How the trauma of life is passed down in SPERM, affecting the mental health of future generations


  • The changes are so strong they can even influence a man’s grandchildren
  • They make the offspring more prone to conditions like bipolar disorder

The children of people who have experienced extremely traumatic events are more likely to develop mental health problems.

And new research shows this is because experiencing trauma leads to changes in the sperm.

These changes can cause a man’s children to develop bipolar disorder and are so strong they can even influence the man’s grandchildren.

Psychologists have long known that traumatic experiences can induce behavioural disorders that are passed down from one generation to the next.

However, they are only just beginning to understand how this happens.

Researchers at the University of Zurich and ETH Zurich now think they have come one step closer to understanding how the effects of traumas can be passed down the generations.

The researchers found that short RNA molecules – molecules that perform a wide range of vital roles in the body – are made from DNA by enzymes that read specific sections of the DNA and use them as template to produce corresponding RNAs.

Other enzymes then trim these RNAs into mature forms.

Cells naturally contain a large number of different short RNA molecules called microRNAs.

They have regulatory functions, such as controlling how many copies of a particular protein are made.

The researchers studied the number and kind of microRNAs expressed by adult mice exposed to traumatic conditions in early life and compared them with non-traumatised mice.

They discovered that traumatic stress alters the amount of several microRNAs in the blood, brain and sperm – while some microRNAs were produced in excess, others were lower than in the corresponding tissues or cells of control animals.

These alterations resulted in misregulation of cellular processes normally controlled by these microRNAs.

After traumatic experiences, the mice behaved markedly differently – they partly lost their natural aversion to open spaces and bright light and showed symptoms of depression.

Men who have experienced traumatic events are more likely to have children with mental health problems

Men who have experienced traumatic events are more likely to have children with mental health problems

 These behavioural symptoms were also transferred to the next generation via sperm, even though the offspring were not exposed to any traumatic stress themselves.

The metabolisms of the offspring of stressed mice were also impaired – their insulin and blood sugar levels were lower than in the offspring of non-traumatised parents.

‘We were able to demonstrate for the first time that traumatic experiences affect metabolism in the long-term and that these changes are hereditary,’ said Professor Isabelle Mansuy.

‘With the imbalance in microRNAs in sperm, we have discovered a key factor through which trauma can be passed on.’

However, certain questions remain open, such as how the dysregulation in short RNAs comes about.

Professor Mansuy said: ‘Most likely, it is part of a chain of events that begins with the body producing too many stress hormones.’

Importantly, acquired traits other than those induced by trauma could also be inherited through similar mechanisms, the researcher suspects.

Source:dailymail.co.uk

Advertisements

Physicists Say They’ve Created a Fluid With ‘Negative Mass’


Researchers in the US say they’ve created a fluid with negative mass in the lab… which is exactly as mind-bending as it sounds.

What it means is that, unlike pretty much every other known physical object, when you push this fluid, it accelerates backwards instead of moving forwards. Such an oddity could tell scientists about some of the strange behaviour that happens within black holes and neutron stars.

 But let’s take a step back for a second here, because how can something have negative mass?

Hypothetically speaking, matter should be able to have negative mass in the same way that an electric charge can be either negative or positive.

On paper that works, but it’s still debated in the science world whether negative mass objects can really exist without breaking the laws of physics – something that’s not helped by the fact that the very concept is hard for us mere humans to wrap our heads around.

Isaac Newton’s Second Law of Motion is often written as the formula f=ma, or force equals an object’s mass times its acceleration.

If we rewrite it as acceleration is equal to a force divided by the object’s mass, and make the mass negative, it would have negative acceleration – just imagine sliding a glass across a table and having it push back against your hand.

However, just because it seems foreign to us, doesn’t mean it’s impossible, and previous theoretical research has shown some early evidence that negative mass could exist within our Universe without breaking the theory of general relativity.

 

More than that, many physicists think that negative mass could be linked to some of the weird things we’ve detected in the Universe, such as dark energyblack holes, and neutron stars.

As a result, researchers have been actively trying to recreate negative mass in the lab, with some early success.

But now researchers from Washington State University say they’ve successfully managed to get a fluid of superchilled atoms to act as though it has negative mass – and suggest it could finally be used to study some of the stranger phenomena happening in the deep Universe.

“What’s a first here is the exquisite control we have over the nature of this negative mass, without any other complications,” said one of the researchers, Michael Forbes.

To create this strange fluid, the team used lasers to cool rubidium atoms to a fraction above absolute zero, creating what’s known as a Bose-Einstein condensate.

In this state, particles move incredibly slowly and follow the strange principles of quantum mechanics, rather than classical physics – which means they start to behave like waves, with a location that can’t be precisely pinpointed.

The particles also sync up and move in unison, forming what’s known as a superfluid – a substance that flows without losing energy to friction.

The team used lasers to keep this superfluid at the icy temperatures, but also to trap it in a tiny bowl-like field measuring less than 100 microns across.

While the superfluid remained contained in that space it had regular mass and, as far as Bose-Einstein condensates go, was pretty normal. But then the team forced the superfluid to escape.

Using a second set of lasers, they kicked the atoms back and forth to change their spin, breaking the ‘bowl’ and allowing the rubidium to come rushing out so fast that it behaved as if it had negative mass.

