“The moral test of a government is how it treats those who are at the dawn of life, the children; those who are in the twilight of life, the aged; and those who are in the shadow of life, the sick and the needy, and the handicapped.” – Hubert Humphrey
passionate pachyderms
Pharmacist Steve steve@steveariens.com 502.938.2414
In July 2024, Joseph Zucchi, PA-C, MPAS, wrote about how stigma and misconceptions were creating barriers to GLP-1 obesity medication uptake, on top of systemic barriers like high costs and inadequate insurance coverage. As part of our review of the past year’s biggest events, Zucchi revisited this topic to share his perspective on the proposal from the Centers for Medicare & Medicaid Services (CMS) to expand coverage of these life-changing medications.
Imagine a disease so prevalent it affects more than two-fifths of the adult population and one-fifth of children, yet its most effective treatments remain out of reach for those who need them most. This is the reality of obesity, a condition that drives chronic disease but is met with barriers to care at every turn. Obesity isn’t a mere lifestyle choice or lack of willpower; it’s a complex, chronic disease that heightens the risk of many of the most common chronic conditions: diabetes, heart disease, hypertension, osteoarthritis, and more.
Yet, despite the power of GLP-1 anti-obesity medications to reduce these risks, many insurers continue to deny coverage, leaving millions of Americans to fend for themselves.
Obesity: The Most Costly and Preventable Health Risk Factor
Obesity affects over 40% of American adults, making it one of the most prevalent chronic diseases in the U.S. This disease carries more than just physical weight — it costs us in quality of life, productivity, and billions of dollars in healthcare expenses. It burdens our hospitals and our health system, and, most importantly, it leads to unnecessary suffering and premature death. Obesity-related conditions cost the U.S. over $170 billion annually and that number is only growing.
Obesity medications, particularly GLP-1 receptor agonists like semaglutide (Wegovy, Ozempic) and tirzepatide (Zepbound, Mounjaro), have changed the landscape of obesity treatment. These drugs address the physiological drivers of obesity by curbing appetite, reducing food cravings, and improving insulin sensitivity. Beyond only helping people lose weight, these drugs are approved for type 2 diabetes and sleep apnea, and can reduce the risk of heart disease and possibly obesity-related cancers.
Yet, despite the health benefits, less than half of private and public insurance plans currently offer coverage for anti-obesity medications.
A Promising Step Forward
A potential turning point came in November, when the White House announced a proposal to expand Medicare and Medicaid coverage for obesity medications. This long-overdue change could provide access to life-changing medications for an estimated 7.4 million Americans
Historically, Medicare has excluded drugs used for weight-loss from its coverage, leaving millions of older Americans without affordable options for treatment. This exclusion has also made these drugs an optional drug benefit for Medicaid programs, leading to variation by state.
Under this new proposal, CMS would permit coverage of anti-obesity medications for the treatment of obesity when such drugs are indicated to reduce excess body weight and maintain weight reduction long-term for individuals with obesity.” This would not apply to patients who are overweight but who don’t have obesity. The plan could save about 75% of the cost for Medicaid beneficiaries, and up to 95% of the out-of-pocket costs for Medicare enrollees, reducing financial barriers to treatment.
This proposed rule signals an important shift in the federal approach to obesity management, aligning with the medical community’s consensus that obesity is a chronic disease requiring long-term care. It also highlights the economic and ethical imperative of addressing obesity proactively, rather than reactively.
The Double Standard of Coverage
Even with this encouraging progress, the private insurance landscape remains inconsistent. Insurers readily cover medications for high blood pressure, diabetes, and high cholesterol — diseases often linked to obesity — but frequently balk at covering treatments for obesity itself. This double standard is akin to offering treatment for a heart attack but denying preventive care to avoid it.
Why does a medication become “worthy” of coverage only after someone’s health has declined to the point of needing multiple drugs to manage preventable diseases?
The reluctance to cover obesity medications has consequences that extend far beyond individual patients. Untreated obesity costs employers billions in reduced productivity and contributes to rising rates of chronic diseases. Worse, the lack of coverage drives some patients to seek cheaper, unregulated alternatives, such as compounded or counterfeit drugs. These risky options lack FDA oversight and can lead to overdose and severe side effects. By denying coverage, insurers are not only failing their members but also exacerbating public health risks. Finally, denying coverage reinforces harmful stereotypes. One of the most damaging misconceptions about obesity is that it’s merely the result of poor personal choices, and critics label these medications as a “quick fix.” By expanding private insurance coverage of GLP-1 medications, insurers can align with the medical societies and federal agencies that recognize obesity as a disease.
A Path Forward
The White House’s proposal is a major step in the right direction, but it also underscores the need for broader systemic change.
Beyond insurance plans, pharmaceutical companies must also work to make these medications more affordable, helping to ensure that access isn’t limited by cost. Failing to promote affordability across the board perpetuates our reactive, expensive healthcare model that treats symptoms rather than root causes.
This is a pivotal moment for healthcare in America. The proposed rule from the White House offers hope for millions struggling with obesity, but it must be matched by action from private insurers. Obesity is a disease, and it’s time everyone treats it as one. Our healthcare system cannot afford to turn a blind eye to the preventive power of anti-obesity medications.
Back in the day, when I was in pharmacy school we were taught that we were an IMPORTANT PART OF THE SYSTEM. We were to make sure that the pt was not allergic to a new medication(s), the new medication(s) could cause some serious drug to drug interaction – especially a level 1 interaction, or the dose was too HIGH or too LOW! Back in the day, if I was not sure about the pt’s new medication(s) and the three major “don’t go there”. I had my best luck with trying to get the prescriber to make some changes/adjustments to what he/she had prescribed, was to tell the prescriber that the FDA professional literature did not support whatever I had a question about. I found that more prescribers would reconsider their choices. As I matured, I changed my tactics. I would ask the prescriber, if the could help me understand why I shouldn’t be concerned about whatever he/she was prescribing for this pt?
