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The FDA Is Ignoring Patients In Clinical Trials

Imagine having two daughters who both have a rare disease and watching them struggle — to be understood, to remember things, to learn, to be comfortable in social settings, to follow one-step directions, to be able to bond with friends and family.

Now, imagine a clinical trial showed promise for your older daughter. You notice a remarkable difference in her daily living, and suddenly, your home is more peaceful, and she is starting to thrive. The treatment is potentially life-changing. You now have hope for your older daughter and her younger sister.

But then, the medicine is potentially at risk of not even being reviewed by the U.S. Food and Drug Administration (FDA), let alone approved. As a parent, what would you do? What would you say to the FDA?

This is my family's story with galactosemia, a genetic disease that can be life-threatening for newborns and causes severe, lifelong complications. Galactosemia is an inherited disorder caused by the inability to break down a simple sugar in our diets and bodies called galactose, due to an error in the metabolism. When galactose isn't broken down, it causes a buildup of toxins that can lead to long-term complications, such as cognitive and developmental delay, memory issues, speech delays, behavioral challenges such as sensory processing disorder, learning disorders, tremors and seizures, and more. There are currently no treatment options approved for galactosemia, and until there are, I will continue to fight for my daughters, five-year-old Ansell and one-year-old Louise.

Galactosemia is an exhausting and devastating reality. It affects our entire family. Our voices, and the voices of all patients, parents and caregivers of a person living with galactosemia, need to be heard in the FDA's decision to approve or deny this treatment — a treatment that has changed my daughters' lives in every aspect measured by the trial.

The pediatric trial for govorestat (AT-007) started when Ansell was three years old. She was already showing severe symptoms, and I knew she needed to be in the trial. But I also knew it was going to take a huge commitment from her and our family. We had to take many days off work and travel to participate in regular study visits, where Ansell had to undergo days and days of difficult testing. Just to start the trial, Ansell had to get blood drawn 16 times before she could start. I can't begin to explain how hard those days were.

Since those first days of the trial, Ansell has continued to be a warrior. She has endured day-long home health visits with six blood draws a day and exhausting fasting windows. Our family, including our two older children, prioritized Ansell's participation in the clinical trial and made many sacrifices to support her.

Although this is not what I imagined our lives would be, I would do it again without flinching. Ansell and our family have given up a lot, because we believe that galactosemia is worth treating. We believe Ansell, and now Louise, deserve to live the lives most kids will get to live: making their own choices and financial decisions, pursuing careers they are passionate about, having families and living independently.

Although we didn't know whether Ansell was on active treatment or on a placebo during the trial, I saw marked improvement in her ability to express herself, remember friends' names, regulate her emotions and build relationships. I began to feel tremendous hope that govorestat could offer a more independent, fulfilling life for her and her younger sister.

The galactosemia community fought for govorestat to be approved a year and a half ago, under the FDA's accelerated approval pathway. Rare disease studies are at a disadvantage because of the small patient population sizes and the lack of previously validated clinical endpoints and knowledge about these conditions. The accelerated approval pathway is vital because it allows drugs that have been proven safe to be approved based on only biomarker data, such as the govorestat data showing it significantly decreased galactitol toxin. This would have allowed all galactosemia patients to be on therapy while additional outcomes, such as cognition and activities of daily living, were studied.

However, sadly, our community's urgent plea to the FDA for accelerated approval was denied without any explanation or feedback. Now, after a long wait, the placebo-controlled clinical trial evaluating clinical and functional outcomes is complete, and the data recently announced.

The govorestat trial used a composite endpoint evaluating improvement across speech, language, behavior and activities of daily living. It also evaluated cognition and tremor. The overall endpoint missed statistical significance but had a strong trend in the right direction. Measurements of speech and language did not reach statistical significance — likely because almost all patients in the study received speech therapy. However, both measurements of behavior and activities of daily living were highly statistically significantly improved with govorestat therapy. Improving activities of daily living is very meaningful, and includes things that we typically take for granted, like being able to dress, feed and bathe yourself. Improving behavioral symptoms is also important for kids living with galactosemia, and includes things like reducing disruptive actions in school, participating in social activities, and developing and maintaining friendships.

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On behalf of the galactosemia community and on behalf of my daughters, I strongly implore the FDA to consider the patient voice when determining review and approval of govorestat for the treatment of galactosemia. No one knows a child better than his or her parents, and the improvements I have seen in Ansell cannot be denied. A treatment is needed now for our community, and for my daughters.

We shouldn't needlessly wait. Ansell and Louise, and the broader community of people living or caring for someone with galactosemia, should not be denied access to a potentially life-changing treatment that can help them now.

Brittany Cudzilo is the vice president of the Galactosemia Foundation and a mother of four children. She has started a petition to the FDA at Change.Org.

