kidney, which aids in decisions about treatment. Additional workup with a positron emission tomography scan may be performed with ambiguous findings on a CT scan, such as slight enlargement of lymph nodes. However, this is usually not a first-line imaging test.
The role of many urine-based molecular tests in the diagnosis of bladder cancer is still evolving and thus their use is not routine for this indication.
The most common of these urine-based molecular tests is the FISH test, also referred to as UroVysion. As the name implies, FISH fluorescently labels the DNA of cells shed into the urine for abnormalities in specific chromosomes involved in bladder cancer pathogenesis, which are chromosomes 3, 7, 13, and 17. As such, it is less likely to be influenced by the subjectivity of pathologist interpretation, especially given that it is more agnostic to inflammatory changes that may make cells appear atypical.
“The FISH test is used mainly to assess response in patients with NMIBC receiving intravesical therapy such as Bacillus Calmette-Guerin,” Shah said. “It can also be used to evaluate for the presence of bladder cancer in patients with an indeterminate urine cytology.”
Second-line tucatinib plus trastuzumab combo gets accelerated approval in metastatic disease
The FDA has granted accelerated approval to tucatinib (Tukysa) in combination with trastuzumab (Herceptin) for adult patients with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer who have progressed following treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, Seagen announcedopens in a new tab or window.
This is the first FDA-approved treatment for HER2-positive metastatic colorectal cancer, the company noted.
Approval was based on results from the phase II MOUNTAINEER trialopens in a new tab or window, showing a 38% overall response rate (95% CI 28-49) with the combination per blinded independent central review. Complete responses were observed in 3.6% of patients and partial responses were seen in 35%. The median duration of response was 12.4 months (95% CI 8.5-20.5).
“Historically, patients with HER2-positive metastatic colorectal cancer who have progressed following frontline therapy have had poor outcomes,” said lead investigator John Strickler, MD, of Duke University Medical Center in Durham, North Carolina, in a press release. “The FDA approval of a chemotherapy-free combination regimen that specifically targets HER2 is great news for these patients.”
The multicenter, open-label, randomized, phase II MOUNTAINEER trial evaluated 84 patients with RAS wild-type, HER2-positive unresectable or metastatic colorectal cancer following previous treatment with standard-of-care therapies. They had not received prior anti-HER2 therapy.
At study entry, 64% and 70% of these patients had liver or lung metastases, respectively.
Patients received tucatinib 300 mg twice daily orally in combination with trastuzumab intravenously (8 mg/kg loading dose, then 6 mg/kg every 3 weeks thereafter) until disease progression or unacceptable toxicity.
The prescribing information for tucatinib includes warnings and precautions for diarrhea, hepatotoxicity, and embryo-fetal toxicity, some of which may be severe or fatal.
The most common adverse reactions (≥20%) in patients treated with the combination were diarrhea, fatigue, rash, nausea, abdominal pain, infusion-related reactions, and pyrexia. Serious adverse reactions occurred in 22% of patients, with intestinal obstruction (7%), urinary tract infection (3.5%), and pneumonia, abdominal pain, and rectal perforation (2.3% each) being the most common.
Adverse reactions leading to permanent discontinuation of tucatinib occurred in 6% of patients.
Identified patients likely to benefit following surgery, large prospective study showed
Tumor-informed circulating tumor DNA (ctDNA) testing for residual disease was able to distinguish patients with colorectal cancer (CRC) at risk for recurrence after surgery, as well as those who could safely avoid adjuvant chemotherapy, according to a large prospective study from Japan.
Over a median follow-up of 16.7 months, 61% of patients who were ctDNA-positive 4 weeks after surgery had recurrences, compared with 10% of those who were ctDNA-negative (HR 10.0, 95% CI 7.7-14.0, P<0.0001), reported Eiji Oki, MD, PhD, of Kyushu University in Fukuoka, and colleagues.
At 18 months, disease-free survival (DFS) rates in the two groups were 38.4% and 90.5%, respectively — a trend that was observed across all pathological stages.
In multivariate analysis for DFS in patients with pathological stage II-III disease, ctDNA positivity 4 weeks after surgery was the most significant prognostic factor associated with increased risk for recurrence (HR 10.82, 95% CI 7.07-16.60, P<0.001).