I took the position, that if the prescriber justified his beliefs, I documented that I spoke with the prescriber and prescriber has no interest in changing the pt’s prescription. I would also consult with the pt to my concerns of what the prescriber had written for them and whatever adverse events that they need to be on the lookout for. If things “went off the rails” for the pt. The prescriber and the pt made their own decisions and I had CYA myself.
Below is a email that Dr Ibsen sent me and asked me to share!
Kirsten was fired from her job.
I spent several hours of my time, finagling faxes and emails and FMLA forms.
I am beyond upset about this.
Kirsten has allowed me to share this story I am sending it to Steve Ariens For his blog to publish
This is a sickening situation. She came to me for help because her pain was untreated due to her severe inflammatory illness: ankylosing spondylitis.
Her previous doctor would only give her 10 mg of oxycodone four days a day.
At her request, I put her on 15 mg of oxycodone four times a day.
Her most recent prescription the pharmacist refused to Phil saying “I don’t know why she has to come to this Pharmacy”
This was very upsetting and destabilizing for Kirsten.
Eventually, she was fired from her job because of it.
A Ankylosing spondylitis
P Because of an interruption in her care, she lost her job. So now we have a person instead of working for a living and supporting her six-year-old daughter she now has to either look for work or take unemployment or file for disability. She was stable until this incident happened with her pharmacist.
I’m not sure what legal options Kirsten has, but I’m suggesting she talked to the insurance commissioner in the state of Montana. I thought it would also be a good idea for her to file a complaint against this pharmacist with the board of pharmacy because the pharmacist got her fired from her job. Whether or not she has a torque case or confined representation that will be up to Kirsten and her legal advisor.
Right now, I can categorically say she’s without work as a single mother because of the actions of her pharmacist.
Kirsten was fired from her job.
I spent several hours of my time, finagling faxes and emails and FMLA forms.
I am beyond upset about this.
Kirsten has allowed me to share this story I am sending it to Steve Ariens For his blog to publish
This is a sickening situation. She came to me for help because her pain was untreated due to her severe inflammatory illness: ankylosing spondylitis.
Her previous doctor would only give her 10 mg of oxycodone four days a week.
At her request, I put her on 15 mg of oxycodone four times a day.
Her most recent prescription the pharmacist refused to Phil saying “I don’t know why she has to come to this Pharmacy”
This was very upsetting and destabilizing for Kirsten.
Eventually, she was fired from her job because of it.
A Ankylosing spondylitis
P Because of an interruption in her care, she lost her job. So now we have a person instead of working for a living and supporting her six-year-old daughter she now has to either look for work or take unemployment or file for disability. She was stable until this incident happened with her pharmacist.
I’m not sure what legal options Kirsten has, but I’m suggesting she talked to the insurance commissioner in the state of Montana. I thought it would also be a good idea for her to file a complaint against this pharmacist with the board of pharmacy because the pharmacist got her fired from her job. Whether or not she has a torque case or confined representation that will be up to Kirsten and her legal advisor.
Right now, I can categorically say she’s without work as a single mother because of the actions of her pharmacist.
UPDATE Sunday 6:50 PM (EST): Our outside cameras around our house, it looks like it just started raining and the ambient temp is 26F. Educated guess is that it is FREEZING RAIN. To point, we still have electricity from Duke Energy.
They are forecasting a major weather event for our area. Because of the Ohio river near us, that is a “huge heat sink” and since Barb & I have lived in the area all our life, it can help shift a weather front a mile or so to 10s of miles.
The weather is now scheduled to encroach our area around 7 AM tomorrow ( Sunday) and continue on until late on Monday.
They tell us that we are on the edge of snow/ice line. South of us may get up to 0.75″ of ICE and we may get up to 0.5″ of ice. We are suppose to get some snow first, then the freezing rain, and then some more snow – up to 6″, and somewhere along the way we may get some sleet. North of us – up towards Indianapolis may get up to 12″ of snow.
Regardless of what happens, we will be fine. We have a 20Kw whole house generator and abt 300 gal of propane in a buried tank in our yard to feed our generator and our central furnace.
Our generator is a auto-start, if Duke Energy’s system fails because of the ice, it will start automatically after abt 15 second. It automatically “exercises” itself every week – on Wednesday – and runs for 12 minutes. I checked the “log” on the generator a couple of days ago and it ran for its scheduled 12 minutes on Wednesday.
If/when the electricity fails, I am not sure if we will have cable/internet and/or cell service. So I am writing this now and when/if it all starts tomorrow, I will be able to just hit SEND.
UPDATE –This Pt posted a updated last night that SHE IS OK!
State Attorney Generals have sued the 3 major drug wholesalers and major chain pharmacies and getting them to agree to pay millions/billions in fines because – according the DOJ/DEA – they were accused of contributing to our fabricated Rx opioid/opiates crisis. They also agreed to sell/dispense fewer controlled Rx meds to pharmacies and pharmacies dispense fewer Rx controlled meds to pts. Totally disregarding the valid medical necessity of any pts.
Here is a 8 page synopsis of the nearly 600 page agreement with the three major drug wholesalers – that control abt 85% of the market.
The 3-4 major PBMs are financially straggling community pharmacies – both chains and independent pharmacies. I have read where for the first time in nearly 10 years the DEA is not going to reduce pharma production quotas in 2025. Which suggests to me, that the state AGs agreement with the three major wholesalers and the major chain pharmacy, along with what appears that all the Rx controlled meds that have been allocated/rationed to all those pharmacies that are closing their doors for good. Are not being reallocated to the community pharmacies that are still open, but are just dropped out of the distribution channels.
About a third of America’s pharmacies have closed since 2010 – abt 20,000 pharmacies. https://www.usnews.com/news/health-news/articles/2024-12-04/almost-a-third-of-u-s-retail-pharmacies-have-closed-since-2010. Just imagine the number of controlled Rxs meds are no longer available for pharmacies to order from their drug wholesaler. It appears that more and more chronic pain pts have been pushed to the “end of their rope” with few or no pain management meds. As the woman who made the post below.
I’m done. I’ll can’t take this anymore. Love you all and please take care.
Esophagectomy outcomes trended in the wrong direction at hospitals owned by private-equity companies, a review of more than 9,000 cases showed.
