The Rise of Non-Tuberculosis Mycobacterial Lung Disease.

The incidence and number of deaths from non-tuberculous mycobacterial (NTM) disease have been steadily increasing globally. These lesser known "cousins" of Mycobacterium tuberculosis (TB) were once thought to be harmless environmental saprophytics and only dangerous to individuals with defective lung structure or the immunosuppressed. However, NTM are now commonly infecting seemingly immune competent children and adults at increasing rates through pulmonary infection. This is of concern as the pathology of NTM is difficult to treat. Indeed, NTM have become extremely antibiotic resistant, and now have been found to be internationally dispersed through person-to-person contact. The reasons behind this NTM increase are only beginning to be elucidated. Solutions to the problem are needed given NTM disease is more common in the tropics. Importantly, 40% of the world's population live in the tropics and due to climate change, the Tropics are expanding which will increase NTM infection regions. This review catalogs the global and economic disease burden, at risk populations, treatment options, host-bacterial interaction, immune dynamics, recent developments and research priorities for NTM disease.

Guidelines-based treatment associated with improved economic outcomes in nontuberculous mycobacterial lung disease.

Background: The prevalence of nontuberculous mycobacterial lung disease (NTMLD) in the US has increased; however, data characterizing the associated healthcare utilization and expenditure at the national level are limited. Objective: To examine associations between economic outcomes and the use of anti-Mycobacterium avium complex (MAC) guidelines-based treatment (GBT) for newly-diagnosed NTMLD in a US national managed care claims database (Optum® Clinformatics® Data Mart). Methods: NTMLD was defined as having ≥2 claims for NTMLD (ICD-9 031.0; ICD-10 A31.0) on separate occasions ≥30 days apart (between 2007 and 2016). The cohort included patients insured continuously over a period of at least 36 months (12 months before initial NTMLD diagnostic claim and for the subsequent 24 months). Treatment was classified as GBT (consistent with American Thoracic Society/Infectious Diseases Society of America guidelines), non-GBT, or untreated. All-cause hospitalization rates and total healthcare expenditures at Year 2 were assessed as outcomes of the treatment prescribed in Year 1 after NTMLD diagnosis. Results: A total of 1,039 patients met study criteria for NTMLD (GBT, n = 294; non-GBT, n = 298; untreated, n = 447). After adjustment for baseline characteristics, GBT was associated with a significantly lower all-cause hospitalization risk vs non-GBT (odds ratio [OR] = 0.53; 95% CI = 0.33-0.85, p = 0.008), and vs being untreated (OR = 0.57; 95% CI = 0.35-0.91, p = 0.020). Adjusted total healthcare expenditure in Year 2 with GBT ($69,691) was lower than that with non-GBT ($77,624) with a difference of -$7,933 (95% CI = -$14,968 to -$899; p = 0.03). Conclusions: Patients with NTMLD in a US managed care claims database who were prescribed GBT had lower hospitalization risk than those who were prescribed non-GBT or were untreated. GBT was associated with lower total healthcare expenditure compared with non-GBT.

Health Care Utilization and Expenditures Following Diagnosis of Nontuberculous Mycobacterial Lung Disease in the United States.

