Individuals aged 15-65 years, including pregnant women, should be screened for HIV infection, and those at risk should be given prophylaxis, according to draft recommendations issued by the U.S. Preventive Services Task Force. The screening recommendation extends to younger adolescents and older adults at increased risk for HIV infection. The recommendations are level A.

varnent/Wikimedia Commons/CC BY-SA 3.0

HIV remains a significant public health issue in the United States, with rates rising among individuals aged 25-29 years, although the overall number of cases has dropped slightly, according to the USPSTF report.

HIV prevention is a multistep process that includes not only screening but also wearing condoms during sex and using clean needles and syringes if injecting drugs, the researchers noted.

However, those at high risk for HIV, such as intravenous drug users, can help reduce their risk by taking a daily pill, the researchers wrote.

In an evidence report submitted to the Agency for Healthcare Research and Quality, researchers reviewed the Cochrane databases, MEDLINE, and Embase for studies up to June 2018. Based on data from 11 trials, pre-exposure prophylaxis (PrEP) consisting of antiretroviral therapy was associated with decreased risk of HIV infection, compared with placebo or no PrEP, with consistent effects across risk categories, the investigators noted.

The most common HIV risk factors include man-to-man sexual contact, injection drug use, having sex without a condom, exchanging sex for drugs or money, and having sex with an HIV-infected partner, according to the USPSTF report.

Although PrEP was associated with renal and gastrointestinal adverse effects, most were mild and resolved when the therapy either ended or continued long term. The use of PrEP does not absolve high-risk individuals from observing safety in sex activity and intravenous drug use, the researchers noted.

The Task Force’s draft recommendation statements and draft evidence reviews are available for public comment and are posted on the Task Force website at www.uspreventiveservicestaskforce.org. Comments can be submitted from Nov. 20, 2018, to Dec. 26, 2018, at www.uspreventiveservicestaskforce.org/tfcomment.htm.

Individuals aged 15-65 years, including pregnant women, should be screened for HIV infection, and those at risk should be given prophylaxis, according to draft recommendations issued by the U.S. Preventive Services Task Force. The screening recommendation extends to younger adolescents and older adults at increased risk for HIV infection. The recommendations are level A.

varnent/Wikimedia Commons/CC BY-SA 3.0

HIV remains a significant public health issue in the United States, with rates rising among individuals aged 25-29 years, although the overall number of cases has dropped slightly, according to the USPSTF report.

HIV prevention is a multistep process that includes not only screening but also wearing condoms during sex and using clean needles and syringes if injecting drugs, the researchers noted.

However, those at high risk for HIV, such as intravenous drug users, can help reduce their risk by taking a daily pill, the researchers wrote.

In an evidence report submitted to the Agency for Healthcare Research and Quality, researchers reviewed the Cochrane databases, MEDLINE, and Embase for studies up to June 2018. Based on data from 11 trials, pre-exposure prophylaxis (PrEP) consisting of antiretroviral therapy was associated with decreased risk of HIV infection, compared with placebo or no PrEP, with consistent effects across risk categories, the investigators noted.

The most common HIV risk factors include man-to-man sexual contact, injection drug use, having sex without a condom, exchanging sex for drugs or money, and having sex with an HIV-infected partner, according to the USPSTF report.

Although PrEP was associated with renal and gastrointestinal adverse effects, most were mild and resolved when the therapy either ended or continued long term. The use of PrEP does not absolve high-risk individuals from observing safety in sex activity and intravenous drug use, the researchers noted.

The Task Force’s draft recommendation statements and draft evidence reviews are available for public comment and are posted on the Task Force website at www.uspreventiveservicestaskforce.org. Comments can be submitted from Nov. 20, 2018, to Dec. 26, 2018, at www.uspreventiveservicestaskforce.org/tfcomment.htm.

Individuals aged 15-65 years, including pregnant women, should be screened for HIV infection, and those at risk should be given prophylaxis, according to draft recommendations issued by the U.S. Preventive Services Task Force. The screening recommendation extends to younger adolescents and older adults at increased risk for HIV infection. The recommendations are level A.

varnent/Wikimedia Commons/CC BY-SA 3.0

HIV remains a significant public health issue in the United States, with rates rising among individuals aged 25-29 years, although the overall number of cases has dropped slightly, according to the USPSTF report.

HIV prevention is a multistep process that includes not only screening but also wearing condoms during sex and using clean needles and syringes if injecting drugs, the researchers noted.

However, those at high risk for HIV, such as intravenous drug users, can help reduce their risk by taking a daily pill, the researchers wrote.

In an evidence report submitted to the Agency for Healthcare Research and Quality, researchers reviewed the Cochrane databases, MEDLINE, and Embase for studies up to June 2018. Based on data from 11 trials, pre-exposure prophylaxis (PrEP) consisting of antiretroviral therapy was associated with decreased risk of HIV infection, compared with placebo or no PrEP, with consistent effects across risk categories, the investigators noted.

The most common HIV risk factors include man-to-man sexual contact, injection drug use, having sex without a condom, exchanging sex for drugs or money, and having sex with an HIV-infected partner, according to the USPSTF report.

Although PrEP was associated with renal and gastrointestinal adverse effects, most were mild and resolved when the therapy either ended or continued long term. The use of PrEP does not absolve high-risk individuals from observing safety in sex activity and intravenous drug use, the researchers noted.

The Task Force’s draft recommendation statements and draft evidence reviews are available for public comment and are posted on the Task Force website at www.uspreventiveservicestaskforce.org. Comments can be submitted from Nov. 20, 2018, to Dec. 26, 2018, at www.uspreventiveservicestaskforce.org/tfcomment.htm.

The Food and Drug Administration has approved rifamycin (Aemcolo) for the treatment of traveler’s diarrhea caused by noninvasive strains of Escherichia coli.

FDA approval was based on results of three clinical trials. The efficacy of rifamycin was shown in a trial of 264 adults with traveler’s diarrhea in Guatemala and Mexico. Compared with placebo, rifamycin significantly reduced symptoms of the condition. The safety of rifamycin was illustrated in a pair of studies including 619 adults with traveler’s diarrhea who took rifamycin orally for 3-4 days. The most common adverse events were headache and constipation.

Traveler’s diarrhea is the most common travel-related illness, affecting 10%-40% of travelers. It can be caused by a multitude of pathogens, but bacteria from food or water is the most common source. High-risk areas include much of Asia, the Middle East, Mexico, Central and South America, and Africa.

Rifamycin was not effective in patients with diarrhea complicated by fever and/or bloody stool or in diarrhea caused by a pathogen other than E. coli.

“Travelers’ diarrhea affects millions of people each year, and having treatment options for this condition can help reduce symptoms of the condition,” Edward Cox, MD, MPH, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in the press release.

Find the full press release on the FDA website.
 

[email protected]

The Food and Drug Administration has approved rifamycin (Aemcolo) for the treatment of traveler’s diarrhea caused by noninvasive strains of Escherichia coli.

FDA approval was based on results of three clinical trials. The efficacy of rifamycin was shown in a trial of 264 adults with traveler’s diarrhea in Guatemala and Mexico. Compared with placebo, rifamycin significantly reduced symptoms of the condition. The safety of rifamycin was illustrated in a pair of studies including 619 adults with traveler’s diarrhea who took rifamycin orally for 3-4 days. The most common adverse events were headache and constipation.

Traveler’s diarrhea is the most common travel-related illness, affecting 10%-40% of travelers. It can be caused by a multitude of pathogens, but bacteria from food or water is the most common source. High-risk areas include much of Asia, the Middle East, Mexico, Central and South America, and Africa.

Rifamycin was not effective in patients with diarrhea complicated by fever and/or bloody stool or in diarrhea caused by a pathogen other than E. coli.

“Travelers’ diarrhea affects millions of people each year, and having treatment options for this condition can help reduce symptoms of the condition,” Edward Cox, MD, MPH, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in the press release.

Find the full press release on the FDA website.
 

[email protected]

The Food and Drug Administration has approved rifamycin (Aemcolo) for the treatment of traveler’s diarrhea caused by noninvasive strains of Escherichia coli.

FDA approval was based on results of three clinical trials. The efficacy of rifamycin was shown in a trial of 264 adults with traveler’s diarrhea in Guatemala and Mexico. Compared with placebo, rifamycin significantly reduced symptoms of the condition. The safety of rifamycin was illustrated in a pair of studies including 619 adults with traveler’s diarrhea who took rifamycin orally for 3-4 days. The most common adverse events were headache and constipation.

Traveler’s diarrhea is the most common travel-related illness, affecting 10%-40% of travelers. It can be caused by a multitude of pathogens, but bacteria from food or water is the most common source. High-risk areas include much of Asia, the Middle East, Mexico, Central and South America, and Africa.

