What Makes Target Health Different From Other CROs?
CROs provide drug, device and biologics development services for the pharmaceutical, device and biotechnology industry. When Target Health was founded 20 years ago, a colleague told us that no matter what happens in the pharmaceutical industry, there will always be a need for data and expertise in regulatory affairs.
We took that advice seriously and as of today Target Health represents over 30 clients at FDA from Australia, Denmark, England, France, Germany, Israel, Korea, Sweden Switzerland, and the US. In addition, our data management team and software tools for the paperless clinical trial are the best in the Industry.
To put the icing on the cake, last year Target e*CRF, our eDC system, was used in 3 regulatory approvals (2 in the US and 1 in Europe) and we were directly involved in the planning and execution of 2 complete NDAs and the clinical design for a 3rd NDA. For the 4th approval in Europe, we did all the early development and program execution in the US until the company was purchased by an international pharmaceutical company.
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 104). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel or Ms. Joyce Hays. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website at www.targethealth.com
American Civil War Medicine
Period painting of a US Civil War soldier, wounded by a Minie ball, lies in bed with a gangrenous amputated arm
Roughly three in five Union casualties and two in three Confederate casualties died of disease.
It has been said that the American Civil War was the first “modern war” in terms of technology and lethality of weapons, but that it was simultaneously fought “at the end of the medical Middle Ages.” Very little was known about the causes of 1) ___, and so a minor wound could easily become infected and take a life. Battlefield surgeons were under qualified and hospitals were generally poorly supplied and staffed. The most common battlefield operation was amputation. If a soldier was badly wounded in the arm or leg, amputation was usually the only solution. Surprisingly, about 75% of amputees survived the operation. Contrary to popular belief, few soldiers experienced amputation without any anesthetic. Heavy doses of chloroform were administered; in fact, a few soldiers died of chloroform poisoning, rather than their wounds. If wound produced pus, it was thought that it meant the wound was healing, when in fact it meant the injury was 2) ___.
In the war, both armies researched advancement in the development of battlefield recovery techniques. In the Union, a new medicinal wing was created under the jurisdiction of a “Medical Director of the Army”, the first field hospitals, small tents with a few tables or beds for the 3) ___, were developed, and a system of transport of the wounded to general hospitals was created, the first wooden ambulances which could hold at max around 4 wounded laying down, 1 or 2 medical officials, and a driver for the horses. The Confederacy advanced mainly by learning from Union camps they overtook, but generally had a less established medical service largely as a result of its more limited resources, vast rural areas, limited 4) ___ knowledge, and a much lesser amount of medical professionals available. The single most seen battle injury was simple flesh wounds that led to amputations of limbs due to lack of proper techniques in removing lodged bullets. Both of the armies used similar techniques in amputation – quickly drugging the soldier and removing the limb which was generally affected by the wound, or could be infected easily, effectively using skin from the extracted limb to cover the stub.
Before the Civil War, armies tended to be small, largely because of the logistics of supply and training. Musket fire, renowned for its inaccuracy, kept casualty rates lower than they might have been. The advent of railroads, industrial production, and canned food allowed for much larger armies, and the Minie ball rifle brought about much higher casualty rates. The work of Florence 5) ___in the Crimean War brought the deplorable situation of military hospitals to the public attention, although reforms were often slow in coming.
The hygiene of the camps was poor, especially at the beginning of the war when men who had seldom been far from home were brought together for training with thousands of strangers. First came epidemics of the 6) ___ diseases of chicken pox, mumps, whooping cough, and, especially, measles. Operations in the South meant a dangerous and new disease environment, bringing diarrhea, dysentery, typhoid fever, and malaria. There were no antibiotics, so the surgeons prescribed coffee, whiskey, and quinine. Harsh weather; bad water; inadequate shelter in winter quarters; poor policing of camps; and dirty camp hospitals took their toll. This was a common scenario in wars from time immemorial, and conditions faced by the Confederate army were even worse.
When the war began, there were no plans in place to treat wounded or 7) ___ Union soldiers. After the Battle of Bull Run, the United States government took possession of several private hospitals in Washington, D.C., Alexandria, Virginia, and surrounding towns. Union commanders believed the war would be short and there would be no need create a long standing source of care for the armies medical needs. This view changed after the appointment of General George B. McClellan and the organization of the Army of the Potomac. McClellan appointed the first medical director of the army, surgeon Charles S. Tripler, on August 12, 1861.
Tripler created plans to enlist regimental surgeons to travel with armies in the field, and the creation of general hospitals for the badly wounded to be taken to for recovery and further treatment. To implement the plan, orders were issued that each regiment must recruit one surgeon and one assistant surgeon to serve before they could be deployed for duty. These men served in the initial makeshift regimental hospitals. In 1862 William A. Hammond became surgeon general and launched a series of reforms. He founded the Army Medical Museum, and had plans for a hospital and a medical school in Washington; a central laboratory for chemical and pharmaceutical preparations was created; much more extensive recording was required from the hospitals and the surgeons. Hammond raised the requirements for admission into the Army Medical Corps. The number of hospitals was greatly increased and he paid close attention to aeration. New surgeons were promoted to serving at the brigade level with the rank of Major. The Surgeon Majors were assigned staffs and were charged with overseeing a new brigade level hospital that could serve as an intermediary level between the regimental and general hospitals. Surgeon Majors were also charged with ensuring that regimental surgeons were in compliance with the orders issued by the Medical Director of the Army.