BACKGROUND: Nontuberculous mycobacterial lung disease (NTMLD) is an important public health concern that has been increasing in prevalence. OBJECTIVES: To (a) describe hospitalizations and health care expenditures among patients with newly diagnosed NTMLD and (b) estimate attributable hospitalizations and expenditures to NTMLD in the United States. METHODS: In this matched cohort study, patients and controls were identified from a large U.S. national managed care insurance database containing aggregated health claims of up to 18 million fully covered members annually. NTMLD was defined based on diagnostic claims for NTMLD on ≥ 2 separate occasions ≥ 30 days apart between 2007 and 2016. Thirty-six months of continuous enrollment (12 months before and 24 months after the first diagnostic claim) was required. Health care utilization and standardized health care expenditures were summarized over 12 months before NTMLD diagnosis and for 2 subsequent years. The percentage of patients that were hospitalized in years 1 and 2 was evaluated using a generalized mixed effects model with adjustment for baseline hospitalizations, Charlson Comorbidity Index, and baseline diseases. A general estimating equation model was used to evaluate health care expenditures. RESULTS: There were 1,039 patients in the NTMLD cohort and 2,078 in the control cohort. NTMLD patients had a 55.0% risk of hospitalization in year 1 (95% CI = 45.4-64.3) and a 38.8% risk in year 2 (95% CI = 30.0-48.4). The adjusted risk of hospitalization was significantly higher in the NTMLD group compared with the control group in year 1 (OR = 4.64; 95% CI = 3.74-5.76; P < 0.001) and year 2 (OR = 2.26; 95% CI = 1.78-2.87; P < 0.001). Year 1 adjusted mean health care expenditures for the total NTMLD patient population were $72,475 (95% CI = $58,510-$86,440) and for the matched control population were $28,405 (95% CI = $8,859-$47,950), with a difference of $44,070 (95% CI = $27,132-$61,008; P < 0.001). Year 2 adjusted mean expenditures for the overall NTMLD patient group were $48,114 (95% CI = $31,722-$64,507) and for the matched control group were $28,990 (95% CI = $9,429-$48,552), with a difference of $19,124 (95% CI = $7,865-$30,383; P < 0.001). CONCLUSIONS: Patients with NTMLD have a significantly greater risk of hospitalization and higher total health care expenditures than matched control patients without NTMLD. DISCLOSURES: This study was financially sponsored by Insmed. Marras reports fees from Insmed, Astra Zeneca, RedHill, and Horizon, all outside the current work. Mirsaeidi has nothing to disclose. Eagle, Q. Zhang, Chou, and Leuchars are employees of Insmed. R. Zhang is a contracted consultant at Insmed. The views expressed here are those of the authors and are not to be attributed to their respective affiliations.

Financial Implications of Atypical Mycobacterial Infections After Cosmetic Tourism: Is It Worth the Risk?

BACKGROUND: Cosmetic tourism has become increasingly popular despite many associated risks. The economic impact of atypical mycobacterial infections in cosmetic tourism is poorly defined in the literature. We sought to investigate the costs and clinical course of patients with these infections. METHODS: A retrospective review of all patients managed by the Plastic Surgery Division at Columbia University Medical Center from 2013 to 2014 with atypical mycobacterial surgical site infections after cosmetic surgery outside the United States was performed. Data including patient demographics, procedure costs, clinical course, impact on daily life, and costs associated with complications were collected using hospital billing information, patient questionnaires, telephone interviews, and clinical charts. Cost analysis was done to identify the personal and societal costs of these complications. RESULTS: Data from 10 patients were collected and analyzed. Management of mycobacterial infections cost an average of $98,835.09 in medical charges. The indirect cost of these infections was $24,401 with a mean return to work time of 6.7 months. Total patient savings from cosmetic tourism was $3419. The total cost of a mycobacterial infection was greater than $123,236.47. Although the incidence of mycobacterial infection abroad is unknown, the potential cost of an infection alone outweighs the financial benefits of cosmetic tourism if the risk exceeds 2.77%. CONCLUSIONS: Atypical mycobacterial infections as a result of cosmetic tourism come at considerable cost to patients and the health care system. When our results are taken into consideration with other risks of cosmetic tourism, the financial risks likely far outweigh the benefits.

Burden of non-tuberculous mycobacterial pulmonary disease in Germany.

The objective of this study was to estimate the burden of disease in incident patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD).A sample of 7 073 357 anonymised persons covered by German public statutory health insurances was used to identify patients with NTM-PD. In total, 125 patients with newly diagnosed NTM-PD in 2010 and 2011 were matched with 1250 control patients by age, sex and Charlson Comorbidity Index, and followed for 39 months.The incidence rate for NTM-PD was 2.6 per 100 000 insured persons (95% CI 2.2-3.1). The mortality rate for patients with NTM-PD and the control group in the observational period was 22.4% and 6%, respectively (p<0.001). Mean direct expenditure per NTM-PD patient was €39 559.60 (95% CI 26 916.49-52 202.71), nearly 4-fold (3.95, 95% CI 3.73-4.19) that for a matched control (€10 006.71, 95% CI 8907.24-11 106.17). Hospitalisations were three times higher in the NTM-PD group and accounted for 63% of the total costs. Attributable annual direct costs and indirect work-loss costs in NTM-PD patients were €9093.20 and €1221.05 per control patient, respectively. Only 74% of NTM-PD patients received antibiotics and nearly 12% were prescribed macrolide monotherapy.Although NTM-PD is considered rare, the attributable mortality and financial burden in Germany are high. Efforts to heighten awareness of appropriate therapy are urgently needed.

