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Testicular Pain Leads to a Rare Diagnosis
A 26-year-old man presented to uroligy clinicians with right testicular pain and a right epididymal mass. It was a challenge to diagnose the cause—until he revealed some essential clues.
The differential diagnosis included testicular malignancy and lymphoma. However, tumor markers were within normal limits. Tests for HIV and syphilis were negative. The clinicians also considered granulomatous or chronic orchitis, but after treatment with nonsteroidal anti-inflammatory drugs, the pain and palpable epididymal mass had resolved. Then, follow-up testicular ultrasound images showed new diffuse heterogeneous hypoechoic lesions in the right testis.
The patient elected to have a right radical orchiectomy with sperm cryopreserved. He recovered well, and semen analysis did not show any abnormalities.
Pathology of the surgical specimen revealed necrotizing and nonnecrotizing granulomas. At this point, the patient recollected that he had developed cervical lymphadenopathy and oral ulcers several weeks after traveling to South America, 8 months before presenting with the testicular symptoms.
Combined with another clue—frequent exposure to cats during his South America trip—the patient’s symptoms now created a clearer picture. He had been diagnosed with toxoplasmosis at the time but had not received treatment because he was immunocompetent. The patient’s symptoms had resolved spontaneously, and he said he had been in his usual health between then and when he developed the testicular pain.
Based on this new information, the clinicians conducted immunohistochemical tests, which revealed isolated cysts about 20 µm in diameter, confirming a diagnosis of testicular toxoplasmosis. They started him on systemic toxoplasmosis treatment; he has been in good health since.
The clinicians note that toxoplasmosis is highly prevalent, infecting up to 30% of the world’s population. Cat feces is one source of infection with Toxoplasma gondii, which is typically asymptomatic. In immunocompetent patients, it tends to present as an acute infection that is benign and self-limited.
Only a few cases of testicular toxoplasmosis have been reported in the literature, and all have been in immunocompromised patients. Because this patient was immunocompetent, the case is unique, being the only one reported as yet. Given the immunocompetence, the clinicians say, the patient demonstrates the need for clinicians to have a high index of suspicion.
Source:
Wong V, Amarasekera C, Kundu S. BMJ Case Rep. 2018;2018. pii: bcr-2018-224962.
A 26-year-old man presented to uroligy clinicians with right testicular pain and a right epididymal mass. It was a challenge to diagnose the cause—until he revealed some essential clues.
The differential diagnosis included testicular malignancy and lymphoma. However, tumor markers were within normal limits. Tests for HIV and syphilis were negative. The clinicians also considered granulomatous or chronic orchitis, but after treatment with nonsteroidal anti-inflammatory drugs, the pain and palpable epididymal mass had resolved. Then, follow-up testicular ultrasound images showed new diffuse heterogeneous hypoechoic lesions in the right testis.
The patient elected to have a right radical orchiectomy with sperm cryopreserved. He recovered well, and semen analysis did not show any abnormalities.
Pathology of the surgical specimen revealed necrotizing and nonnecrotizing granulomas. At this point, the patient recollected that he had developed cervical lymphadenopathy and oral ulcers several weeks after traveling to South America, 8 months before presenting with the testicular symptoms.
Combined with another clue—frequent exposure to cats during his South America trip—the patient’s symptoms now created a clearer picture. He had been diagnosed with toxoplasmosis at the time but had not received treatment because he was immunocompetent. The patient’s symptoms had resolved spontaneously, and he said he had been in his usual health between then and when he developed the testicular pain.
Based on this new information, the clinicians conducted immunohistochemical tests, which revealed isolated cysts about 20 µm in diameter, confirming a diagnosis of testicular toxoplasmosis. They started him on systemic toxoplasmosis treatment; he has been in good health since.
The clinicians note that toxoplasmosis is highly prevalent, infecting up to 30% of the world’s population. Cat feces is one source of infection with Toxoplasma gondii, which is typically asymptomatic. In immunocompetent patients, it tends to present as an acute infection that is benign and self-limited.
Only a few cases of testicular toxoplasmosis have been reported in the literature, and all have been in immunocompromised patients. Because this patient was immunocompetent, the case is unique, being the only one reported as yet. Given the immunocompetence, the clinicians say, the patient demonstrates the need for clinicians to have a high index of suspicion.
Source:
Wong V, Amarasekera C, Kundu S. BMJ Case Rep. 2018;2018. pii: bcr-2018-224962.
A 26-year-old man presented to uroligy clinicians with right testicular pain and a right epididymal mass. It was a challenge to diagnose the cause—until he revealed some essential clues.
The differential diagnosis included testicular malignancy and lymphoma. However, tumor markers were within normal limits. Tests for HIV and syphilis were negative. The clinicians also considered granulomatous or chronic orchitis, but after treatment with nonsteroidal anti-inflammatory drugs, the pain and palpable epididymal mass had resolved. Then, follow-up testicular ultrasound images showed new diffuse heterogeneous hypoechoic lesions in the right testis.
The patient elected to have a right radical orchiectomy with sperm cryopreserved. He recovered well, and semen analysis did not show any abnormalities.
Pathology of the surgical specimen revealed necrotizing and nonnecrotizing granulomas. At this point, the patient recollected that he had developed cervical lymphadenopathy and oral ulcers several weeks after traveling to South America, 8 months before presenting with the testicular symptoms.
Combined with another clue—frequent exposure to cats during his South America trip—the patient’s symptoms now created a clearer picture. He had been diagnosed with toxoplasmosis at the time but had not received treatment because he was immunocompetent. The patient’s symptoms had resolved spontaneously, and he said he had been in his usual health between then and when he developed the testicular pain.
Based on this new information, the clinicians conducted immunohistochemical tests, which revealed isolated cysts about 20 µm in diameter, confirming a diagnosis of testicular toxoplasmosis. They started him on systemic toxoplasmosis treatment; he has been in good health since.
The clinicians note that toxoplasmosis is highly prevalent, infecting up to 30% of the world’s population. Cat feces is one source of infection with Toxoplasma gondii, which is typically asymptomatic. In immunocompetent patients, it tends to present as an acute infection that is benign and self-limited.
Only a few cases of testicular toxoplasmosis have been reported in the literature, and all have been in immunocompromised patients. Because this patient was immunocompetent, the case is unique, being the only one reported as yet. Given the immunocompetence, the clinicians say, the patient demonstrates the need for clinicians to have a high index of suspicion.
