personal_noteS – Page 18

Opioids (2)

Prescription Opioid

As a treatment: Prescription opioids can be used to treat moderate-to-severe pain and are often prescribed following surgery or injury, or for health conditions such as cancer.

In recent years, there has been a dramatic increase in the acceptance and use of prescription opioids for the treatment of chronic, non-cancer pain, such as back pain or osteoarthritis, despite serious risks and the lack of evidence about their long-term effectiveness.

Image result for Prescription opioid volume peaked in 2011 at 240 billion milligrams of morphine equivalents and have declined by 29% to 171 billion — Source: IQVIA

Prescription opioid usage in the United States increased considerably from the mid 1990’s to its peak in 2011, at 240 billion MMEs (morphine milligram equivalents). It is now declining rapidly with the largest single year change in 2017 with a decline of 23.3 billion MMEs or 12.0%.

The most common drugs involved in prescription opioid overdose deaths include:

- Methadone
- Oxycodone (such as OxyContin®)
- Hydrocodone (such as Vicodin®)

Abuse Deterrent

What is an Abuse Deterrent Opioid: with abuse-deterrent formulation properties that are expected to meaningfully deter certain types of abuse and/or make abuse more difficult or less rewarding.

As a general framework, abuse-deterrent formulations can currently be categorized as follows:

Physical/chemical barriers – Physical barriers can prevent chewing, crushing, cutting, grating, or grinding of the dosage form. Chemical barriers, such as gelling agents, can resist extraction of the opioid using common solvents like water, simulated biological media, alcohol, or other organic solvents. Physical and chemical barriers can limit drug release following mechanical manipulation, or change the physical form of a drug, rendering it less amenable to abuse.
Agonist/antagonist combinations – An opioid antagonist can be added to interfere with, reduce, or defeat the euphoria associated with abuse. The antagonist can be sequestered and released only upon manipulation of the product. For example, a drug product can be formulated such that the substance that acts as an antagonist is not clinically active when the product is swallowed, but becomes active if the product is crushed and injected or snorted.
Aversion – Substances can be added to the product to produce an unpleasant effect if the dosage form is manipulated or is used at a higher dosage than directed. For example, the formulation can include a substance irritating to the nasal mucosa if ground and snorted.
Delivery System (including use of depot injectable formulations and implants) – Certain drug release designs or the method of drug delivery can offer resistance to abuse. For example, sustained-release depot injectable formulation or a subcutaneous implant may be difficult to manipulate.
New molecular entities and prodrugs– The properties of a new molecular entity (NME) or prodrug could include the need for enzymatic activation, different receptor binding profiles, slower penetration into the central nervous system, or other novel effects. Prodrugs with abuse-deterrent properties could provide a chemical barrier to the in vitro conversion to the parent opioid, which may deter the abuse of the parent opioid. New molecular entities and prodrugs are subject to evaluation of abuse potential for purposes of the Controlled Substances Act (CSA).
Combination – Two or more of the above methods could be combined to deter abuse.
Novel approaches – This category encompasses novel approaches or technologies that are not captured in the previous categories.

Opioids with FDA-Approved Labeling Describing Abuse-Deterrent Properties

FDA has approved these opioids with labeling describing abuse-deterrent properties consistent with the FDA’s Guidance for Industry: Abuse-Deterrent Opioids – Evaluation and Labeling:

There are currently NO generic opioids with FDA-approved abuse-deterrent labeling.

Opioids (1)

Opioids

Opioids are drugs formulated to replicate the pain-educing properties of opium. Prescription painkillers like morphine (吗啡), oxycodone (羟考酮) and hydrocodone (氢可酮) are opioids.

There are four categories:

Natural opioids (including morphine and codeine 可待因) and semi-synthetic opioids (drugs like oxycodone, hydrocodone, hydromorphone 氢吗啡酮, and oxymorphone 羟吗啡酮)
Methadone (美沙酮), a synthetic opioid
Synthetic opioids other than methadone (drugs like tramadol and fentanyl)
Heroin, an illicit (illegally made) opioid synthesized from morphine that can be a white or brown powder, or a black sticky substance.