Statistically significant differences existed for 30-day mortality, any complication, serious complications, and failure to rescue, all favoring non-equity hospitals. Private-equity ownership was associated with lower procedural volume, although only 5.5% of all cases came from private-equity hospitals.
Additional studies are required to identify drivers of the outcome disparities, improve performance, and inform policy decisions involving allocation of care for select surgical procedures, reported Jonathan Williams, MD, of the University of Michigan in Ann Arbor, and co-authors in JAMA Surgeryopens in a new tab or window.
“These findings suggest that poorer postoperative outcomes at private equity-acquired health centers may be attributed to characteristic structural differences associated with private equity acquisition,” the authors stated.
“Our sensitivity analysis, which analyzed comparative outcomes for similarly low-volume non-acquired and private equity-acquired health centers, showed a persistence in worse 30-day mortality and any complication rates for patients undergoing esophagectomy at private equity-acquired centers,” they added. “This finding suggests that there are additional contributing institutional factors at play at private equity-acquired health centers than simply a volume-outcome association for esophagectomy care.”
Structural elements potentially contributing to the outcome disparities might include intensive care unit organization and multidisciplinary care teams, which have been linked to fewer adverse events, as well as failure to rescue, nurse-to-patient ratio, and teaching hospital status.
Failure to rescue has received increased attention in surgical outcomes research, particularly for high-complexity procedures, Williams and colleagues noted. The outcome is based on the theory that the incidence of complications is not the primary driver of postoperative mortality, but instead delays or omissions in recognition and treatment of complications.
“The results of this study both confirm this association and show an association between hospital acquisition status and failure to rescue,” the authors stated.
The study was limited to Medicare patients, and older patients have an increased risk of complications, noted Aaron R. Dezube, MD, and Virginia Litle, MD, both of St. Elizabeth’s Medical Center in Brighton, Massachusetts, in an accompanying commentaryopens in a new tab or window. Additionally, the complication rates were low. As such, the findings might have limited generalizability to younger patients and high-volume academic centers.
Despite the limitations, the sensitivity analysis showed that non-acquired hospitals outperformed private equity-acquired facilities.
“The message from this article is the necessity to keep an eye not only on esophagectomy outcomes, but also on all complex surgical procedures among hospital types, and to raise the alarm if needed,” Dezube and Litle wrote. “Either private equity-acquired hospitals need to invest in quality databases, hire more staff, and educate staff on perioperative care, or they need to recognize the private inequity they are providing for complex cases.”
Private equity acquisition of health systems has increased involvement in the management of acute-care hospitals, Williams and co-authors noted in their introduction.
“The impetus of private equity acquisition of a healthcare institution is to directly manage and modify care delivery operations with a central goal of maximizing profit and limiting costly inefficiencies,” they continued. “As private equity acquisition of health systems has become more prevalent, both professional physician societies and governmental agencies have called for further investigationopens in a new tab or window of the association of these practices with care quality.”
Growing involvement of private-equity interests in hospital management has created a need to examine associations between private-equity acquisition and the quality of care for complex surgical procedures, such as esophagectomy.
Toward that end, the authors analyzed data from the Medicare Provider Analysis and Review to identify beneficiaries 65 or older who underwent elective esophagectomy from January 2016 through December 2020. They searched the Agency for Healthcare Research and Quality (AHRQ) Compendium of U.S. Health Systems to identify centers acquired by a private-equity entity. Finally, they linked the American Hospital Association Annual Survey to the AHRQ compendium by means of facilities’ unique CMS Certification Number.
During the study period, 954 centers performed esophagectomy, consisting of 132 private equity-acquired and 822 non-acquired centers. The number of hospitals performing esophagectomy declined over the study period. As compared with non-acquired centers, private equity-acquired hospitals had a lower annual esophagectomy case volume (2 vs 7, P<0.001), lower nurse-to-patient ratio (7.9 vs 9.6, P<0.001), were less likely to be a teaching institution (3.8% vs 24.5%, P<0.001), and more likely to be concentrated in the South (60.2% vs 32.8%) and West (27.8% vs 22.5%, P<0.001).
The analysis included 9,462 esophagectomy procedures, 517 (5.5%) of which were performed at private equity-acquired hospitals. Comparison of outcomes for non-acquired versus private equity-acquired hospitals produced the following results:
30-day mortality: 4.9% vs 8.1%, OR 1.82, P=0.002
Serious complication: 14.3% vs 17.5%, OR 1.35, P=0.03
Any complication: 30.1% vs 36.6%, OR 1.46, P=0.001
Failure to rescue: 3.4% vs 5.9%, OR 1.86, P=0.004
Readmission: 19.2% vs 21.1%, OR 1.13, P=0.28
“Our findings suggest that center-level factors outside of case volume alone may influence outcomes for patients undergoing high-complexity operations, which may better inform center designations by advocacy groups who have historically been focused on case volume alone,” the authors stated in their conclusions. “Further investigations into structural drivers of outcome differences at private equity-acquired health centers are necessary to inform potential regulations for esophagectomy care and other similar high-complexity surgical conditions.”
I got a phone call yesterday. Actually this young woman was trying to send me a text message, pushed the wrong button(s) and ended up calling me.
She was probably in her 30’s, she said she had a 12 y/o who had developmental issues. She told me that she had been diagnosed with a STAGE 4 CANCER. She was being treated at one of those very large very recognizable MAJOR Health care system – east of the Mississippi.
She told me that she was told a few months ago that her cancer WAS CURED and they would start to reduce her pain management. Then a month or so ago, they told her that they were wrong, but they were going to continue reducing her pain management meds and her prognosis was MAYBE – ONE YEAR!
Maybe the doctors are more concerned about the $$ that are going to be expended on a terminal pts. So I asked www.perplexity.ai: how much money is typically spent on healthcare in a person last two years of life.