As for the association of adjuvant chemotherapy with postsurgical ctDNA status, the investigators found that patients with stage II-III CRC with postsurgical ctDNA positivity significantly benefited from adjuvant chemotherapy (HR 6.59, 95% CI 3.53-12.30, P<0.0001), and this trend was observed across all pathological stages:
High-risk stage II: HR 5.84 (95% CI 1.36-25.10)
Stage III: HR 7.02 (95% CI 3.46-14.20)
Stage IV: HR 4.00 (95% CI 1.85-8.80)
Furthermore, a multivariate analysis of ctDNA-positive patients with stages II-IV disease showed that a lack of adjuvant chemotherapy was a significantly negative prognostic factor (HR 5.03, 95% CI 3.17-8.90, P=0.001), the team reported. On the other hand, there was no statistically significant benefit associated with adjuvant chemotherapy in ctDNA-negative patients (HR 1.71, 95% CI 0.80-3.70, P=0.167).
Results of the analysis showed that postsurgical ctDNA status is a more significant prognostic biomarker than the currently used high-risk clinicopathological features and can potentially be predictive of adjuvant chemotherapy benefit, said Oki and co-authors.
The findings are “potentially practice changing and clearly in the direction we want to go,” said Aasma Shaukat, MD, MPH, director of Outcomes Research in the Division of Gastroenterology and Hepatology at NYU Grossman School of Medicine in New York City, who was not involved with the study.
“We’ve been trying to move toward precision medicine for decades, and in oncology the way it applies is understanding which patients are most likely to benefit from chemotherapy, with the goal of increasing disease-free survival and overall survival,” she told MedPage Today. “We have some markers, but they are not very targeted, and as a result a lot of people who won’t benefit end up suffering the toxicity and cost of chemotherapy, while individuals who are likely to benefit sometimes get skipped.”
The commercial assay used in the study (Signatera) is “all we would need to offer individuals 4 weeks after surgery,” Shaukat continued. “We could very confidently make decisions about who would benefit from additional chemotherapy, and perhaps keep them disease free for a longer period of time.”
For the research, the team used whole exome sequencing, and the results were analyzed to design a tumor-informed, personalized ctDNA assay. A total of 8,374 genes were selected for 1,039 patients, with TP53 (25.6%) and APC (17.5%) the most frequently selected. More than half of the genes were unique to each patient — suggesting, the investigators explained, that there is “large variability in the mutational landscape of CRC outside of known hotspot regions.”
“This highlights the importance of personalized ctDNA analysis based on patient-specific somatic tumor mutations,” Oki and co-authors added.
“The question now,” Shaukat said, “is how this goes from this research to actually developing into an assay. And I think we’ll probably see several different iterations. It’s very difficult to do an over-8,000 gene exome every time, so what may happen is that they may refine it and narrow it down to the genes of interest so that it still gives us that detailed information — it is able to discern and distinguish — yet is more streamlined.”
Case report is published days ahead of FDA lecanemab decision
A fatal bleeding event in an Alzheimer’s clinical trial participant may have been linked with the investigational anti-amyloid agent lecanemab, a case report suggested.
However, drug trialists are not willing to assign blame yet, especially as lecanemab’s fate hangs in a potential FDA approval for early Alzheimer’s disease later this week.
The trial participant was homozygous for the APOE4 allele and had a last lecanemab infusion 4 days before the stroke occurred. A head MRI performed 81 days before the stroke showed mild small-vessel disease, with no microhemorrhages, edema, or amyloid-related imaging abnormalities (ARIA); CT performed just before tPA administration showed no hemorrhage, either, according to neurocritical care specialist Sherry Chou, MD, and colleagues of Northwestern University Feinberg School of Medicine in Chicago.
The patient received IV tPA, as there were no contraindications to thrombolysis. Problems emerged 50 minutes into the infusion, when hypertension suddenly developed and forced tPA infusion to be stopped. CT showed extensive, multifocal intraparenchymal hemorrhages without systemic bleeding.
Chou and colleagues administered cryoprecipitate and tranexamic acid. They also gave multiple antiseizure medications for the frequent, nonconvulsive seizures seen on electroencephalography. Three days later, the patient underwent endotracheal intubation, and imaging showed acute right thalamocapsular infarction and innumerable multifocal cortical and subcortical hemorrhages with surrounding edema.
At the request of the family, the patient received comfort measures before dying. Autopsy showed extensive multifocal intraparenchymal hemorrhages, cerebral amyloid angiopathy, Alzheimer’s disease neuropathologic changes, and diffuse histiocytic vasculitis with necrotizing vasculopathy involving amyloid deposition within blood vessel walls.
“The extensive number and variation in sizes of the cerebral hemorrhages in this patient would be unusual as a complication of tPA solely related to cerebrovascular amyloid. The findings raise the possibility of cerebral hemorrhages and necrotizing vasculopathy associated with tPA infusion in a patient with cerebrovascular amyloid who had received lecanemab,” Chou’s group wrote.