“Once you push, it accelerates backwards,” said Forbes. “It looks like the rubidium hits an invisible wall.”

So far, the researchers state that the negative mass fluid confirms what other teams have seen in their research, but it’s very early days.

It’s yet to be seen whether this escaping superfluid will be reliable and accurate enough to test out some of the very strange suggestions about negative mass in the lab, and before we get too excited, other teams need to replicate the results independently.

But the research has now been published in the peer-reviewed journal Physical Review Letters for anyone to try their hand at. So hopefully it won’t be long before we see the experiment recreated.

One thing’s for sure, physics just keeps getting weirder, and we’re pretty excited to see what happens next.

source:www.sciencealert.com

Canadian river vanished in just four days


First ever observed case of ‘river piracy’ saw the Slims river disappear as intense glacier melt suddenly diverted its flow into another watercourse

A view of the ice canyon that now carries meltwater from the Kaskawulsh glacier, seen here on the right, away from the Slims river and toward the Kaskawulsh river.
A view of the ice canyon that now carries meltwater from the Kaskawulsh glacier, seen here on the right, away from the Slims river and toward the Kaskawulsh river. 

An immense river that flowed from one of Canada’s largest glaciers vanished over the course of four days last year, scientists have reported, in an unsettling illustration of how global warming dramatically changes the world’s geography.

The abrupt and unexpected disappearance of the Slims river, which spanned up to 150 metres at its widest points, is the first observed case of “river piracy”, in which the flow of one river is suddenly diverted into another.

The continental-scale rearrangement was documented by a team of scientists who had been monitoring the incremental retreat of the glacier for years. But on a 2016 fieldwork expedition they were confronted with a landscape that had been radically transformed.

https://interactive.guim.co.uk/uploader/embed/2017/04/yukon_map/giv-3902r6J93i3f2WM0/

“We went to the area intending to continue our measurements in the Slims river, but found the riverbed more or less dry,” said James Best, a geologist at the University of Illinois. “The delta top that we’d been sailing over in a small boat was now a dust storm. In terms of landscape change it was incredibly dramatic.”

Dan Shugar, a geoscientist at the University of Washington Tacoma and the paper’s lead author, added: “The water was somewhat treacherous to approach, because you’re walking on these old river sediments that were really goopy and would suck you in. And day by day we could see the water level dropping.”

The team flew a helicopter over the glacier and used drones to investigate what was happening in the other valley, which is less accessible.

“We found that all of the water that was coming out from the front of the glacier, rather than it being split between two rivers, it was going into just one,” said Best.

The Kaskawulsh River, seen here near its headwaters, is running higher now thanks to the addition of water that used to flow into the Slims River.
 The Kaskawulsh River, seen here near its headwaters, is running higher now thanks to the addition of water that used to flow into the Slims River. Photograph: Jim Best/University of Illinois

While the Slims had been reduced to a mere trickle, the reverse had happened to the south-flowing Alsek river, a popular whitewater rafting river that is a Unesco world heritage site. The previous year, the two rivers had been comparable in size, but the Alsek was now 60 to 70 times larger than the Slims, flow measurements revealed.

The data also showed how abrupt the change had been, with the Slims’ flow dropping precipitously from the 26 to 29 May 2016.

Geologists have previously found evidence of river piracy having taken place in the distant past. “But nobody to our knowledge has documented it happening in our lifetimes,” said Shugar. “People had looked at the geological record, thousands or millions of years ago, not the 21st century, where it’s happening under our noses.”

Prof Lonnie Thompson, a paleoclimatologist at Ohio State University who was not involved in the work, said the observations highlight how incremental temperature increases can produce sudden and drastic environmental impacts. “There are definitely thresholds which, once passed in nature, everything abruptly changes,” he said.

Between 1956 and 2007, the Kaskawulsh glacier retreated by 600-700m. In 2016, there was a sudden acceleration of the retreat, and the pulse of meltwater led to a new channel being carved through a large ice field. The new channel was able to deliver water to the Alsek’s tributary whose steeper gradient resulted in the Slims headwater being suddenly rerouted along a new southwards trajectory.

In a geological instant, the local landscape was redrawn.

Where the Slims once flowed, Dall sheep from Kluane National Park are now making their way down to eat the fresh vegetation, venturing into territory where they can legally be hunted. The formerly clear air is now often turned into a dusty haze as powerful winds whip up the exposed riverbed sediment. Fish populations are being redistributed and lake chemistry is being altered. Waterfront land, which includes the small communities of Burwash Landing and Destruction Bay, is now further from shore.

Sections of the newly exposed bed of Kluane Lake contain small pinnacles. Wind has eroded sediments with a harder layer on top that forms a protective cap as the wind erodes softer and sandier sediment below. These pinnacles, just a few centimeters high, are small-scale versions of what are sometimes termed “hoodoos.”
 Sections of the newly exposed bed of Kluane Lake contain small pinnacles. Wind has eroded sediments with a harder layer on top that forms a protective cap as the wind erodes softer and sandier sediment below. These pinnacles, just a few centimeters high, are small-scale versions of what are sometimes termed “hoodoos.” 