In the Union, skilled, well-funded medical organizers took proactive action, especially in the much enlarged United States Army Medical Department, and the United States Sanitary Commission, a new private agency. Numerous other new agencies also targeted the medical and morale needs of soldiers, including the United States Christian Commission as well as smaller private agencies such as the Women’s Central Association of Relief for Sick and Wounded in the Army (WCAR) founded in 1861 by Henry Whitney Bellows, and Dorothea Dix. Systematic funding appeals raised public consciousness, as well as millions of dollars. Many thousands of 8) ___ worked in the hospitals and rest homes, most famously poet Walt Whitman. Frederick Law Olmstead, a famous landscape architect, (creator of NYC Central Park) was the highly efficient executive director of the Sanitary Commission.
States could use their own tax money to support their troops as Ohio did. Following the unexpected carnage at the battle of Shiloh in April 1862, the Ohio state government sent 3 steamboats to the scene as floating 9) ___ with doctors, nurses and medical supplies. The state fleet expanded to eleven hospital ships. The state also set up 12 local offices in main transportation nodes to help Ohio soldiers moving back and forth. Field hospitals were initially in the open air, with tent hospitals that could hold only six patients first being used in 1862; after many major battles the injured had to receive their care in the open. As the war progressed, nurses were enlisted, generally two per regiment. In the general hospitals one nurse was employed for about every ten patients. The first permanent general hospitals were ordered constructed during December 1861 in the major hubs of military activity in the eastern and western United States. An elaborate system of ferrying wounded and sick soldiers from the brigade hospitals to the general hospitals was set up. At first the system proved to be insufficient and many soldiers were dying in mobile hospitals at the front and could not be transported to the general hospitals for needed care. The situation became apparent to military leaders in the Peninsular Campaign in June 1862 when several thousand soldiers died for lack of medical treatment. Dr. Jonathan Letterman was appointed to succeed Tripler as the second Medical Director of the Army in 1862 and completed the process of putting together a new ambulance corps. Each regiment was assigned two wagons, one carrying medical supplies, and a second to serve as a transport for wounded soldiers. The 10) ___ corps was placed under the command of Surgeon Majors of the various brigades. In August 1863 the number of transport wagons was increased to three per regiment.
Union medical care improved dramatically during 1862. By the end of the year each regiment was being regularly supplied with a standard set of medical supplies included medical books, supplies of medicine, small hospital furniture like bed-pans, containers for mixing medicines, spoons, vials, bedding, lanterns, and numerous other implements. A new layer of medical treatment was added in January 1863. A division level hospital was established under the command of a Surgeon-in-Chief. The new divisional hospitals took over the role of the brigade hospitals as a rendezvous point for transports to the general hospitals. The wagons transported the wounded to nearby railroad depots where they could be quickly transported to the general hospitals at the military supply hubs. The divisional hospitals were given large staffs, nurses, cooks, several doctors, and large tents to accommodate up to one hundred soldiers each. The new division hospitals began keeping detailed medical 11) ___ of patients. The divisional hospitals were established at a safe distance from battlefields where patients could be safely helped after transport from the regimental or brigade hospitals.
Although the divisional hospitals were placed in safe locations, because of their size they could not be quickly packed in the event of a retreat. Several divisional hospitals were lost to Confederates during the war, but in almost all occasions their patients and 12) ___ were immediately paroled if they would swear to no longer bear arms in the conflict. On a few occasions, the hospitals and patients were held several days and exchanged for Confederate prisoners of war.
The U.S. Army learned many lessons and in 1886, it established the Hospital Corps. The Sanitary Commission collected enormous amounts of statistical data, and opened up the problems of storing information for fast access and mechanically searching for data patterns.
ANSWERS: 1) disease; 2) infected; 3) wounded; 4) medicinal; 5) Nightingale; 6) childhood; 7) sick; 8) volunteers; 9) hospitals; 10) ambulance; 11) records; 12) doctors
Florence Nightingale 1820 – 1910
Young Florence Nightingale
Florence Nightingale was a celebrated English social reformer and statistician, and the founder of modern nursing. She came to prominence while serving as a nurse during the Crimean War, where she tended to wounded British soldiers. She was dubbed “The Lady with the Lamp” after her habit of making rounds at night. Nightingale’s achievements are all the more impressive when they are considered against the background of social restraints on women in Victorian England. Her father, William Edward Nightingale, was an extremely wealthy landowner, and the family moved in the highest circles of English society. In those days, women of Nightingale’s class did not attend universities and did not pursue professional careers; their purpose in life was to marry and bear children. Nightingale was fortunate. Her father believed women should be educated, and he personally taught her Italian, Latin, Greek, philosophy, history and – most unusual of all for women of the time – writing and mathematics.
Florence Nightingale mentored Linda Richards, “America’s first trained nurse”, and enabled her to return to the USA with adequate training and knowledge to establish high-quality nursing schools. Linda Richards went on to become a great nursing pioneer in the USA and Japan.
Before the experiments of the mid-1860s by Pasteur and Lister, hardly anyone took germ theory seriously; even afterwards, many medical practitioners were unconvinced. However, in the early 1880s, Florence Nightingale wrote an article for a textbook in which she advocated strict precautions designed, she said, to kill germs. Nightingale’s work served as an inspiration for nurses in the American Civil War. The Union government approached her for advice in organizing field medicine. Although her ideas met official resistance, they inspired the volunteer body of the United States Sanitary Commission.
Florence Nightingale exhibited a gift for mathematics from an early age and excelled in the subject under the tutorship of her father. Later, Nightingale became a pioneer in the visual presentation of information and statistical graphics. She used methods such as the pie chart, which had first been developed by William Playfair in 1801. Indeed, Nightingale is described as “a true pioneer in the graphical representation of statistics”, and is credited with developing a form of the pie chart now known as the polar area diagram, or occasionally the Nightingale rose diagram, equivalent to a modern circular histogram. Nightingale used these techniques in order to illustrate seasonal sources of patient mortality in the military field hospital she managed.