In a written response, CLARITY AD investigators Marwan Sabbagh, MD, of Barrow Neurological Institute in Phoenix, Arizona, and Christopher van Dyck, MD, of Yale School of Medicine, clarified that autopsy findings may have been affected by several intervening events since the time of the patient’s hemorrhage.
The duo also highlighted the known risk of intracerebral hemorrhage — and uncommon cases of vasculitis — in persons with CAA not on anti-amyloid therapy.
“We agree that this case raises important management issues for patients with Alzheimer’s disease, particularly patients who are homozygous for the APOE4 allele,” Sabbagh and van Dyck said.
Having occurred during CLARITY AD’s extension phase, the death was not counted among the 13 deaths (six in the lecanemab arm and seven in placebo) in the trial report of nearly 1,800 people.
Also not included was a 79-year-old woman’s deathopens in a new tab or window — also during the extension phase of CLARITY AD — that occurred more recently after the patient experienced extensive brain swelling and bleeding and seizures. Previously, a man in his late 80s died of a brain hemorrhage after using lecanemab and apixaban (Eliquis) for atrial fibrillation, though lecanemab developer Eisai argued that the death was unrelated to the drug.
During the randomized phase of CLARITY, no deaths had been judged to be related to lecanemab or occurred with ARIA. ARIA with edema or effusions occurred in 12.6% of people who received lecanemab. Combined cerebral microhemorrhages, cerebral macrohemorrhages, and superficial siderosis occurred in 17.3%, study authors reported.
CLARITY’s main finding was that lecanemab was associated with a statistically significant albeit modest reduction in clinical decline after 18 months in people with early Alzheimer’s disease.
The FDA is expected to announce in the upcoming days whether to grant lecanemab accelerated approval for early Alzheimer’s disease. Some have suggested the agency requires a risk evaluation and mitigation strategy in face of fears of the drug’s ARIA risks.
Falls are the greatest health risk for most older adults. Here’s how to protect yourself.
Every second, someone age 65 or older suffers a fall, making it the No. 1 cause of injury-related death in this age group. According to the CDC, about 20% of falls in adults lead to life-altering changes, primarily from broken bones or head injury.
“The best way to protect yourself is to address the three main physical conditions that contribute to falls: weak stabilizer muscles, poor core strength, and balance issues,” says Carina O’Neill, a specialist in physical medicine and rehabilitation at Harvard-affiliated Spaulding Rehabilitation Hospital.
Stabilizer muscles. The stabilizer muscles keep you upright and allow you to easily change directions. Two essential stabilizers for fall prevention are the gluteus medius (located on the side of the hip) and the gluteus maximus (the largest buttock muscle). “These work both together and independently to allow us to stand upright and stabilize the back and pelvis as we move during activities,” says O’Neill.
Core strength. Core strength is vital for fall prevention, as your body’s core is the epicenter from which every movement revolves. “As we walk, our bodies constantly have to adapt to ever-changing ground levels,” says O’Neill. “Adequate core stability and strength help you better react to these sudden changes and prevent potential falls.” The core consists of several muscle groups: the rectus abdominis (the “six-pack” or “abs”); the obliques, located on the sides and front of your abdomen; and the transverse abdominis muscles, which lie under the obliques and attach to your spine.
Stabilizer and core muscles weaken over time as men naturally lose muscle mass, a condition called sarcopenia. “These muscles further weaken from a sedentary lifestyle or when people follow a regular exercise program that neglects these areas,” says O’Neill.
Balance. Sense of balance naturally wanes over time, as do reflexes and coordination. This makes it easier to topple and harder to catch yourself if you do have a misstep. Another cause of poor balance is deterioration of the inner ear’s vestibular system. It feeds information to the brain about motion, head position, and spatial orientation, and it, too, becomes less effective as we age.
Defense is the best offense when it comes to fall prevention. “Take steps now to address areas that place you at a higher risk for falls,” O’Neill advises. Here are some strategies for shoring up your stabilizer muscles, core strength, and balance.
Headed for a fall? You can check your fall risk with some simple tests. Place one foot in front of the other so the toes and heel touch (like how you would measure distance on the floor) and try to stand without losing your balance for up to a minute. Another version is to walk heel-to-toe, like on a tightrope, for 20 steps. “If you have trouble maintaining balance and stability with either of these, you should discuss it with your doctor,” says Carina O’Neill, a specialist in physical medicine and rehabilitation at Harvard-affiliated Spaulding Rehabilitation Hospital.
Side to side
Side-to-side leg movements, like those you make when playing tennis or pickleball, can strengthen the gluteus medius and gluteus maximus muscles. If you’re not into racquet sports, there are many exercises that work. One is the clam, a simple floor exercise that targets both muscles. Here’s how to do it:
Lie on your right side, your left leg on top of your right, and your knees comfortably bent.