Rifamycin was not effective in patients with diarrhea complicated by fever and/or bloody stool or in diarrhea caused by a pathogen other than E. coli.

“Travelers’ diarrhea affects millions of people each year, and having treatment options for this condition can help reduce symptoms of the condition,” Edward Cox, MD, MPH, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research, said in the press release.

Find the full press release on the FDA website.
 

[email protected]

CHICAGO – Patients with systemic lupus erythematosus (SLE) have an incidence of treatment-resistant hypertension (TRH) twice the rate of matched controls, and all-cause mortality in affected SLE patients is sharply higher than in individuals whose SLE is not complicated by comorbid TRH, Annette Oeser reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

TRH is thus an important yet underappreciated comorbidity for clinicians to recognize in patients with SLE, added Ms. Oeser of Vanderbilt University, Nashville, Tenn.

She presented a single-center, retrospective study of 1,044 SLE patients and 5,241 controls matched by age, race, and sex. During an average of 6 and maximum of 17 years of follow-up, 10% of SLE patients and 5% of controls developed TRH. The incidence was 14.7 cases per 1,000 person-years in the SLE population and 7.4 per 1,000 in controls. Of note, the incidence curves began to diverge within the first months following diagnosis of the autoimmune disease.

TRH was defined in the conventional way as an inability to achieve a blood pressure of 140/90 mm Hg or less while on three antihypertensive drugs having different mechanisms or as the simultaneous use of four or more antihypertensive agents, noted Ms. Oeser, the study coordinator, who presented the findings on behalf of senior investigator Cecilia P. Chung, MD, a rheumatologist at Vanderbilt.

The SLE patients with TRH were older than those without TRH by a margin of 47 versus 41 years of age. A total of 45% of SLE patients with TRH were black, compared with 21% of those without TRH. The group with SLE and TRH also had a higher C-reactive protein (10.2 versus 3.3 mg/L), a higher erythrocyte sedimentation rate (40 versus 24 mm/hr), a lower estimated glomerular filtration rate (65.0 versus 88.2 mL/min per 1.73 m²), and a higher creatinine (1.1 versus 0.8 mg/day).

Overall, 25% of SLE patients with TRH died during follow-up, as did 10% of those without resistant hypertension, for an unadjusted 289% increased risk of all-cause mortality. Upon adjustment for age, sex, calendar year, end-stage renal disease, and creatinine, the SLE patients with TRH still remained at a 78% increased risk of mortality.

Ms. Oeser and Dr. Chung reported having no financial conflicts regarding the study, which was supported by Vanderbilt University, the Rheumatology Research Foundation, the National Institutes of Health, and the Lupus Research Alliance.

[email protected]

SOURCE: Chung CP et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 706.

CHICAGO – Patients with systemic lupus erythematosus (SLE) have an incidence of treatment-resistant hypertension (TRH) twice the rate of matched controls, and all-cause mortality in affected SLE patients is sharply higher than in individuals whose SLE is not complicated by comorbid TRH, Annette Oeser reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

TRH is thus an important yet underappreciated comorbidity for clinicians to recognize in patients with SLE, added Ms. Oeser of Vanderbilt University, Nashville, Tenn.

She presented a single-center, retrospective study of 1,044 SLE patients and 5,241 controls matched by age, race, and sex. During an average of 6 and maximum of 17 years of follow-up, 10% of SLE patients and 5% of controls developed TRH. The incidence was 14.7 cases per 1,000 person-years in the SLE population and 7.4 per 1,000 in controls. Of note, the incidence curves began to diverge within the first months following diagnosis of the autoimmune disease.

TRH was defined in the conventional way as an inability to achieve a blood pressure of 140/90 mm Hg or less while on three antihypertensive drugs having different mechanisms or as the simultaneous use of four or more antihypertensive agents, noted Ms. Oeser, the study coordinator, who presented the findings on behalf of senior investigator Cecilia P. Chung, MD, a rheumatologist at Vanderbilt.

The SLE patients with TRH were older than those without TRH by a margin of 47 versus 41 years of age. A total of 45% of SLE patients with TRH were black, compared with 21% of those without TRH. The group with SLE and TRH also had a higher C-reactive protein (10.2 versus 3.3 mg/L), a higher erythrocyte sedimentation rate (40 versus 24 mm/hr), a lower estimated glomerular filtration rate (65.0 versus 88.2 mL/min per 1.73 m²), and a higher creatinine (1.1 versus 0.8 mg/day).

Overall, 25% of SLE patients with TRH died during follow-up, as did 10% of those without resistant hypertension, for an unadjusted 289% increased risk of all-cause mortality. Upon adjustment for age, sex, calendar year, end-stage renal disease, and creatinine, the SLE patients with TRH still remained at a 78% increased risk of mortality.

Ms. Oeser and Dr. Chung reported having no financial conflicts regarding the study, which was supported by Vanderbilt University, the Rheumatology Research Foundation, the National Institutes of Health, and the Lupus Research Alliance.

[email protected]

SOURCE: Chung CP et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 706.

CHICAGO – Patients with systemic lupus erythematosus (SLE) have an incidence of treatment-resistant hypertension (TRH) twice the rate of matched controls, and all-cause mortality in affected SLE patients is sharply higher than in individuals whose SLE is not complicated by comorbid TRH, Annette Oeser reported at the annual meeting of the American College of Rheumatology.

Bruce Jancin/MDedge News

TRH is thus an important yet underappreciated comorbidity for clinicians to recognize in patients with SLE, added Ms. Oeser of Vanderbilt University, Nashville, Tenn.

She presented a single-center, retrospective study of 1,044 SLE patients and 5,241 controls matched by age, race, and sex. During an average of 6 and maximum of 17 years of follow-up, 10% of SLE patients and 5% of controls developed TRH. The incidence was 14.7 cases per 1,000 person-years in the SLE population and 7.4 per 1,000 in controls. Of note, the incidence curves began to diverge within the first months following diagnosis of the autoimmune disease.

TRH was defined in the conventional way as an inability to achieve a blood pressure of 140/90 mm Hg or less while on three antihypertensive drugs having different mechanisms or as the simultaneous use of four or more antihypertensive agents, noted Ms. Oeser, the study coordinator, who presented the findings on behalf of senior investigator Cecilia P. Chung, MD, a rheumatologist at Vanderbilt.

The SLE patients with TRH were older than those without TRH by a margin of 47 versus 41 years of age. A total of 45% of SLE patients with TRH were black, compared with 21% of those without TRH. The group with SLE and TRH also had a higher C-reactive protein (10.2 versus 3.3 mg/L), a higher erythrocyte sedimentation rate (40 versus 24 mm/hr), a lower estimated glomerular filtration rate (65.0 versus 88.2 mL/min per 1.73 m²), and a higher creatinine (1.1 versus 0.8 mg/day).

Overall, 25% of SLE patients with TRH died during follow-up, as did 10% of those without resistant hypertension, for an unadjusted 289% increased risk of all-cause mortality. Upon adjustment for age, sex, calendar year, end-stage renal disease, and creatinine, the SLE patients with TRH still remained at a 78% increased risk of mortality.

Ms. Oeser and Dr. Chung reported having no financial conflicts regarding the study, which was supported by Vanderbilt University, the Rheumatology Research Foundation, the National Institutes of Health, and the Lupus Research Alliance.

[email protected]

SOURCE: Chung CP et al. Arthritis Rheumatol. 2018;70(Suppl 10): Abstract 706.

Question: Regarding medical care aboard cruise ships, which of the following is incorrect?

A. It is difficult to prove negligence because of jurisdictional issues.

B. The American College of Emergency Physicians has published practice guidelines.

C. Cruise line owners are immune from liability under the Barbetta rule.

D. The Franza decision may be a game changer.

E. Lawsuits are on the increase.

Answer: A. More and more people are cruising, with the number of passengers on North American lines reaching nearly 18 million in 2017, about one-third out of Florida. Medical illnesses and accidents predictably occur at sea, and unfortunately, substandard and negligent care occasionally follows some of these mishaps.

However, up until recently, courts have immunized cruise line owners from legal liability by relying on the so-called Barbetta rule, which is based on historical notions of limited resources at sea and the impossibility of exerting control over the conduct of a ship’s health care providers.

A 2007 Florida case is illustrative. The doctor aboard a Carnival cruise ship failed to diagnose acute appendicitis in a 14-year-old girl who had complained of several days of abdominal symptoms. As a result, the patient ruptured her appendix, and this eventually resulted in sterility. The parents sued the cruise line, which denied liability because the doctor was not an employee, a fact specifically disclosed in the cruise ticket.

Although the doctor’s contract stated that he was an independent contractor, the District Court of Appeal of Florida reasoned that, in a claim based on agency, it is the right of control rather than actual control itself that matters.