Opioids—mainly synthetic opioids (other than methadone)—are currently the main driver of drug overdose deaths. Opioids were involved in 47,600 overdose deaths in 2017 (67.8% of all drug overdose deaths).

Opioids such as morphine and codeine are naturally derived from opium poppy plants more commonly grown in Asia, Central America and South America. Heroin is an illegal drug synthesized from morphine.

Hydrocodone (such as Vicodin) and oxycodone (such as OxyContin) are semi-synthetic opioids, manufactured in labs with natural and synthetic ingredients.

Fentanyl is a fully synthetic opioid, originally developed as a powerful anesthetic for surgery. It is also administered to alleviate severe pain associated with terminal illnesses like cancer. The drug is up to 100 times more powerful than morphine.

Methadone is another fully synthetic opioid. It is commonly dispensed to recovering heroin addicts to relieve the symptoms of withdrawal.

Three Waves of Opioid Overdose Deaths

From 1999-2017, almost 400,000 people died from an overdose involving any opioid, including prescription and illicit opioids.

This rise in opioid overdose deaths can be outlined in three distinct waves.

The first wave began with increased prescribing of opioids in the 1990s³, with overdose deaths involving prescription opioids (natural and semi-synthetic opioids and methadone) increasing since at least 1999.
The second wave began in 2010, with rapid increases in overdose deaths involving heroin.
The third wave began in 2013, with significant increases in overdose deaths involving synthetic opioids – particularly those involving illicitly-manufactured fentanyl (IMF). The IMF market continues to change, and IMF can be found in combination with heroin, counterfeit pills, and cocaine.

「News of the Week」A letter from Larry and Sergey

Google’s co-founders retired from management positions in Alphabet and wrote a blog to the public;

They will continue their involvement as co-founders, shareholders and members of Alphabet’s Board of Directors.

Sundar Pichai, CEO of Google, becomes CEO of both Google and Alphabet.

Alphabet’s press release on Dec 3.

WSJ – Google Management Shuffle Points to Retreat From Alphabet Experiment

Dots to connect: Waymo’s rollout, potential spin-off of independent assets, Alphabet’s bottom-line, more detailed reporting, internal control issues, etc.

Our very first founders’ letter in our 2004 S-1 began:

“Google is not a conventional company. We do not intend to become one. Throughout Google’s evolution as a privately held company, we have managed Google differently. We have also emphasized an atmosphere of creativity and challenge, which has helped us provide unbiased, accurate and free access to information for those who rely on us around the world.”

We believe those central tenets are still true today. The company is not conventional and continues to make ambitious bets on new technology, especially with our Alphabet structure. Creativity and challenge remain as ever-present as before, if not more so, and are increasingly applied to a variety of fields such as machine learning, energy efficiency and transportation. Nonetheless, Google’s core service—providing unbiased, accurate, and free access to information—remains at the heart of the company.

However, since we wrote our first founders’ letter, the company has evolved and matured. Within Google, there are all the popular consumer services that followed Search, such as Maps, Photos, and YouTube; a global ecosystem of devices powered by our Android and Chrome platforms, including our own Made by Google devices; Google Cloud, including GCP and G Suite; and of course a base of fundamental technologies around machine learning, cloud computing, and software engineering. It’s an honor that billions of people have chosen to make these products central to their lives—this is a trust and responsibility that Google will always work to live up to.

And structurally, the company evolved into Alphabet in 2015. As we said in the Alphabet founding letter in 2015:

“Alphabet is about businesses prospering through strong leaders and independence.”

Since we wrote that, hundreds of Phoenix residents are now being driven around in Waymo cars—many without drivers! Wing became the first drone company to make commercial deliveries to consumers in the U.S. And Verily and Calico are doing important work, through a number of great partnerships with other healthcare companies. Some of our “Other Bets” have their own boards with independent members, and outside investors.

Those are just a few examples of technology companies that we have formed within Alphabet, in addition to investment subsidiaries GV and Capital G, which have supported hundreds more. Together with all of Google’s services, this forms a colorful tapestry of bets in technology across a range of industries—all with the goal of helping people and tackling major challenges.