In 1860, Nightingale laid the foundation of professional nursing with the establishment of her nursing school at St Thomas’ Hospital in London. It was the first secular nursing school in the world, now part of King’s College London. The Nightingale Pledge taken by new nurses was named in her honor, and the annual International Nurses Day is celebrated around the world on her birthday. Her social reforms include improving healthcare for all sections of British society; improving healthcare and advocating for better hunger relief in India; helping to abolish laws regulating prostitution that were overly harsh to women; and expanding the acceptable forms of female participation in the workforce.
Nightingale was born to a wealthy upper-class family, at a time when women of her class were expected to focus on marriage and child bearing. Unitarian religious inspiration led her to devote her life to serving others, both directly and as a reformer. Nightingale rejected proposals of marriage so as to be free to pursue her calling. Her father had progressive social views, providing his daughter with a well-rounded education that included mathematics and supported her desire to lead an active life. Nightingale’s ability to effect reform rested on her exceptional analytic skills, her high reputation, and her network of influential friends. Starting in her mid-30s, she suffered from chronic poor health, but continued working almost until her death at the age of ninety.
In her youth she was respectful of her family’s opposition to her working as a nurse, only announcing her decision to enter the field in 1844. Despite the intense anger and distress of her mother and sister, she rebelled against the expected role for a woman of her status to become a wife and mother. Nightingale worked hard to educate herself in the art and science of nursing, in spite of opposition from her family and the restrictive social code for affluent young English women.
In Rome in 1847, she met Sidney Herbert, a politician who had been Secretary at War (1845–1846). Herbert would be Secretary of War again during the Crimean War; he and his wife were instrumental in facilitating Nightingale’s nursing work in the Crimea.
Nightingale circa 1854
While traveling in Thebes, she wrote of being “called to God” while a week later near Cairo she wrote in her diary: “God called me in the morning and asked me would I do good for him alone without reputation.” Later in 1850, she visited the Lutheran religious community at Kaiserswerth-am-Rhein in Germany, where she observed Pastor Theodor Fliedner and the deaconesses working for the sick and the deprived. She regarded the experience as a turning point in her life, and issued her findings anonymously in 1851. The Institution of Kaiserswerth on the Rhine, for the Practical Training of Deaconesses, etc. was her first published work; she also received four months of medical training at the institute which formed the basis for her later care. On 22 August 1853, Nightingale took the post of superintendent at the Institute for the Care of Sick Gentlewomen in Upper Harley Street, London, a position she held until October 1854.
A print of the jewel awarded to Nightingale by Queen Victoria, for her services to British soldiers in the war
The territory of Crimea was conquered and controlled many times throughout its history. The Cimmerians, Greeks, Scythians, Goths, Huns, Bulgars, Khazars, the state of Kievan Rus’, Byzantine Greeks, Kipchaks, Ottoman Turks, Golden Horde Tatars and the Mongols, all controlled Crimea in its early history. In the 13th century, it was partly controlled by the Venetians and by the Genovese. They were followed by the Crimean Khanate and the Ottoman Empire in the 15th to 18th centuries. The Russian Empire conquered Crimea in the 18th to 20th centuries followed by Germany during World War II, then the Russian Soviet Federative Socialist Republic and later the Ukrainian Soviet Socialist Republic. Finally it was within the Soviet Union during most of the rest of the 20th century. Crimea is now an autonomous parliamentary republic, within Ukraine, which is governed by the Constitution of Crimea in accordance with the laws of Ukraine.
The Crimean war was part of a long-running contest between major European powers for influence over territories of the declining Ottoman Empire. About 250,000 men died on the Russian side and the same number on the British-French-Turkish-Austrian side – many of them victims to disease. The war did not settle the relations of the powers in eastern Europe. It made, however, the new Russian emperor Alexander II realize Russia was a backward country that had to sharpen up to compete successfully with other European powers. A further result of the war was that Austria, having sided with Great Britain and France, lost the support of Russia in central European affairs. Austria became dependent on Britain and France, which failed to support that country, leading to the Austrian defeats in 1859 and 1866 that, in turn, led to the unification of Italy and Germany.
The Crimean War (1854-56) developed because of an argument between the French and Russian religious fraternities over who should have access and right to holy areas in the Middle East, namely Nazareth and Jerusalem. The whole debate had been escalated to a level beyond all reason. The situation was compounded when the Russians, under the directive of Tsar Nicholas I, moved troops into the area, supposedly to shield the aforementioned sacred grounds, and positioned Russian troops in the Middle East, then a part of the Turkish Ottoman Empire. When the Russians upped the stakes by massacring a small fleet of Turkish boats, the Turks and their allies (mainly British & French) responded with war.
A tinted lithograph by William Simpson illustrating conditions of the sick and injured in Balaklava
A ward of the hospital at Scutari where Nightingale worked, from an 1856 lithograph
“Nightingale receiving the Wounded at Scutari”, a portrait by Jerry Barrett
Florence Nightingale’s most famous contribution came during the Crimean War, which became her central focus when reports got back to Britain about the horrific conditions for the wounded. On 21 October 1854, she and the staff of 38 women volunteer nurses that she trained, including her aunt Mai Smith, were sent (under the authorization of Sidney Herbert) to the Ottoman Empire. They were deployed about 339 miles across the Black Sea from Balaklava in the Crimea, where the main British camp was based. Nightingale arrived early in November 1854 at Selimiye Barracks in Scutari (modern-day Uskudar in Istanbul). Her team found that poor care for wounded soldiers was being delivered by overworked medical staff in the face of official indifference. Medicines were in short supply, hygiene was being neglected, and mass infections were common, many of them fatal. There was no equipment to process food for the patients.