I referred her to a physician who I know is very emphatic and taking on pts who he refers to as “pain refuges”. By referring, I mean that I gave her the doc’s two phone numbers & email and after I got off the phone with her… and call this doc and gave him a “heads-up” and the Cliff’s notes of what her health issues were!
how much money is typically spent on healthcare in a person last two years of life
Healthcare spending in the last two years of life is substantial and varies across countries, but generally represents a significant portion of lifetime healthcare expenditure. Here’s an overview of the typical costs:
## United States
In the US, healthcare spending in the final years of life is particularly high:
– The average healthcare cost in the last 12 months of life is approximately $80,000[4]. – For the last 3 years of life, the total healthcare expenditure averages around $155,000[4]. – A more detailed study found that the mean total healthcare cost in the last 2 years of life was $316,579 in 2000 dollars[1].
I remember when we had the pharmacy and Home Medical Equipment business and a female – who was a nurse – had come into town because her Father was dying of Lung Cancer. She was wanting to get her Father home Oxygen and she had talked to her Father’s pulmonologist about home oxygen and she said that the pulmonologist response to her was “.. he is dying, there is really no need “. I don’t remember what we did, but I know my home care staff would do just about anything to get a pt’s needs taken care of.
how many people become chronic pain patients every day from accidents, injuries or new diagnosis of a painful disease
Based on the search results, approximately 52.4 new cases of chronic pain occur per 1,000 persons per year in the United States[4][6]. This translates to about 143 new cases of chronic pain per day per million people. The USA has abt 340 million population- translates to abt 50,000 new chronic pts every year.
To put this in perspective:
1. The incidence rate of chronic pain (52.4 cases per 1,000 person-years) is higher than that of other common chronic conditions: – Diabetes: 7.1 cases per 1,000 person-years – Depression: 15.9 cases per 1,000 person-years – Hypertension: 45.3 cases per 1,000 person-years[4]
2. Among those who reported non-chronic pain in 2019, about 14.9% developed chronic pain by 2020, highlighting the importance of early pain management[4].
3. Chronic pain is highly persistent, with 61.4% of those reporting chronic pain in 2019 still experiencing it a year later[4].
4. For high-impact chronic pain (HICP), which limits life or work activities, the incidence rate is 12.0 cases per 1,000 person-years[6].
5. Motor vehicle accidents and work-related injuries are common causes of chronic pain[5]. A study found that 44% of individuals who had sustained severe accidental injuries reported accident-related pain 3 years after the incident[5].
These statistics underscore the significant burden of chronic pain in the U.S. population and emphasize the need for effective early interventions and pain management strategies[4][6].
It is a fairly well accepted theory that under/untreated pain can/may cause elevated blood pressure and also that the 4 or 5 different categories of Pharma produced blood pressure meds will not do little/nothing to lower the pt’s blood pressure, because there is a separate biological pathway that is used to elevate blood pressure that the pharma meds do not address.
It is a known fact that high blood pressure can cause kidney damage. IF a pt has been told that their pain meds are going to be lowered. Would it be a good idea for the pt to request lab test for these substances that are generated by the kidneys – to establish a base line – and when the pt’s blood pressure goes up – especially to HYPERTENSIVE CRISIS LEVEL to ask that they be run again and if they have changed dramatically and especially if they are outside of the normal range, would it suggest that the pt is/could be experiencing kidney damage because of their under/untreated pain. There is a number of damage to a pt’s body caused by elevated blood pressure, and the higher the blood pressure the more likely the damage will progress at a more rapid rate. The DEA has always “hung their hat” on the claim that there is no way to document that a pt is dealing with pain and/or the intensity of their pain. If the pt has had their pain meds reduced and their blood pressure has gone up – especially to HYPERTENSIVE CRISIS LEVEL and their lab values from substance created by the kidney are now outside of normal values, could we back the DEA down? Would it be a good idea to put the pt back on their pain meds for 30 to 60 days and see if the pt’s blood pressure goes back down. Then perhaps it is time for some clinical trials to establish the relationship between under/untreated pain, high blood pressure and the lab values of those specific substances created by the kidneys being out of range. All practitioners are suppose be healers and allowing a pt to be at risk of all the potential damages of high blood pressure because of the failure to treat the pt’s chronic pain. The same theory should apply to Pharmacist who claim that they are “not comfortable” to fill pain meds for a pt. Could some clinical trials turn the CDC dosing guidelines UPSIDE DOWN and be justification to have those guidelines and the MME system TOSSED IN THE TRASH?
Are there any substances produced by the kidneys that will affect or control blood pressure
Yes, the kidneys produce several substances that affect and control blood pressure:
1. Renin: This enzyme is produced by special cells in the kidneys and released into the bloodstream when blood pressure drops too low[2]. Renin plays a crucial role in activating the renin-angiotensin-aldosterone system (RAAS), which regulates blood pressure[3].
2. Angiotensin: While not directly produced by the kidneys, angiotensin is part of the RAAS. Renin from the kidneys acts on angiotensinogen (produced by the liver) to form angiotensin I, which is then converted to angiotensin II. Angiotensin II causes blood vessel constriction, increasing blood pressure[6].
3. Urotensin: The kidneys produce urotensin, which causes blood vessels to constrict and helps raise blood pressure[7].
4. Nitric oxide and prostaglandins: These substances, produced by the kidneys, help regulate blood flow and pressure within the kidneys and can influence overall blood pressure[1].
The kidneys also play a crucial role in regulating blood pressure by controlling sodium excretion. When too little sodium is excreted, blood pressure is likely to increase[7]. Additionally, the kidneys’ ability to excrete sodium in response to elevated blood pressure (pressure natriuresis) is a major factor in long-term blood pressure regulation[1][3].
Is there a way to detect those substances in the patient’s blood
Yes, there are several ways to detect kidney-produced substances that affect blood pressure in a patient’s blood:
## Renin Test
A renin test, often performed alongside an aldosterone test, can measure the levels of renin in the blood[1][5]. This test is particularly useful for:
– Diagnosing the cause of high blood pressure, especially in younger patients – Determining if high blood pressure is related to salt sensitivity – Identifying potential adrenal gland issues
The test involves taking a blood sample, typically in the morning when renin levels are highest[1].