It therefore held that: “for purposes of fulfilling cruise line’s duty to exercise reasonable care, the ship’s doctor is an agent of cruise line whose negligence should be imputed to cruise line ... regardless of the contractual status ascribed to the doctor” and to the extent cruise ticket sought to limit cruise line’s liability for negligence of doctor, it was invalid.

However, the Florida Supreme Court quashed this decision, because federal maritime law has historically protected shipowners from liability flowing from the medical negligence of shipboard physicians.¹

The Barbetta rule was named after a 1988 case in which Florence L. Barbetta suffered serious medical complications during a Mexican cruise out of Florida. The ship’s doctor was alleged to have been negligent for his failure to diagnose diabetes.² The lower court dismissed the case, and the appellate court affirmed.

The appellate court noted that an impressive number of courts from many jurisdictions have, for almost 100 years, followed the same basic rule: If the doctor is negligent in treating a passenger, that negligence will not be imputed to the carrier unless the carrier itself was negligent in hiring the doctor.

Citing approvingly from another case, the appellate court noted: “[A] shipping company is not in the business of providing medical services to passengers; it does not possess the expertise requisite to supervise a physician or surgeon carried on board a ship as a convenience to passengers. A ship is not a floating hospital; a ship’s physician is an independent medical expert engaged on the basis of his professional qualifications and carried on board a ship for the convenience of passengers, who are free to contract with him for any medical services they may require.”

However, courts now appear ready to jettison this rule.

In the 2014 case of Franza v. Royal Caribbean Cruises, Ltd., a passenger fell and hit his head while his ship was at port in Bermuda.³ He died several days later, allegedly because of negligence and delay by the ship’s medical staff. The lower courts barred the lawsuit, based on Barbetta, but on appeal, the 11th Circuit Court reversed. It rejected the historical justifications for immunizing shipowners from liability, concluding that past reasons were no longer applicable to modern-day cruise ships.

The court wrote: “Here, the roots of the Barbetta rule snake back to a wholly different world. Instead of 19th-century steamships, we now confront state-of-the-art cruise ships that house thousands of people and operate as floating cities complete with well-stocked modern infirmaries and urgent-care centers. In place of independent doctors and nurses, we must now acknowledge that medical professionals routinely work for corporate masters. And whereas ships historically went ‘off the grid’ when they set sail, modern technology enables distant ships to communicate instantaneously with the mainland in meaningful ways.”

However, the injured person must still prove that the doctor or nurse was acting as a ship employee rather than an independent contractor. Some of the factors to be considered include whether the cruise line advertised its medical center or medical staff to passengers, whether it retained the right to hire and fire medical staff, and methods of payment.

This 2014 11th Circuit Court ruling has particular impact on Florida, because the state’s federal court system falls within its jurisdiction, and many cruise lines – such as Carnival, Celebrity, Disney, Norwegian, Royal Caribbean, and Silversea Cruises – are headquartered in Florida. Because most ocean liners hire medical professionals who are foreign nationals, seeking legal remedy against the individuals can be difficult.

As a result, suing the cruise line directly can serve as the simplest way to obtain compensation. Some major cruise lines have already seen an increase in personal injury lawsuits. According to Bloomberg Law, there were 164 such federal injury suits in 2016, 188 in 2017, and 83 cases in just the first 3 months of 2018.

The popular press recently highlighted the latest example of medical malpractice at sea. A cruise worker was awarded $3.34 million after a young, inexperienced doctor prescribed a large dose of intravenous promethazine for nausea. Instead of using 6.25 mg, the usual dose, he prescribed 25 mg, which was inadvertently injected into the ulnar artery. The caustic drug, known to injure vascular walls, caused severe damage with extravasation, and tissue swelling, ending in compartment syndrome.

Furthermore, he had to wait 24 hours before arriving in port for treatment. By then, his arm was gangrenous and had to be amputated. The defense had argued unsuccessfully that the plaintiff had a venous anomaly to account for the injury.⁴

These changes in the law augur well for the cruising public. The Franza decision puts cruise line owners on notice that they no longer enjoy blanket immunity, and will be held responsible for the negligence of their health care providers. Hopefully, this will ensure a more uniform and adequate standard of care.

The American College of Emergency Physicians has published specific guidelines regarding medical standards aboard cruise ships. In addition to having established medical policies and procedures, and a dedicated medical emergency telephone number, they must have at least one doctor available 24/7 to provide emergency medical care and maintain certain equipment on board, such as pulse oximeters, cardiac monitors, defibrillators, an EKG device, as well as a laboratory.

Norwegian Cruise Line has taken a step further: It recently installed the capability to consult in real time with the Cleveland Clinic for diagnostic and treatment advice.
 

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].

References

1. Carlisle v. Carnival Corporation, et al., 953 So.2d 461, 2007.

2. Barbetta v. S/S Bermuda Star, 848 F.2d 1364 (5th Cir. 1988).

3. Franza v. Royal Caribbean Cruises Ltd., 772 F.3d 1225 (11th Cir. 2014).

4. Loncar v. NCL Bahamas, International Center for Dispute Resolution, Case # 01-16-0004-3640, June 13, 2018.

Question: Regarding medical care aboard cruise ships, which of the following is incorrect?

A. It is difficult to prove negligence because of jurisdictional issues.

B. The American College of Emergency Physicians has published practice guidelines.

C. Cruise line owners are immune from liability under the Barbetta rule.

D. The Franza decision may be a game changer.

E. Lawsuits are on the increase.

Answer: A. More and more people are cruising, with the number of passengers on North American lines reaching nearly 18 million in 2017, about one-third out of Florida. Medical illnesses and accidents predictably occur at sea, and unfortunately, substandard and negligent care occasionally follows some of these mishaps.

However, up until recently, courts have immunized cruise line owners from legal liability by relying on the so-called Barbetta rule, which is based on historical notions of limited resources at sea and the impossibility of exerting control over the conduct of a ship’s health care providers.

A 2007 Florida case is illustrative. The doctor aboard a Carnival cruise ship failed to diagnose acute appendicitis in a 14-year-old girl who had complained of several days of abdominal symptoms. As a result, the patient ruptured her appendix, and this eventually resulted in sterility. The parents sued the cruise line, which denied liability because the doctor was not an employee, a fact specifically disclosed in the cruise ticket.

Although the doctor’s contract stated that he was an independent contractor, the District Court of Appeal of Florida reasoned that, in a claim based on agency, it is the right of control rather than actual control itself that matters.

It therefore held that: “for purposes of fulfilling cruise line’s duty to exercise reasonable care, the ship’s doctor is an agent of cruise line whose negligence should be imputed to cruise line ... regardless of the contractual status ascribed to the doctor” and to the extent cruise ticket sought to limit cruise line’s liability for negligence of doctor, it was invalid.

However, the Florida Supreme Court quashed this decision, because federal maritime law has historically protected shipowners from liability flowing from the medical negligence of shipboard physicians.¹

The Barbetta rule was named after a 1988 case in which Florence L. Barbetta suffered serious medical complications during a Mexican cruise out of Florida. The ship’s doctor was alleged to have been negligent for his failure to diagnose diabetes.² The lower court dismissed the case, and the appellate court affirmed.

The appellate court noted that an impressive number of courts from many jurisdictions have, for almost 100 years, followed the same basic rule: If the doctor is negligent in treating a passenger, that negligence will not be imputed to the carrier unless the carrier itself was negligent in hiring the doctor.

Citing approvingly from another case, the appellate court noted: “[A] shipping company is not in the business of providing medical services to passengers; it does not possess the expertise requisite to supervise a physician or surgeon carried on board a ship as a convenience to passengers. A ship is not a floating hospital; a ship’s physician is an independent medical expert engaged on the basis of his professional qualifications and carried on board a ship for the convenience of passengers, who are free to contract with him for any medical services they may require.”

However, courts now appear ready to jettison this rule.

In the 2014 case of Franza v. Royal Caribbean Cruises, Ltd., a passenger fell and hit his head while his ship was at port in Bermuda.³ He died several days later, allegedly because of negligence and delay by the ship’s medical staff. The lower courts barred the lawsuit, based on Barbetta, but on appeal, the 11th Circuit Court reversed. It rejected the historical justifications for immunizing shipowners from liability, concluding that past reasons were no longer applicable to modern-day cruise ships.

The court wrote: “Here, the roots of the Barbetta rule snake back to a wholly different world. Instead of 19th-century steamships, we now confront state-of-the-art cruise ships that house thousands of people and operate as floating cities complete with well-stocked modern infirmaries and urgent-care centers. In place of independent doctors and nurses, we must now acknowledge that medical professionals routinely work for corporate masters. And whereas ships historically went ‘off the grid’ when they set sail, modern technology enables distant ships to communicate instantaneously with the mainland in meaningful ways.”