Source:
Wong V, Amarasekera C, Kundu S. BMJ Case Rep. 2018;2018. pii: bcr-2018-224962.
ACIP votes to recommend new strains for the 2018-2019 flu vaccine
Thirteen members of the Advisory Committee on Immunization Practices (ACIP) voted to approve the influenza vaccine recommendations for 2018-2019, while one member abstained from voting at the summer ACIP meeting.
The 2018-2019 recommendation maintains the core recommendation that influenza vaccines should be administered to all persons 6 months or older who have no contraindications.
FluMist Quadrivalent (LAIV4) also is being updated for the 2018-2019 season. At the February meeting of ACIP, the committee approved language that providers may provide any licensed, age-appropriate influenza vaccine, and LAIV4 is considered in this set of vaccine options.
Prior to this approval, there was a discussion of the safety of the 2017-2018 vaccine. For many of the available vaccines, there were no new safety concerns raised from reports during the flu season. Monitoring during the 2018-2019 will yield more safety monitoring data concerning pregnancy and influenza vaccinations and anaphylaxis in persons with an egg allergy.
The committee’s recommendations must be approved by the Centers for Disease Control and Prevention’s director before they are considered official recommendations.
Thirteen members of the Advisory Committee on Immunization Practices (ACIP) voted to approve the influenza vaccine recommendations for 2018-2019, while one member abstained from voting at the summer ACIP meeting.
The 2018-2019 recommendation maintains the core recommendation that influenza vaccines should be administered to all persons 6 months or older who have no contraindications.
FluMist Quadrivalent (LAIV4) also is being updated for the 2018-2019 season. At the February meeting of ACIP, the committee approved language that providers may provide any licensed, age-appropriate influenza vaccine, and LAIV4 is considered in this set of vaccine options.
Prior to this approval, there was a discussion of the safety of the 2017-2018 vaccine. For many of the available vaccines, there were no new safety concerns raised from reports during the flu season. Monitoring during the 2018-2019 will yield more safety monitoring data concerning pregnancy and influenza vaccinations and anaphylaxis in persons with an egg allergy.
The committee’s recommendations must be approved by the Centers for Disease Control and Prevention’s director before they are considered official recommendations.
Thirteen members of the Advisory Committee on Immunization Practices (ACIP) voted to approve the influenza vaccine recommendations for 2018-2019, while one member abstained from voting at the summer ACIP meeting.
The 2018-2019 recommendation maintains the core recommendation that influenza vaccines should be administered to all persons 6 months or older who have no contraindications.
FluMist Quadrivalent (LAIV4) also is being updated for the 2018-2019 season. At the February meeting of ACIP, the committee approved language that providers may provide any licensed, age-appropriate influenza vaccine, and LAIV4 is considered in this set of vaccine options.
Prior to this approval, there was a discussion of the safety of the 2017-2018 vaccine. For many of the available vaccines, there were no new safety concerns raised from reports during the flu season. Monitoring during the 2018-2019 will yield more safety monitoring data concerning pregnancy and influenza vaccinations and anaphylaxis in persons with an egg allergy.
The committee’s recommendations must be approved by the Centers for Disease Control and Prevention’s director before they are considered official recommendations.
REPORTING FROM AN ACIP MEETING
Autism Spectrum Disorders Are on the Rise
The estimated prevalence of autism spectrum disorder (ASD) is higher than previously recorded, according to the Autism and Developmental Disabilities Monitoring (ADDM) Network. Between 2000- 2014, the prevalence increased from 6.7 to 16.8 per 1,000 children, a jump of about 150%.
Autism and Developmental Disabilities Monitoring is a surveillance system that estimates the prevalence of autism spectrum disorder among children aged 8 years who live within 11 sites (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Autism and Developmental Disabilities Monitoring does not depend on family or practitioner reporting to determine ASD case status. Instead, staff conduct surveillance in a 2-phase process: reviewing children’s evaluation records from data sources in the community (including “developmental assessments completed by a wide range of health and education providers”), and compiling them into a comprehensive record that is then reviewed by ≤ 1 experienced clinicians.
Certain characteristics remained similar in 2014 compared with earlier surveillance years, ADDM researchers say. For instance, the median age of earliest known ASD diagnosis was 52 months in 2014, compared with close to 53 months in previous years.
However, male-to-female prevalence changed slightly, from 4.5:1 to 4:1, driven by a greater relative increase in ASD prevalence among girls since 2012. Autism and Developmental Disabilities Monitoring also points to a trend that begun in 2002 of a decrease in the ratios of white to black children and white to Hispanic children. Historically, ADDM researchers say, estimates have been 20% to 30% higher among white children compared with black children and 50% to 70% higher compared with Hispanic children. In 2014, those numbers dropped to 7% (the lowest difference ever observed by ADDM) and 22%, respectively.
Implementation of the new DSM-5 case definition had little effect on the overall number of children identified with ASD in 2014, ADDM researchers say.
The estimated prevalence of autism spectrum disorder (ASD) is higher than previously recorded, according to the Autism and Developmental Disabilities Monitoring (ADDM) Network. Between 2000- 2014, the prevalence increased from 6.7 to 16.8 per 1,000 children, a jump of about 150%.
Autism and Developmental Disabilities Monitoring is a surveillance system that estimates the prevalence of autism spectrum disorder among children aged 8 years who live within 11 sites (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Autism and Developmental Disabilities Monitoring does not depend on family or practitioner reporting to determine ASD case status. Instead, staff conduct surveillance in a 2-phase process: reviewing children’s evaluation records from data sources in the community (including “developmental assessments completed by a wide range of health and education providers”), and compiling them into a comprehensive record that is then reviewed by ≤ 1 experienced clinicians.
Certain characteristics remained similar in 2014 compared with earlier surveillance years, ADDM researchers say. For instance, the median age of earliest known ASD diagnosis was 52 months in 2014, compared with close to 53 months in previous years.
However, male-to-female prevalence changed slightly, from 4.5:1 to 4:1, driven by a greater relative increase in ASD prevalence among girls since 2012. Autism and Developmental Disabilities Monitoring also points to a trend that begun in 2002 of a decrease in the ratios of white to black children and white to Hispanic children. Historically, ADDM researchers say, estimates have been 20% to 30% higher among white children compared with black children and 50% to 70% higher compared with Hispanic children. In 2014, those numbers dropped to 7% (the lowest difference ever observed by ADDM) and 22%, respectively.