A statistical analysis, published in the journal Nature Geoscience, suggests that the dramatic changes can almost certainly be attributed to anthropogenic climate change. The calculations put chance of the piracy having occured due to natural variability at 0.5%. “So it’s 99.5% that it occurred due to warming over the industrial era,” said Best.

Thompson, who has documented glacial retreat on Mount Kilimanjaro, predicts that there will be an acceleration in the observations of river piracy events as glaciers retreat globally.

“I think we could see similar divergence in streams in the Himalayas as well as throughout the Third Pole region, the Andes of Peru, other sites in northern Canada and Alaska,” he said. “Often these events occur in remote and poor parts of our planet and thus go largely unnoticed by the larger population but greatly impact the livelihood of many families downstream.”

Source:www.theguardian.com

AI. Storytelling.


Web page not available

https://www.theatlantic.com/technology/archive/2016/07/the-six-main-arcs-in-storytelling-identified-by-a-computer/490733/

Generic drugs: Review and experiences from South India


Abstract

The cost of pharmaceuticals, as a percentage of total healthcare spending, has been rising worldwide. This has resulted in strained national budgets and a high proportion of people without access to essential medications. Though India has become a global hub of generic drug manufacturing, the expected benefits of cheaper drugs are not translating into savings for ordinary people. This is in part due to the rise of branded generics, which are marketed at a price point close to the innovator brands. Unbranded generic medicines are not finding their way into prescriptions due to issues of confidence and perception, though they are proven to be much cheaper and comparable in efficacy to branded medicines. The drug inventory of unbranded generic manufacturers fares reasonably when reviewed using the World Health Organization-Health Action International (WHO-HAI) tool for analysing drug availability. Also, unbranded generic medicines are much cheaper when compared to the most selling brands and they can bring down the treatment costs in primary care and family practice. We share our experience in running a community pharmacy for an urban health center in the Pathanamthitta district of Kerala State, which is run solely on generic medicines. The drug availability at the community pharmacy was 73.3% when analyzed using WHO-HAI tool and the savings for the final consumers were up to 93.1%, when compared with most-selling brand of the same formulation.

Keywords: Drug availability, drug industry/legislation and jurisprudence, drugs, economic competition, essential medicines, generic*, generic medicines, global health, India, patents as topic/legislation and jurisprudence*, poverty, unbranded generics

Introduction

The World Health Organization (WHO) estimates that almost 30% of the world population lacks access to essential medicines and that the figure will rise to more than 50% in some countries of Africa and Asia.[1] The cost of the pharmaceuticals is the main factor that hampers access to medicines and the governments in poor countries seem to be doing very little to counter this problem. The public sector availability of essential medicines was less than 50% in most of the countries of Africa and Asia.[2] This is appalling in the face of increases in healthcare expenditure in most of the developing nations, mostly financed through secured loans by international development banks and consortia.

The situation in India is not very different than that of other developing nations. Healthcare expenditures have been growing in India, both in real terms and also when considered as a proportion of the Gross Domestic Product (GDP).[3] However, even with this recent increase in healthcare spending, India’s expenditure on health is nowhere near that of OECD (Organisation for Economic Cooperation and Development) nations.[4] The total public spending on healthcare in India accounted for only around 1.2% of GDP in 2012, with the per-capita spending on health around USD 160. This is a miniscule amount when compared against the OECD per-capita healthcare spending of USD 3,484 in 2012.[3,4] This shows that the healthcare spending in the country is set to rise further in the coming years and the healthcare industry is all set for a boom time.

The cost of medicines and pharmaceuticals as a percentage of total healthcare spending has also been rising worldwide.[5] It is the fastest-growing item in the healthcare budgets worldwide and it varies between 20-60% in various healthcare budgets of countries.[6] By 2020, the prescription drug market in United States of America is set to grow to USD 700 billion (B) and China will be USD 260 B.[5] Though no credible predictions about the Indian pharmaceutical industry are available, it is quite safe to assume that Indian pharmaceutical industry will also grow manifold. The growth of the pharmaceutical market worldwide and its increased share in total healthcare spending will reignite the age-old debate on how to balance the cost of innovation in drug research and universal access to the fruits of that research.[7]

Rise of Generics

The role of generic medicines in reducing the healthcare expenditure has been recognised for a long time. Multiple studies have proven that saving through substitution of originator brands by cheaper generic medicines, savings in the range of 10-90% can be achieved.[8] Most national governments have been encouraging the use of generic medicines worldwide and many healthcare systems have policies of substituting expensive branded original medications with generic medicines.[9] In the United States, generic substitution (GS) is an accepted practice and at the end of 2012, almost 80% of all the prescriptions were of generic medications. This has resulted in a substantial moderation of expenditure growth in widely used drugs and significant savings to the economy.[6] In the United Kingdom, GS is now a standard practice in hospitals operated by the National Health Service (NHS) and medical schools have included generic prescribing as a part of their medical training.[10]