However, the injured person must still prove that the doctor or nurse was acting as a ship employee rather than an independent contractor. Some of the factors to be considered include whether the cruise line advertised its medical center or medical staff to passengers, whether it retained the right to hire and fire medical staff, and methods of payment.

This 2014 11th Circuit Court ruling has particular impact on Florida, because the state’s federal court system falls within its jurisdiction, and many cruise lines – such as Carnival, Celebrity, Disney, Norwegian, Royal Caribbean, and Silversea Cruises – are headquartered in Florida. Because most ocean liners hire medical professionals who are foreign nationals, seeking legal remedy against the individuals can be difficult.

As a result, suing the cruise line directly can serve as the simplest way to obtain compensation. Some major cruise lines have already seen an increase in personal injury lawsuits. According to Bloomberg Law, there were 164 such federal injury suits in 2016, 188 in 2017, and 83 cases in just the first 3 months of 2018.

The popular press recently highlighted the latest example of medical malpractice at sea. A cruise worker was awarded $3.34 million after a young, inexperienced doctor prescribed a large dose of intravenous promethazine for nausea. Instead of using 6.25 mg, the usual dose, he prescribed 25 mg, which was inadvertently injected into the ulnar artery. The caustic drug, known to injure vascular walls, caused severe damage with extravasation, and tissue swelling, ending in compartment syndrome.

Furthermore, he had to wait 24 hours before arriving in port for treatment. By then, his arm was gangrenous and had to be amputated. The defense had argued unsuccessfully that the plaintiff had a venous anomaly to account for the injury.⁴

These changes in the law augur well for the cruising public. The Franza decision puts cruise line owners on notice that they no longer enjoy blanket immunity, and will be held responsible for the negligence of their health care providers. Hopefully, this will ensure a more uniform and adequate standard of care.

The American College of Emergency Physicians has published specific guidelines regarding medical standards aboard cruise ships. In addition to having established medical policies and procedures, and a dedicated medical emergency telephone number, they must have at least one doctor available 24/7 to provide emergency medical care and maintain certain equipment on board, such as pulse oximeters, cardiac monitors, defibrillators, an EKG device, as well as a laboratory.

Norwegian Cruise Line has taken a step further: It recently installed the capability to consult in real time with the Cleveland Clinic for diagnostic and treatment advice.
 

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].

References

1. Carlisle v. Carnival Corporation, et al., 953 So.2d 461, 2007.

2. Barbetta v. S/S Bermuda Star, 848 F.2d 1364 (5th Cir. 1988).

3. Franza v. Royal Caribbean Cruises Ltd., 772 F.3d 1225 (11th Cir. 2014).

4. Loncar v. NCL Bahamas, International Center for Dispute Resolution, Case # 01-16-0004-3640, June 13, 2018.

Question: Regarding medical care aboard cruise ships, which of the following is incorrect?

A. It is difficult to prove negligence because of jurisdictional issues.

B. The American College of Emergency Physicians has published practice guidelines.

C. Cruise line owners are immune from liability under the Barbetta rule.

D. The Franza decision may be a game changer.

E. Lawsuits are on the increase.

Answer: A. More and more people are cruising, with the number of passengers on North American lines reaching nearly 18 million in 2017, about one-third out of Florida. Medical illnesses and accidents predictably occur at sea, and unfortunately, substandard and negligent care occasionally follows some of these mishaps.

However, up until recently, courts have immunized cruise line owners from legal liability by relying on the so-called Barbetta rule, which is based on historical notions of limited resources at sea and the impossibility of exerting control over the conduct of a ship’s health care providers.

A 2007 Florida case is illustrative. The doctor aboard a Carnival cruise ship failed to diagnose acute appendicitis in a 14-year-old girl who had complained of several days of abdominal symptoms. As a result, the patient ruptured her appendix, and this eventually resulted in sterility. The parents sued the cruise line, which denied liability because the doctor was not an employee, a fact specifically disclosed in the cruise ticket.

Although the doctor’s contract stated that he was an independent contractor, the District Court of Appeal of Florida reasoned that, in a claim based on agency, it is the right of control rather than actual control itself that matters.

It therefore held that: “for purposes of fulfilling cruise line’s duty to exercise reasonable care, the ship’s doctor is an agent of cruise line whose negligence should be imputed to cruise line ... regardless of the contractual status ascribed to the doctor” and to the extent cruise ticket sought to limit cruise line’s liability for negligence of doctor, it was invalid.

However, the Florida Supreme Court quashed this decision, because federal maritime law has historically protected shipowners from liability flowing from the medical negligence of shipboard physicians.¹

The Barbetta rule was named after a 1988 case in which Florence L. Barbetta suffered serious medical complications during a Mexican cruise out of Florida. The ship’s doctor was alleged to have been negligent for his failure to diagnose diabetes.² The lower court dismissed the case, and the appellate court affirmed.

The appellate court noted that an impressive number of courts from many jurisdictions have, for almost 100 years, followed the same basic rule: If the doctor is negligent in treating a passenger, that negligence will not be imputed to the carrier unless the carrier itself was negligent in hiring the doctor.

Citing approvingly from another case, the appellate court noted: “[A] shipping company is not in the business of providing medical services to passengers; it does not possess the expertise requisite to supervise a physician or surgeon carried on board a ship as a convenience to passengers. A ship is not a floating hospital; a ship’s physician is an independent medical expert engaged on the basis of his professional qualifications and carried on board a ship for the convenience of passengers, who are free to contract with him for any medical services they may require.”

However, courts now appear ready to jettison this rule.

In the 2014 case of Franza v. Royal Caribbean Cruises, Ltd., a passenger fell and hit his head while his ship was at port in Bermuda.³ He died several days later, allegedly because of negligence and delay by the ship’s medical staff. The lower courts barred the lawsuit, based on Barbetta, but on appeal, the 11th Circuit Court reversed. It rejected the historical justifications for immunizing shipowners from liability, concluding that past reasons were no longer applicable to modern-day cruise ships.

The court wrote: “Here, the roots of the Barbetta rule snake back to a wholly different world. Instead of 19th-century steamships, we now confront state-of-the-art cruise ships that house thousands of people and operate as floating cities complete with well-stocked modern infirmaries and urgent-care centers. In place of independent doctors and nurses, we must now acknowledge that medical professionals routinely work for corporate masters. And whereas ships historically went ‘off the grid’ when they set sail, modern technology enables distant ships to communicate instantaneously with the mainland in meaningful ways.”

However, the injured person must still prove that the doctor or nurse was acting as a ship employee rather than an independent contractor. Some of the factors to be considered include whether the cruise line advertised its medical center or medical staff to passengers, whether it retained the right to hire and fire medical staff, and methods of payment.

This 2014 11th Circuit Court ruling has particular impact on Florida, because the state’s federal court system falls within its jurisdiction, and many cruise lines – such as Carnival, Celebrity, Disney, Norwegian, Royal Caribbean, and Silversea Cruises – are headquartered in Florida. Because most ocean liners hire medical professionals who are foreign nationals, seeking legal remedy against the individuals can be difficult.

As a result, suing the cruise line directly can serve as the simplest way to obtain compensation. Some major cruise lines have already seen an increase in personal injury lawsuits. According to Bloomberg Law, there were 164 such federal injury suits in 2016, 188 in 2017, and 83 cases in just the first 3 months of 2018.

The popular press recently highlighted the latest example of medical malpractice at sea. A cruise worker was awarded $3.34 million after a young, inexperienced doctor prescribed a large dose of intravenous promethazine for nausea. Instead of using 6.25 mg, the usual dose, he prescribed 25 mg, which was inadvertently injected into the ulnar artery. The caustic drug, known to injure vascular walls, caused severe damage with extravasation, and tissue swelling, ending in compartment syndrome.

Furthermore, he had to wait 24 hours before arriving in port for treatment. By then, his arm was gangrenous and had to be amputated. The defense had argued unsuccessfully that the plaintiff had a venous anomaly to account for the injury.⁴

These changes in the law augur well for the cruising public. The Franza decision puts cruise line owners on notice that they no longer enjoy blanket immunity, and will be held responsible for the negligence of their health care providers. Hopefully, this will ensure a more uniform and adequate standard of care.

The American College of Emergency Physicians has published specific guidelines regarding medical standards aboard cruise ships. In addition to having established medical policies and procedures, and a dedicated medical emergency telephone number, they must have at least one doctor available 24/7 to provide emergency medical care and maintain certain equipment on board, such as pulse oximeters, cardiac monitors, defibrillators, an EKG device, as well as a laboratory.

Norwegian Cruise Line has taken a step further: It recently installed the capability to consult in real time with the Cleveland Clinic for diagnostic and treatment advice.
 