After Nightingale sent a plea to The Times for a government solution to the poor condition of the facilities, the British Government commissioned Isambard Kingdom Brunel to design a prefabricated hospital which could be built in England and shipped to the Dardanelles. The result was Renkioi Hospital, a civilian facility which under the management of Dr. Edmund Alexander Parkes had a death rate less than 1/10th that of Scutari.
The first edition of the Dictionary of National Biography (1911) asserted that Nightingale reduced the death rate from 42% to 2% either by making improvements in hygiene herself or by calling for the Sanitary Commission. However, death rates actually began to rise to the highest of all hospitals in the region. During her first winter at Scutari, 4,077 soldiers died there, with 10x more soldiers dying from illnesses such as typhus, typhoid, cholera and dysentery than from battle wounds. With overcrowding, defective sewers and lack of ventilation, the Sanitary Commission had to be sent out by the British government to Scutari in March 1855, almost six months after Florence Nightingale had arrived. When the commission flushed out the sewers and improved ventilation, the death rates were sharply reduced.
After she returned to Britain and began collecting evidence before the Royal Commission on the Health of the Army, Nightingdale came to believe that most of the soldiers at the hospital were killed by poor living conditions. This experience influenced her later career, when she advocated sanitary living conditions as of great importance. Consequently, she reduced peacetime deaths in the army and turned attention to the sanitary design of hospitals.
Traumatic Brain Injury From the Civil War Until Today
Credit: Dr. Stanley B. Burns
The photo above shows a 21-year-old corporal who was shot in the head at the Battle of Farmville in 1865, shortly before the South surrendered in the Civil War. Years after he was discharged, his physician noted, “He has many symptoms of disturbance to the brain.”
What is Traumatic Brain Injury?
Traumatic brain injury (TBI), a form of acquired brain injury, occurs when a sudden trauma causes damage to the brain. TBI can result when the head suddenly and violently hits an object, or when an object pierces the skull and enters brain tissue. Symptoms of a TBI can be mild, moderate, or severe, depending on the extent of the damage to the brain. A person with a mild TBI may remain conscious or may experience a loss of consciousness for a few seconds or minutes. Other symptoms of mild TBI include headache, confusion, lightheadedness, dizziness, blurred vision or tired eyes, ringing in the ears, bad taste in the mouth, fatigue or lethargy, a change in sleep patterns, behavioral or mood changes, and trouble with memory, concentration, attention, or thinking. A person with a moderate or severe TBI may show these same symptoms, but may also have a headache that gets worse or does not go away, repeated vomiting or nausea, convulsions or seizures, an inability to awaken from sleep, dilation of one or both pupils of the eyes, slurred speech, weakness or numbness in the extremities, loss of coordination, and increased confusion, restlessness, or agitation.
Anyone with signs of moderate or severe TBI should receive medical attention as soon as possible. Because little can be done to reverse the initial brain damage caused by trauma, medical personnel try to stabilize an individual with TBI and focus on preventing further injury. Primary concerns include insuring proper oxygen supply to the brain and the rest of the body, maintaining adequate blood flow, and controlling blood pressure. Imaging tests help in determining the diagnosis and prognosis of a TBI patient. Patients with mild to moderate injuries may receive skull and neck X-rays to check for bone fractures or spinal instability. For moderate to severe cases, the imaging test is a computed tomography (CT) scan. Moderately to severely injured patients receive rehabilitation that involves individually tailored treatment programs in the areas of physical therapy, occupational therapy, speech/language therapy, physiatry (physical medicine), psychology/psychiatry, and social support.
Approximately half of severely head-injured patients will need surgery to remove or repair hematomas (ruptured blood vessels) or contusions (bruised brain tissue). Disabilities resulting from a TBI depend upon the severity of the injury, the location of the injury, and the age and general health of the individual. Some common disabilities include problems with cognition (thinking, memory, and reasoning), sensory processing (sight, hearing, touch, taste, and smell), communication (expression and understanding), and behavior or mental health (depression, anxiety, personality changes, aggression, acting out, and social inappropriateness). More serious head injuries may result in stupor, an unresponsive state, but one in which an individual can be aroused briefly by a strong stimulus, such as sharp pain; coma, a state in which an individual is totally unconscious, unresponsive, unaware, and unarousable; vegetative state, in which an individual is unconscious and unaware of his or her surroundings, but continues to have a sleep-wake cycle and periods of alertness; and a persistent vegetative state (PVS), in which an individual stays in a vegetative state for more than a month.
The National Institute of Neurological Disorders and Stroke (NINDS) conducts TBI research in its laboratories at the National Institutes of Health (NIH) and also supports TBI research through grants to major medical institutions across the country. This research involves studies in the laboratory and in clinical settings to better understand TBI and the biological mechanisms underlying damage to the brain. This research will allow scientists to develop strategies and interventions to limit the primary and secondary brain damage that occurs within days of a head trauma, and to devise therapies to treat brain injury and improve long-term recovery of function.
Treatment of Infectious Disease – From the Civil War to the Present (2013)
A Union field hospital during the Battle of Savage Station, June 1862
Photo: Library of Congress
The American Civil War represents a landmark in military and medical history as the last large-scale conflict fought without knowledge of the germ theory of disease. Unsound hygiene, dietary deficiencies, and battle wounds set the stage for epidemic infection, while inadequate information about disease causation greatly hampered disease prevention, diagnosis, and treatment. Pneumonia, typhoid, diarrhea/dysentery, and malaria were the predominant illnesses. Altogether, two-thirds of the approximately 660,000 deaths of soldiers were caused by uncontrolled infectious diseases, and epidemics played a major role in halting several major campaigns. These delays, coming at a crucial point early in the war, prolonged the fighting by as much as 2 years
Many infectious diseases are increasingly difficult to treat because of antimicrobial-resistant organisms, including HIV infection, staphylococcal infection, tuberculosis, influenza, gonorrhea, candida infection, and malaria. Between 5-10% of all hospital patients develop an infection. About 90,000 of these patients die each year as a result of their infection, up from 13,300 patient deaths in 1992. According to the Centers for Disease Control and Prevention (April 2011), antibiotic resistance in the United States costs an estimated $20 billion a year in excess health care costs, $35 million in other societal costs and more than 8 million additional days that people spend in the hospital. People infected with antimicrobial-resistant organisms are more likely to have longer hospital stays and may require more complicated treatment.