Implementation of the new DSM-5 case definition had little effect on the overall number of children identified with ASD in 2014, ADDM researchers say.
The estimated prevalence of autism spectrum disorder (ASD) is higher than previously recorded, according to the Autism and Developmental Disabilities Monitoring (ADDM) Network. Between 2000- 2014, the prevalence increased from 6.7 to 16.8 per 1,000 children, a jump of about 150%.
Autism and Developmental Disabilities Monitoring is a surveillance system that estimates the prevalence of autism spectrum disorder among children aged 8 years who live within 11 sites (Arizona, Arkansas, Colorado, Georgia, Maryland, Minnesota, Missouri, New Jersey, North Carolina, Tennessee, and Wisconsin). Autism and Developmental Disabilities Monitoring does not depend on family or practitioner reporting to determine ASD case status. Instead, staff conduct surveillance in a 2-phase process: reviewing children’s evaluation records from data sources in the community (including “developmental assessments completed by a wide range of health and education providers”), and compiling them into a comprehensive record that is then reviewed by ≤ 1 experienced clinicians.
Certain characteristics remained similar in 2014 compared with earlier surveillance years, ADDM researchers say. For instance, the median age of earliest known ASD diagnosis was 52 months in 2014, compared with close to 53 months in previous years.
However, male-to-female prevalence changed slightly, from 4.5:1 to 4:1, driven by a greater relative increase in ASD prevalence among girls since 2012. Autism and Developmental Disabilities Monitoring also points to a trend that begun in 2002 of a decrease in the ratios of white to black children and white to Hispanic children. Historically, ADDM researchers say, estimates have been 20% to 30% higher among white children compared with black children and 50% to 70% higher compared with Hispanic children. In 2014, those numbers dropped to 7% (the lowest difference ever observed by ADDM) and 22%, respectively.
Implementation of the new DSM-5 case definition had little effect on the overall number of children identified with ASD in 2014, ADDM researchers say.
VA Care Matches—or Bests—Non-VA Care
Researchers from RAND Corp. compared performance between each VA facility and 3 corresponding non-VA settings with similar geographic settings, size, and complexity of care, using recent data on patient safety, mortality and readmission, inpatient and outpatient effectiveness, and patient-centered care.
VA hospitals performed on average the same as or significantly better than the non-VA hospitals on all 6 measures of inpatient safety, all 3 inpatient mortality measures, and 12 inpatient effectiveness measures. VA facilities also performed significantly better than commercial HMOs and Medicaid HMOs for all 16 outpatient effectiveness measures. Compared with Medicare HMOs, the VA did significantly better on 14 measures and did not differ on 2.
However, the VA performance was worse than the non-VA hospitals on 3 readmission measures and 2 effectiveness measures. For example, VA inpatient performance was significantly lower on the patient experience measure for pain management.
The researchers saw “high variation” across VA facilities in performance on some quality measures, although they note that variation was even greater among non-VA hospitals. “The variation among VA health facilities shows that veterans in some areas are not receiving the same high-quality care that other VA facilities are able to provide,” said Carrie Farmer, a co-author of the study.
Researchers from RAND Corp. compared performance between each VA facility and 3 corresponding non-VA settings with similar geographic settings, size, and complexity of care, using recent data on patient safety, mortality and readmission, inpatient and outpatient effectiveness, and patient-centered care.
VA hospitals performed on average the same as or significantly better than the non-VA hospitals on all 6 measures of inpatient safety, all 3 inpatient mortality measures, and 12 inpatient effectiveness measures. VA facilities also performed significantly better than commercial HMOs and Medicaid HMOs for all 16 outpatient effectiveness measures. Compared with Medicare HMOs, the VA did significantly better on 14 measures and did not differ on 2.
However, the VA performance was worse than the non-VA hospitals on 3 readmission measures and 2 effectiveness measures. For example, VA inpatient performance was significantly lower on the patient experience measure for pain management.
The researchers saw “high variation” across VA facilities in performance on some quality measures, although they note that variation was even greater among non-VA hospitals. “The variation among VA health facilities shows that veterans in some areas are not receiving the same high-quality care that other VA facilities are able to provide,” said Carrie Farmer, a co-author of the study.
Researchers from RAND Corp. compared performance between each VA facility and 3 corresponding non-VA settings with similar geographic settings, size, and complexity of care, using recent data on patient safety, mortality and readmission, inpatient and outpatient effectiveness, and patient-centered care.
VA hospitals performed on average the same as or significantly better than the non-VA hospitals on all 6 measures of inpatient safety, all 3 inpatient mortality measures, and 12 inpatient effectiveness measures. VA facilities also performed significantly better than commercial HMOs and Medicaid HMOs for all 16 outpatient effectiveness measures. Compared with Medicare HMOs, the VA did significantly better on 14 measures and did not differ on 2.
However, the VA performance was worse than the non-VA hospitals on 3 readmission measures and 2 effectiveness measures. For example, VA inpatient performance was significantly lower on the patient experience measure for pain management.
The researchers saw “high variation” across VA facilities in performance on some quality measures, although they note that variation was even greater among non-VA hospitals. “The variation among VA health facilities shows that veterans in some areas are not receiving the same high-quality care that other VA facilities are able to provide,” said Carrie Farmer, a co-author of the study.
Additional training may be warranted for clinicians administering DTaP
Additional training may be needed for providers who administer DTaP vaccine to prevent errors in vaccination, but reported Pedro Moro, MD, MPH, of the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases and his associates in Pediatrics.
After Dr. Moro and his associates performed an automated analysis of all reports included in the Vaccine Adverse Event Reporting System (VAERS), which is coadministered by the CDC and the Food and Drug Administration, as well as a clinical review of reported deaths and a random sampling of serious reports in the database, they concluded that safety findings concerning DTaP were consistent with those from prelicensure trials and postlicensure studies.
DTaP vaccines, which included Infanrix, Daptacel, Pediarix, Kinrix, and Pentacel, were coadministered with one or more other vaccines in 43,984 (88%) of cases reported; of the reports included in the data mining, 5,627 (11%) were classified as serious, including 844 (2%) deaths. Of all reports received in the prelicensure clinical trials, injection site reactions and systemic reactions, such as fever and vomiting, were the most common reactions to DTaP vaccine.