Dr. Tan is emeritus professor of medicine and former adjunct professor of law at the University of Hawaii, Honolulu. This article is meant to be educational and does not constitute medical, ethical, or legal advice. For additional information, readers may contact the author at [email protected].

References

1. Carlisle v. Carnival Corporation, et al., 953 So.2d 461, 2007.

2. Barbetta v. S/S Bermuda Star, 848 F.2d 1364 (5th Cir. 1988).

3. Franza v. Royal Caribbean Cruises Ltd., 772 F.3d 1225 (11th Cir. 2014).

4. Loncar v. NCL Bahamas, International Center for Dispute Resolution, Case # 01-16-0004-3640, June 13, 2018.

CHICAGO – An investigative heart pump for unloading the left ventricle in patients who had an ST-elevation myocardial infarction (STEMI) yielded similar safety and efficacy outcomes with a 30-minute delay in reperfusion or the standard approach of immediate reperfusion.

Courtesy Abiomed

That’s according to results of a pilot feasibility trial presented at the American Heart Association scientific sessions.

The trial, titled the DTU (Door to Unload)–STEMI trial, evaluated the Impella CP (Abiomed) device used for unloading the left ventricle (LV). “No prohibitive safety signals that would preclude proceeding to a larger pivotal study of left ventricle unloading and delaying reperfusion for 30 minutes were identified,” said principal investigator Navin Kapur, MD, of Tufts Medical Center.

The trial evaluated 50 patients who received the Impella device in two different groups: one that underwent immediate reperfusion after LV unloading, the other that had a 30-minute delay before reperfusion. The study found no significant difference in major adverse cardiovascular or cerebral events between the two groups (there were two in the delayed group vs. none in the immediate group), and no difference in infarct size increase as a percentage of LV mass at 30 days between the groups, Dr. Kapur said.

Door-to-balloon times averaged 73 minutes in the immediate reperfusion group and 97 minutes in the delayed reperfusion group, with door-to-unload times averaging around 60 minutes in both groups. “We were able to see successful enrollment and distribution across multiple sites and multiple operators, suggesting the feasibility of this approach,” Dr. Kapur said.

He noted “one of the most important messages” of the study was that no patients in either arm required percutaneous coronary intervention. “What this suggests is that, when we look at operator behavior, operators were comfortable with initiating LV unloading and waiting 30 minutes,” Dr. Kapur said.

The primary endpoint of the trial was to determine if delayed reperfusion led to an increase in infarct size. “We did not see that,” he noted. “And among patients with an anterior ST-segment elevation sum in leads V1-V4 of more than 6 mm Hg, infarct size normalized to the area at risk was significantly lower with 30 minutes of LV unloading before reperfusion, compared to LV unloading with immediate reperfusion.”

The next step is to initiate a pivotal trial of the device, Dr. Kapur said. “The findings from the DTU-STEMI pilot trial will inform the pivotal trial based on preclinical data showing that LV unloading attenuates myocardial ischemia and also preconditions the myocardium to allow it to be more receptive to reperfusion with a reduction in reperfusion injury,” he said. The pivotal trial will have two similar arms: one using the standard of care of immediate reperfusion and the other utilizing the 30-minute delay.

In his discussion of the DTU-STEMI trial, Holger Thiele, MD, of the Leipzig (Germany) Heart Institute and the University of Leipzig, expressed concern with the lack of a standard-of-care group in the trial. “Thus, the primary efficacy endpoint on infarct size cannot be reliably compared,” he said. “Based on the small sample size, there’s no reliable information on safety.”

Dr. Kapur reported financial relationships with Abiomed, Boston Scientific, Abbott, Medtronic, and MD Start. Dr. Thiele had no financial disclosures.

SOURCE: Kapur NK et al. AHA scientific sessions, LBCT-19578

CHICAGO – An investigative heart pump for unloading the left ventricle in patients who had an ST-elevation myocardial infarction (STEMI) yielded similar safety and efficacy outcomes with a 30-minute delay in reperfusion or the standard approach of immediate reperfusion.

Courtesy Abiomed

That’s according to results of a pilot feasibility trial presented at the American Heart Association scientific sessions.

The trial, titled the DTU (Door to Unload)–STEMI trial, evaluated the Impella CP (Abiomed) device used for unloading the left ventricle (LV). “No prohibitive safety signals that would preclude proceeding to a larger pivotal study of left ventricle unloading and delaying reperfusion for 30 minutes were identified,” said principal investigator Navin Kapur, MD, of Tufts Medical Center.

The trial evaluated 50 patients who received the Impella device in two different groups: one that underwent immediate reperfusion after LV unloading, the other that had a 30-minute delay before reperfusion. The study found no significant difference in major adverse cardiovascular or cerebral events between the two groups (there were two in the delayed group vs. none in the immediate group), and no difference in infarct size increase as a percentage of LV mass at 30 days between the groups, Dr. Kapur said.

Door-to-balloon times averaged 73 minutes in the immediate reperfusion group and 97 minutes in the delayed reperfusion group, with door-to-unload times averaging around 60 minutes in both groups. “We were able to see successful enrollment and distribution across multiple sites and multiple operators, suggesting the feasibility of this approach,” Dr. Kapur said.

He noted “one of the most important messages” of the study was that no patients in either arm required percutaneous coronary intervention. “What this suggests is that, when we look at operator behavior, operators were comfortable with initiating LV unloading and waiting 30 minutes,” Dr. Kapur said.

The primary endpoint of the trial was to determine if delayed reperfusion led to an increase in infarct size. “We did not see that,” he noted. “And among patients with an anterior ST-segment elevation sum in leads V1-V4 of more than 6 mm Hg, infarct size normalized to the area at risk was significantly lower with 30 minutes of LV unloading before reperfusion, compared to LV unloading with immediate reperfusion.”

The next step is to initiate a pivotal trial of the device, Dr. Kapur said. “The findings from the DTU-STEMI pilot trial will inform the pivotal trial based on preclinical data showing that LV unloading attenuates myocardial ischemia and also preconditions the myocardium to allow it to be more receptive to reperfusion with a reduction in reperfusion injury,” he said. The pivotal trial will have two similar arms: one using the standard of care of immediate reperfusion and the other utilizing the 30-minute delay.

In his discussion of the DTU-STEMI trial, Holger Thiele, MD, of the Leipzig (Germany) Heart Institute and the University of Leipzig, expressed concern with the lack of a standard-of-care group in the trial. “Thus, the primary efficacy endpoint on infarct size cannot be reliably compared,” he said. “Based on the small sample size, there’s no reliable information on safety.”

Dr. Kapur reported financial relationships with Abiomed, Boston Scientific, Abbott, Medtronic, and MD Start. Dr. Thiele had no financial disclosures.

SOURCE: Kapur NK et al. AHA scientific sessions, LBCT-19578

CHICAGO – An investigative heart pump for unloading the left ventricle in patients who had an ST-elevation myocardial infarction (STEMI) yielded similar safety and efficacy outcomes with a 30-minute delay in reperfusion or the standard approach of immediate reperfusion.

Courtesy Abiomed

That’s according to results of a pilot feasibility trial presented at the American Heart Association scientific sessions.

The trial, titled the DTU (Door to Unload)–STEMI trial, evaluated the Impella CP (Abiomed) device used for unloading the left ventricle (LV). “No prohibitive safety signals that would preclude proceeding to a larger pivotal study of left ventricle unloading and delaying reperfusion for 30 minutes were identified,” said principal investigator Navin Kapur, MD, of Tufts Medical Center.

The trial evaluated 50 patients who received the Impella device in two different groups: one that underwent immediate reperfusion after LV unloading, the other that had a 30-minute delay before reperfusion. The study found no significant difference in major adverse cardiovascular or cerebral events between the two groups (there were two in the delayed group vs. none in the immediate group), and no difference in infarct size increase as a percentage of LV mass at 30 days between the groups, Dr. Kapur said.

Door-to-balloon times averaged 73 minutes in the immediate reperfusion group and 97 minutes in the delayed reperfusion group, with door-to-unload times averaging around 60 minutes in both groups. “We were able to see successful enrollment and distribution across multiple sites and multiple operators, suggesting the feasibility of this approach,” Dr. Kapur said.

He noted “one of the most important messages” of the study was that no patients in either arm required percutaneous coronary intervention. “What this suggests is that, when we look at operator behavior, operators were comfortable with initiating LV unloading and waiting 30 minutes,” Dr. Kapur said.

The primary endpoint of the trial was to determine if delayed reperfusion led to an increase in infarct size. “We did not see that,” he noted. “And among patients with an anterior ST-segment elevation sum in leads V1-V4 of more than 6 mm Hg, infarct size normalized to the area at risk was significantly lower with 30 minutes of LV unloading before reperfusion, compared to LV unloading with immediate reperfusion.”