Microbes, such as bacteria, viruses, fungi, and parasites, are living organisms that evolve over time. Their primary function is to reproduce, thrive, and spread quickly and efficiently. Therefore, microbes adapt to their environments and change in ways that ensure their survival. If something stops their ability to grow, such as an antimicrobial, genetic changes can occur that enable the microbe to survive. There are several ways this happens.
Natural (Biological) Causes and Selective Pressure: In the presence of an antimicrobial, microbes are either killed or, if they carry resistance genes, survive. These survivors will replicate, and their progeny will quickly become the dominant type throughout the microbial population.
Mutation: Most microbes reproduce by dividing every few hours, allowing them to evolve rapidly and adapt quickly to new environmental conditions. During replication, mutations arise and some of these mutations may help an individual microbe survive exposure to an antimicrobial.
Gene Transfer: Microbes also may get genes from each other, including genes that make the microbe drug resistant.
Societal Pressures: The use of antimicrobials, even when used appropriately, creates a selective pressure for resistant organisms. However, there are additional societal pressures that act to accelerate the increase of antimicrobial resistance.
Inappropriate Use: Selection of resistant microorganisms is exacerbated by inappropriate use of antimicrobials. Sometimes healthcare providers will prescribe antimicrobials inappropriately, wishing to placate an insistent patient who has a viral infection or an as-yet undiagnosed condition.
Inadequate Diagnostics: More often, healthcare providers must use incomplete or imperfect information to diagnose an infection and thus prescribe an antimicrobial just-in-case or prescribe a broad-spectrum antimicrobial when a specific antibiotic might be better. These situations contribute to selective pressure and accelerate antimicrobial resistance.
Hospital Use: Critically ill patients are more susceptible to infections and, thus, often require the aid of antimicrobials. However, the heavier use of antimicrobials in these patients can worsen the problem by selecting for antimicrobial-resistant microorganisms. The extensive use of antimicrobials plus close contact among sick patients creates a fertile environment for the spread of antimicrobial-resistant germs.
Agricultural Use: More than half of the antibiotics produced in the United States are used for agricultural purposes. However, there is still much debate about whether drug-resistant microbes in animals pose a significant public health burden. The decades-long saga over the withdrawal of approval of certain uses of certain classes of antibiotics in food-producing animals is likely to continue for some time given an August 8, 2012 decision from the U.S. District Court for the Southern District of New York. The decision stems from a 2011 lawsuit filed against FDA by the National Resources Defense Council (“NRDC”) and three other member groups of “Keep Antibiotics Working.”
Soldier Who Lost All Four Limbs in Iraq Bomb Blast Receives Double Arm Transplant
This picture shows a prosthetics factory in the late 1800s. Almost 150 patents were issued for artificial limb designs between 1861 and 1873
The most extensive bilateral arm transplant to date has been successfully achieved thanks to an interdisciplinary team of doctors and nurses at John Hopkins Hospital. The operation, which was performed on December 18, lasted 13 hours and involved 16 physicians from orthopedics, vascular medicine, plastic surgery, and other disciplines from five hospitals.
Brendan Marrocco, injured by a roadside bomb in 2009, was the first soldier to survive after losing all four limbs in the Iraq war. Today, the 26-year-old patient, can flex his left arm at the elbow along with slightly rotating his wrist, though the feeling in his hands have not returned.
For the procedures, two different approaches were involved for each arm to preserve the residual limbs. The right arm had an above-elbow transplant by connecting the bone, muscles, blood vessels, nerves and skin between the donor arm and recipient. For the left side, the elbow joint was preserved, as were some of the nerves, so the surgical team transplanted the entire donor forearm muscles over his remaining tissues, then rerouted the nerves to the new muscle. Because of the complexity involved in connecting all the tissues together, the team practiced on cadaver arms four times over a span of 18 months prior to the surgery.
The risk of transplant rejection is high, so the Hopkins team employed an innovative approach of infusing the patient with bone marrow cells harvested from the donor’s lower vertebrae. This allows for only some of the standard three-drug regiments used to prevent limb rejection, which is important because the anti-rejection drugs can compromise the immune system and damage organs. Since the patient is young, it was important that a shortened lifespan was not one of the consequences of receiving the double transplant.
Though the costs of the procedure and rehabilitation are being covered by the DOD’s Armed Forces Institute of Regenerative Medicine and John Hopkins, all the physicians involved volunteered their services.
Brendan now joins a growing list of patients worldwide to receive double arm transplants and becomes only the seventh to do so in the US. As doctors become more confident in the procedure and collaborate with various specialists, these double transplants will likely increase. A widely reported story last fall of a Texas woman who lost all of her limbs due to an invasive streptococcal infection (the flesh-eating bacteria) has been approved to also receive a double arm transplant, and was last known to be waiting for a donor.
Though the first reported double arm transplant was successfully performed in Germany in 2008, some limb transplants have been rejected. In 2010, a Turkish man received a quadruple limb transplant, but the limbs had to be removed after “metabolic complications.”
TARGET HEALTH excels in Regulatory Affairs. Each week we highlight new information in this challenging area
FDA Approval of Generic Version of Cancer Drug Doxil Is Expected To Help Resolve Shortage
Generic drugs approved by the FDA must have the same high quality and strength as brand-name drugs. The generic manufacturing and packaging sites must pass the same quality standards as those of brand-name drugs.