In India, the procurement price of essential medicines is generally lower than the mean International Reference Pricing (IRP) but availability of these drugs in the public sector has always been a problem. The exorbitant cost of some of the commonly used medications in private pharmacies makes it inaccessible to majority of the poor.[11] Also, the difference between procurement prices and retail prices in case of some of the generic medicines, were as high as 28 times, which shows a very high margin of profit-taking in view of limited price control mechanisms.[11] It is in this light, that the government revised the National Pharmaceutical Pricing Policy in 2012. It gave methods to calculate ceiling prices for drugs which are under the National List of Essential Medicines (NLEM) which was modified in 2011. It gave a formula for deciding the ceiling prices for drugs under NLEM, using a market-based pricing (MBP) method, taking into account the prices of all manufacturers having a market share of more than 1% nationally.[12] The Drug Price Control Order of 2013 was a follow-up to the National Pharmaceutical Pricing Policy and gave the price ceiling for 348 drugs and over 600 formulations. However, the action was considered inadequate by many activists lobbying for cheaper drugs and they termed it as a sell-out to international pharmaceutical companies.[13]

Indian Pharmaceutical Industry

The multiplicity of brands and manufacturers makes it difficult to decipher the actual market dynamics and the structural issues in the Indian pharmaceutical industry. The complexity of the market and the intensity of the competition between companies in India have made the country a hub for manufacture of generic medicines, earning a sobriquet “pharmacy of the developing world.”[14] This, along with a favorable governmental stance has made India a powerhouse in this field, bringing it into direct confrontation with certain developed nations where most of the big multinational pharmaceutical companies are located[14] There have been many instances when the Indian Patents Office and the Supreme Court of India effectively used certain flexibilities of the Trade Related Aspects of Intellectual Property Rights (TRIPS) agreement of the World Trade Organization and also the safeguards embedded in the Indian Patents Act. The compulsory licensing of Sorafenib, a drug used in treatment of advanced liver and renal cancer and the rejection of patent application for Imatinib, a drug used in the treatment of leukaemia, were considered as landmark decisions by many state and non-state organizations involved in pharmaceutical sector.[15,16]

Considering the Indian scenario, we can divide the brands into innovator brands (IB), most-selling generics (MSG), and least-priced generics (LPG).[17] The IBs will be at the highest price point, followed by MSGs and LPGs. A new category of generic drugs known as unbranded generics (UB) are also coming into the market now. These drugs are usually manufactured by not-for-profit organizations or are subsidised by certain non-governmental organizations (NGO).[18] Though the price points of these different categories of drugs are different, their efficacies are comparable. This fact has been proved by multiple studies all over the world and it belittles the reasoning which goes behind differential pricing of the same drug.[19,20] Even though it has been proved that there is not much difference in efficacy between the above categories of drugs, physicians tend to prescribe drugs manufactured by highly-reputed companies. Their trust is often misplaced as most of these leading companies market drugs manufactured by less-known manufacturers.[18]

A Model Community Pharmacy: Experiences from South India

Pushpagiri Medical College, which is a teaching hospital in Kerala state of India partnered with a social organization, Bodhana Social Service Society, involved in poverty alleviation and income generation programmes, to start an urban health center with an objective to improve patient accessibility to cost-effective medical care. The urban health center serves a population of 10,000, spread over 5 municipal wards of Tiruvalla municipality and was intended as a model for cost-effective primary care. A comprehensive population survey was carried out before the start of the project and the health center started functioning in September 2014. As a part of the initiative, a community pharmacy was opened to stock unbranded generic drugs manufactured by two non-governmental organizations. Low-Cost Standard Therapeutics (LOCOST), Baroda and Comprehensive Medical Supplies India (CMSI), Chennai were the two NGOs providing us with the drugs which were needed at the community pharmacy.[21,22] The drugs were provided to us at a nominal cost, after we provided an undertaking that the Pushpagiri Medical College is a charitable institution with no intention of making profits. Also, the physicians working at the health center made a collective decision to prescribe all the drugs generically and the pharmacist was advised to dispense the cheapest generic brand.

The drug inventory available with these not-for-profit manufacturers were fairly comprehensive when reviewed using the World Health Organization-Health Action International (WHO-HAI) tool for quantifying availability of essential medicines.[23] The WHO-HAI tool is a validated method for measuring availability of drugs in a health system and includes 30 core medicines: 14 essential medicines for global burden of disease and 16 medicines specific to the WHO region [Table 1].[24]

Table 1

Drug inventory of LOCOST, Baroda and CMSI, Chennai: Review using WHO-HAI tool for WHO South East Asian Region

The WHO-HAI tool showed a drug availability of 73.3% for LOCOST, Baroda and 43.3% for CMSI, Chennai. This is much better when compared to drug inventory in public hospitals in other parts of India, assessed using the same methodology.[11] There are a multitude of companies and NGOs manufacturing UB medicines and the drug inventory of a health system can be made comprehensive through a mixed purchase model where procurement is done from multiple vendors.[23]

Similarly, unbranded generic drugs offered significant savings to the health system in terms of costs involved for procurement. When reviewed against the MSBs, UB medicines were costing only a fraction of the maximum retail price (MRP) of MSPs [Table 2].