## Angiotensin II and Angiotensin (1-7) Test
This test directly measures the levels of Angiotensin II and Angiotensin (1-7) in plasma using liquid chromatography-tandem mass spectrometry (LC-MS/MS)[3]. It can be used as:
– An adjunct to plasma renin activity and aldosterone measurements – A tool for investigating potential associations with outcomes of coronavirus infection
## Urotensin II Test
While less common, urotensin II levels can be measured in blood serum. This test has been used in research settings to study conditions like inflammatory bowel disease and may have implications for blood pressure regulation[4].
## ACE (Angiotensin-Converting Enzyme) Test
The ACE test measures the level of angiotensin-converting enzyme in the blood[7]. This enzyme plays a crucial role in the renin-angiotensin-aldosterone system, which regulates blood pressure.
When conducting these tests, it’s important to consider factors that may affect the results, such as:
– Time of day – Patient’s body position – Medications (especially blood pressure medications) – Salt intake – Stress levels – Pregnancy
Healthcare providers may need to adjust a patient’s medications or diet before conducting these tests to ensure accurate results[1][6].
would those substances be higher or lower in the pt’s blood if the pt’s blood pressure in higher
In patients with higher blood pressure, the levels of substances produced by the kidneys that affect blood pressure can vary:
## Renin
Renin levels can be either high or low in patients with high blood pressure, depending on the underlying cause:
– High renin: This may indicate salt sensitivity or kidney problems[3][5]. – Low renin: This could suggest a condition called low renin hypertension (LRH) or primary aldosteronism[7][3].
## Angiotensin II
Angiotensin II levels are typically higher in patients with hypertension:
– Higher than normal angiotensin II levels cause excess fluid retention and high blood pressure[6]. – Elevated angiotensin II can contribute to heart enlargement in hypertensive patients[6].
## Aldosterone
Aldosterone levels can also be elevated in some forms of hypertension:
– High aldosterone with low renin may indicate primary aldosteronism, a cause of high blood pressure[3][5]. – Elevated aldosterone causes the kidneys to retain more water and salt, increasing blood volume and pressure[5].
## Angiotensinogen
Recent research has shown a positive association between angiotensinogen levels and blood pressure:
– Higher angiotensinogen levels are associated with higher odds of prevalent hypertension[2]. – The relationship between angiotensinogen and blood pressure appears to be stronger in males compared to females[2].
It’s important to note that the relationship between these substances and blood pressure is complex and can vary depending on the specific cause of hypertension. Measuring these substances, particularly through tests like the renin activity test and aldosterone levels, can help healthcare providers determine the underlying cause of high blood pressure and guide appropriate treatment.
what are the normal lab values for these substances Renin, Angiotensin, Urotensin, renin-angiotensin system activity, Nitric oxide and prostaglandins
Based on the provided search results, here are the normal lab values for some of the substances you inquired about:
## Renin
The normal range for Plasma Renin Activity (PRA) in adults varies slightly depending on the source:
– 0.7 to 3.3 ng/mL/hr (or 0.7 to 3.3 mcg/L/hr in SI units)[1] – 0.2 to 1.6 ng/mL/hour while lying down and 0.5 to 4.0 ng/mL/hour while standing[4]
## Nitric Oxide
For serum nitric oxide metabolites (NOx):
– Men: 11.5 to 76.4 micromol/L – Women: 10.1 to 65.6 micromol/L[3]
For exhaled nitric oxide (FeNO):
Values below 25 parts per billion (ppb) are considered low
Values above 50 ppb are considered high and consistent with type 2 inflammation
It’s worth noting that nitric oxide levels can vary based on factors such as age, height, gender, and certain medical conditions.
## Prostaglandin D2
For adults:
– 35-115 pg/mL[7]
## Angiotensin, Urotensin, and Renin-Angiotensin System Activity
The search results do not provide specific normal values for angiotensin, urotensin, or direct measurements of renin-angiotensin system activity.
It’s important to note that “normal” values can vary depending on the specific laboratory, testing method, and patient factors such as age, sex, and medical conditions. Additionally, some tests, like the aldosterone-renin ratio (ARR), use combinations of these values for diagnostic purposes. For example, an ARR greater than or equal to 20 with serum aldosterone greater than or equal to 15 ng/dL may indicate probable primary aldosteronism[2].
Flawed Drugs: Indian drugmaker Glenmark Pharmaceuticals issued a string of recalls for pills that didn’t dissolve properly. In one case, the company said the problem could be deadly.
Anemic Response: Since the recalls, the FDA still hasn’t visited the factory in India that manufactured the drugs or stopped Glenmark from shipping other drugs made there to the U.S.
Death Reports: Glenmark got reports of three deaths of patients who took the recalled pills. The cause is unclear. A lawsuit alleges the pills killed a Maine woman. Glenmark denies it.
The drug potassium chloride has been on the market for decades, widely prescribed to help the nerves and muscles — including the heart — function properly in patients with low potassium. Too much of it, however, can kill you.
At high doses, it is so effective at stopping the heart that some states have used injections of it for executions.
So the danger was obvious in May, when Indian drugmaker Glenmark Pharmaceuticals recalled nearly 47 million capsules for a dire flaw: The extended-release medication wasn’t dissolving properly, a defect that could lead to a perilous spike in potassium. The U.S. Food and Drug Administration deemed it the most serious kind of recall, a defective drug that had the potential to kill people.
At the time of the recall, the FDA, which is charged with protecting Americans from unsafe drugs, was already on notice about troubles at Glenmark.
The Mumbai-based company had four recalls in the previous eight months and would have two more in following months, all for the same dangerous tendency for pills to dissolve improperly. All the faulty medications were made at the same Glenmark factory in central India, government records show.
Yet the FDA hasn’t stopped Glenmark from shipping pills from the factory to American patients. Nor did it send investigators to the Indian facility to figure out what had gone wrong. Its last inspection of the plant was more than four years ago, before the COVID-19 pandemic.
“They should have been camping out there,” said Patrick Stone, a former FDA inspector who now advises pharmaceutical companies.
Since the May recall, Glenmark told regulators it has received reports of three deaths, three hospitalizations and four other serious problems in patients who took the recalled potassium chloride capsules, FDA records show. It’s unclear if the drug was the cause.