Doxorubicin hydrochloride liposome injection is currently on the FDA’s drug shortage list. For products on the shortage list, the FDA’s Office of Generic Drugs is using a priority review system to expedite the review of generic applications to help alleviate shortages.
The FDA has approved the first generic version of the cancer drug Doxil (doxorubicin hydrochloride liposome injection). The generic is made by Sun Pharma Global FZE (Sun) and will be available in 20 milligram and 50 milligram vials.
In February 2012, to address the shortage of doxorubicin hydrochloride liposome injection, the FDA announced it would exercise enforcement discretion for temporary controlled importation of Lipodox (doxorubicin hydrochloride liposome injection), an alternative to Doxil, produced by Sun and its authorized distributor, Caraco Pharmaceutical Laboratories Ltd. At that point Lipodox was not approved in the US. Enforcement discretion was also used to release one lot of Janssen’s Doxil made under an unapproved manufacturing process.
For the present time, FDA intends to continue exercising enforcement discretion for importation of Lipodox, and to male available, limited supplies of Doxil. Once supplies of Sun’s generic doxorubicin hydrochloride liposome injection are sufficient to meet projected demand, FDA expects to stop exercising enforcement discretion for any unapproved doxorubicin HCl liposomal product.
Food From North and South
The dish below was served at a tasting at a Manhattan hotel, the Roger Smith, on Lexington Avenue near 47th Street. The event was organized by a historian, Andrew F. Smith. The recipe was found in a cookbook published in the Civil War era and adapted by Mr. Smith and by the Roger Smith’s executive chef, Daniel Mowles.
1 and 1/2 pounds skirt steak (in 1/8-inch slices)
1/2 cup soy sauce
1/2 cup Worcestershire sauce
2 teaspoons salt
1/2 teaspoon black pepper
1/2 teaspoon onion powder
1/2 teaspoon garlic powder
1/2 teaspoon chili flakes
Mix soy sauce, Worcestershire sauce, salt, black pepper, onion powder, garlic powder and chili flakes in a bowl and marinate the beef in mix for 24 hours. Place on a rack in a 150-degree oven for 4 hours until crispy.
American Civil War Recipes
Union Hardtack and Confederate Johnnie Cakes
The photograph, below, shows what a Commissary looked like during the war. Large wooden barrels containing salted meat, coffee beans, and sugar are stacked next to crates of hardtack. It took a lot of food to feed the army even for one day!
Temporary Union Commissary Depot (photo Library of Congress)
Feeding the troops was the responsibility of the Commissary Department, and both the Union and Confederacy had one. The job of this organization was to purchase food for the armies, store it until it could be used, and then supply the soldiers. It was difficult to supply so many men in so many places and the North had a greater advantage as their commissary system was already established at the outbreak of the war, while the Confederacy struggled for many years to obtain food and then get it to their armies. Choices of what to give the troops was limited as they did not have the conveniences to preserve food like we have today.
Meats were salted or smoked while other items such as fruits and vegetables were dried or canned. They did not understand proper nutrition so often there was a lack of certain foods necessary for good health. Each side did what they could to provide the basics for the soldiers to survive. Because it was so difficult to store for any length of time, the food soldiers received during the Civil War was not very fancy and they did not get a great variety of items.
The Confederate Cookbook: Family Favorites from the Sons of Confederate Veterans
340 of Dixie’s finest recipes courtesy of contemporary Confederate kitchens from Florida to Alaska. Here you’ll find the delicious, traditional dishes that evoke the flavor of the Old South, as well as savory regional favorites from all over the country. Fascinating historic anecdotes and previously unpublished, nostalgic sepia-toned images of identified Confederate soldiers are here for maximum visual appeal, along with easy-to-use instructions for making memorable dishes. The daily allowance of food issued to soldiers was called rations. Everything was given out uncooked so the soldiers were left up to their own ingenuity to prepare their meals. Small groups would often gather together to cook and share their rations and they called the group a “mess”, referring to each other as “messmates”. Others prided themselves in their individual taste and prepared their meals alone. If a march was imminent, the men would cook everything at once and store it in their haversack, a canvas bag made with a sling to hang over the shoulder. Haversacks had an inner cloth bag that could be removed and washed, though it did not prevent the bag from becoming a greasy, foul-smelling container after several weeks of use. The soldier’s diet was very simple – meat, coffee, sugar, and a dried biscuit called hardtack. Of all the items soldiers received, it was this hard bread that they remembered and joked about the most.
Hardtack was a biscuit made of flour with other simple ingredients, and issued to Union soldiers throughout the war. Hardtack crackers made up a large portion of a soldier’s daily ration. It was square or sometimes rectangular in shape with small holes baked into it, similar to a large soda cracker. Large factories in the north baked hundreds of hardtack crackers every day, packed them in wooden crates and shipped them out by wagon or rail. If the hardtack was received soon after leaving the factory, they were quite tasty and satisfying. Usually, the hardtack did not get to the soldiers until months after it had been made. By that time, they were very hard, so hard that soldiers called them “tooth dullers” and “sheet iron crackers”. Sometimes they were infested with small bugs the soldiers called weevils, so they referred to the hardtack as “worm castles” because of the many holes bored through the crackers by these pests. The wooden crates were stacked outside of tents and warehouses until it was time to issue them. Soldiers were usually allowed six to eight crackers for a three-day ration. There were a number of ways to eat them- plain or prepared with other ration items. Soldiers would crumble them into coffee or soften them in water and fry the hardtack with some bacon grease. One favorite soldier dish was salted pork fried with hardtack crumbled into the mixture. Soldiers called this “skillygallee”, and it was a common and easily prepared meal.
