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Cureus Aug 2022There is increasing literature mentioning severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19 infection) causing acute pancreatitis (AP). It... (Review)
Review
There is increasing literature mentioning severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (COVID-19 infection) causing acute pancreatitis (AP). It is hypothesized that SARS-Cov-2 causes pancreatic injury either by direct cytotoxic effect of the virus on pancreatic cells through the angiotensin-converting enzyme 2 (ACE2) receptors - the main receptors for the virus located on pancreatic cells - or by the cytokine storm that results from COVID-19 infection or a component of both. Many viruses are related to AP including mumps, coxsackievirus, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and as data evolves SARS-CoV-2 virus may be one of them as well. We conducted a systematic literature review to explore the current literature and provide an overview of the evidence of AP in COVID-19 infection. We studied the presence of AP in patients with SARS-CoV-2 infection and calculated the time of diagnosis of SARS-CoV-2 infection with respect to the time of diagnosis of AP. We also studied the age, gender, clinical manifestations, time of onset of symptoms, laboratory values, imaging findings, mortality, length of stay, comorbidities, need for Intensive Care Unit (ICU) care, and excluded any other common causes of AP. We included 40 articles comprising 46 patients. All patients had a positive SARS-CoV-2 polymerase chain reaction (PCR) test and all patients had AP as per Atlanta's criteria. The most common clinical presentation was abdominal pain in 29 (63.0%). Edematous pancreas was the most common Computed Tomography Abdomen Pelvis (CTAP) scan finding in these patients (35 patients). Seventeen (37%) patients required ICU admission and six (13%) patients died. Our study provides an important overview of the available data on AP in COVID-19 patients and concludes that AP is an important complication in COVID-19 infection and should be considered as an important differential in patients with COVID-19 infection who complain of abdominal pain.
PubMed: 36168341
DOI: 10.7759/cureus.28380 -
Cureus Aug 2022() bacterial infection has long been scrutinized as one of the potential risk factors for the development of pancreatic cancer with quite inconsistent and unequivocal... (Review)
Review
() bacterial infection has long been scrutinized as one of the potential risk factors for the development of pancreatic cancer with quite inconsistent and unequivocal data. Little is known about the risk factors involved with this malignancy. In this systematic review, we aimed to examine the relationship between infection and pancreatic cancer based on the evidence from the existing observational studies across the world. We searched major electronic databases such as PubMed, MEDLINE, Science Direct, and Cochrane Library. After a careful and thorough screening process, we selected 15 observation studies for this systematic review. Six of 15 studies found a significant association between infection and pancreatic cancer. Additionally, four of these studies found a significant relationship between the cytotoxin-associated gene A strain of and pancreatic cancer. Based on the evidence from the selected studies, a weak association was observed between infection and cancer of the pancreas, especially in European and Asian populations compared to the North American population. The cross-sectional evidence from the case-control studies only suggests the existence of an association but does not provide substantial evidence of the causative relationship. Further large-scale, prospective cohort studies are warranted in the future to understand this contradictory relationship better.
PubMed: 36185865
DOI: 10.7759/cureus.28543 -
Vaccines Aug 2022Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event... (Review)
Review
BACKGROUND
Solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection is extremely rare but can occur. T-cell recognition of antigen is the primary and central event that leads to the cascade of events that result in rejection of a transplanted organ.
OBJECTIVES
To describe the results of a systematic review for solid organ rejections following SARS-CoV-2 vaccination or COVID-19 infection.
METHODS
For this systematic review and meta-analysis, we searched Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, Scopus and Nature through the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines for studies on the incidence of solid organ rejection post-SARS-CoV-2 vaccination or COVID-19 infection, published from 1 December 2019 to 31 May 2022, with English language restriction.