The next step is to initiate a pivotal trial of the device, Dr. Kapur said. “The findings from the DTU-STEMI pilot trial will inform the pivotal trial based on preclinical data showing that LV unloading attenuates myocardial ischemia and also preconditions the myocardium to allow it to be more receptive to reperfusion with a reduction in reperfusion injury,” he said. The pivotal trial will have two similar arms: one using the standard of care of immediate reperfusion and the other utilizing the 30-minute delay.

In his discussion of the DTU-STEMI trial, Holger Thiele, MD, of the Leipzig (Germany) Heart Institute and the University of Leipzig, expressed concern with the lack of a standard-of-care group in the trial. “Thus, the primary efficacy endpoint on infarct size cannot be reliably compared,” he said. “Based on the small sample size, there’s no reliable information on safety.”

Dr. Kapur reported financial relationships with Abiomed, Boston Scientific, Abbott, Medtronic, and MD Start. Dr. Thiele had no financial disclosures.

SOURCE: Kapur NK et al. AHA scientific sessions, LBCT-19578

A novel formulation of methylphenidate could provide morning relief to pediatric patients with attention-deficit hyperactivity disorder. Also today, CARE MD protocol could help treat somatic disorders, children with poor cardiorespiratory fitness have a higher risk of type 2 diabetes, and ganglion stimulation boosts cerebral blood flow and improves stroke outcomes.
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Apple Podcasts
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A novel formulation of methylphenidate could provide morning relief to pediatric patients with attention-deficit hyperactivity disorder. Also today, CARE MD protocol could help treat somatic disorders, children with poor cardiorespiratory fitness have a higher risk of type 2 diabetes, and ganglion stimulation boosts cerebral blood flow and improves stroke outcomes.
Amazon Alexa
Apple Podcasts
Google Podcasts

A novel formulation of methylphenidate could provide morning relief to pediatric patients with attention-deficit hyperactivity disorder. Also today, CARE MD protocol could help treat somatic disorders, children with poor cardiorespiratory fitness have a higher risk of type 2 diabetes, and ganglion stimulation boosts cerebral blood flow and improves stroke outcomes.
Amazon Alexa
Apple Podcasts
Google Podcasts

Photo courtesy of the CDC

Phase 2 results suggest a three-drug regimen may improve response rates in patients with proteasome inhibitor (PI)-refractory multiple myeloma (MM).

The combination—nelfinavir, bortezomib, and dexamethasone (NeVd)—produced an objective response rate (ORR) of 65% in this trial.

In comparison, past studies have shown response rates of 24% to 36% in the PI-refractory MM population.^1,2,3

“The unprecedented ORR of NeVd observed in this heavily pretreated, multi-refractory setting warrants further investigation to explore the potential of nelfinavir in combination with PIs . . . ,” Christoph Driessen, of Kantonsspital St. Gallen in Switzerland, and his colleagues wrote in a letter to Blood.

The researchers noted that NeVd previously demonstrated activity in a phase 1 trial of MM patients who were refractory to both bortezomib and lenalidomide.

For the phase 2 study (NCT02188537), Dr. Driessen and his colleagues tested NeVd in MM patients who were refractory to their most recent PI-containing regimen and were previously exposed to or intolerant of at least one immunomodulatory drug.

The 34 patients had a median age of 67 (range, 42-82). Sixty-two percent were male, 38% had poor-risk cytogenetics, and most had a performance status of 0 (59%) or 1 (32%).

All patients had received lenalidomide, 47% had prior pomalidomide, 76% had prior high-dose chemotherapy, and 76% had a prior transplant.

All patients were bortezomib-refractory, 79% were refractory to a PI and lenalidomide, 44% were refractory to a PI and pomalidomide, and 38% were refractory to a PI, lenalidomide, and pomalidomide.

In this study, the patients received:

• Nelfinavir at 2500 mg on days 1 to 14 twice daily
• Bortezomib at 1.3 mg/m² subcutaneously on days 1, 4, 8, and 11
• Dexamethasone at 20 mg orally on days 1 to 2, 4 to 5, 8 to 9, and 11 to 12.

The patients were treated for up to six 21-day cycles. They received a median of 4.5 cycles (range, 1-6).

Results

The ORR was 65%, with 17 partial responses (PRs) and five very good PRs. Three patients had a minimal response, and four had stable disease.

The ORR (PR or better) was:

• 77% in patients with poor-risk cytogenetics
• 67% in patients with fewer than five prior therapies
• 63% in patients with five or more prior therapies
• 70% in patients refractory to bortezomib and lenalidomide
• 60% in patients refractory to bortezomib and pomalidomide
• 62% in patients refractory to bortezomib, lenalidomide, and pomalidomide.

The researchers said the clinical benefit of NeVd may have been underestimated in this trial because patients were only able to receive six cycles of treatment on study due to a lack of external funding support.

“The time course of paraprotein levels also suggests that individual patients might potentially have experienced myeloma control if NeVd had been continued until progression,” the researchers wrote.

Five patients did receive more than six cycles of NeVd on a compassionate-use basis. In all, 27 patients received additional anti-myeloma treatment during follow-up.

The median progression-free survival was 12 weeks for the entire cohort and 16 weeks among patients who achieved a PR or better.

The median overall survival was 12 months, and 17 patients had died as of November 2016.

The researchers said the most common adverse events in this trial were anemia (97%), thrombocytopenia (82%), hypertension (53%), diarrhea (47%), fatigue (38%), and dyspnea (35%).

There were four deaths during treatment—three due to septicemia and one from heart failure. Three of the deaths were associated with underlying pneumonia.

“Although this mortality rate is consistent with the background mortality among patients with heavily pretreated, refractory myeloma, these findings suggest that prophylactic antibiotic therapy should be considered in those with low neutrophil counts and/or advanced age undergoing NeVd treatment,” the researchers wrote.

This work was supported by the Swiss Group for Clinical Cancer Research, the Swiss State Secretariat for Education, Research and Innovation, the Rising Tide Foundation for Clinical Cancer Research, and the Gateway for Cancer Research.

Most of the researchers declared no competing financial interests, but one reported personal fees from Celgene, Takeda, Amgen, Novartis, and Janssen-Cilag that were unrelated to this trial.

1. Lokhorst HM et al. N Engl J Med. 2015; 373(13):1207-1219.

2. Dimopoulos MA et al. Blood. 2016;128(4): 497-503.

3. Siegel DS et al. Blood. 2012;120(14):2817-2825.

Photo courtesy of the CDC

Phase 2 results suggest a three-drug regimen may improve response rates in patients with proteasome inhibitor (PI)-refractory multiple myeloma (MM).

The combination—nelfinavir, bortezomib, and dexamethasone (NeVd)—produced an objective response rate (ORR) of 65% in this trial.

In comparison, past studies have shown response rates of 24% to 36% in the PI-refractory MM population.^1,2,3

“The unprecedented ORR of NeVd observed in this heavily pretreated, multi-refractory setting warrants further investigation to explore the potential of nelfinavir in combination with PIs . . . ,” Christoph Driessen, of Kantonsspital St. Gallen in Switzerland, and his colleagues wrote in a letter to Blood.

The researchers noted that NeVd previously demonstrated activity in a phase 1 trial of MM patients who were refractory to both bortezomib and lenalidomide.

For the phase 2 study (NCT02188537), Dr. Driessen and his colleagues tested NeVd in MM patients who were refractory to their most recent PI-containing regimen and were previously exposed to or intolerant of at least one immunomodulatory drug.

The 34 patients had a median age of 67 (range, 42-82). Sixty-two percent were male, 38% had poor-risk cytogenetics, and most had a performance status of 0 (59%) or 1 (32%).

All patients had received lenalidomide, 47% had prior pomalidomide, 76% had prior high-dose chemotherapy, and 76% had a prior transplant.

All patients were bortezomib-refractory, 79% were refractory to a PI and lenalidomide, 44% were refractory to a PI and pomalidomide, and 38% were refractory to a PI, lenalidomide, and pomalidomide.

In this study, the patients received:

• Nelfinavir at 2500 mg on days 1 to 14 twice daily
• Bortezomib at 1.3 mg/m² subcutaneously on days 1, 4, 8, and 11
• Dexamethasone at 20 mg orally on days 1 to 2, 4 to 5, 8 to 9, and 11 to 12.

The patients were treated for up to six 21-day cycles. They received a median of 4.5 cycles (range, 1-6).

Results

The ORR was 65%, with 17 partial responses (PRs) and five very good PRs. Three patients had a minimal response, and four had stable disease.

The ORR (PR or better) was:

• 77% in patients with poor-risk cytogenetics
• 67% in patients with fewer than five prior therapies
• 63% in patients with five or more prior therapies
• 70% in patients refractory to bortezomib and lenalidomide
• 60% in patients refractory to bortezomib and pomalidomide
• 62% in patients refractory to bortezomib, lenalidomide, and pomalidomide.