In a 5% random sample of the 4,783 serious nondeath reports included in the study, 25% were neurologic, 23% gastrointestinal, and 20% were caused by general disorders and vaccine site conditions. Fully 80% of those flagged as neurologic were seizure related. In another 79%, for which intussusception was the most common gastrointestinal condition, all but two cases had rotavirus vaccine coadministered with DTaP. Altogether, there were 182 cases of anaphylaxis reported.
Serious events were characterized as death, life-threatening illness, hospitalization, lengthening of existing hospital stay, or permanent disability. In cases of death, reports that followed DTaP vaccine were manually reviewed by a physician, who evaluated autopsy report, death certificate, or medical records. The authors also included in their evaluation of records any reports of postvaccine anaphylaxis.
Of the 844 deaths, death certificates, autopsy reports, or medical records were obtained for 86%. Among these, sudden infant death syndrome (SIDS) was found to be the most frequent cause of death in 48%; of these, 62% were male infants, and 91% were infants under 6 months of age.
“It would not be uncommon to observe a coincidental close temporal relationship between vaccination and SIDS because this condition peaks at a time when children receive a relatively large number of recommended vaccinations,” said Dr. Moro and his associates. “There is a large body of evidence in which it is shown that vaccination is not causally associated with SIDS.”
The authors identified disproportional reporting for injection site reactions, as well as other events and conditions, to which they attribute, at least in part, administration of the wrong vaccine or formulation and administration at the wrong site. Such mistakes can be lessened or even prevented with provider education and training on appropriate recommendations and package insert specifications put forth by the CDC’s Advisory Committee on Immunization Practices, they advised.
While the authors praised VAERS for the wealth of timely data it has offered in detecting potential safety issues that may require further investigation, Dr. Moro cautioned that it is a passive surveillance system with limitations that warrant “careful interpretation of its findings.” Its purpose is to improve immunization programs.
Because it does not “meet the definition of research,” the work performed in this study was not subject to institutional review board evaluation and informed consent requirements, the authors added. VAERS generally is not able to assess whether vaccines are the direct cause of adverse events, primarily because of underreporting or overreporting, biased reporting, and inconsistency in quality and completeness of information reported. Because it does not tally number of vaccines administered, it is also unable to provide data needed to calculate incidence rates.
The authors had no relevant financial disclosures. The study was funded by the CDC and the FDA.
SOURCE: Moro P et al. Pediatrics. 2018. doi: 10.1542/peds.2017-4171.
The Vaccine Adverse Event Reporting System offers confirmation that DTaP vaccines are safe and have a reasonably low frequency of adverse events. Despite this, the U.S.-based resurgence of pertussis shortly after acellular vaccines were introduced legitimately raised concerns over the efficacy of DTaP, which is now known to have a shorter duration of protection than its predecessor, the diphtheria, tetanus toxoids, whole-cell pertussis vaccine. Consequently, older children, adolescents, and adults are left unprotected without periodic booster doses, Flor M. Muñoz, MD, wrote in an editorial accompanying the study by Moro et al.
The World Health Organization’s recommendation to countries that never made the switch to DTaP is to continue using the whole-cell vaccines “because of their consistent higher efficacy” points to “an imperative need to develop more immunogenic pertussis vaccines that are also safe,” she observed.
“Active research is ongoing for the development of novel vaccines, including live attenuated vaccines, whole-cell vaccines with reduced endotoxin content to be less reactogenic, outer membrane vesicles–based vaccines, and acellular vaccine formulations prepared with new adjuvants or additional and novel antigens.
“As we go back to the drawing board in the fight against Bordetella pertussis, much work is needed to learn more about this fascinating pathogen and its interactions with humans to improve our understanding of how immunity and long-lasting protection can be achieved, to engineer and produce novel vaccines, and to design and perform the clinical studies that will eventually lead to the control of pertussis disease and its global impact with safe and effective vaccines for all,” Dr. Muñoz added.
Dr. Muñoz is affiliated with the section of infectious diseases in the department of pediatrics at Baylor College of Medicine and Texas Children’s Hospital, both in Houston. Her comments here were summarized from her editorial accompanying the article by Moro et al (Pediatrics. 2018. doi: 10.1542/peds.2018-1036). Dr. Munoz said she had no relevant financial disclosures and received no external funding.
The Vaccine Adverse Event Reporting System offers confirmation that DTaP vaccines are safe and have a reasonably low frequency of adverse events. Despite this, the U.S.-based resurgence of pertussis shortly after acellular vaccines were introduced legitimately raised concerns over the efficacy of DTaP, which is now known to have a shorter duration of protection than its predecessor, the diphtheria, tetanus toxoids, whole-cell pertussis vaccine. Consequently, older children, adolescents, and adults are left unprotected without periodic booster doses, Flor M. Muñoz, MD, wrote in an editorial accompanying the study by Moro et al.
The World Health Organization’s recommendation to countries that never made the switch to DTaP is to continue using the whole-cell vaccines “because of their consistent higher efficacy” points to “an imperative need to develop more immunogenic pertussis vaccines that are also safe,” she observed.
“Active research is ongoing for the development of novel vaccines, including live attenuated vaccines, whole-cell vaccines with reduced endotoxin content to be less reactogenic, outer membrane vesicles–based vaccines, and acellular vaccine formulations prepared with new adjuvants or additional and novel antigens.
“As we go back to the drawing board in the fight against Bordetella pertussis, much work is needed to learn more about this fascinating pathogen and its interactions with humans to improve our understanding of how immunity and long-lasting protection can be achieved, to engineer and produce novel vaccines, and to design and perform the clinical studies that will eventually lead to the control of pertussis disease and its global impact with safe and effective vaccines for all,” Dr. Muñoz added.
Dr. Muñoz is affiliated with the section of infectious diseases in the department of pediatrics at Baylor College of Medicine and Texas Children’s Hospital, both in Houston. Her comments here were summarized from her editorial accompanying the article by Moro et al (Pediatrics. 2018. doi: 10.1542/peds.2018-1036). Dr. Munoz said she had no relevant financial disclosures and received no external funding.
The Vaccine Adverse Event Reporting System offers confirmation that DTaP vaccines are safe and have a reasonably low frequency of adverse events. Despite this, the U.S.-based resurgence of pertussis shortly after acellular vaccines were introduced legitimately raised concerns over the efficacy of DTaP, which is now known to have a shorter duration of protection than its predecessor, the diphtheria, tetanus toxoids, whole-cell pertussis vaccine. Consequently, older children, adolescents, and adults are left unprotected without periodic booster doses, Flor M. Muñoz, MD, wrote in an editorial accompanying the study by Moro et al.