RESULTS
One hundred thirty-six cases from fifty-two articles were included in the qualitative synthesis of this systematic review (56 solid organs rejected post-SARS-CoV-2 vaccination and 40 solid organs rejected following COVID-19 infection). Cornea rejection (44 cases) was the most frequent organ observed post-SARS-CoV-2 vaccination and following COVID-19 infection, followed by kidney rejection (36 cases), liver rejection (12 cases), lung rejection (2 cases), heart rejection (1 case) and pancreas rejection (1 case). The median or mean patient age ranged from 23 to 94 years across the studies. The majority of the patients were male ( = 51, 53.1%) and were of White (Caucasian) ( = 51, 53.7%) and Hispanic ( = 15, 15.8%) ethnicity. A total of fifty-six solid organ rejections were reported post-SARS-CoV-2 vaccination [Pfizer-BioNTech ( = 31), Moderna ( = 14), Oxford Uni-AstraZeneca ( = 10) and Sinovac-CoronaVac ( = 1)]. The median time from SARS-CoV-2 vaccination to organ rejection was 13.5 h (IQR, 3.2-17.2), while the median time from COVID-19 infection to organ rejection was 14 h (IQR, 5-21). Most patients were easily treated without any serious complications, recovered and did not require long-term allograft rejection therapy [graft success ( = 70, 85.4%), graft failure ( = 12, 14.6%), survived ( = 90, 95.7%) and died ( = 4, 4.3%)].
CONCLUSION
The reported evidence of solid organ rejections post-SARS-CoV-2 vaccination or COIVD-19 infection should not discourage vaccination against this worldwide pandemic. The number of reported cases is relatively small in relation to the hundreds of millions of vaccinations that have occurred, and the protective benefits offered by SARS-CoV-2 vaccination far outweigh the risks.
PubMed: 36016180
DOI: 10.3390/vaccines10081289 -
International Journal of Surgery... May 2024The impact of different pre-transplant dialysis modalities on post-transplant outcomes for pancreas-kidney transplantation is currently unclear. This study aims to...
BACKGROUND
The impact of different pre-transplant dialysis modalities on post-transplant outcomes for pancreas-kidney transplantation is currently unclear. This study aims to assess the association between pretransplant dialysis modalities (hemodialysis and peritoneal dialysis) and outcomes following pancreas-kidney transplantation.
METHODS
We searched PubMed, EMBASE, and the Cochrane Library for relevant studies published from inception until December 1, 2023. We included studies that examined the relationship between pre-transplant dialysis modalities and clinical outcomes for pancreas-kidney transplantation. The primary outcomes considered were patient, pancreas and kidney graft survival, and intra-abdominal infection.
RESULTS
A total of 13 studies involving 1503 pancreas-kidney transplant recipients were included. Pretransplant hemodialysis was associated with improved pancreas graft survival (hazard ratio = 0.71, 95% confidence interval [CI]: 0.51 - 0.99, I² = 12%) and a decreased risk of intra-abdominal infection (odds ratio [OR] = 0.69, 95% CI: 0.51 - 0.93, I² = 5%). However, no significant association was found between the dialysis modalities and patient or kidney graft survival. Furthermore, pre-transplant hemodialysis was linked to a reduced risk of anastomotic leak (OR = 0.32, 95% CI: 0.161 - 0.68, I² = 0%) and graft thrombosis (OR = 0.56, 95% CI: 0.33 - 0.96, I² = 20%).
CONCLUSION
Pre-transplant hemodialysis is the preferred dialysis modality while awaiting pancreas-kidney transplantation, although well-designed prospective studies are needed to confirm these findings.
PubMed: 38701525
DOI: 10.1097/JS9.0000000000001542 -
Journal of Lower Genital Tract Disease Apr 2019The risk of cervical cancer (CC) among women immunosuppressed for a variety of reasons is well documented in the literature. Although there is improved organ function,...