Table 2

Comparison of drug prices of most-selling brands and their generic counterparts: drugs identified by WHO-HAI tool for WHO South East Asian Region[17,25]

The community pharmacy has been in operation since September 2014, and stocks over 120 formulations manufactured by unbranded generic manufacturers. In addition, it also supplies LSG to augment the drug inventory of the pharmacy. There is a family physician and a general practitioner who run the center, apart from regular specialist visits from Pushpagiri Medical College Hospital. The urban health center has an outpatient load of 20-25 patients a day within 6 months of starting operations. The staff from the center is providing services to 3 old-age homes and a few surrounding schools and the drugs from the community pharmacy is being used for free supply during the medical camps conducted by the department of community medicine.

The patients and the physicians have responded positively to this novel initiative and the general acceptability has been found to be high, though objective studies to assess the same are yet to be done. Some physicians have suggested replicating this model in other similar health initiatives also. The financial sustainability of the model is still unproven, and the urban health center along with the community pharmacy is being sustained with large subsidies provided by Pushpagiri Medical College and Bodhana Social Service Society. The cost of setting-up such a facility was around INR 500,000, which includes the furniture, basic medical equipment, basic lab accessories, and first round of procurement for the community pharmacy and is exclusive of the capital expenditure on the building. The average monthly expenditure in running the health center, has been around INR 150,000 a month, including salaries, cost of consumables and medicines and exclusive of building rent and depreciation. The income earned by the center is around INR 40,000, and there is an excess of expenditure over income to the range of more than INR 100,000 a month, which is subsidised by Pushpagiri Medical College and Bodhana Social Service Society. Both the organizations are charitable societies run by a prominent religious group and the subsidies are meant to further their commitment to social causes.

The community pharmacy concept faced the following key challenges:

  • Absence of intermediaries for drug procurement results in inordinate delays in transit, mainly on account of the tardy services rendered by private logistics companies
  • Advance payment in full has to be remitted to the bank accounts of these NGOs for supply of drugs, which goes against the standard practice of procurement followed in hospitals. This has been an issue with the internal audit department
  • The difference between procurement price and the MRP is minimal and this is causing worries of long-term financial sustainability of the community pharmacy model
  • Packaging of the drugs is unattractive in some cases, resulting in difficulty to convince patients about the efficacy of the drug
  • We have faced difficulty in convincing some of the specialist doctors on the quality of the drug, despite providing ample literature proving the efficacy of unbranded generic drugs.

The Way Forward

Many studies have revealed apprehensions among physicians in prescribing UB medicines to their patients. Most of these apprehensions are related to quality of the product and the fear of losing patients.[26] Along with these unfounded concerns, poor patient acceptability due to various issues like poor packaging, lack of brand promotion initiatives, etc., are affecting the extend of penetration of UB drugs in the country, even though India is becoming a lifeline for all developing countries in the supply of generic medicines.[27] The government and the policy makers in India and other similar developing countries should focus on building the confidence of physicians and the patients regarding unbranded generic medications. The demand side management should include a multifaceted approach in which issues of different stakeholders are addressed and affirmative actions taken in favour of unbranded generic medicine manufacturers.[27] Another important issue is concerning the inherent deficiencies and implementation status of the Drug Price Control Order of 2013. The said order has been criticised extensively for being myopic in its approach, as the number of formulations included is less than 20% of the whole pharmaceutical market. Also, it gave ample space for pharmaceutical companies to tweak their marketing strategies by focussing on formulations and dosages not covered by the Drug Price Control Order. It also leaves out the important area of fixed-dose combinations (FDCs), a potential loop-hole for the pharmaceutical companies to exploit fully. It is indeed distressing to note that more than 90% of the diabetic drug market is out of the purview of this order.[13] The policy makers in the country needs to get a realisation that the share of drugs in out-of-pocket expenditure (OPP) is around 80% in India and a tighter regulatory framework is needed to protect the consumers against exploitation.[28]

In the future, we intend to do a study on the perception about generic drugs, among the treating physicians and the patients who form the clientele of the community pharmacy. This can help us to understand the issues which affect the actual stakeholders and find means to improve the acceptability and penetration of generic medicines. Also, after the yearly financial audit, we plan to do a cost-benefit analysis to objectively analyse the efficacy of the model in monetary terms.