The World Health Organization’s recommendation to countries that never made the switch to DTaP is to continue using the whole-cell vaccines “because of their consistent higher efficacy” points to “an imperative need to develop more immunogenic pertussis vaccines that are also safe,” she observed.
“Active research is ongoing for the development of novel vaccines, including live attenuated vaccines, whole-cell vaccines with reduced endotoxin content to be less reactogenic, outer membrane vesicles–based vaccines, and acellular vaccine formulations prepared with new adjuvants or additional and novel antigens.
“As we go back to the drawing board in the fight against Bordetella pertussis, much work is needed to learn more about this fascinating pathogen and its interactions with humans to improve our understanding of how immunity and long-lasting protection can be achieved, to engineer and produce novel vaccines, and to design and perform the clinical studies that will eventually lead to the control of pertussis disease and its global impact with safe and effective vaccines for all,” Dr. Muñoz added.
Dr. Muñoz is affiliated with the section of infectious diseases in the department of pediatrics at Baylor College of Medicine and Texas Children’s Hospital, both in Houston. Her comments here were summarized from her editorial accompanying the article by Moro et al (Pediatrics. 2018. doi: 10.1542/peds.2018-1036). Dr. Munoz said she had no relevant financial disclosures and received no external funding.
Additional training may be needed for providers who administer DTaP vaccine to prevent errors in vaccination, but reported Pedro Moro, MD, MPH, of the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases and his associates in Pediatrics.
After Dr. Moro and his associates performed an automated analysis of all reports included in the Vaccine Adverse Event Reporting System (VAERS), which is coadministered by the CDC and the Food and Drug Administration, as well as a clinical review of reported deaths and a random sampling of serious reports in the database, they concluded that safety findings concerning DTaP were consistent with those from prelicensure trials and postlicensure studies.
DTaP vaccines, which included Infanrix, Daptacel, Pediarix, Kinrix, and Pentacel, were coadministered with one or more other vaccines in 43,984 (88%) of cases reported; of the reports included in the data mining, 5,627 (11%) were classified as serious, including 844 (2%) deaths. Of all reports received in the prelicensure clinical trials, injection site reactions and systemic reactions, such as fever and vomiting, were the most common reactions to DTaP vaccine.
In a 5% random sample of the 4,783 serious nondeath reports included in the study, 25% were neurologic, 23% gastrointestinal, and 20% were caused by general disorders and vaccine site conditions. Fully 80% of those flagged as neurologic were seizure related. In another 79%, for which intussusception was the most common gastrointestinal condition, all but two cases had rotavirus vaccine coadministered with DTaP. Altogether, there were 182 cases of anaphylaxis reported.
Serious events were characterized as death, life-threatening illness, hospitalization, lengthening of existing hospital stay, or permanent disability. In cases of death, reports that followed DTaP vaccine were manually reviewed by a physician, who evaluated autopsy report, death certificate, or medical records. The authors also included in their evaluation of records any reports of postvaccine anaphylaxis.
Of the 844 deaths, death certificates, autopsy reports, or medical records were obtained for 86%. Among these, sudden infant death syndrome (SIDS) was found to be the most frequent cause of death in 48%; of these, 62% were male infants, and 91% were infants under 6 months of age.
“It would not be uncommon to observe a coincidental close temporal relationship between vaccination and SIDS because this condition peaks at a time when children receive a relatively large number of recommended vaccinations,” said Dr. Moro and his associates. “There is a large body of evidence in which it is shown that vaccination is not causally associated with SIDS.”
The authors identified disproportional reporting for injection site reactions, as well as other events and conditions, to which they attribute, at least in part, administration of the wrong vaccine or formulation and administration at the wrong site. Such mistakes can be lessened or even prevented with provider education and training on appropriate recommendations and package insert specifications put forth by the CDC’s Advisory Committee on Immunization Practices, they advised.
While the authors praised VAERS for the wealth of timely data it has offered in detecting potential safety issues that may require further investigation, Dr. Moro cautioned that it is a passive surveillance system with limitations that warrant “careful interpretation of its findings.” Its purpose is to improve immunization programs.
Because it does not “meet the definition of research,” the work performed in this study was not subject to institutional review board evaluation and informed consent requirements, the authors added. VAERS generally is not able to assess whether vaccines are the direct cause of adverse events, primarily because of underreporting or overreporting, biased reporting, and inconsistency in quality and completeness of information reported. Because it does not tally number of vaccines administered, it is also unable to provide data needed to calculate incidence rates.
The authors had no relevant financial disclosures. The study was funded by the CDC and the FDA.
SOURCE: Moro P et al. Pediatrics. 2018. doi: 10.1542/peds.2017-4171.
Additional training may be needed for providers who administer DTaP vaccine to prevent errors in vaccination, but reported Pedro Moro, MD, MPH, of the Centers for Disease Control and Prevention’s National Center for Immunization and Respiratory Diseases and his associates in Pediatrics.
After Dr. Moro and his associates performed an automated analysis of all reports included in the Vaccine Adverse Event Reporting System (VAERS), which is coadministered by the CDC and the Food and Drug Administration, as well as a clinical review of reported deaths and a random sampling of serious reports in the database, they concluded that safety findings concerning DTaP were consistent with those from prelicensure trials and postlicensure studies.
DTaP vaccines, which included Infanrix, Daptacel, Pediarix, Kinrix, and Pentacel, were coadministered with one or more other vaccines in 43,984 (88%) of cases reported; of the reports included in the data mining, 5,627 (11%) were classified as serious, including 844 (2%) deaths. Of all reports received in the prelicensure clinical trials, injection site reactions and systemic reactions, such as fever and vomiting, were the most common reactions to DTaP vaccine.
In a 5% random sample of the 4,783 serious nondeath reports included in the study, 25% were neurologic, 23% gastrointestinal, and 20% were caused by general disorders and vaccine site conditions. Fully 80% of those flagged as neurologic were seizure related. In another 79%, for which intussusception was the most common gastrointestinal condition, all but two cases had rotavirus vaccine coadministered with DTaP. Altogether, there were 182 cases of anaphylaxis reported.