EXECUTIVE SUMMARY
The risk of cervical cancer (CC) among women immunosuppressed for a variety of reasons is well documented in the literature. Although there is improved organ function, quality of life and life expectancy gained through use of immunosuppressant therapy, there may be increased long-term risk of cervical neoplasia and cancer and the need for more intense screening, surveillance, and management. Although guidance for CC screening among HIV-infected women (see Table 1) has been supported by evidence from retrospective and prospective studies, recommendations for CC screening among non-HIV immunosuppressed women remains limited because quality evidence is lacking. Moreover, CC screening guidelines for HIV-infected women have changed because better treatments evolved and resulted in longer life expectancy.The objective of this report was to summarize current knowledge of CC, squamous intraepithelial lesions, and human papillomavirus (HPV) infection in non-HIV immunocompromised women to determine best practices for CC surveillance in this population and provide recommendations for screening. We evaluated those with solid organ transplant, hematopoietic stem cell transplant, and a number of autoimmune diseases.A panel of health care professionals involved in CC research and care was assembled to review and discuss existing literature on the subject and come to conclusions about screening based on available evidence and expert opinion. Literature searches were performed using key words such as CC, cervical dysplasia/squamous intraepithelial lesion, HPV, and type of immunosuppression resulting in an initial group of 346 articles. Additional publications were identified from review of citations in these articles. All generated abstracts were reviewed to identify relevant articles. Articles published within 10 years were considered priority for review. Reviews of the literature were summarized with relevant statistical comparisons. Recommendations for screening generated from each group were largely based on expert opinion. Adherence to screening, health benefits and risks, and available clinical expertise were all considered in formulating the recommendations to the degree that information was available.
RESULTS
Solid Organ Transplant: Evidence specific for renal, heart/lung, liver, and pancreas transplants show a consistent increase in risk of cervical neoplasia and invasive CC, demonstrating the importance of long-term surveillance and treatment. Reports demonstrate continued risk long after transplantation, emphasizing the need for screening throughout a woman's lifetime.Hematopoietic Stem Cell Transplant: Although there is some evidence for an increase in CC in large cohort studies of these patients, conflicting results may reflect that many patients did not survive long enough to evaluate the incidence of slow-growing or delayed-onset cancers. Furthermore, history of cervical screening or previous hysterectomy was not included in registry study analysis, possibly leading to underestimation of CC incidence rates.Genital or chronic graft versus host disease is associated with an increase in high-grade cervical neoplasia and posttransplant HPV positivity.Inflammatory Bowel Disease: There is no strong evidence to support that inflammatory bowel disease alone increases cervical neoplasia or cancer risk. In contrast, immunosuppressant therapy does seem to increase the risk, although results of observational studies are conflicting regarding which type of immunosuppressant medication increases risk. Moreover, misclassification of cases may underestimate CC risk in this population. Recently published preventive care guidelines for women with inflammatory bowel disease taking immunosuppressive therapy recommend a need for continued long-term CC screening.Systemic Lupus Erythematosus and Rheumatoid Arthritis: The risk of cervical high-grade neoplasia and cancer was higher among women with systemic lupus erythematosus than those with rheumatoid arthritis (RA), although studies were limited by size, inclusion of women with low-grade neoplasia in main outcomes, and variability of disease severity or exposure to immunosuppressants. In studies designed to look specifically at immunosuppressant use, however, there did seem to be an increase in risk, identified mostly in women with RA. Although the strength of the evidence is limited, the increase in risk is consistent across studies.Type 1 DM: There is a paucity of evidence-based reports associating type 1 DM with an increased risk of cervical neoplasia and cancer.
RECOMMENDATIONS
The panel proposed that CC screening guidelines for non-HIV immunocompromised women follow either the (1) guidelines for the general population or (2) current center for disease control guidelines for HIV-infected women. The following are the summaries for each group reviewed, and more details are noted in accompanying table:Solid Organ Transplant: The transplant population reflects a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance.Hematopoietic Stem Cell Transplant: These women have a greater risk of CC than the general population and guidelines for HIV-infected women are a reasonable approach for screening. A new diagnosis of genital or chronic graft versus host disease in a woman post-stem cell transplant results in a greater risk of CC than in the general population and should result in more intensive screening and surveillance.Inflammatory Bowel Disease: Women with inflammatory bowel disease being treated with immunosuppressive drugs are at greater risk of cervical neoplasia and cancer than the general population and guidelines for HIV-infected women are a reasonable approach for screening and surveillance. Those women with inflammatory bowel disease not on immunosuppressive therapy are not at an increased risk and should follow screening guidelines for the general population.Systemic Lupus Erythematosus and Rheumatoid Arthritis: All women with systemic lupus erythematosus, whether on immunosuppressant therapy or not and those women with RA on immunosuppressant therapy have a greater risk of cervical neoplasia and cancer than the general population and should follow CC screening guidelines for HIV-infected women. Women with RA not on immunosuppressant therapy should follow CC screening guidelines for the general population.Type 1 Diabetes Mellitus: Because of a lack of evidence of increased risk of cervical neoplasia and cancer among women with type 1 DM, these women should follow the screening guidelines for the general population.