Keeping your feet together, raise your left knee, rotating the left leg until it makes a 90° angle to the right leg (or as high as is comfortable).
Hold for a second and slowly return to the starting position.
Do eight to 10 repetitions to complete one set. Do two to three sets.
Change sides, and complete the same number of repetitions and sets with the opposite leg.
For more of a challenge, wrap a resistance band around both legs above the knee.
Bridge and plank
Bridge and plank poses are two exercises that O’Neill recommends to strengthen your core.
Bridge. Lie on your back with your knees bent and feet flat on the floor, hip-width apart. Place your arms at your sides. Relax your shoulders against the floor. Tighten your buttocks and abdominal muscles, press your heels into the floor, and lift your hips as high as is comfortable, or until they are in line with your shoulders and knees. Hold for a second. Return to the starting position. Do this eight to 12 times. Rest 30 to 90 seconds, and repeat the entire set.
Plank. Lie facedown with your forearms resting on the floor. Tighten your abs and raise your body to form a straight line from your head to your feet. Hold for 15 to 30 seconds. Rest 30 to 60 seconds, and repeat one or two more times. You can also hold the plank from a full push-up position, or on your forearms with your knees on the ground.
Other contributors Health conditions can further contribute to falls. Examples include arthritis (which can cause stiffness in the ankles, knees, and hip), peripheral neuropathy (nerve disease) involving the feet or lower legs, and heart arrhythmia (a change in heartbeat speed or rhythm that can cause weakness, dizziness, or fainting). Vision problems like cataracts, glaucoma, and age-related macular degeneration also can contribute to balance problems.
Tai chi
According to O’Neill, one of the best ways to improve balance is practicing tai chi. The ancient Chinese martial art consists of slow controlled movements focusing on weight distribution and rotation. Numerous studies have supported its use to improve balance and coordination and reduce fall risk among older adults and others at high risk for falls, like stroke survivors.
Another exercise for improving balance is one-legged standing. Stand on one leg for 30 to 60 seconds, using a counter or the back of a chair for support as needed. Switch legs and repeat. Go back and forth between the two poses several times.
Today’s teens and tweens have never known a world without social media. There are still a lot of open questions about how sites like TikTok and Instagram may shape their development — and stories focusing on the potential negative impacts of social media tend to dominate the news.
But a recent study published in JAMA Pediatrics is the latest in a growing body of research that suggests the relationship that young people have with social media is too complicated to be categorized as simply good or bad.
The study, which tracked 169 middle-school students, aimed “to better understand the links between how often teens check social media and how their brains respond to social feedback over time,” study co-author Maria Teresa Maza, a doctoral student at the Developmental Social Neuroscience Lab at the University of North Carolina, said via an email. The results show that the brains of teens who use social media more frequently show greater sensitivity to social feedback — but it’s not so clear whether that’s a problem.
The study scanned the brains of students from three public middle schools in rural North Carolina over the course of three years, having gathered self-reported data from the students about how many times per day they checked Facebook, Instagram, and Snapchat. While the students were in the scanner, they played a computerized game in which they would anticipate and receive social feedback, which was communicated via images of adolescents with facial expressions that could be positive, negative, or neutral.
“We found that certain regions of the brain showed different sensitivity to this social feedback over those three years, and that this changing sensitivity was different for the group of teens who checked social media habitually and those who did not,” Maza said. In other words, over the course of the study, the teens who checked social media more frequently showed greater activity in the regions of the brain related to motivation, control, and salience — how much a given stimulus stands out to an individual — while playing the game. Meanwhile, their peers who used social media less often became less responsive to social feedback.
The study establishes correlation, not causation, between participants’ neural patterns and their social media behavior. So it’s not clear whether checking these apps more frequently leads to greater sensitivity to feedback, or if young people who are more sensitive to feedback are also more prone to scrolling their social feeds. The study also doesn’t take a position on whether greater sensitivity to social feedback is inherently positive or negative. “Given how individualized social media behaviors and experiences can be, this sensitivity may be helpful for some and less helpful for others,” Maza said.
“For example, an increasing sensitivity to social information might prompt future compulsive social media checking,” she continued. “However, a greater sensitivity and awareness of social feedback — particularly digital feedback — might help teens navigate digital-social spaces better, which may be very important in their increasingly digital worlds.”
Maza said that she and her colleagues are in the process of launching a new study exploring digital media use starting with third- and fourth-graders, with the hope of better understanding the impact of digital media contexts on development. https://embed.actionbutton.co/widget/widget-iframe.html?widgetId=SPK-SUVBQA== Nick Allen, professor of psychology at the University of Oregon and director of the university’s Center for Digital Mental Health, said in an interview that the new study is an important one. “When you talk to young people about their experience with social media, it’s actually quite a varied experience,” he said.