Serious events were characterized as death, life-threatening illness, hospitalization, lengthening of existing hospital stay, or permanent disability. In cases of death, reports that followed DTaP vaccine were manually reviewed by a physician, who evaluated autopsy report, death certificate, or medical records. The authors also included in their evaluation of records any reports of postvaccine anaphylaxis.
Of the 844 deaths, death certificates, autopsy reports, or medical records were obtained for 86%. Among these, sudden infant death syndrome (SIDS) was found to be the most frequent cause of death in 48%; of these, 62% were male infants, and 91% were infants under 6 months of age.
“It would not be uncommon to observe a coincidental close temporal relationship between vaccination and SIDS because this condition peaks at a time when children receive a relatively large number of recommended vaccinations,” said Dr. Moro and his associates. “There is a large body of evidence in which it is shown that vaccination is not causally associated with SIDS.”
The authors identified disproportional reporting for injection site reactions, as well as other events and conditions, to which they attribute, at least in part, administration of the wrong vaccine or formulation and administration at the wrong site. Such mistakes can be lessened or even prevented with provider education and training on appropriate recommendations and package insert specifications put forth by the CDC’s Advisory Committee on Immunization Practices, they advised.
While the authors praised VAERS for the wealth of timely data it has offered in detecting potential safety issues that may require further investigation, Dr. Moro cautioned that it is a passive surveillance system with limitations that warrant “careful interpretation of its findings.” Its purpose is to improve immunization programs.
Because it does not “meet the definition of research,” the work performed in this study was not subject to institutional review board evaluation and informed consent requirements, the authors added. VAERS generally is not able to assess whether vaccines are the direct cause of adverse events, primarily because of underreporting or overreporting, biased reporting, and inconsistency in quality and completeness of information reported. Because it does not tally number of vaccines administered, it is also unable to provide data needed to calculate incidence rates.
The authors had no relevant financial disclosures. The study was funded by the CDC and the FDA.
SOURCE: Moro P et al. Pediatrics. 2018. doi: 10.1542/peds.2017-4171.
FROM PEDIATRICS
Key clinical point: No new or unexpected safety issues were found with DTaP.
Major finding: Nearly 90% of adverse events reported were not considered serious.
Study details: Large-scale data mining and records review from the Vaccine Adverse Event Reporting System.
Disclosures: The authors had no relevant financial disclosures. The study was funded by the Centers for Disease Control and Prevention and the Food and Drug Administration.
Source: Moro P et al. Pediatrics. 2018. doi: 10.1542/peds.2017-4171.
New Guidelines for Nonmelanoma Skin Cancer: What You Need to Know
British good practice paper offers MCL diagnosis pearls
Immunohistochemical panels used in the diagnosis of mantle cell lymphoma should include cyclin D1 and SOX11 immunostaining, according to a good practice paper from the British Society of Haematology.
Pamela McKay, MD, of the Beatson West of Scotland Cancer Centre, Glasgow, and her colleagues provided based on a review of literature from 1980 to 2017. The good practice paper aims to offer best practice advice based on consensus where the evidence is limited. Specifically, the paper incorporates new information on molecular pathology and the use of positron emission tomography/computed tomography (PET/CT) scanning in staging of disease.
The top recommendations related to MCL diagnosis include performing lymph node excision or adequate core biopsy for diagnosis of nodal MCL. For non-nodal presentation, a tissue biopsy or peripheral blood can be used. Additionally, immunohistochemical panels should include cyclin D1 and SOX11 immunostaining.
In cases of atypical morphology, aberrant immunophenotype, equivocal cyclin D1 positivity, or unusual clinical presentation, the authors recommended fluorescence in situ hybridization (FISH) to demonstrate the presence of the t(11;14) translocation. They also recommended recording the Ki67 Proliferation Index at baseline, with an index of greater than 30% being indicative of a poorer outcome.
In terms of staging disease, Dr. McKay and her associates recommended that patients undergo staging with CT of the neck, chest, abdomen, and pelvis. They recommended against routine use of fluorodeoxyglucose PET for MCL staging, but said it could be considered if radical radiotherapy is being proposed for early-stage disease.
For cases with suspicion of central nervous system involvement, lumbar puncture with cytospin and immunophenotyping is recommended.
They recommended that all MCL patients have either their simplified or combined MCL international prognostic index score recorded at baseline.
All the authors made a declaration of interest to the British Society of Haematology and task force chairs, which may be viewed on request.
SOURCE: McKay P et al. Br J Haematol. 2018 Jun 8. doi: 10.1111/bjh.15281.
Immunohistochemical panels used in the diagnosis of mantle cell lymphoma should include cyclin D1 and SOX11 immunostaining, according to a good practice paper from the British Society of Haematology.
Pamela McKay, MD, of the Beatson West of Scotland Cancer Centre, Glasgow, and her colleagues provided based on a review of literature from 1980 to 2017. The good practice paper aims to offer best practice advice based on consensus where the evidence is limited. Specifically, the paper incorporates new information on molecular pathology and the use of positron emission tomography/computed tomography (PET/CT) scanning in staging of disease.
The top recommendations related to MCL diagnosis include performing lymph node excision or adequate core biopsy for diagnosis of nodal MCL. For non-nodal presentation, a tissue biopsy or peripheral blood can be used. Additionally, immunohistochemical panels should include cyclin D1 and SOX11 immunostaining.
In cases of atypical morphology, aberrant immunophenotype, equivocal cyclin D1 positivity, or unusual clinical presentation, the authors recommended fluorescence in situ hybridization (FISH) to demonstrate the presence of the t(11;14) translocation. They also recommended recording the Ki67 Proliferation Index at baseline, with an index of greater than 30% being indicative of a poorer outcome.
In terms of staging disease, Dr. McKay and her associates recommended that patients undergo staging with CT of the neck, chest, abdomen, and pelvis. They recommended against routine use of fluorodeoxyglucose PET for MCL staging, but said it could be considered if radical radiotherapy is being proposed for early-stage disease.
For cases with suspicion of central nervous system involvement, lumbar puncture with cytospin and immunophenotyping is recommended.
They recommended that all MCL patients have either their simplified or combined MCL international prognostic index score recorded at baseline.
All the authors made a declaration of interest to the British Society of Haematology and task force chairs, which may be viewed on request.
SOURCE: McKay P et al. Br J Haematol. 2018 Jun 8. doi: 10.1111/bjh.15281.
Immunohistochemical panels used in the diagnosis of mantle cell lymphoma should include cyclin D1 and SOX11 immunostaining, according to a good practice paper from the British Society of Haematology.