A federal lawsuit alleges that the pills were responsible for the death of Mary Louise Cormier, a 91-year-old woman in Maine. A letter informing her of the recall arrived three weeks after she died.
The FDA’s anemic response underscores longstanding weaknesses in the way the agency oversees the safety of generic medications manufactured in foreign factories. The agency failed to act on clear patterns of trouble, was slow to warn the public about the potentially deadly pills and never mentioned that millions of them had been sold to consumers.
From the day of the first recall in October 2023 through the next 12 months, the FDA oversaw 22 recalls for drugs that didn’t dissolve correctly and could cause harm, agency data shows. That single Glenmark factory was responsible for more than 30%, a ProPublica analysis found.
“The FDA is always late to respond,” Stone said. “This should have been dealt with immediately.”
The FDA has long said it polices foreign plants by prioritizing inspections based on risk. For routine inspections, the agency uses a computer model that weighs prior recalls, the date and results of the most recent inspection, and other factors. FDA employees decide when to send investigators for more urgent visits based on signs that something is amiss. But the agency would not explain why Glenmark’s string of recalls didn’t meet that threshold.
What’s more, federal regulators were aware of significant deficiencies at three of Glenmark’s four other factories that have made drugs for the U.S. market, FDA records show. The breakdowns were so grave at one plant that the FDA barred drugs made there from entering the country.
The FDA’s failings date back decades. In her book “Bottle of Lies,” journalist Katherine Eban exposed the agency’s struggles to identify and combat corruption in the global pharmaceutical industry amid a huge demand for cheap generic drugs in the U.S. The book detailed how a whistleblower in 2005 started feeding the FDA insider details about unsafe medications at a different Indian drugmaker, but it took federal officials almost nine years to wrap up a criminal case.
The majority of the factories making drugs for U.S. patients are in other countries, many of which churn out the generics that make up more than 90% of prescriptions filled here. Yet the investigative arm of Congress has repeatedly found that the FDA has too few inspectors to adequately oversee these plants.
The consequences of lax oversight were unmistakable when the U.S. Centers for Disease Control and Prevention reported in 2023 that four people died and others had to have their eyeballs removed after they used contaminated eyedrops made by a different Indian company. The FDA had never inspected that factory before people got sick.
Fed up with what they called “institutional weaknesses and dysfunction” in the oversight of foreign drugmakers, the House Committee on Energy and Commerce in June demanded that the head of the FDA turn over documents about inspections in India and China.
A spokesperson for the FDA declined to answer questions about the Glenmark recalls or inspection history, saying the agency could not publicly discuss potential or ongoing compliance matters. “When there are quality issues identified that could result in harm, patients should rest assured that the FDA does everything within our authority to work with firms to ensure a recall is conducted most effectively,” FDA spokesperson Amanda Hils wrote in an email. A recent reorganization, she added, “will ultimately help the agency be more efficient and cohesive in our inspection and investigation efforts.”
Officials with Glenmark also declined to answer detailed questions. In a court document, the company denied being responsible for the death of Cormier, the woman in Maine.
“Due to the ongoing litigation, we are unable to provide further information at this time but Glenmark is fully committed to maintaining the highest standards of quality and regulatory compliance in all our operations,” a Glenmark spokesperson wrote in an email. “We continue to work closely with the FDA to ensure compliance with manufacturing operations and quality systems.”
Overseas compliance with U.S. manufacturing standards is crucial in a drug market where foreign factories like the ones operated by Glenmark make a wide range of injections and pills that treat some of the most vulnerable patients in the U.S., including those with cancer, heart disease, epilepsy and kidney ailments. What happens in a factory a half a world away can have deadly consequences.
Glenmark’s major troubles with the FDA began in 2019 at a factory far from the one that made the potassium chloride.
That spring, FDA investigators went to the company’s Himachal Pradesh plant in northern India and reviewed more than 100 complaints about products made there: A steroid cream was gritty, a medication was watery, and tubes of medicines were cracked and punctured
The inspectors found so many problems at the facility that the agency sent Glenmark what’s known as a warning letter, a disciplinary tool the FDA uses to lay out significant violations of federal requirements and demand changes. Too often, Glenmark didn’t identify the root causes of problems and failed to come up with plans to prevent the same defects in the future, the director of the FDA’s Office of Manufacturing Quality wrote to Glenmark’s chairman.
“Your quality system for investigations is inadequate and does not ensure consistent production of safe and effective products,” the FDA official wrote.
This became a recurrent theme for Glenmark in subsequent years as FDA investigators dinged one plant after another for failing to follow manufacturing processes that prevent defective drugs from winding up in American medicine cabinets.
FDA records show the problems stretched from India to the U.S., where Glenmark has a factory outside of Charlotte, North Carolina. In August 2021, Glenmark recalled every product it made at that plant. The recall notices said they failed to meet manufacturing standards.
In the spring of 2022, FDA investigators spent more than a month in that factory, documenting 17 violations that resulted in a warning letter for that plant as well.
The problems snowballed in the fall of 2022. The FDA sent Glenmark’s chairman yet another warning letter, this time about its factory in Goa, India, which the agency said failed to thoroughly investigate discrepancies among batches of drugs and lacked the procedures necessary to ensure that its products had the strength, quality and purity that Glenmark claimed. And FDA officials were so concerned after a subsequent inspection of Glenmark’s Himachal Pradesh factory that they placed it on the agency’s dreaded import alert list, which allowed federal regulators to prevent drugs made there from entering the U.S.
At that point, three of the five Glenmark factories that had made drugs for American consumers were in trouble with the FDA.
But one plant has escaped scrutiny in the last few years: the Glenmark facility that made the recalled potassium chloride.
The factory, in Madhya Pradesh, India, previously had a mixed record with the FDA. The agency had sent inspectors every year between 2015 and 2020, finding problems in half the visits.
In 2018, the FDA asked Glenmark to voluntarily make improvements after inspectors found evidence that drafts of internal investigations were shredded in the quality department, among other deficiencies.
Subsequent inspections in September 2019 and February 2020, though, went well.