Allen is the lead researcher partnering with Google on a study that looks at how smartphones may be affecting our minds and sense of well-being. The study, which is still ongoing, examines not only the potential risks of too much time spent on our mobile devices, but also the ways in which researchers might leverage smartphones to provide mental health support to more people.
Smartphones and social media are not going away, Allen said. “The key question is, how do we shape those technologies to maximize the benefits and minimize the risks?”
Allen said he thinks public education campaigns on social media use among young people, and even curriculums built into schools, could be helpful in the future. For example, as adult content becomes easily accessible for young people through social media, schools may want to have open conversations about sharing or restricting certain content.
“Some of those can be focused on kids, some of those can be focused on parents,” he said.
Other research suggests that many young people are already finding ways to use social media to manage their mental well-being. In a 2020 survey conducted by the nonprofits Hopelab and Common Sense as well as the California Health Care Foundation, more than 1,500 teens and young adults were asked about how they used digital media during the Covid-19 pandemic. Young people with depression were nearly twice as likely as those without depression to say they used social media almost constantly (34% vs. 18%) — a finding that could, in a vacuum, be interpreted as worrisome.
But the survey also found that 43% of respondents said that using social media actually made them feel better when they’re feeling depressed, stressed, or anxious, while just 17% said that social media made them feel worse. And 26% of people with depression said that social media was “very” important for getting support or advice, up from 11% in an earlier 2018 survey.
“There are aspects of social media usage, including displacement of healthy behaviors such as sleep, exposure to hate speech, and heightened social comparisons, that indeed negatively impact youth well-being,” Hopelab Chief Science Officer Jana Haritatos said via email. “At the same time, we also find that these social platforms serve as an important connector, information source, and support system for many young people, particularly those who may otherwise lack in-person alternatives, such as LGBTQ+ young people.”
Looking ahead, Haritatos said, “an important priority for the next generation of social media research is greater access to objective data” on how young people use platforms, so that researchers don’t rely exclusively on self-reported usage patterns. In addition, Haritatos said, “we need longitudinal research that dives deeper into the associations between young people’s identities and their use of social media platforms.”
In the end, it may turn out that what’s important when it comes to teens’ development is less how much time they spend on social media — and more what they see and experience when they’re online.
Doctors are reporting a troubling trend when it comes to fentanyl.
The powerful drug, they say, isn’t just causing overdoses — it’s also making it more difficult to begin addiction treatment. In particular, fentanyl appears more likely to cause severe withdrawal symptoms for patients put on buprenorphine, a key medication used to treat opioid use disorder.
The development adds yet another layer of crisis to the country’s drug epidemic, which killed nearly 108,000 Americans last year. Even as fentanyl sends overdose deaths soaring, it threatens to make the world’s most-prescribed addiction drug inaccessible to the increasing number of patients who need it.
“It’s the clinical challenge of my career,” said Sarah Kawasaki, an addiction doctor and psychiatry professor at Pennsylvania State University. Inductions, or the process of starting patients on buprenorphine treatment, have become “progressively more difficult” in the past five years, she said, as fentanyl has spread throughout the drug supply.
To make matters worse, Kawasaki added, buprenorphine is one of just two medications commonly prescribed to treat opioid addiction. The other, methadone, is highly regulated; patients can only access it at specialized clinics that typically require them to appear in person each day to receive a single dose.
“We have 20 different ways to treat strep throat, but two medications that work well in the treatment of opioid use disorder,” Kawasaki said. “When you eliminate one and make the other really hard to get, it is a setup for failure.”
While doctors across the U.S. and Canada, where fentanyl is also pervasive, have reported that buprenorphine inductions have become more difficult in recent years, the phenomenon is hard to measure or explain. Theories include fentanyl’s raw potency, or that it is lipophilic — it sticks to fat molecules — and remains in the body for longer than other opioids.
Buprenorphine is what’s known as a partial agonist, meaning that it binds tightly but incompletely to the same brain receptors that give a euphoric effect when opioids bind to them. But it binds to the receptor awkwardly, like a puzzle piece that doesn’t quite fit. As a result, patients with opioids already in their system can feel what’s known as “precipitated withdrawal” as the addiction medication shoves the fentanyl aside.
As a result, it’s normal for doctors to wait several hours until patients start experiencing withdrawal symptoms before they administer buprenorphine. At that point, the “bupe,” as it is known, helps to treat withdrawal symptoms like anxiety or gastrointestinal distress, as well as eliminate future opioid cravings.