Pamela McKay, MD, of the Beatson West of Scotland Cancer Centre, Glasgow, and her colleagues provided based on a review of literature from 1980 to 2017. The good practice paper aims to offer best practice advice based on consensus where the evidence is limited. Specifically, the paper incorporates new information on molecular pathology and the use of positron emission tomography/computed tomography (PET/CT) scanning in staging of disease.
The top recommendations related to MCL diagnosis include performing lymph node excision or adequate core biopsy for diagnosis of nodal MCL. For non-nodal presentation, a tissue biopsy or peripheral blood can be used. Additionally, immunohistochemical panels should include cyclin D1 and SOX11 immunostaining.
In cases of atypical morphology, aberrant immunophenotype, equivocal cyclin D1 positivity, or unusual clinical presentation, the authors recommended fluorescence in situ hybridization (FISH) to demonstrate the presence of the t(11;14) translocation. They also recommended recording the Ki67 Proliferation Index at baseline, with an index of greater than 30% being indicative of a poorer outcome.
In terms of staging disease, Dr. McKay and her associates recommended that patients undergo staging with CT of the neck, chest, abdomen, and pelvis. They recommended against routine use of fluorodeoxyglucose PET for MCL staging, but said it could be considered if radical radiotherapy is being proposed for early-stage disease.
For cases with suspicion of central nervous system involvement, lumbar puncture with cytospin and immunophenotyping is recommended.
They recommended that all MCL patients have either their simplified or combined MCL international prognostic index score recorded at baseline.
All the authors made a declaration of interest to the British Society of Haematology and task force chairs, which may be viewed on request.
SOURCE: McKay P et al. Br J Haematol. 2018 Jun 8. doi: 10.1111/bjh.15281.
FROM THE BRITISH JOURNAL OF HAEMATOLOGY
New NIH consortium aims to coordinate pediatric research programs
across its institutes and centers.
Almost all of the 27 institutes and centers of the NIH fund at least some kind of child health research, totaling more than $4 billion in the 2017 fiscal year, according to an NIH statement. “The new consortium aims to harmonize these activities, explore gaps and opportunities in the overall pediatric research portfolio, and set priorities.”
Research funded by NIH “has resulted in tremendous advances against diseases and conditions that affect child health and well-being, including asthma, cancer, autism, obesity, and intellectual and developmental disabilities,” explained Diana W. Bianchi, MD, in the statement. Dr. Bianchi is director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the lead NIH institute for the consortium.
The new consortium, which will be led by the NICHD director, will meet several times a year.
across its institutes and centers.
Almost all of the 27 institutes and centers of the NIH fund at least some kind of child health research, totaling more than $4 billion in the 2017 fiscal year, according to an NIH statement. “The new consortium aims to harmonize these activities, explore gaps and opportunities in the overall pediatric research portfolio, and set priorities.”
Research funded by NIH “has resulted in tremendous advances against diseases and conditions that affect child health and well-being, including asthma, cancer, autism, obesity, and intellectual and developmental disabilities,” explained Diana W. Bianchi, MD, in the statement. Dr. Bianchi is director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the lead NIH institute for the consortium.
The new consortium, which will be led by the NICHD director, will meet several times a year.
across its institutes and centers.
Almost all of the 27 institutes and centers of the NIH fund at least some kind of child health research, totaling more than $4 billion in the 2017 fiscal year, according to an NIH statement. “The new consortium aims to harmonize these activities, explore gaps and opportunities in the overall pediatric research portfolio, and set priorities.”
Research funded by NIH “has resulted in tremendous advances against diseases and conditions that affect child health and well-being, including asthma, cancer, autism, obesity, and intellectual and developmental disabilities,” explained Diana W. Bianchi, MD, in the statement. Dr. Bianchi is director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the lead NIH institute for the consortium.
The new consortium, which will be led by the NICHD director, will meet several times a year.
FDA approves pembrolizumab for relapsed/refractory PMBCL
The immune checkpoint inhibitor in adult and pediatric patients.
The Food and Drug Administration based the accelerated approval on results from 53 patients with relapsed or refractory primary mediastinal large B-cell lymphoma in the KEYNOTE-170 trial. In the phase 2 trial, patients received 200 mg of pembrolizumab intravenously for 3 weeks until unacceptable toxicity or documented disease progression occurred. This continued for up to 24 months in patients who did not display progression. The overall response rate to pembrolizumab was 45% (95% CI, 32-60), which included both complete (11%) and partial (34%) responses. The median duration of response was not met within the follow-up period (median, 9.7 months) and the median time to first objective response was 2.8 months.
The recommended dose for pembrolizumab in adults is 200 mg every 3 weeks. It is recommended that pediatric patients receive 2 mg/kg every 3 weeks, with a maximum dose of 200 mg.
The most common adverse reactions to pembrolizumab were musculoskeletal pain, upper respiratory tract infection, pyrexia, fatigue, cough, dyspnea, diarrhea, nausea, arrhythmia, and headache. In total, a quarter of patients with adverse reactions required systemic treatment with a corticosteroid and 26% of patients had serious adverse reactions.
Pembrolizumab was approved via the FDA’s accelerated approval process, which allows for earlier approval of drugs that treat serious medical conditions and fulfill an unmet medical need. The drug was approved based on tumor response rate and durability of response, the FDA noted.
The immune checkpoint inhibitor in adult and pediatric patients.
The Food and Drug Administration based the accelerated approval on results from 53 patients with relapsed or refractory primary mediastinal large B-cell lymphoma in the KEYNOTE-170 trial. In the phase 2 trial, patients received 200 mg of pembrolizumab intravenously for 3 weeks until unacceptable toxicity or documented disease progression occurred. This continued for up to 24 months in patients who did not display progression. The overall response rate to pembrolizumab was 45% (95% CI, 32-60), which included both complete (11%) and partial (34%) responses. The median duration of response was not met within the follow-up period (median, 9.7 months) and the median time to first objective response was 2.8 months.
The recommended dose for pembrolizumab in adults is 200 mg every 3 weeks. It is recommended that pediatric patients receive 2 mg/kg every 3 weeks, with a maximum dose of 200 mg.
The most common adverse reactions to pembrolizumab were musculoskeletal pain, upper respiratory tract infection, pyrexia, fatigue, cough, dyspnea, diarrhea, nausea, arrhythmia, and headache. In total, a quarter of patients with adverse reactions required systemic treatment with a corticosteroid and 26% of patients had serious adverse reactions.