Topics: Adult; Aged; Aged, 80 and over; Female; Humans; Immunocompromised Host; Mass Screening; Middle Aged; Papillomavirus Infections; Practice Guidelines as Topic; Squamous Intraepithelial Lesions of the Cervix; Uterine Cervical Neoplasms; Young Adult
PubMed: 30907775
DOI: 10.1097/LGT.0000000000000468 -
Pancreatology : Official Journal of the... 2013Pancreatic adenocarcinoma (PAC) is an aggressive cancer with a poor prognosis. To date, PAC causes are still largely unknown. Antigens and replicative sequences of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreatic adenocarcinoma (PAC) is an aggressive cancer with a poor prognosis. To date, PAC causes are still largely unknown. Antigens and replicative sequences of oncogenic hepatitis B (HBV) and hepatitis C (HCV) virus were detected in different extra-hepatic tissues, including pancreas.
OBJECTIVE
a systematic review and meta-analysis of epidemiological studies assessing PAC risk in patients with HBV/HCV chronic infections.
METHODS
In September 2012, we extracted the articles published in Medline, Embase and the Cochrane Library, using the following search terms: "chronic HBV" and "HCV", "hepatitis", "PAC", "risk factors", "epidemiology". Only case/control (C/C), prospective/retrospective cohort studies (PCS/RCS) written in English were collected.
RESULTS
four hospital-based C/C studies and one PCS, in HBV-infected patients and two hospital-based C/C studies and one RCS in HCV-infected subjects met inclusion criteria. In these studies HBsAg positivity enhanced significantly PAC risk (RR = 1.18, 95% CI:1.04-1.33), whereas HBeAg positivity (RR = 1.31, 95% CI:0.85-2.02) as well as HBsAg negative/HBcAb positive/HBsAb positive pattern (RR = 1.12, 95% CI:0.78-1.59) and HBsAg negative/HBcAb positive/HBsAb negative pattern (RR = 1.30, 95% CI:0.93-1.84) did not. Relationship between PAC risk and anti-HCV positivity was not significant, although it reached a borderline value (RR = 1.160, 95% CI:0.99-1.3).
CONCLUSIONS
HBV/HCV infection may represent a risk factor for PAC, but the small number of available researches, involving mainly populations of Asian ethnicity and the substantial variation between different geographical areas in seroprevalence of HBV/HCV-antigens/antibodies and genotypes are limiting factors to present meta-analysis.
Topics: Adenocarcinoma; Hepatitis B; Hepatitis C; Humans; Pancreatic Neoplasms
PubMed: 23561973
DOI: 10.1016/j.pan.2013.01.005 -
Endocrine, Metabolic & Immune Disorders... 2021Coronaviruses are a big family of viruses that can infect mammalians and birds. In humans they mainly cause respiratory tract infections, with a large spectrum of...
Coronaviruses are a big family of viruses that can infect mammalians and birds. In humans they mainly cause respiratory tract infections, with a large spectrum of severity, from mild, self-limited infections to highly lethal forms as severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV) and Coronavirus Disease 2019 (COVID-19). Scanty data are reported for the involvement of endocrine glands in human coronaviruses, in particular SARS-CoV-2. In this review, we summarize endocrinological involvement in human coronaviruses, including data on animal coronaviruses. Avians, ferrets and bovine are affected by specific coronavirus syndromes, with variable involvement of endocrine glands. SARS-CoV and SARS-CoV-2 use angiotensin-converting enzyme 2 (ACE2) as a target receptor, so ACE2 plays a central role in viral transmission and initial organ involvement. Autoptic studies on SARS patients revealed that thyroid, parathyroid, pituitary gland, endocrine pancreas and especially adrenals and testis could be impaired by different mechanisms (direct damage by SARS-CoV, inflammation, vascular derangement and autoimmune reactions) and few clinical studies have evidenced functional endocrine impairment. Only few data are available for COVID-19 and gonads and endocrine pancreas seem to be involved. International endocrinological societies have brought some recommendations for the COVID-19 pandemic, but further studies need to be performed, especially to detect long-term hormonal sequelae.