References

1. The World Medicines Situation 2011. The World Health Organisation. [Last accessed on 2015 Mar 2]. Available from: http://apps.who.int/medicinedocs/documents/s18772en/s18772en.pdf .
2. Cameron A, Ewen M, Ross-Degnan D, Ball D, Laing R. Medicine prices, availability, and affordability in 36 developing and middle-income countries: A secondary analysis. Lancet. 2009;373:240–9. [PubMed]
3. Health Expenditure, Total (% of GDP) | Data | Table. [Last accessed on 2015 Mar 2]. Available from: http://data.worldbank.org/indicator/SH.XPD.TOTL.ZS .
4. Microsoft Word-Briefing-Note-INDIA-2014-doc-Briefing-Note-INDIA-2014.pdf. [Last accessed on 2015 Mar 2]. Available from: http://www.oecd.org/els/health-systems/Briefing-Note-INDIA-2014.pdf .
5. Daemmrich A, Mohanty A. Healthcare reform in the United States and China: Pharmaceutical market implications. J Pharm Policy Pract. 2014;7:9. [PMC free article] [PubMed]
6. Hoffman JM, Li E, Doloresco F, Matusiak L, Hunkler RJ, Shah ND, et al. Projecting future drug expenditures–2012. Am J Health Syst Pharm. 2012;69:405–21. [PubMed]
7. Sax P. Spending on medicines in Israel in an international context. Isr Med Assoc J. 2005;7:286–91.[PubMed]
8. Cameron A, Mantel-Teeuwisse AK, Leufkens HG, Laing RO. Switching from originator brand medicines to generic equivalents in selected developing countries: How much could be saved? Value Health. 2012;15:664–73. [PubMed]
9. Hassali MA, Alrasheedy AA, McLachlan A, Nguyen TA, Al-Tamimi SK, Ibrahim MI, et al. The experiences of implementing generic medicine policy in eight countries: A review and recommendations for a successful promotion of generic medicine use. Saudi Pharm. 2014;22:491–503. [PMC free article][PubMed]
10. Duerden MG, Hughes DA. Generic and therapeutic substitutions in the UK: Are they a good thing? Br J Clin Pharmacol. 2010;70:335–41. [PMC free article] [PubMed]
11. Kotwani A, Ewen M, Dey D, Iyer S, Lakshmi PK, Patel A, et al. Prices and availability of common medicines at six sites in India using a standard methodology. Indian J Med Res. 2007;125:645–54.[PubMed]
12. Copy of f1.pdf – NPPPNotification.pdf [Internet] [Cited 2015 Mar 2, Last accessed on 2015 Mar 2]. Available from: http://www.nppaindia.nic.in/NPPPNotification.pdf .
13. Paying the Price – The Hindu. [Last accessed on 2015 Mar 2]. Available from: http://www.thehindu.com/opinion/op-ed/paying-the-price/article4912732.ece .
14. Kapczynski A. Engineered in India–patent law 2.0. N Engl J Med. 2013;369:497–9. [PubMed]
15. Bhaumik S. India’s rejection of Novartis’s patent is but a small step in the right direction. BMJ. 2013;346:f2412. [PubMed]
16. Lancet Oncology. Is India ready to lead the battle for fair access to medicines? Lancet Oncol. 2013;14:437. [PubMed]
17. Bhargava A, Kalantri SP. The crisis in access to essential medicines in India: Key issues which call for action. Indian J Med Ethics. 2013;10:86–95. [PubMed]
18. Amit G, Rosen A, Wagshal AB, Bonneh DY, Liss T, Grosbard A, et al. Efficacy of substituting innovator propafenone for its generic formulation in patients with atrial fibrillation. Am J Cardiol. 2004;93:1558–60. [PubMed]
19. Kesselheim AS, Stedman MR, Bubrick EJ, Gagne JJ, Misono AS, Lee JL, et al. Seizure outcomes following the use of generic versus brand-name antiepileptic drugs: A systematic review and meta-analysis. Drugs. 2010;70:605–21. [PMC free article] [PubMed]
20. Asia Pacific Ecumenical News-News. [Last accessed on 2015 Mar 2]. Available from: http://apenews.org/newsread.asp?nid=163 .
21. LOCOST: Medicines within the Common Man’s Reach | The Alternative. [Last accessed on 2015 Mar 2]. Available from: http://www.thealternative.in/business/locost- affordable-medicine-drugscommon-man-reach .
22. Where Are We Now: Assessing the Price, Availability and Affordability of Essential Medicines in Delhi as India Plans Free Medicine for All. [Last accessed on 2015 Mar 2]. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3733775 . [PMC free article] [PubMed]
23. Madden JM, Meza E, Ewen M, Laing RO, Stephens P, Ross-Degnan D. Measuring medicine prices in Peru: Validation of key aspects of WHO/HAI survey methodology. Rev Panam Salud Publica. 2010;27:291–9. [PubMed]
24. Drug Price List. List of Generic Names in Alphabetical Order. [Last accessed on 2015 Mar 2]. Available from: http://www.medindia.net/drug-price .
25. Generic Index | DrugsUpdate India. [Last accessed on 2015 Mar 2]. Available from: http://www.drugsupdate.com/generic/listing .
26. Waning B, Diedrichsen E, Moon S. A lifeline to treatment: The role of Indian generic manufacturers in supplying antiretroviral medicines to developing countries. J Int AIDS Soc. 2010;13:35. [PMC free article][PubMed]
27. Shrank WH, Choudhry NK, Liberman JN, Brennan TA. The use of generic drugs in prevention of chronic disease is far more cost-effective than thought, and may save money. Health Aff (Millwood) 2011;30:1351–7. [PubMed]
28. Thakkar KB, Billa G. Light at the end of the tunnel: The Great Indian Pharmacoeconomics story. Front Pharmacol. 2013;4:153. [PMC free article] [PubMed]
Source:www.ncbi.nlm.nih.gov

Generic Drugs: Questions and Answers


What are generic drugs?

A generic drug is identical — or bioequivalent — to a brand name drug in dosage form, safety, strength, route of administration, quality, performance characteristics and intended use. Although generic drugs are chemically identical to their branded counterparts, they are typically sold at substantial discounts from the branded price. According to the Congressional Budget Office, generic drugs save consumers an estimated $8 to $10 billion a year at retail pharmacies. Even more billions are saved when hospitals use generics.

Generic vs Brand: Same Quality and Performance

Is there a generic equivalent for my brand-name drug?