The researchers said the clinical benefit of NeVd may have been underestimated in this trial because patients were only able to receive six cycles of treatment on study due to a lack of external funding support.

“The time course of paraprotein levels also suggests that individual patients might potentially have experienced myeloma control if NeVd had been continued until progression,” the researchers wrote.

Five patients did receive more than six cycles of NeVd on a compassionate-use basis. In all, 27 patients received additional anti-myeloma treatment during follow-up.

The median progression-free survival was 12 weeks for the entire cohort and 16 weeks among patients who achieved a PR or better.

The median overall survival was 12 months, and 17 patients had died as of November 2016.

The researchers said the most common adverse events in this trial were anemia (97%), thrombocytopenia (82%), hypertension (53%), diarrhea (47%), fatigue (38%), and dyspnea (35%).

There were four deaths during treatment—three due to septicemia and one from heart failure. Three of the deaths were associated with underlying pneumonia.

“Although this mortality rate is consistent with the background mortality among patients with heavily pretreated, refractory myeloma, these findings suggest that prophylactic antibiotic therapy should be considered in those with low neutrophil counts and/or advanced age undergoing NeVd treatment,” the researchers wrote.

This work was supported by the Swiss Group for Clinical Cancer Research, the Swiss State Secretariat for Education, Research and Innovation, the Rising Tide Foundation for Clinical Cancer Research, and the Gateway for Cancer Research.

Most of the researchers declared no competing financial interests, but one reported personal fees from Celgene, Takeda, Amgen, Novartis, and Janssen-Cilag that were unrelated to this trial.

1. Lokhorst HM et al. N Engl J Med. 2015; 373(13):1207-1219.

2. Dimopoulos MA et al. Blood. 2016;128(4): 497-503.

3. Siegel DS et al. Blood. 2012;120(14):2817-2825.

Photo courtesy of the CDC

Phase 2 results suggest a three-drug regimen may improve response rates in patients with proteasome inhibitor (PI)-refractory multiple myeloma (MM).

The combination—nelfinavir, bortezomib, and dexamethasone (NeVd)—produced an objective response rate (ORR) of 65% in this trial.

In comparison, past studies have shown response rates of 24% to 36% in the PI-refractory MM population.^1,2,3

“The unprecedented ORR of NeVd observed in this heavily pretreated, multi-refractory setting warrants further investigation to explore the potential of nelfinavir in combination with PIs . . . ,” Christoph Driessen, of Kantonsspital St. Gallen in Switzerland, and his colleagues wrote in a letter to Blood.

The researchers noted that NeVd previously demonstrated activity in a phase 1 trial of MM patients who were refractory to both bortezomib and lenalidomide.

For the phase 2 study (NCT02188537), Dr. Driessen and his colleagues tested NeVd in MM patients who were refractory to their most recent PI-containing regimen and were previously exposed to or intolerant of at least one immunomodulatory drug.

The 34 patients had a median age of 67 (range, 42-82). Sixty-two percent were male, 38% had poor-risk cytogenetics, and most had a performance status of 0 (59%) or 1 (32%).

All patients had received lenalidomide, 47% had prior pomalidomide, 76% had prior high-dose chemotherapy, and 76% had a prior transplant.

All patients were bortezomib-refractory, 79% were refractory to a PI and lenalidomide, 44% were refractory to a PI and pomalidomide, and 38% were refractory to a PI, lenalidomide, and pomalidomide.

In this study, the patients received:

• Nelfinavir at 2500 mg on days 1 to 14 twice daily
• Bortezomib at 1.3 mg/m² subcutaneously on days 1, 4, 8, and 11
• Dexamethasone at 20 mg orally on days 1 to 2, 4 to 5, 8 to 9, and 11 to 12.

The patients were treated for up to six 21-day cycles. They received a median of 4.5 cycles (range, 1-6).

Results

The ORR was 65%, with 17 partial responses (PRs) and five very good PRs. Three patients had a minimal response, and four had stable disease.

The ORR (PR or better) was:

• 77% in patients with poor-risk cytogenetics
• 67% in patients with fewer than five prior therapies
• 63% in patients with five or more prior therapies
• 70% in patients refractory to bortezomib and lenalidomide
• 60% in patients refractory to bortezomib and pomalidomide
• 62% in patients refractory to bortezomib, lenalidomide, and pomalidomide.

The researchers said the clinical benefit of NeVd may have been underestimated in this trial because patients were only able to receive six cycles of treatment on study due to a lack of external funding support.

“The time course of paraprotein levels also suggests that individual patients might potentially have experienced myeloma control if NeVd had been continued until progression,” the researchers wrote.

Five patients did receive more than six cycles of NeVd on a compassionate-use basis. In all, 27 patients received additional anti-myeloma treatment during follow-up.

The median progression-free survival was 12 weeks for the entire cohort and 16 weeks among patients who achieved a PR or better.

The median overall survival was 12 months, and 17 patients had died as of November 2016.

The researchers said the most common adverse events in this trial were anemia (97%), thrombocytopenia (82%), hypertension (53%), diarrhea (47%), fatigue (38%), and dyspnea (35%).

There were four deaths during treatment—three due to septicemia and one from heart failure. Three of the deaths were associated with underlying pneumonia.

“Although this mortality rate is consistent with the background mortality among patients with heavily pretreated, refractory myeloma, these findings suggest that prophylactic antibiotic therapy should be considered in those with low neutrophil counts and/or advanced age undergoing NeVd treatment,” the researchers wrote.

This work was supported by the Swiss Group for Clinical Cancer Research, the Swiss State Secretariat for Education, Research and Innovation, the Rising Tide Foundation for Clinical Cancer Research, and the Gateway for Cancer Research.

Most of the researchers declared no competing financial interests, but one reported personal fees from Celgene, Takeda, Amgen, Novartis, and Janssen-Cilag that were unrelated to this trial.

1. Lokhorst HM et al. N Engl J Med. 2015; 373(13):1207-1219.

2. Dimopoulos MA et al. Blood. 2016;128(4): 497-503.

3. Siegel DS et al. Blood. 2012;120(14):2817-2825.

Photo by Chad McNeeley

A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).

The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.

However, the 3-year rate of relapse was similar across the age groups.

Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.

The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.

The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).

At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.

Results

The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).

NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).

Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).

In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).

The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.

After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”

Therefore, age remains an independent risk factor.

The investigators did not report conflicts of interest.

Photo by Chad McNeeley

A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).

The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.

However, the 3-year rate of relapse was similar across the age groups.

Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.

The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.

The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).

At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.

Results

The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).

NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).

Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).

In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).

The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.

After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”

Therefore, age remains an independent risk factor.

The investigators did not report conflicts of interest.

Photo by Chad McNeeley

A retrospective study suggests elderly patients with non-Hodgkin lymphoma (NHL) are more likely to die, but not relapse, within a year of allogeneic hematopoietic stem cell transplant (allo-HSCT).

The rate of non-relapse mortality (NRM) at 1 year was significantly higher for elderly patients than for middle-aged or young patients.

However, the 3-year rate of relapse was similar across the age groups.

Charalampia Kyriakou, MD, PhD, of University College London in the U.K., and her colleagues reported these findings in Biology of Blood and Marrow Transplantation.

The investigators analyzed 3,919 patients with NHL who underwent allo-HSCT between 2003 and 2013.

The patients had follicular lymphoma (n=1,461), diffuse large B-cell lymphoma (n=1,192), mantle cell lymphoma (n=823), and peripheral T-cell lymphoma (n=443).

At the time of transplant, about 85% of patients were chemo-sensitive, with the remainder being chemo-refractory.

Results

The investigators compared outcomes in patients assigned to three age groups—young (18-50), middle-aged (51-65), and elderly (66-77).

NRM at 1 year was 13% for young patients, 20% for middle-aged patients, and 33% for elderly patients (P<0.001).

Overall survival at 3 years was 60% in young patients, 54% in middle-aged patients, and 38% in the elderly (P<0.001).

In contrast to these significant associations between age and survival, the rate of relapse at 3 years remained relatively consistent—30% in young patients, 31% in middle-aged patients, and 28% in elderly patients (P=0.355).

The increased risk of NRM in elderly patients could not be fully explained by comorbidities, although these were more common in the elderly.

After analyzing information from a subset of patients, the investigators concluded that “the presence of comorbidities is a significant risk factor for NRM and survival, but this does not fully explain the outcome disadvantages in our [elderly] group.”

Therefore, age remains an independent risk factor.

The investigators did not report conflicts of interest.

Photo by Junior Libby

A recent survey suggests Americans are nearly as worried about the cost of a cancer diagnosis as they are about dying from cancer.

The cost of cancer care was a top concern even among people who had no prior experience with cancer.