Topics: Angiotensin-Converting Enzyme 2; Animals; COVID-19; Endocrine Glands; Endocrine System; Endocrine System Diseases; Humans; Middle East Respiratory Syndrome Coronavirus; SARS-CoV-2
PubMed: 32888287
DOI: 10.2174/1871530320666200905123332 -
The Cochrane Database of Systematic... Sep 2014Pancreas or kidney-pancreas transplantation improves survival and quality of life for people with type 1 diabetes mellitus and kidney failure. Immunosuppression after... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreas or kidney-pancreas transplantation improves survival and quality of life for people with type 1 diabetes mellitus and kidney failure. Immunosuppression after transplantation is associated with complications. Steroids have adverse effects on cardiovascular risk factors such as hypertension, hyperglycaemia or hyperlipidaemia, increase risk of infection, obesity, cataracts, myopathy, bone metabolism alterations, dermatologic problems and cushingoid appearance. Whether avoiding steroids changes outcomes is unclear.
OBJECTIVES
We aimed to assess the safety and efficacy of steroid early withdrawal (treatment for less than 14 days after transplantation), late withdrawal (after 14 days after transplantation) or steroid avoidance in patients receiving a pancreas (including a vascularized organ) alone (PTA), simultaneous with a kidney (SPK) or after kidney transplantation (PAK).
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register (to 18 June 2014) through contact with the Trials' Search Co-ordinator. We handsearched: reference lists of nephrology textbooks, relevant studies, recent publications and clinical practice guidelines; abstracts from international transplantation society scientific meetings; and sent emails and letters seeking information about unpublished or incomplete studies to known investigators.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or cohort studies of steroid avoidance (including early withdrawal) versus steroid maintenance or versus late withdrawal in pancreas or pancreas with kidney transplant recipients. We defined steroid avoidance as complete avoidance of steroid immunosuppression, early steroid withdrawal as steroid treatment for less than 14 days after transplantation and late withdrawal as steroid withdrawal after 14 days after transplantation.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the retrieved titles and abstracts, and where necessary the full text reports to determine which studies satisfied the inclusion criteria. Authors of included studies were contacted to obtain missing information. Statistical analyses were performed using random effects models and results expressed as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Cohort studies were not meta-analysed, but their findings summarised descriptively.
MAIN RESULTS
Three RCTs enrolling 144 participants met our inclusion criteria. Two compared steroid avoidance versus late steroid withdrawal and one compared late steroid withdrawal versus steroid maintenance. All studies included SPK and only one also included PTA. All studies had an overall moderate risk of bias and presented only short-term results (six to 12 months). Two studies (89 participants) compared steroid avoidance or early steroid withdrawal versus late steroid withdrawal. There was no clear evidence of an impact on mortality (2 studies, 89 participants: RR 1.64, 95% CI 0.21 to 12.75), risk of kidney loss censored for death (2 studies, 89 participants: RR 0.35, 95% CI 0.04 to 3.09), risk of pancreas loss censored for death (2 studies, 89 participants: RR 1.05, 95% CI 0.36 to 3.04), or acute kidney rejection (1 study, 49 participants: RR 2.08, 95% CI 0.20 to 21.50), however results were uncertain and consistent with no difference or important benefit or harm of steroid avoidance/early steroid withdrawal. The study that compared late steroid withdrawal versus steroid maintenance observed no deaths, no graft loss or acute kidney rejection at six months in either group and reported uncertain effects on acute pancreas rejection (RR 0.88, 95% CI 0.06 to 13.35). Of the possible adverse effects only infection was reported by one study. There were significantly more UTIs reported in the late withdrawal group compared to the steroid avoidance group (1 study, 25 patients: RR 0.41, 95% CI 0.26 to 0.66).We also identified 13 cohort studies and one RCT which randomised tacrolimus versus cyclosporin. These studies in general showed that steroid-sparing and withdrawal strategies had benefits in lowering HbAc1 and risk of infections (BK virus and CMV disease) and improved blood pressure control without increasing the risk of rejection. However, two studies found an increased incidence of acute pancreas rejection (HR 2.8, 95% CI 0.89 to 8.81, P = 0.066 in one study and 43.3% in the steroid withdrawal group versus 9.3% in the steroid maintenance, P < 0.05 at three years in the other) and one study found an increased incidence of acute kidney rejection (18.7% in the steroid withdrawal group versus 2.8% in the steroid maintenance, P < 0.05) at three years.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence for the benefits and harms of steroid withdrawal in pancreas transplantation in the three RCTs (144 patients) identified. The results showed uncertain results for short-term risk of rejection, mortality, or graft survival in steroid-sparing strategies in a very small number of patients over a short period of follow-up. Overall the data was sparse, so no firm conclusions are possible. Moreover, the 13 observational studies findings generally concur with the evidence found in the RCTs.