With fentanyl, however, doctors are sometimes forced to wait a full day, if not longer, to make sure buprenorphine doesn’t cause severe discomfort. In some cases, even patients experiencing withdrawal because they refrained from drug use for many hours — typically ideal candidates for buprenorphine — find that their symptoms get worse, not better, once they begin using the medication. Many don’t come back for another dose, known in doctors’ parlance as a “failed induction.”
Doctors warn those failed attempts can be dangerous — not just because they risk patients returning to fentanyl use, but also because those patients might feel so miserable that they refuse to ever try buprenorphine again.
Some clinicians report that patients have become more likely to request methadone, despite its inconveniences. Kawasaki, who works at a clinic that offers both methadone and buprenorphine, said she’s had trouble enrolling patients in a clinical trial about buprenorphine induction because her patients are opting for the drug less likely to cause withdrawal symptoms.
Though the phenomenon is widespread, doctors haven’t reached a consensus about how to move forward. Nor have they received much guidance from medical societies and local health officials, leaving doctors to rely informally on word of mouth, email chains, and new scientific papers.
One recent set of recommendations from the Substance Abuse and Mental Health Services Administration did little beyond acknowledge the issue, warning that patients using fentanyl long-term and at high doses “may not be appropriate for buprenorphine.”
“There’s a patchwork of induction strategies at this point,” said David Fiellin, an addiction physician and the director of Yale University’s Program in Addiction Medicine. “In a lot of ways, we’re in an area without much science.”UPCOMING EVENT
The knowledge gap led Fiellin to issue a recent call in the Journal of Addiction Medicine for “rapid research” analyzing the relationship between the type and quantity of drugs used and difficulties beginning buprenorphine treatment.
In the meantime, however, doctors are employing strategies that vary dramatically. Some have begun administering radically larger amounts of buprenorphine in an effort to overcome withdrawal symptoms by brute force — as much as 32 milligrams, or four times a typical first dose.
Some doctors, like Kawasaki, also use common medications to treat any remaining symptoms of physical discomfort and anxiety, including antihistamines, ibuprofen, and drugs to combat nausea and gastrointestinal problems.
Others have tried the opposite approach: “microdosing” buprenorphine in increasing amounts over the course of several days, avoiding a moment where a sudden, large buprenorphine dose causes immediate withdrawal. Samantha Young, a doctor and researcher at the British Columbia Centre for Substance Use, said she sometimes prescribes shorter-acting opioids typically used for pain, like hydromorphone, to help alleviate withdrawal symptoms as patients build up to larger buprenorphine doses.
“When I teach residents and medical students about buprenorphine, I tell them it’s an art based on the science,” Young said.
Others, still, have tried the controversial approach of administering naloxone, a drug used to reverse opioid overdoses, even to patients who are not overdosing. The result is a very short period of intense withdrawal, setting the patient up for a first buprenorphine dose that alleviates discomfort instead of causing it.
Any strategy that works is promising, Fiellin said. But the fact that it’s become harder for doctors to prescribe buprenorphine is concerning in its own right. While the medication is highly effective, it’s also tightly regulated, meaning convincing doctors who aren’t addiction specialists to prescribe it has long been challenging. The newfound difficulties, he said, risk reversing recent progress.
“There was a period of 10 or 15 years where bupe initiation was not seen as a challenge, so it was much more common that nonspecialists would take on buprenorphine prescribing,” Fiellin said. “Unfortunately, we’re in a situation where now initiation is seen as a huge challenge, and I worry that’s going to set us back with respect to expanding the number of clinicians who are prescribing buprenorphine.”
Still, some physicians remain optimistic. And patients who want to begin buprenorphine treatment shouldn’t despair, they say. Ultimately, buprenorphine induction for people using fentanyl is still possible, despite its difficulties. The pervasiveness of fentanyl in the North American drug supply “does make the induction a bit more challenging,” Young said. “But just so people know: We’ve developed a lot of methods — if you want to get on bupe, and you use fentanyl, great! We can definitely do that for you, without you being in withdrawal.”
Some existing medications could be used to treat type 2 diabetes. Philippe Clement/Arterra/Universal Images Group via Getty Images
A new study finds that an older class of antipsychotic medications can lower blood sugar in people with type 2 diabetes.
These drugs may address the needs of people who cannot take existing diabetes medications, or for whom they have become less effective.
The antipsychotics address the expression of an enzyme that has recently been tied to hyperglycemia in mice.
With type 2 diabetes (T2D) on the riseTrusted Source, there is an expanding need for effective treatments. Researchers from the University of Alberta (UAlberta) in Canada have been exploring existing non-diabetes drugs as new therapeutic options for people with T2D.