At the same time, cancer patients/survivors admitted to delaying or forgoing care due to costs, and caregivers reported taking “dramatic” actions to pay for their loved one’s care.

These are findings from the American Society of Clinical Oncology (ASCO)’s second annual National Cancer Opinion Survey.

The survey was conducted online by The Harris Poll from July 10, 2018, to August 10, 2018. It included 4,887 U.S. adults age 18 and older—1,001 of whom have or had cancer.

Cost among top concerns

Death and pain/suffering were the top concerns related to a cancer diagnosis. Fifty-four percent of respondents said death would be one of their greatest concerns if they were diagnosed with cancer, and the same percentage rated pain/suffering a top concern.

Forty-four percent of respondents said paying for cancer treatment would be a top concern, and 45% said the same about the financial impact of a cancer diagnosis on their family. When combined, financial issues were a top concern for 57% of respondents.

Paying for treatment was a top concern for:

• 36% of respondents who had/have cancer
• 51% of caregivers
• 43% of people with no prior cancer experience.

The financial impact on family was a top concern for:

• 39% of respondents who had/have cancer
• 55% of caregivers
• 42% of people with no prior cancer experience.

Cutting costs

Sixty-one percent of caregivers surveyed said they or another relative have taken a “dramatic” step to help pay for their loved one’s care, including:

• Dipping into savings accounts (35%)
• Working extra hours (23%)
• Taking an early withdrawal from a retirement account or college fund (14%)
• Postponing retirement (14%)
• Taking out a second mortgage or other type of loan (13%)
• Taking an additional job (13%)
• Selling family heirlooms (9%).

Twenty percent of cancer patients/survivors said they have taken actions to reduce treatment costs, including:

• Delaying scans (7%)
• Skipping or delaying appointments (7%)
• Skipping doses of prescribed treatment (6%)
• Postponing or not filling prescriptions (5%)
• Refusing treatment (3%).

“Patients are right to be concerned about the financial impact of a cancer diagnosis on their families,” said Richard L. Schilsky, MD, ASCO’s chief medical officer.

“It’s clear that high treatment costs are taking a serious toll not only on patients, but also on the people who care for them. If a family member has been diagnosed with cancer, the sole focus should be helping them get well. Instead, Americans are worrying about affording treatment, and, in many cases, they’re making serious personal sacrifices to help pay for their loved ones’ care.”

Photo by Junior Libby

A recent survey suggests Americans are nearly as worried about the cost of a cancer diagnosis as they are about dying from cancer.

The cost of cancer care was a top concern even among people who had no prior experience with cancer.

At the same time, cancer patients/survivors admitted to delaying or forgoing care due to costs, and caregivers reported taking “dramatic” actions to pay for their loved one’s care.

These are findings from the American Society of Clinical Oncology (ASCO)’s second annual National Cancer Opinion Survey.

The survey was conducted online by The Harris Poll from July 10, 2018, to August 10, 2018. It included 4,887 U.S. adults age 18 and older—1,001 of whom have or had cancer.

Cost among top concerns

Death and pain/suffering were the top concerns related to a cancer diagnosis. Fifty-four percent of respondents said death would be one of their greatest concerns if they were diagnosed with cancer, and the same percentage rated pain/suffering a top concern.

Forty-four percent of respondents said paying for cancer treatment would be a top concern, and 45% said the same about the financial impact of a cancer diagnosis on their family. When combined, financial issues were a top concern for 57% of respondents.

Paying for treatment was a top concern for:

• 36% of respondents who had/have cancer
• 51% of caregivers
• 43% of people with no prior cancer experience.

The financial impact on family was a top concern for:

• 39% of respondents who had/have cancer
• 55% of caregivers
• 42% of people with no prior cancer experience.

Cutting costs

Sixty-one percent of caregivers surveyed said they or another relative have taken a “dramatic” step to help pay for their loved one’s care, including:

• Dipping into savings accounts (35%)
• Working extra hours (23%)
• Taking an early withdrawal from a retirement account or college fund (14%)
• Postponing retirement (14%)
• Taking out a second mortgage or other type of loan (13%)
• Taking an additional job (13%)
• Selling family heirlooms (9%).

Twenty percent of cancer patients/survivors said they have taken actions to reduce treatment costs, including:

• Delaying scans (7%)
• Skipping or delaying appointments (7%)
• Skipping doses of prescribed treatment (6%)
• Postponing or not filling prescriptions (5%)
• Refusing treatment (3%).

“Patients are right to be concerned about the financial impact of a cancer diagnosis on their families,” said Richard L. Schilsky, MD, ASCO’s chief medical officer.

“It’s clear that high treatment costs are taking a serious toll not only on patients, but also on the people who care for them. If a family member has been diagnosed with cancer, the sole focus should be helping them get well. Instead, Americans are worrying about affording treatment, and, in many cases, they’re making serious personal sacrifices to help pay for their loved ones’ care.”

Photo by Junior Libby

A recent survey suggests Americans are nearly as worried about the cost of a cancer diagnosis as they are about dying from cancer.

The cost of cancer care was a top concern even among people who had no prior experience with cancer.

At the same time, cancer patients/survivors admitted to delaying or forgoing care due to costs, and caregivers reported taking “dramatic” actions to pay for their loved one’s care.

These are findings from the American Society of Clinical Oncology (ASCO)’s second annual National Cancer Opinion Survey.

The survey was conducted online by The Harris Poll from July 10, 2018, to August 10, 2018. It included 4,887 U.S. adults age 18 and older—1,001 of whom have or had cancer.

Cost among top concerns

Death and pain/suffering were the top concerns related to a cancer diagnosis. Fifty-four percent of respondents said death would be one of their greatest concerns if they were diagnosed with cancer, and the same percentage rated pain/suffering a top concern.

Forty-four percent of respondents said paying for cancer treatment would be a top concern, and 45% said the same about the financial impact of a cancer diagnosis on their family. When combined, financial issues were a top concern for 57% of respondents.

Paying for treatment was a top concern for:

• 36% of respondents who had/have cancer
• 51% of caregivers
• 43% of people with no prior cancer experience.

The financial impact on family was a top concern for:

• 39% of respondents who had/have cancer
• 55% of caregivers
• 42% of people with no prior cancer experience.

Cutting costs

Sixty-one percent of caregivers surveyed said they or another relative have taken a “dramatic” step to help pay for their loved one’s care, including:

• Dipping into savings accounts (35%)
• Working extra hours (23%)
• Taking an early withdrawal from a retirement account or college fund (14%)
• Postponing retirement (14%)
• Taking out a second mortgage or other type of loan (13%)
• Taking an additional job (13%)
• Selling family heirlooms (9%).

Twenty percent of cancer patients/survivors said they have taken actions to reduce treatment costs, including:

• Delaying scans (7%)
• Skipping or delaying appointments (7%)
• Skipping doses of prescribed treatment (6%)
• Postponing or not filling prescriptions (5%)
• Refusing treatment (3%).

“Patients are right to be concerned about the financial impact of a cancer diagnosis on their families,” said Richard L. Schilsky, MD, ASCO’s chief medical officer.

“It’s clear that high treatment costs are taking a serious toll not only on patients, but also on the people who care for them. If a family member has been diagnosed with cancer, the sole focus should be helping them get well. Instead, Americans are worrying about affording treatment, and, in many cases, they’re making serious personal sacrifices to help pay for their loved ones’ care.”

Clinical question: Is bacteremia from certain microbes associated with colorectal cancer?

Background: Streptococcus bovis bacteremia is classically associated with colorectal cancer. A number of other bacterial species have been found in colorectal cancer microbiota and may even exert oncogenic effects. However, it is not known whether bacteremia from these microbes is associated with ­colorectal cancer.

Study design: Retrospective cohort study.

Dr. Scarpato is clinical instructor in the division of hospital medicine, University of Colorado, Denver.

Clinical question: Is bacteremia from certain microbes associated with colorectal cancer?

Background: Streptococcus bovis bacteremia is classically associated with colorectal cancer. A number of other bacterial species have been found in colorectal cancer microbiota and may even exert oncogenic effects. However, it is not known whether bacteremia from these microbes is associated with ­colorectal cancer.

Study design: Retrospective cohort study.

Dr. Scarpato is clinical instructor in the division of hospital medicine, University of Colorado, Denver.

Clinical question: Is bacteremia from certain microbes associated with colorectal cancer?

Background: Streptococcus bovis bacteremia is classically associated with colorectal cancer. A number of other bacterial species have been found in colorectal cancer microbiota and may even exert oncogenic effects. However, it is not known whether bacteremia from these microbes is associated with ­colorectal cancer.

Study design: Retrospective cohort study.

Dr. Scarpato is clinical instructor in the division of hospital medicine, University of Colorado, Denver.