Pembrolizumab was approved via the FDA’s accelerated approval process, which allows for earlier approval of drugs that treat serious medical conditions and fulfill an unmet medical need. The drug was approved based on tumor response rate and durability of response, the FDA noted.
The immune checkpoint inhibitor in adult and pediatric patients.
The Food and Drug Administration based the accelerated approval on results from 53 patients with relapsed or refractory primary mediastinal large B-cell lymphoma in the KEYNOTE-170 trial. In the phase 2 trial, patients received 200 mg of pembrolizumab intravenously for 3 weeks until unacceptable toxicity or documented disease progression occurred. This continued for up to 24 months in patients who did not display progression. The overall response rate to pembrolizumab was 45% (95% CI, 32-60), which included both complete (11%) and partial (34%) responses. The median duration of response was not met within the follow-up period (median, 9.7 months) and the median time to first objective response was 2.8 months.
The recommended dose for pembrolizumab in adults is 200 mg every 3 weeks. It is recommended that pediatric patients receive 2 mg/kg every 3 weeks, with a maximum dose of 200 mg.
The most common adverse reactions to pembrolizumab were musculoskeletal pain, upper respiratory tract infection, pyrexia, fatigue, cough, dyspnea, diarrhea, nausea, arrhythmia, and headache. In total, a quarter of patients with adverse reactions required systemic treatment with a corticosteroid and 26% of patients had serious adverse reactions.
Pembrolizumab was approved via the FDA’s accelerated approval process, which allows for earlier approval of drugs that treat serious medical conditions and fulfill an unmet medical need. The drug was approved based on tumor response rate and durability of response, the FDA noted.
Benefits of nicotine preloading undercut by reduced varenicline usage
Nicotine preloading with patches 4 weeks before making a quit attempt was not significantly associated with according to Paul Aveyard, PhD, and his associates at Nuffield Department of Primary Care Health Sciences, University of Oxford (England).
The primary study outcome, biochemically validated abstinence at 6 months, was achieved by 17.5% of the 899 people who preloaded with a 21-mg/24-hr nicotine patch for 4 weeks and by 14.4% of the 893 in the control group. After 1 year, 14.0% of people in the preloading group maintained long-term abstinence, compared with 11.3% in the control group. In addition, 35.5% of the preloading group and 32.3% of the control group achieved abstinence 4 weeks from baseline.
The unadjusted odds ratio for the effect of preloading at 6 months was 1.25 (95% confidence interval, 0.97-1.62; P = .08) and not statistically significant. However, when reduced varenicline usage in the preloading group was taken into account, the effect of preloading did reach statistical significance (OR, 1.34; 95% CI, 1.03-1.73; P = .03). Similar results were found at 1 year and at 4 weeks, where the preloading effect did not reach significance until adjusted for varenicline usage.
“Nicotine preloading with a 21-mg/24-hr nicotine patch for 4 weeks seems to be efficacious, safe, and well tolerated, but probably deters the use of varenicline, the most effective smoking cessation drug. If it were possible to overcome this unintended consequence, preloading could lead to a worthwhile increase in long-term smoking abstinence,” the investigators concluded.
SOURCE: Aveyard P et al. BMJ. 2018 Jun 13. doi: 10.1136/bmj.k2164.
Nicotine preloading with patches 4 weeks before making a quit attempt was not significantly associated with according to Paul Aveyard, PhD, and his associates at Nuffield Department of Primary Care Health Sciences, University of Oxford (England).
The primary study outcome, biochemically validated abstinence at 6 months, was achieved by 17.5% of the 899 people who preloaded with a 21-mg/24-hr nicotine patch for 4 weeks and by 14.4% of the 893 in the control group. After 1 year, 14.0% of people in the preloading group maintained long-term abstinence, compared with 11.3% in the control group. In addition, 35.5% of the preloading group and 32.3% of the control group achieved abstinence 4 weeks from baseline.
The unadjusted odds ratio for the effect of preloading at 6 months was 1.25 (95% confidence interval, 0.97-1.62; P = .08) and not statistically significant. However, when reduced varenicline usage in the preloading group was taken into account, the effect of preloading did reach statistical significance (OR, 1.34; 95% CI, 1.03-1.73; P = .03). Similar results were found at 1 year and at 4 weeks, where the preloading effect did not reach significance until adjusted for varenicline usage.
“Nicotine preloading with a 21-mg/24-hr nicotine patch for 4 weeks seems to be efficacious, safe, and well tolerated, but probably deters the use of varenicline, the most effective smoking cessation drug. If it were possible to overcome this unintended consequence, preloading could lead to a worthwhile increase in long-term smoking abstinence,” the investigators concluded.
SOURCE: Aveyard P et al. BMJ. 2018 Jun 13. doi: 10.1136/bmj.k2164.
Nicotine preloading with patches 4 weeks before making a quit attempt was not significantly associated with according to Paul Aveyard, PhD, and his associates at Nuffield Department of Primary Care Health Sciences, University of Oxford (England).
The primary study outcome, biochemically validated abstinence at 6 months, was achieved by 17.5% of the 899 people who preloaded with a 21-mg/24-hr nicotine patch for 4 weeks and by 14.4% of the 893 in the control group. After 1 year, 14.0% of people in the preloading group maintained long-term abstinence, compared with 11.3% in the control group. In addition, 35.5% of the preloading group and 32.3% of the control group achieved abstinence 4 weeks from baseline.
The unadjusted odds ratio for the effect of preloading at 6 months was 1.25 (95% confidence interval, 0.97-1.62; P = .08) and not statistically significant. However, when reduced varenicline usage in the preloading group was taken into account, the effect of preloading did reach statistical significance (OR, 1.34; 95% CI, 1.03-1.73; P = .03). Similar results were found at 1 year and at 4 weeks, where the preloading effect did not reach significance until adjusted for varenicline usage.
“Nicotine preloading with a 21-mg/24-hr nicotine patch for 4 weeks seems to be efficacious, safe, and well tolerated, but probably deters the use of varenicline, the most effective smoking cessation drug. If it were possible to overcome this unintended consequence, preloading could lead to a worthwhile increase in long-term smoking abstinence,” the investigators concluded.
SOURCE: Aveyard P et al. BMJ. 2018 Jun 13. doi: 10.1136/bmj.k2164.
FROM THE BMJ