The study has found that a class of older antipsychotic drugs reduces blood sugar levels by targeting an enzyme tied to hyperglycemia in diabetes.
The enzyme the drugs inhibit is succinyl CoA:3-ketoacid CoA transferase or SCOT. The drugs belong to the diphenylbutylpiperidines medication class, abbreviated as DPBP.
Many people with T2D cannot benefit from metformin — the primary drug prescribed for lowering blood sugar — or other existing diabetes medications.
About one-third of patientsTrusted Source with T2D cannot benefit from metformin due to variable drug responses associated with genetic and non-genetic factors
Its corresponding author John R. Ussher, associate professor at the Faculty of Pharmacy and Pharmaceutical Sciences, explained to Medical News Today that new therapies are also needed for people with late-stage T2D:
“They become less responsive to the multiple medications that improve their blood sugar control by increasing insulin secretion.”
“Type 2 diabetes is very prevalent in our society, with enormous costs on the population from a health standpoint, and financially for our health system overall,” said Dr. Jason Ng, endocrinologist at the UPMC Endocrinology & Diabetes Center in Pittsburgh, PA. (Dr. Ng was not involved in the study.)
“Developing novel therapies to help improve sugar control in type 2 diabetic patients is a key method in improving outcomes both in the micro and macroenvironment,” alongside lifestyle and dietary changes, said Dr. Ng.
Developing a new drug takes a long time — The PhRMA Foundation estimates it takes an average of 10 years. It is also an expensive process. Reimagining uses for an already existing drug is a far speedier, simpler process.
When re-purposing approved drugs for new uses, much of this work has already been done.
Basic safety concerns have already been satisfied, so clinical trials, which are still necessary, can take place more quickly.
Similarly, much of the time and money that goes into development has already been spent, simplifying the process considerably.
In 2020, the UAlberta researchers published a studyTrusted Source documenting the link between SCOT and hyperglycemia in mice.
They also demonstrated that a DPBP drug, pimozide, could lower the expression of SCOT, and that this resulted in an improvement in blood sugar levels.
That study had identified DPBP drugs through computer modeling. The new research finds that the entire class of drugs can inhibit SCOT expression.
In addition to a drug’s primary action, many also produce secondary effects, such as the DPBP drugs’ ability to inhibit SCOT.
This connection opens up new therapeutic options since diabetes drugs typically decrease blood sugar through an increase in insulin levels.
“[DPBP drugs’ ability to lower SCOTs expression is] a potential new mechanism in which we can promote a sugar lowering effect in patients with type 2 diabetes and obesity, which is promising but needs further study.” — Dr. Jason Ng
At healthy levels, SCOT helps the body burn ketones as an alternate fuel when glucose is in short supply. Inhibiting SCOT expression prevents the use of this backup energy source, a concern expressed in the study.
According to Dr. Ussher, ”the consequence is indeed an increase in blood ketone levels, which may increase the risk of ketoacidosis as a side effect.”
He noted, however, that his team’s pre-clinical studies in animals suggest that this is likely to be no more severe than ketoacidosis that occurs with a ketogenic diet. He said that it will be important to monitor ketone levels for those taking DPBP medications.
“It is imperative that we understand what the long-term consequences may be for inhibiting SCOT in humans,” he stressed.
As antipsychotic medications, the DPBP class of drugs target dopamine receptors in the brain. As such, their often-reported side effects include drowsiness, dizziness, and fatigue.
“We are interested in determining whether we can modify the structure of the DPBPs so that they are unable to penetrate the brain but preserve their ability to inhibit SCOT everywhere else in the body,” said Dr. Ussher.
Doing so would not only eliminate the side effects but also allow the brain to continue utilizing ketones for energy as needed.
“We have actually made some progress in this area and hope to publish our follow-up studies in this direction in the next year or two,” Dr. Ussher added.
For now, the best advice for people hoping to avoid T2D or to get the disease under control, according to Dr. Ng, is “Eating a healthy diet that is not carb-heavy, getting plenty of physical activity, getting plenty of sleep, and reducing stress.”
“These are all common ways to feel healthier, and they all also help your body maintain good insulin sensitivity, reduce the risk of developing obesity, and in turn, reduce the risk of developing type 2 diabetes.”
More than 30 percent of North Americans over the age of 85 suffer from dementia. A study presented at the International Stroke Conference 2019 shows that having harmful bacteria in your colon increases risk for dementia (Scientific Reports, Jan 30, 2019;9(1008)). The study followed 128 outpatients, average age 74, visiting a memory loss clinic. Compared to those who did not have dementia, those with dementia had: • markedly increased MRI evidence of brain bleeds and strokes • markedly decreased colon levels of Bacteroides (enterotype I), which are healthful bacteria that decrease inflammation and help to lower high cholesterol and high blood pressure • markedly increased harmful colon bacteria of enterotype III that increase inflammation • increased stool concentrations of ammonia, indole, skatole, and phenol that are produced by harmful colon bacteria when they try to invade colon cells.