Signs And Symptoms Of Pancreatic Cancer

Some people get cancer of the pancreas, the organ in your abdomen that makes digestive enzymes and hormones such as insulin. The cancerous mass can interfere with the pancreas' function and lead to symptoms such as stomach or back pain, jaundice (yellowed skin), diarrhea, nausea, weight loss, and diabetes.

Early in the disease, pancreatic cancer is typically asymptomatic (doesn't cause any symptoms). Symptoms from pancreatic cancer often start gradually and intermittently, so people may dismiss them. Often by the time symptoms are more significant, the cancer is already large, or it has already spread. This makes it more difficult to treat.

But not everyone with pancreatic cancer will have all these symptoms. Most people who have one of these symptoms have a different medical condition and not pancreatic cancer.

For most people with pancreatic cancer, jaundice is one of the first symptoms. Jaundice refers to a yellowing of the skin and/or the whites of the eyes. It occurs when there is some sort of build-up of bile, a substance made in the liver that helps break down fats.

Normally bile travels from the liver to the gallbladder and out through the intestines and the feces. But since the pancreas is located nearby, a pancreatic mass may block the flow of bile, leading to jaundice. It can also cause the skin to become itchy and the urine to turn dark brown.

If the mass is located in a specific spot, this might happen before the pancreatic cancer is advanced. Sometimes pancreatic cancer can also cause jaundice because the cancer has already spread to the liver.

In people over 40, new jaundice carries a cancer risk of over 20%. This figure includes not just pancreatic cancer but other kinds of cancer as well. However, many other different medical conditions can also cause jaundice and related symptoms.

Upper stomach pain is another common symptom of pancreatic cancer. Because of the anatomy of the pancreas, which is found on the backside of the abdomen, back pain is also relatively common. The pain may tend to be worse after meals. However, most people who have stomach pain and/or back pain have it from other causes.

Nausea and vomiting are very common symptoms of pancreatic cancer. The cancer may press up against the stomach, which can make vomiting worse. Unintended weight loss from poor appetite and decreased food intake is also common.

Pancreatic cancer sometimes causes diarrhea, which may be due to decreased pancreatic digestive enzymes. However, other people with pancreatic cancer may notice constipation instead.

Stools that appear greasy are particularly concerning, as they might be a sign that bile and digestive enzymes aren't making it to the intestines to break down fat. The stool may also be lighter in color instead of dark brown.

Although most people with diabetes do not get pancreatic cancer, it sometimes is the first sign of the disease. Damage to the pancreas can impair its ability to make insulin. In some people, this leads to diabetes, which is characterized by consistently elevated glucose levels in the blood (high blood sugar). Diabetes from damage to the pancreas is sometimes called pancreatogenic (type 3c) diabetes.

Diabetes might be picked up on a blood test without any initial symptoms. You may also notice symptoms of diabetes, like excess thirst, hunger, and urination.

Diabetes isn't as common as some other symptoms of pancreatic cancer. Of people eventually diagnosed with pancreatic cancer, about 1 in 4 first receive a diagnosis of diabetes.

People with some kinds of cancer, including pancreatic cancer, are at risk of blood clots. For some people, such blood clots are the first sign that they have pancreatic cancer.

Often this occurs in one of the deep veins of the leg, called deep vein thrombosis. This can cause symptoms like leg pain, swelling, and warmth.

Sometimes such clots travel to the lungs, termed a "pulmonary embolism." This can cause symptoms like chest pain and severe shortness of breath. If severe, it can be life-threatening.

At least 90% of pancreatic cancers are classified as adenocarcinomas, and the symptoms described apply to them. However, a small subset of people have other types of pancreatic cancer. These rare types may have some of the same symptoms, or they might not cause symptoms at all.

However, they may also have additional specific symptoms. For example, an insulinoma is an example of a pancreatic neuroendocrine tumor, which can cause symptoms based on excess hormones produced. An insulinoma might cause symptoms like irritability or headache from too much insulin and resulting low blood sugar.

If you are concerned you might have pancreatic cancer, make an appointment to see a healthcare provider right away, especially if you have a family history. It's particularly important to do so if you are 60 or older and you have weight loss in addition to stomach or back pain, nausea or vomiting, diarrhea or constipation, or new diabetes.

It's also important that you be seen by a health professional quickly if you have jaundice. Tell them you have jaundice when you call, as you need to be evaluated promptly. If you can't schedule it in a relatively short period, you may need an urgent care appointment.

Pancreatic cancer can cause symptoms like stomach pain or back pain, nausea and vomiting, and weight loss. It can also cause symptoms related to jaundice, including yellowed skin or whites of the eyes. Some people with pancreatic cancer experience other symptoms, like those related to diabetes or to blood clots.

Unfortunately, pancreatic cancer is often advanced by the time symptoms become significant, making it more challenging to treat.

Still Have Jaundice

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Jaundice in Newborn