Our second founders’ letter began:

“Google was born in 1998. If it were a person, it would have started elementary school late last summer (around August 19), and today it would have just about finished the first grade.”

Today, in 2019, if the company was a person, it would be a young adult of 21 and it would be time to leave the roost. While it has been a tremendous privilege to be deeply involved in the day-to-day management of the company for so long, we believe it’s time to assume the role of proud parents—offering advice and love, but not daily nagging!

With Alphabet now well-established, and Google and the Other Bets operating effectively as independent companies, it’s the natural time to simplify our management structure. We’ve never been ones to hold on to management roles when we think there’s a better way to run the company. And Alphabet and Google no longer need two CEOs and a President. Going forward, Sundar will be the CEO of both Google and Alphabet. He will be the executive responsible and accountable for leading Google, and managing Alphabet’s investment in our portfolio of Other Bets. We are deeply committed to Google and Alphabet for the long term, and will remain actively involved as Board members, shareholders and co-founders. In addition, we plan to continue talking with Sundar regularly, especially on topics we’re passionate about!

Sundar brings humility and a deep passion for technology to our users, partners and our employees every day. He’s worked closely with us for 15 years, through the formation of Alphabet, as CEO of Google, and a member of the Alphabet Board of Directors. He shares our confidence in the value of the Alphabet structure, and the ability it provides us to tackle big challenges through technology. There is no one that we have relied on more since Alphabet was founded, and no better person to lead Google and Alphabet into the future.

We are deeply humbled to have seen a small research project develop into a source of knowledge and empowerment for billions—a bet we made as two Stanford students that led to a multitude of other technology bets. We could not have imagined, back in 1998 when we moved our servers from a dorm room to a garage, the journey that would follow.

Sundar sent the following email to Googlers on Tuesday, December 3:

Hi everyone,

When I was visiting Googlers in Tokyo a few weeks ago I talked about how Google has changed over the years. In fact, in my 15+ years with Google, the only constant I’ve seen is change. This process of continuous evolution — which the founders often refer to as “uncomfortably exciting” — is part of who we are. That statement will feel particularly true today as you read the news Larry and Sergey have just posted to our blog.

The key message Larry and Sergey shared is this:

While it has been a tremendous privilege to be deeply involved in the day-to-day management of the company for so long, we believe it’s time to assume the role of proud parents—offering advice and love, but not daily nagging!

I first met Larry and Sergey back in 2004 and have been benefiting from their guidance and insights ever since. The good news is I’ll continue to work with them — although in different roles for them and me. They’ll still be around to advise as board members and co-founders.

I want to be clear that this transition won’t affect the Alphabet structure or the work we do day to day. I will continue to be very focused on Google and the deep work we’re doing to push the boundaries of computing and build a more helpful Google for everyone. At the same time, I’m excited about Alphabet and its long term focus on tackling big challenges through technology.

The founders have given all of us an incredible chance to have an impact on the world. Thanks to them, we have a timeless mission, enduring values, and a culture of collaboration and exploration that makes it exciting to come to work every day. It’s a strong foundation on which we will continue to build. Can’t wait to see where we go next and look forward to continuing the journey with all of you.

– Sundar

CB Insights: Everything You Need To Know About What Amazon Is Doing In Financial Services

A 2018 report by CB Insights.

A good reading as I was thinking about future payment industry (also you can find a previous post on How Card Networks May Fail: Top Merchants With Gift Cards + Mobile Wallet)

Full report here; table of contents below

Amazon’s product strategy
Payments
Cash
Lending
Amazon’s Next Financial Pillar
Market strategy outside the US
India
Mexico
Rumors: What will Amazon do next?
Closing thoughts

Master Innovation And Development Plan By Sidewalk Toronto

Earlier this year, I shared 「Video of the Week」Future Cities by Sidewalk Labs.

Now we have many more documents from Sidewalk Toronto. Google is trying to build cities.

The plan will begin with Quayside in Phase I.