Then the COVID-19 pandemic hit, and the FDA put all but the most urgent inspections on hold. An Associated Press analysis this September found that about 2,000 pharmaceutical plants had not been inspected by the FDA in five years.
The FDA doesn’t have enough experienced investigators to figure out what’s wrong at factories where there are signs of trouble, said Peter Baker, a former FDA inspector who consults on pharmaceutical quality.
“It’s really difficult to be proactive when you don’t have people,” Baker said.
People familiar with FDA enforcement say inspectors are often frustrated because they have little say on which facilities they inspect. That decision is made by another arm of the agency that doesn’t have the same sort of on-the-ground view of what’s going on in factories.
Those who have the most to lose — the patients who could be endangered by defective pills — rarely, if ever, learn about the conditions inside the manufacturing plants. The FDA doesn’t make it easy for people to know where a drug is made, let alone whether it was by a factory with a concerning safety record.
To determine that the recalled Glenmark drugs were all made at the Madhya Pradesh factory, ProPublica matched drug-labeling records from the U.S. National Library of Medicine with details in two FDA databases. Because the FDA doesn’t routinely post its inspection reports online, ProPublica obtained these and other records from Redica Systems, a data analytics company that receives this information from the FDA through public-records requests.
The first in the string of recalls from the plant came in October 2023 for a drug that treats iron overload from blood transfusions. Days later, the company announced a second recall, this time for a medication for chest pain. Then came two more for capsules that treat high blood pressure. The potassium chloride recall was Glenmark’s fifth. Two more came after that, for a cholesterol-lowering drug and a rheumatoid arthritis medicine.
The only one mentioned on the FDA’s recalls website was the potassium chloride. In that case, the agency followed its practice of posting a press release from the drug company rather than writing its own alert for the public.
“Public notification is generally issued when a product poses a serious health hazard or has been widely distributed,” the FDA spokesperson wrote in an email.
Records show the agency determined that potential harm from taking the other pills Glenmark recalled was likely to be temporary or reversible. But it never told the public what that harm might be.
Mary Louise Cormier never knew her potassium chloride pills had been recalled.
On June 27, the 91-year-old was taken to the emergency room from her nursing home in Brunswick, Maine. She was lethargic and could give only soft, monosyllabic answers to questions, according to the lawsuit filed by one of her daughters.
A blood test showed that her potassium level was alarmingly high — so high that an emergency room doctor had the lab run the test a second time to make sure the result wasn’t a mistake, according to the lawsuit. A level above 6 millimoles per liter is considered a medical emergency. The tests showed Cormier’s level was 6.9, the lawsuit says.
Cormier — who had raised five children, cared for babies in the foster care system and once ran a day care out of her home — suffered cardiac arrest and died, the suit says.
The lawsuit, filed in federal court in Newark, New Jersey, accuses Glenmark of a “systematic disregard for drug safety” and alleges the company sold pills “more suitable for an execution” than for the vulnerable patients they were supposed to help. Cormier’s pharmacy confirmed that her pills came from recalled batches, the lawsuit says. The suit is seeking class-action status.
In a court filing, Glenmark denied the allegations. The company’s attorneys listed dozens of defenses, including that the injuries claimed were the result of preexisting or unrelated medical conditions and that the product contained an adequate warning. There can be other reasons for a spike in potassium, and ProPublica was unable to independently verify key details in the suit. Cormier’s daughter referred a reporter to her attorney, Aaron Block, who declined to release Cormier’s medical records, citing the early stage of the litigation.
It’s not clear when Cormier’s pharmacy first learned the pills could be dangerous, but news of recalls can often take time to reach pharmacists — and longer to get to patients. The suit says Cormier’s pharmacy dispensed the pills on June 25. That was the day the FDA posted the recall on its website and three days before Cormier died. Medicines in the U.S. often pass through distributors. The manufacturer is responsible for notifying its distributors, who then have to notify their customers and so on down the supply chain.
News of the recall didn’t reach Cormier’s family until three weeks after her death. As her family was preparing for her memorial, a letter arrived. Cormier’s health insurance company was writing with “important drug recall information” about her potassium chloride: “Our records show that you may have recently filled a prescription for this product.” The letter made it clear that the pills may cause high potassium levels, potentially leading to cardiac arrest and death.
Glenmark knew there was a problem with its potassium chloride at least a month before Cormier died.
On May 29, a Glenmark executive wrote a letter to distributors saying a batch of potassium chloride had failed to dissolve correctly in a test, so the company was issuing a recall. The executive told the distributors that the recall was “being made with the knowledge of the Food and Drug Administration” and used red capital letters to mark the notice “URGENT.” The letter was sent via FedEx overnight. But the company and the FDA didn’t tell the public at the time.
In late June, Glenmark recalled dozens more batches, including the pills that the lawsuit says Cormier took.
On June 25, about four weeks after the Glenmark executive had written to distributors, the FDA finally alerted the public.
Glenmark and the FDA declined to say why the initial recall in May didn’t include all of the faulty pills or why they didn’t tell the public sooner. Speaking generally, Hils, the FDA spokesperson, said that the agency does not have the authority to mandate recalls of most drugs, with a limited exception for controlled substances. The agency’s role, she said, is “to oversee a company’s recall strategy, assess the adequacy of the company’s action, and classify the recall.”
Since then, Glenmark has told the FDA about reports it received of the deaths, hospitalizations and other serious health problems in patients who took the recalled potassium chloride. Companies are required to file reports to the FDA’s Adverse Event Reporting System so the agency can monitor the safety of drugs. The FDA’s online database includes only bare-bones details, so ProPublica was unable to independently verify what happened in each case. While the FDA would not comment on these complaints, the agency generally warns, “For any given report, there is no certainty that a suspected drug caused the reaction.”
A majority of the reports said the patients suffered from abnormal heart rhythms, while the second-most-common complaint was of muscle problems. Glenmark’s public alert said that the recalled pills could cause irregular heartbeats and severe muscle weakness.
Glenmark’s top executives have told financial analysts on earnings calls that the company has invested in improvements to its factories.