To find out if there is a generic equivalent for your brand-name drug, use Drugs@FDA, a catalog of FDA-approved drug products, as well as drug labeling.

You can also search for generic equivalents by using the “Electronic Orange Book.” Search by proprietary “brand” name,” then search again by using the active ingredient name. If other manufacturers are listed besides the “brand name” manufacturer when searching by the “active ingredient,” they are the generic product manufacturers.

Since there is a lag time after generic products are approved and they appear in the “Orange Book,” you should also consult the most recent monthly approvals for “First Generics“.

Are generic drugs as effective as brand-name drugs?

Yes. A generic drug is the same as a brand-name drug in dosage, safety, strength, quality, the way it works, the way it is taken and the way it should be used.

FDA requires generic drugs have the same high quality, strength, purity and stability as brand-name drugs.

Not every brand-name drug has a generic drug. When new drugs are first made they have drug patents. Most drug patents are protected for 20 years. The patent, which protects the company that made the drug first, doesn’t allow anyone else to make and sell the drug. When the patent expires, other drug companies can start selling a generic version of the drug. But, first, they must test the drug and the FDA must approve it.

Creating a drug costs lots of money. Since generic drug makers do not develop a drug from scratch, the costs to bring the drug to market are less; therefore, generic drugs are usually less expensive than brand-name drugs. But, generic drug makers must show that their product performs in the same way as the brand-name drug.

How are generic drugs approved?

Drug companies must submit an abbreviated new drug application (ANDA) for approval to market a generic product. The Drug Price Competition and Patent Term Restoration Act of 1984, more commonly known as the Hatch-Waxman Act, made ANDAs possible by creating a compromise in the drug industry. Generic drug companies gained greater access to the market for prescription drugs, and innovator companies gained restoration of patent life of their products lost during FDA’s approval process.

New drugs, like other new products, are developed under patent protection. The patent protects the investment in the drug’s development by giving the company the sole right to sell the drug while the patent is in effect. When patents or other periods of exclusivity expire, manufacturers can apply to the FDA to sell generic versions.

The ANDA process does not require the drug sponsor to repeat costly animal and clinical research on ingredients or dosage forms already approved for safety and effectiveness. This applies to drugs first marketed after 1962.

What standards do generic drugs have to meet?

Health professionals and consumers can be assured that FDA approved generic drugs have met the same rigid standards as the innovator drug. To gain FDA approval, a generic drug must:

  • contain the same active ingredients as the innovator drug(inactive ingredients may vary)
  • be identical in strength, dosage form, and route of administration
  • have the same use indications
  • be bioequivalent
  • meet the same batch requirements for identity, strength, purity, and quality
  • be manufactured under the same strict standards of FDA’s good manufacturing practice regulations required for innovator products.

Source:www.fda.gov

Are generics really the same as branded drugs?


In October the Food and Drug Administration took a highly unusual step: It declared that a generic drug it had previously approved — a version of the popular antidepressant Wellbutrin — was not in fact “bioequivalent” to the name-brand version. The FDA withdrew its approval.

If you’re a layperson, this is the way you probably think of generics: They’re the exact same products in different packaging; generics companies can sell such medications for a fraction of the cost of the originals because they don’t have to spend huge sums on drug development and marketing.

That apparent miracle explains why more than 80% of all U.S. prescriptions dispensed in 2012 were generic. Using nonbranded medications saved Americans $193 billion this past year, according to the Generic Pharmaceutical Association.

The FDA’s rules effectively acknowledge that. The agency’s definition of bioequivalence is surprisingly broad: A generic’s maximum concentration of active ingredient in the blood must not fall more than 20% below or 25% above that of the brand name. This means a potential range of 45%, by that measure, among generics labeled as being the same.

There are other differences. The generic must contain the same active ingredient as the original. But the additional ingredients, known as excipients, can be different and are often of lower quality. Those differences can affect what’s called bioavailability — the amount of drug that could potentially be absorbed into the bloodstream. As the American Heart Association recently noted, “Some additives traditionally thought to be inert, such as alcohol sugars, cyclodextrans, and polysorbate-80, may alter a drug’s dissolution, thereby impacting its bioavailability.”

That can result in drugs that release active ingredients into the blood far more quickly, leaving patients feeling dizzy or nauseated. Barbara Davit, director of the division of bioequivalence II in the FDA’s Office of Generic Drugs, acknowledges that the agency does not apply “formal statistics” to measuring Tmax, the time it takes for a drug to reach maximum concentration. But reviewers do informally consider it, she says, asserting that applications have been rejected because of Tmax results.

Much of the credit for the FDA’s decision to withdraw its approval for Teva’s version of Wellbutrin goes to Joe Graedon, a pharmacologist, advocate, and co-host, with his wife, Terry, of an NPR radio program called The People’s Pharmacy. Prompted in large part by a deluge of critical reports from listeners who felt sickened by generics or found them ineffective, he undertook his own research. In 2008 he encouraged an independent laboratory to test the generic equivalent of Wellbutrin 300 mg after listeners complained that Teva’s version, Budeprion XL, had made them feel woozy, sick to their stomach, or even suicidal.

Joe Graedon, a pharmacologist and radio host, has pushed for transparency on nonbranded drugs.