Map shows the proposed IDEA District and the Eastern Waterfront. The Quayside neighbourhood, on the northwest perimeter of the district, is blue, representing phase 1 of development. — Source: sidewalktoronto

There will be several focuses

Mobility. A transportation system that reduces the need to own a car by providing safe, convenient, connected, and affordable options for every trip.
Common & social areas. A system of streets, parks, plazas, and open spaces that encourages people to spend more time outdoors, together; health, civic life, learning, and workforce initiatives and facilities that enable people to thrive.
Buildings & Housing. Sustainable and adaptable buildings with mixed uses; affordable residences.
Environmental friendly as a climate-positive community.
Digitalize every possible part of the city.

「Shoe Dog」Nike’s CRM Started In 1966..

Sharing an except from Nike founder Phil Knight’s book Shoe Dog:

“…when he [Johnson] wasn’t selling, he was beaverishly building up his customer data files.

Each new customer got his or her own index card, and each index card contained that customer’s personal information, shoe size, and shoe preferences. This database enabled Johnson to keep in touch with all his customers, at all times, and to keep them all feeling special. He sent them Christmas cards. He sent them birthday cards. He sent them notes of congratulation after they completed a big race or marathon. Whenever I got a letter from Johnson I knew it was one of dozens he’d carried down to the mailbox that day. He had hundreds and hundreds of customer-correspondents, all along the spectrum of humanity, from high school track stars to octogenarian weekend joggers. “

This where Nike’s superior customer relationship management came from… two years after Nike was founded.

More recently, Nike’s SNKRS app launched in 2015 was a hit. The app is where many head for a chance to get Nike limited releases and special products.

It’s become Nike’s latest way to game supply and demand of hyped products. SNKRS keeps shoppers hungry by sending out regular push notifications about drops every week. When consumers inevitably flood the app for the release, many take an L, walking away empty handed. A share of those who do get the shoes never wear them. Instead, they immediately resell them for multiples of what they paid, fueling the burgeoning resale market. [Quartz]

And Nike just launched Chinese version of its Nike App in November, with Nike Fit and Nike App Retail expected to launch next year in China.

A Meatless Future By CBInsights

traditional food companies consolidation/acquisition
startup companies making meat out of labs or plant-based products
- In 2019, one of the world’s biggest alternative protein brands, Beyond Meat, the manufacturer of the plant-based Beyond Burger, went public at a valuation of almost $1.5B

Differences in numbers:

There are other related trends in meal replacement & dairy substitutes,
insect protein and seafoods

Why now:

Forces like urbanization, population growth, and a rising global middle class lead to greater meat consumption
Alternative protein sources can reduce the negative environmental impact associated with meat production
Consumers are seeking healthier food alternatives
Advances in ag tech and synthetic biology are enabling high-tech meatless products
Meatless consumption could alleviate ethical questions around current meat production practices
Alternative meats could reduce contamination, reducing global health problems

Full report here.

CB Insights: 5 Ways Ant Financial & Tencent’s Fintech Growth Playbooks Are Evolving

Beyond the transaction fees charged by AliPay and WeChatPay, CB Insights outlined five major growth opportunities.

Building flywheel effects
Making virtual credit a part of everyday life
Prioritizing health insurance
Diversifying options for savings and investing to expand the market
Focusing on small businesses

See full report here.

Huabei

SoftBank Group Earnings Presentation: WeWork Impacts, 60% Discount, Best Deal In Alibaba

SoftBank Group’s presentation gives a fairly good illustration of what the group is holding, the loss on book due to WeWork and the turnaround plan for it.

The presentation talks a lot about WeWork, but it’s Alibaba that contributes/matters the most right now. Nearly half of ($123 billion out of the $256 billion) its equity values of holding comes from Alibaba.

And given SoftBank Group’s market cap ~$80 billion now, it is a very good source of Alibaba exposure even without hedge (personally I think other holdings are also okay).

The turnaround plan relies a lot on higher occupancy rates and cost cuttings as WeWork manage the properties longer.

Here is the presentation.