The company’s troubles with U.S. regulators are so well known to investors that its compliance officer notified the National Stock Exchange of India in September that FDA inspectors had found no problems at one of its other factories in India. As the news spread, Glenmark’s stock jumped 9%.
It’s one of the first to accuse a data mining firm of helping a health plan overcharge
A western New York health insurance provider for seniors and the CEO of its medical analytics arm have agreed to pay a total of up to $100 million to settle Justice Department allegations of fraudulent billing for health conditions that were exaggerated or didn’t exist.
Independent Health Association of Buffalo, which operates two Medicare Advantage plans, will pay up to $98 million. Betsy Gaffney, CEO of medical records review company DxID, will pay $2 million, according to the settlement agreement. Neither admitted wrongdoing.
“Today’s result sends a clear message to the Medicare Advantage community that the United States will take appropriate action against those who knowingly submit inflated claims for reimbursement,” Michael Granston, a Department of Justice (DOJ) deputy assistant attorney general, said in announcing the settlement on December 20.
Frank Sava, a spokesperson for Independent Health, said in a statement: “The assertions by the DOJ are allegations only, and there has been no determination of liability. This settlement is not an admission of any wrongdoing; it instead allows us to avoid the further disruption, expense, and uncertainty of litigation in a matter that has lingered for over a decade.”
Under the settlement, Independent Health will make “guaranteed payments” of $34.5 million in installments from 2024 through 2028. Whether it pays the maximum amount in the settlement will depend on the health plan’s financial performance.
Michael Ronickher, an attorney for whistleblower Teresa Ross, called the settlement “historic,” saying it was the largest payment yet by a health plan based solely on a whistleblower’s fraud allegations. It also was one of the first to accuse a data mining firm of helping a health plan overcharge.
The settlement is the latest in a whirl of whistleblower actions alleging billing fraud by a Medicare Advantage insurer. Medicare Advantage plans are private health plans that cover more than 33 million members, making up over half of all people eligible for Medicare. They are expected to grow further under the incoming Trump administration.
But as Medicare Advantage has gained popularity, regulators at CMS have struggled to prevent health plans from exaggerating how sick patients are to boost their revenues.
Whistleblowers such as Ross, a former medical coding professional, have helped the government claw back hundreds of millions of dollars in overpayments tied to alleged coding abuses. Ross will receive at least $8.2 million, according to the Justice Department.
Ross said that CMS “created a bounty” for health plans that added medical diagnosis codes as they reviewed patients’ charts — and whether those codes were accurate or not “didn’t seem to bother some people.”
“Billions of dollars are being paid out by CMS for diagnoses that don’t exist,” Ross told KFF Health News in an interview.
Data Mining
DOJ’s civil complaint, filed in September 2021, was unusual in targeting a data analytics venture — and its top executive — for allegedly ginning up bogus payments.
DxID specialized in mining electronic medical records to capture new diagnoses for patients — pocketing up to 20% of the money it generated for the health plan, according to the suit, which said Independent Health used the firm from 2010 through 2017. DxID shut down in 2021.
Gaffney pitched its services to Medicare Advantage plans as “too attractive to pass up,” according to the Justice Department complaint.
“There is no upfront fee, we don’t get paid until you get paid and we work on a percentage of the actual proven recoveries,” Gaffney said, according to the complaint. Timothy Hoover, an attorney for Gaffney, said in a statement that the settlement “is not an admission of any liability by Ms. Gaffney. The settlement simply resolves a dispute and provides closure to the parties.”
‘A Ton of Money’
CMS uses a complex formula that pays health plans higher rates for sicker patients and less for people in good health. Health plans must retain medical records that document all diagnoses they highlight for reimbursement.
Independent Health violated those rules by billing Medicare for a range of medical conditions that either were exaggerated or not supported by patient medical files, such as billing for treating chronic depression that had been resolved, according to the complaint. In one case, an 87-year-old man was coded as having “major depressive disorder” even though his medical records indicated the problem was “transient,” according to the complaint.
DxID also cited chronic kidney disease or renal failure “in the absence of any documentation suggesting that a patient suffered from those conditions,” according to the complaint. Past conditions, such as heart attacks, that required no current treatment, also were coded, according to the DOJ.
The suit alleges that Gaffney said renal failure diagnoses were “worth a ton of money to IH [Independent Health] and the majority of people (over) 70 have it at some level.”
Ross filed the whistleblower case in 2012 against Group Health Cooperative in Seattle, one of the nation’s oldest managed-care groups.
Ross, a former medical coding manager there, alleged that DxID submitted more than $30 million in disease claims — many of which were not valid — on behalf of Group Health for 2010 and 2011. For instance, Ross alleged that the plan billed for “major depression” in a patient described by his doctor as having an “amazingly sunny disposition.”
Group Health, now known as the Kaiser Foundation Health Plan of Washington, denied wrongdoing. But it settled the civil case in November 2020 by agreeing to pay $6.3 million. The DOJ filed a second complaint in 2021, against Independent Health, which also used DxID’s services.
Ross said she lost her job after her suit became public in 2019 and was unable to secure another one in the medical coding field.
“It was rough at times, but we got through it,” she said. Ross, 60, said she is now “happily retired.”
False Claims
Whistleblowers sue under the False Claims Act, a federal law dating to the Civil War that allows private citizens to expose fraud against the government and share in any recovery.
At least two dozen such suits, some dating to 2009, have targeted Medicare Advantage plans for overstating the severity of medical conditions, a practice known in the industry as “upcoding.” Previous settlements from such suits have totaled more than $600 million.
The whistleblowers have played a key role in holding health insurers accountable.
While dozens of CMS audits have concluded that health plans overcharged the government, the agency has done little to recoup money for the U.S. Treasury.
In a surprise action in late January 2023, CMS announced that it would settle for a fraction of the estimated tens of millions of dollars in overpayments uncovered through its audits dating to 2011 and not impose major financial penalties on health plans until a round of audits for 2018 payments, which have yet to be done. Exactly how much plans will end up paying back is unclear.
“I think CMS should be doing more,” said Max Voldman, an attorney who represents Ross.