He was stunned to learn that the generic’s active ingredient dissolved four times more quickly in the first two hours than that of the brand name because of a different time-release mechanism. Graedon began pushing the FDA to release more results from generic-drug companies’ pharmacologic studies. (The FDA generally relies on company tests rather than conduct its own.)

The FDA refused to divulge the data, deeming it proprietary. For five years the agency dismissed complaints from Graedon and others that the generic Wellbutrin wasn’t the same as the original. Eventually, however, patient advocates pressured the regulators to conduct their own tests. The results revealed that on average Teva’s product achieved a 75% concentration within the blood — below the 80% minimum — and in some cases delivered as little as 40%. (This episode is extremely unusual, argues Gordon Johnston, a representative for the Generic Pharmaceutical Association, who says the FDA’s standard “has been demonstrated to assure bioequivalence between brand and generic drugs.” Johnston notes that the agency occasionally withdraws approval for name-brand drugs too.)

At a meeting of the FDA’s advisory committee for pharmaceutical science and clinical pharmacology in 2011, Dr. James Hennessey, clinical director of the division of endocrinology at Beth Israel Deaconess Medical Center in Boston, presented evidence of three different generic formulations of levothyroxine (used to treat hypothyroidism). All were more potent than the branded version and varied from one another. One was 12.5% above, another 9% above, and another 3% above the brand name’s potency. All had been approved as bioequivalent. Noting that “less than 10% dose intervals make clinical differences,” Hennessey told the advisory committee meeting, “These differences are too large.”

The committee voted to support the tightening of bioequivalence standards for narrow therapeutic index drugs. The FDA’s Davit says the agency is working on a proposal to “narrow the acceptance criteria.”

Those are the questions that hover over generics when manufacturers follow the rules. Then there are the issues that occur when they don’t.

With an estimated 80% of active drug ingredients and 40% of finished medications coming from overseas — in some cases from manufacturing plants that the FDA has not yet inspected — quality can be significantly compromised. In November the maker of generic Lipitor, Ranbaxy Pharmaceuticals, recalled 480,000 bottles after tiny shards of glass were found inside pills. (The FDA granted Ranbaxy, India’s largest generics company, permission to produce a version of the anticholesterol medication, a process Fortunechronicled in a 2011 article titled “The War Over Lipitor.” The approval came after a seven-year investigation in which the Justice Department concluded that, among other misbehavior, Ranbaxy had fabricated drug-approval data. The company agreed to pay $500 million and entered into a consent decree.)

The FDA’s position that generics are safe and therapeutically identical has rarely varied. But in October 2010, Dr. Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, acknowledged in a speech to the Generic Pharmaceutical Association, “I’ve heard it enough times from enough people to believe that there are a few products that aren’t meeting quality standards.”

Such admissions have done little to slow the drive toward generics. As Graedon points out, patients, insurers, and the government all benefit from the massive cost savings of using generics. Few have wanted to ask questions. Now, in the wake of the FDA’s action in the Teva case, that may begin to change.

Source:Fortune

Never ignore these 6 signs of hormonal balanace.


Hormonal imbalances often lead to anger, frustrations, and strange emotions with no evident reason, as hormones play a crucial role in health, affecting fertility, mood, and ovulation.

 Yet, their balance can be disrupted, often in perimenopause, puberty, and menopause, as well as due to improper lifestyle habits, pregnancy, contraceptive pills, menstrual cycle, and stress.

Hormonal imbalance and the mood swings it causes negatively affect the people around the person as well, so you should learn its early symptoms and thus diagnose it on time.

These are the six most common signs:

  1. Constant Hunger

Hormonal imbalances often lead to weight gain and food cravings, especially for sugar, which is a result of the high levels of the hormone ghrelin, which stimulates appetite.

  1. Mood Swings

Hormonal imbalances often lead to regular mood swings and feelings of anger, sadness, happiness, and madness for trivial reasons. Mood swings can also appear during the menstrual cycle and the menopause, but they are not so intense.

Progesterone is the happy hormone which gets reduced quicker, and estrogen leads to menopause.

  1. Fatigue

Constant fatigue often leads to feelings of tiredness, as a result of the higher cortisol levels. This hormone is responsible for stress.

  1. Constant Weight Gain

If you are exercising regularly and still gain weight, you might suffer from hormonal imbalance. When the hormones are normal, the metabolism dictates the weight loss.

Yet, in case the hormones are not regulated, the body cannot burn calories properly, and it becomes resistant to weight loss. In this case, you gain most fat in the abdominal area, since the body retains cortisol and estrogen.

  1. Libido loss

Hormonal imbalance reduces the sex drive, as the crucial hormones for the feminine libido, estrogen, testosterone, and the thyroid, are imbalanced. Despite the reduced sexual drive, your vagina might become dry, making the sexual intercourse uncomfortable and painful.

  1. Insomnia

Sleeping difficulties are common in the case of hormonal imbalances, especially during and after menopause, between 2-4 a.m.

The hormonal levels also cause night sweats, and the increased cortisol levels, and the reduced estrogen and progesterone levels influence the quality of the sleep.

Sources and References:
healthandlovepage.com
Cure Joy
Healthy and Natural World
Women In Balance