Topics: Adult; Cohort Studies; Diabetes Mellitus, Type 1; Graft Rejection; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Middle Aged; Pancreas Transplantation; Randomized Controlled Trials as Topic; Steroids; Withholding Treatment
PubMed: 25220222
DOI: 10.1002/14651858.CD007669.pub2 -
Pancreatology : Official Journal of the... Apr 2018Although routinely used, the benefit of surgically placed intraperitoneal drains after pancreas resection is still under debate. To assess the true impact of... (Review)
Review
BACKGROUND
Although routinely used, the benefit of surgically placed intraperitoneal drains after pancreas resection is still under debate. To assess the true impact of intraperitoneal drains in pancreas resection, a systematic review with meta-analysis was performed.
METHODS
For this, the Preferred-Reporting-Items-for-Systematic-review-and-Meta-Analysis/PRISMA-guidelines were conducted and Pubmed/Medline, Embase, Scopus and The Cochrane Library were screened for relevant studies.
RESULTS
8 retrospective and 3 prospective studies were included in the systematic review. No difference was found between patients with or without intraperitoneal drains in mortality (Risk-ratio/RR 0.74, 95%-Confidence-interval/CI: 0.47-1.18, p = 0.20), in Grade B/C-postoperative pancreatic fistulas/POPF (RR 1.31, 95%-CI: 0.74-2.32, p = 0.35), in intraabdominal abscesses (RR 0.92, 95%-CI: 0.65-1.30, p = 0.64), in surgical site infection (RR 1.20, 95%-CI: 0.85-1.70, p = 0.30), in delayed gastric emptying (RR 1.11, 95%-CI: 0.65-1.90, p = 0.71), in postoperative haemorrhages (RR 0.92 95%-CI: 0.63-1.33, p = 0.65), in reoperations (RR 1.15, 95%-CI: 0.87-1.52, p = 0.33), or in radiological reinterventions (RR 0.95, 95%-CI: 0.69-1.31, p = 0.76). The risk for overall morbidity (RR 1.16, 95%-CI: 1.04-1.29, p = 0.008), of any POPF (RR 2.15, 95%-CI: 1.52-3.04, p < 0.0001) and of readmissions (RR 1.23, 95%-CI: 1.04-1.45, p = 0.01) was increased for patients with intraperitoneal drain compared to patients without following pancreatic resection.
CONCLUSION
Regarding the controversial results of the recent prospective, randomized trials this meta-analysis revealed no difference in mortality but an increased risk for postoperative morbidity, POPF and readmissions of patients with intraperitoneal drains after pancreatic resection. Therefore, the indication for intraperitoneal drains should be critically weighed in patients undergoing pancreatic resections.
Topics: Digestive System Surgical Procedures; Drainage; Humans; Pancreas; Peritoneal Cavity; Postoperative Complications; Reoperation
PubMed: 29534868
DOI: 10.1016/j.pan.2018.02.013 -
Health Technology Assessment... Dec 2013Cystic fibrosis (CF) is an inherited condition characterised by the abnormal transport of chloride ions across transporting epithelia. This leads to the production of... (Review)
Review
Colistimethate sodium powder and tobramycin powder for inhalation for the treatment of chronic Pseudomonas aeruginosa lung infection in cystic fibrosis: systematic review and economic model.