Chicken Purlough (Confederate recipe)
Kill and dress one whole chicken.
Place in water to cover, simmer for several hours until tender. (replace water as necessary)
Remove from fire and cool.
Remove bones, fat and skin from chicken and feed to yard critters.
Use remaining broth to cook rice. Add salt, pepper and other spices to taste.
Add boned chicken when rice is partially done. You might add paprika or small red peppers to add not only taste but color.
This is a recipe handed down for many generations as almost everyone was able to maintain chickens as a farmyard food supplement. They provided eggs AND meat. Rice was also plentiful in the south as a staple food.
CRAWDADS (or crayfish to some folks) – Confederate
- 2-3 quarts water
- Juice from 1 lemon (about 1/4 cup)
- 1/2 cup onion, chopped
- 1 stalk celery with leaves, chopped
- 1 clove garlic, chopped
2-3 dozen crawdads, gathered from nearby stream, UPSTREAM from where men have bathed, relieved themselves, or exercised the horses. Chop or twist off upper body of crawdad and throw them to company dog, as only the tail has enough meat to be worth eating. Combine everything except crawdads in pot over fire and heat to boiling. Add crawdads and heat till it boils again, then back off from fire and cook until meat is opaque (white) all the way through. Remove and eat at once or put in cold water to eat later; if left in hot water they will get overdone and tough.
Union Recipe – EGGS ON THE MARCH
Eggs may be roasted by standing them on end in hot ashes. They may be boiled hard to carry in the pockets on forced marches. Now after this gourmet repast, you may feel the need for something to wash it all down with. Keep this trick in mind: If you have any tea left, do not throw it away. Fill your canteens with it. It is infinitely more refreshing than almost any other drink upon a hot, weary march. If, instead of filling your canteen with fresh water, you would boil it in the morning, before starting, with enough tea to flavor it and keeping it from becoming insipid when warmed by the sun, it would be a thousand times more healthy, and the best prevention of dysentery. Water which has been boiled is freed from the bad effects it frequently has. The southern people boil their lemonade, and then allow it to cool before using it. Learn from your enemies how to protect yourselves in their climate.
Union Hardtack Recipe
2 cups of flour
1/2 to 3/4 cup water
1 tablespoon of Crisco or vegetable fat
6 pinches of salt
Mix the ingredients together into a stiff batter, knead several times, and spread the dough out flat to a thickness of 1/2 inch on a non-greased cookie sheet. Bake for one-half an hour at 400 degrees. Remove from oven, cut dough into 3-inch squares, and punch four rows of holes, four holes per row into the dough. Turn dough over, return to the oven and bake another one-half hour. Turn oven off and leave the door closed. Leave the hardtack in the oven until cool. Remove and enjoy!
PLAIN IRISH STEW FOR FIFTY MEN
Cut fifty pounds of mutton into pieces which equal 1/4 pound each. Put them in a pan and add twelve pounds of whole potatoes. In addition, add eight tablespoons of salt and three teaspoons of pepper. Cover all with water, giving about half-a-pint to each pound of meat. Light the fire and 1 to 1 1/2 hours of gentle ebulation will make a most excellent stew. Mash some of the potatoes to thicken the gravy, and serve.
To Roast Any Small Birds
Lard them with slips of bacon, put them on a skewer, tie it to the spit at both ends. Dredge and baste them. Let them roast ten minutes. Take the grated crumb of half a loaf of bread with a piece of butter the size of a walnut. Put it in a stew-pan and shake it over a gentle fire till it is of a light brown. Lay it between your birds and pour over them a little melted butter.
Swamp Cabbage Stew
cajun seasoning or cayenne pepper (not both)
It is hard to tell exact portions as this is a taste to see if it’s right
Cut up salt pork into chunks, fry in cast iron pot. (large) Slice, not chop, onions and cabbage. Fry these in pot with salt pork. Add stewed tomatoes to make a stew. (remember this will cook down so add water if necessary so it doesn’t burn.) Add spices to taste. Add slowly and a little bit at a time, the taste will blend the longer it cooks. Cook at a very low heat for 4-5 hours. Taste at least once every hour so you can tell if you need more seasoning. Served with hush puppys or fried corn bread, this is good.
Confederate Johnnie Cake Recipe
two cups of cornmeal
2/3 cup of milk
2 tablespoons vegetable oil
2 teaspoon baking soda
1/2 teaspoon of salt
Mix ingredients into a stiff batter and form eight biscuit-sized “dodgers”. Bake on a lightly greased sheet at 350 degrees for twenty to twenty five minutes or until brown. Or, spoon the batter into hot cooking oil in a frying pan over a low flame. Remove the corn dodgers and let cool on a paper towel, spread with a little butter or molasses, and you have a real southern treat!
Mix a stiff dough of Indian (corn) meal, a little salt, and water (scalding is best). Flatten it on a board and tilt it up before the campfire until brown on one side. Turn and brown the other side. When our fathers fought the Indians, and ground their corn in mortars, they thought hoe-cake very good. It can also be baked in hot ashes or with hot stones (southern fashion).
Lodge Camp Dutch Oven
The legs are for ease of use in campfires. Flanged lid to place coals on top of oven. Great for stews, chilli, roasts complete recipes for everything including old-fashioned bread. A must for reenactors villages.