You have more than 100 trillion bacteria, of about 1000 different species, living in your colon. Many different studies have shown that what you eat determines which types of bacteria live in your colon and that certain types of bacteria can turn on your immune system to cause inflammation that increases risk for dementia (Curr Opin Pharmacol, 2017;37:87–92), as well as heart attacks, certain cancers, and auto-immune diseases (J. Alzheimers Dis, 2017;58:1–15).
You can encourage growth of healthful bacteria in your colon and discourage the harmful ones by: • Eating lots of fruits, vegetables, whole grains, beans and nuts that are high in fiber, which fosters healthful colon bacteria (Food Funct, Apr 2016;7(4):1788-96) • Restricting mammal meat (J Transl Med, Apr 8, 2017; 15: 73), refined carbohydrates (Diabetes Metab Syndr Obes, 2012;5:175-89), and fried foods (Amer Journal Clin Nutr, Aug 2014;100(2):667–675). See What You Eat Determines Your Microbiome
The Difference between Healthful and Harmful Colon Bacteria Colon bacteria eat the same foods that you do. The healthful bacteria are content to eat what you eat, so they stay in your colon and do not try to cross into your cells and bloodstream, but the harmful bacteria try to find different food by invading the cells lining your colon. Your immune system tries to defend you by producing huge amounts of white blood cells and chemicals that work to destroy the invading bacteria by punching holes in their outer membranes and trying to kill them. This constant invasion of your colon cells by harmful bacteria can cause your immune system to stay overactive. When your immune system stays active all the time (inflammation), it uses the same cells and chemicals that attack invading germs to attack and damage your own cells to increase risk for dementia, heart attacks, certain cancers, and other diseases.
Evidence that Inflammation Increases Dementia Risk Inflammation during midlife is associated with cognitive decline 20 years later (Neurology, Jan 13, 2019). A large prospective study showed that dementia is associated with anything that causes inflammation to damage blood vessels (diabetes, hypertension, smoking, lack of exercise, obesity), even in people who have not had a stroke (JAMA Neurology, August 7, 2017).
Another study showed that giving the healthful colon bacteria, Bifidobacterium breve, to people who suffered from mild cognitive impairment can improve mental functioning (J Prev Alz Dis, 2019;6(1):70-75). However, this may not be so easy to do because the types of bacteria that live in your colon are determined by what you eat and what you do so you cannot change colon bacteria permanently just by taking a dose of bacteria. To change the types of bacteria in your colon permanently, you may sometimes have to take antibiotics first to get rid of the harmful bacteria, and then create an environment in the colon that is conducive to growing healthful bacteria by making permanent changes in diet and lifestyle.
Four studies presented at the Alzheimer’s Association International conference in London (July 2018) showed that healthy older adults who followed a Mediterranean-type diet or the MIND diets reduced their risk for dementia by a third. These diets increase fish, fruits, vegetables, nuts, and whole grains, and restrict sugars and animal fats. See Diets Shown to Reduce Risk for Dementia
Heart Attack Prevention Measures Also Reduce Dementia Risk Just about every risk factor for a heart attack has been shown to also increase risk for dementia and you can reduce your risk for suffering from dementia by up to 70 percent when you follow the healthful habits that help to prevent heart attacks (JAMA, Aug 21, 2018;320(7):657-664): • eat an anti-inflammatory diet • avoid smoking, alcohol, and obesity • exercise, preferably every day • treat diabetes, high blood pressure and high cholesterol See Risk for Dementia Goes Down with Steps to Prevent Heart Attacks
My Recommendations Since recent studies show that dementia may be influenced to a large degree by the types of bacteria living in your colon, I recommend eating the foods that encourage growth of healthful bacteria and discourage the harmful types. Harmful colon bacteria can cause inflammation that can increase your risk for dementia as well as for heart attacks, strokes and certain cancers. You can reduce inflammation by: • eating a plant-based diet with a wide variety of vegetables, whole grains, beans, nuts and fruits • restricting red meat, processed meats, fried foods, sugar-added foods and all drinks with sugar in them • avoiding obesity • avoiding smoke and alcohol • exercising regularly If you are not already eating a healthful plant-based diet and engaging in regular exercise, check with your doctor and then try to start a new diet and exercise program as soon as possible.
ARYAN'S BLOG 