BACKGROUND
Cystic fibrosis (CF) is an inherited condition characterised by the abnormal transport of chloride ions across transporting epithelia. This leads to the production of thick sticky mucus in the lungs, pancreas, liver, intestine and reproductive tract, and an increase in the salt content in sweat. Among other problems, people with CF experience recurrent respiratory infections and have difficulties digesting food. CF affects over 9000 individuals in the UK. CF shortens life expectancy and adversely affects quality of life. In 2010, CF was recorded as the cause of 103 deaths in England and Wales.
OBJECTIVE
To evaluate the clinical effectiveness and cost-effectiveness of colistimethate sodium dry powder for inhalation (DPI) (Colobreathe(®), Forest Laboratories) and tobramycin DPI (TOBI Podhaler(®), Novartis Pharmaceuticals) for the treatment of Pseudomonas aeruginosa lung infection in CF.
DATA SOURCES
Electronic databases were searched in February and March 2011 [MEDLINE, MEDLINE In-Process & Other Non-Indexed citations, EMBASE, The Cochrane Library databases, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, Conference Proceedings Citation Index (CPCI) and Bioscience Information Service (BIOSIS) Previews]. Relevant databases were searched for ongoing and unpublished studies, and bibliographies of relevant systematic reviews and the manufacturers' submissions were also hand-searched.
REVIEW METHODS
A systematic review of the clinical effectiveness and cost-effectiveness of colistimethate sodium DPI and tobramycin DPI for the treatment of chronic P. aeruginosa lung infection in CF was conducted. Existing economic evidence within the literature was reviewed and a de novo health economic model was also developed.
RESULTS
Three randomised controlled trials (RCTs) were included in the clinical effectiveness review. Both colistimethate sodium DPI and tobramycin DPI were reported to be non-inferior to nebulised tobramycin for the outcome forced expiratory volume in first second percentage predicted (FEV1%). It was not possible to draw any firm conclusions as to the relative efficacy of colistimethate sodium DPI compared with tobramycin DPI. The economic analysis suggests that colistimethate sodium DPI produces fewer quality-adjusted life-years (QALYs) than nebulised tobramycin. Given the incremental discounted lifetime cost of tobramycin DPI compared with nebulised tobramycin, it highly unlikely that tobramycin DPI has an incremental cost-effectiveness ratio that is better than £30,000 per QALY gained.
LIMITATION
The uncertainty surrounding the short-term evidence base inevitably results in uncertainty surrounding the long-term clinical effectiveness and cost-effectiveness of colistimethate sodium DPI.
CONCLUSIONS
Both DPI formulations have been shown to be non-inferior to nebulised tobramycin as measured by FEV1%. The results of these trials should be interpreted with caution owing to the means by which the results were analysed, the length of follow-up, and concerns about the ability of FEV1% to accurately represent changes in lung health. Although the increase in QALYs is expected to be lower with colistimethate sodium DPI than with nebulised tobramycin, a price for this intervention had not been agreed at the time of the assessment. Depending on the price of colistimethate sodium DPI, this results either in a situation whereby colistimethate sodium DPI is dominated by nebulised tobramycin or in one whereby the incremental cost-effectiveness of nebulised tobramycin compared with colistimethate sodium DPI is in the range of £24,000-277,000 per QALY gained. The economic analysis also suggests that, given its price, it is unlikely that tobramycin DPI has a cost-effectiveness ratio of < £30,000 per QALY gained when compared with nebulised tobramycin. A RCT to assess the longer-term (≥ 12 months) efficacy of colistimethate sodium DPI and tobramycin DPI in comparison with nebulised treatments would be beneficial. Such a study should include the direct assessment of HRQoL using a relevant preference-based instrument. Future studies should ensure that the European Medicines Agency guidelines are adhered to. In addition, high-quality research concerning the relationship between forced expiratory volume in first second % (FEV1%) predicted or other measures of lung function and survival/health-related quality of life (HRQoL) would be useful.
STUDY REGISTRATION
PROSPERO CRD42011001350.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Administration, Inhalation; Child; Colistin; Cost-Benefit Analysis; Cystic Fibrosis; Disease Progression; Humans; Outcome Assessment, Health Care; Pseudomonas Infections; Pseudomonas aeruginosa; Quality-Adjusted Life Years; Randomized Controlled Trials as Topic; Therapeutic Equivalency; Tobramycin; United Kingdom
PubMed: 24290164
DOI: 10.3310/hta17560