Some of the other items that soldiers received were salt pork, fresh or salted beef, coffee, sugar, salt, vinegar, dried fruit and dried vegetables. If the meat was poorly preserved, the soldiers would refer to it as “salt horse”. Sometimes they would receive fresh vegetables such as carrots, onions, turnips and potatoes. Confederate soldiers did not have as much variety in their rations as Union soldiers did. They usually received bacon and corn meal, tea, sugar or molasses, and fresh vegetables when they were available. While Union soldiers had their “skillygallee”, Confederates had their own version of a quick dish on the march. Bacon was cooked in a frying pan with some water and corn meal added to make a thick, brown gravy similar in consistency to oatmeal. The soldiers called it “coosh” and though it does not sound too appetizing, it was a filling meal and easy to fix.
15 Inch Cast-Iron Skillet
Large Skillet 2.25 inches in depth. Not for standard home stove. Perfect for use on the Grill or over campfires when you are cooking for the “troops”. Opposite handle for easy use of this heavy skillet.
Confederates On Horseback
Sm. rounds of bread, Drained oysters, Thin slice of bacon, spread with anchovy paste or horseradish, Toothpicks.
Toast bread to light brown and butter lightly. Wrap oysters in bacon and secure with a toothpick. Bake at 400 degrees about 5 minutes or until bacon is crisp. Drain well and remove the toothpick. Serve on toast.
You can substitute boiled chicken livers for the oysters for a change
This recipe was found in an 1873 Natchez cookbook, and someone had penciled in the margin.”It got us through the war”.
Below are a few period recipes (kept intact) found from CW soldiers’ dairies.
Apples. eaten raw, w/ or w/out skins w/ Hardtack oar’deuvre.
Apples, sliced and cored tossed into the canteen half w/ the salt pork and some taters. Fried until they’re all dead.
Corn, still in the husk… toss into the fire and watch until they finish steaming. If they start on fire and the kernals are burnt. give em to the reb prisoners and be happy w/ the govt pilot bread.
Camp pot: Sweet taters sliced very thin, salt pork sliced thin, add a handful of dried apples, a couple turnips, cabbage and onions sliced fine if you can “acquire” them. Add the residual coffee beans from the coffee pot and a handful of salt. Cover w/ water and cook until it looks done or until you have to hit the march.
“Happy soldiers Breakfast” Two egges stolen, a handful of flour “borrowed” and a couple parsnips donated from the ground. Take a bit of the issue salt horse and grease the pan. Slice it real thin like and fry it up like bacon. Eat the bacon as you add the sliced parsnips to the pan. Make sure you don’t spill no grease. Once the parsnips is soft eat em up and toss in the eggs and flour and bake into a bread. Site better than nothing and plenty filling.
“Footsore soldiers coffee” Whatever beans the commisary pretends are coffee, add a handful of willow bark and chichory. Boil.
4 ears corn
1 onion (diced)
1 Tablespoon butter
Shuck and remove silk from corn. Cut corn off ear and place in sauté pan with butter and onions. Season the corn with salt and pepper and cook for 15 minutes until golden brown.
Braised Turnip Greens
2 bunches turnip greens
1 onion (sliced)
1 tablespoon salt
1 piece fatback
Rinse greens under cold water and soak for 1 hour. Add greens and onions to boiling water with fat back and salt. Cook for 20 minutes and serve.
Fried Catfish with Confederate Ketchup
2 catfish fillets
1 cup flour or cornmeal
salt and pepper
1 cup pork fat
Roll catfish in cornmeal and fry in a black skillet with pork fat. Cook on each side for 5 minutes and then serve with homemade ketchup.
Constructed of forged iron, this will hold Cast Iron Dutch Ovens. It’s easy to set up and has an adjustable 26” chain so you’ve got control of the heat. Holds up to 40 lbs
Civil War Food – Camden, NJ Historical Society
The Devilish Details
Mark L. Horn, MD, MPH, Chief Medical Officer, Target Health Inc.
With the inspiration of the New York Times Editorial Page (A Cruel Blow to American Families/Sunday, February 3rd/Sunday Review Page 10) and the permission of On Target editors, we shall take a trip into the weeds this week and take note of how seemingly arcane rules can undermine the best of intentions.
Among the most clearly stated and widely appreciated aims of the Affordable Care Act (in fact, perhaps the primary goal of the Act) was expanding the pool of insured. Children, self-evidently among the most vulnerable, were a special concern. Reflecting this concern and also to help secure the political support of the already insured and generally more affluent segments of the population, among the first elements of the Act to become operational was a requirement that children up to age 26 be allowed to continue coverage under parental employer plans. Less affluent (and more likely uninsured) families had to wait but were expected (at least by most) to ultimately receive both insurance and income based premium assistance through the ACA mandated insurance exchanges due to become operational in 2014.
Many of us (me included) while not bothering to read the fine print simply assumed that, for most citizens at least, premium assistance would be designed to enable the purchase of insurance by all those so inclined. The ACA was, for many though admittedly not all, designed to solve the affordability problem. Remaining uninsured, for large numbers of Americans currently excluded from the system, would become a choice instead of a financial necessity.
The arcana of the rule making process has now run its course, and the IRS has determined that the 9.5% income limit, e.g. the percentage of annual income that one’s employer-provided-policy must cost, before an employee becomes eligible to receive a subsidy to purchase insurance on the exchanges applies only to individual, not family policy costs. Therefore, if a modestly paid employee wishes to obtain family coverage, the additional cost for covering dependents does not count in determining eligibility for the subsidy. The financial impact of this is clear: employees opting for family coverage will almost certainly need to pay significantly more than 9.5% of their income. The potential impact on children’s access to care is profound. The Times Editorial cited above observes that reports suggest as many as 460,000 might be adversely affected by this IRS ruling. Note for emphasis that we are talking about 460,000 children.
It is difficult to believe that this is what Congress intended; perhaps we need a Congressional “Children’s Fix” for the ACA calculations analogous to the periodic Congressional “Doc Fix” applied to Medicare reimbursements.
In a political environment seemingly preoccupied with ‘fairness’ this seems eminently fair.