Multistate US Outbreak of Rapidly Growing Mycobacterial Infections Associated with Medical Tourism to the Dominican Republic, 2013-2014(1).

During 2013, the Maryland Department of Health and Mental Hygiene in Baltimore, MD, USA, received report of 2 Maryland residents whose surgical sites were infected with rapidly growing mycobacteria after cosmetic procedures at a clinic (clinic A) in the Dominican Republic. A multistate investigation was initiated; a probable case was defined as a surgical site infection unresponsive to therapy in a patient who had undergone cosmetic surgery in the Dominican Republic. We identified 21 case-patients in 6 states who had surgery in 1 of 5 Dominican Republic clinics; 13 (62%) had surgery at clinic A. Isolates from 12 (92%) of those patients were culture-positive for Mycobacterium abscessus complex. Of 9 clinic A case-patients with available data, all required therapeutic surgical intervention, 8 (92%) were hospitalized, and 7 (78%) required ≥3 months of antibacterial drug therapy. Healthcare providers should consider infection with rapidly growing mycobacteria in patients who have surgical site infections unresponsive to standard treatment.

The Burden of Pulmonary Nontuberculous Mycobacterial Disease in the United States.

RATIONALE: State-specific case numbers and costs are critical for quantifying the burden of pulmonary nontuberculous mycobacterial disease in the United States. OBJECTIVES: To estimate and project national and state annual cases of nontuberculous mycobacterial disease and associated direct medical costs. METHODS: Available direct cost estimates of nontuberculous mycobacterial disease medical encounters were applied to nontuberculous mycobacterial disease prevalence estimates derived from Medicare beneficiary data (2003-2007). Prevalence was adjusted for International Classification of Diseases, 9th Revision, undercoding and the inclusion of persons younger than 65 years of age. U.S. Census Bureau data identified 2010 and 2014 population counts and 2012 primary insurance-type distribution. Medical costs were reported in constant 2014 dollars. Projected 2014 estimates were adjusted for population growth and assumed a previously published 8% annual growth rate of nontuberculous mycobacterial disease prevalence. MEASUREMENTS AND MAIN RESULTS: In 2010, we estimated 86,244 national cases, totaling to $815 million, of which 87% were inpatient related ($709 million) and 13% were outpatient related ($106 million). Annual state estimates varied from 48 to 12,544 cases ($503,000-$111 million), with a median of 1,208 cases ($11.5 million). Oceanic coastline states and Gulf States comprised 70% of nontuberculous mycobacterial disease cases but 60% of the U.S. population. Medical encounters among individuals aged 65 years and older ($562 million) were twofold higher than those younger than 65 years of age ($253 million). Of all costs incurred, medications comprised 76% of nontuberculous mycobacterial disease expenditures. Projected 2014 estimates resulted in 181,037 national annual cases ($1.7 billion). CONCLUSIONS: For a relatively rare disease, the financial cost of nontuberculous mycobacterial disease is substantial, particularly among older adults. Better data on disease dynamics and more recent prevalence estimates will generate more robust estimates.

Burden and trends of hospitalisations associated with pulmonary non-tuberculous mycobacterial infections in Germany, 2005-2011.

BACKGROUND: Representative population-based data on the epidemiology of pulmonary non-tuberculous mycobacterial (PNTM) infections in Europe are limited. However, these data are needed in order to optimise patient care and to facilitate the allocation of healthcare resources. The aim of the present study was to investigate the current burden and the trends of PNTM infection-associated hospitalisations in Germany. METHODS: International Classification of Diseases, 10th revision (ICD-10) discharge diagnosis codes were extracted from the official nationwide diagnosis-related groups (DRG) hospital statistics in order to identify PNTM infection-associated hospitalisations (ICD-10 code A31.0) between 2005 and 2011. Poisson log-linear regression analysis was used to assess the significance of trends. RESULTS: Overall, 5,959 records with PNTM infection as any hospital discharge diagnosis were extracted from more than 125 million hospitalisations. The average annual age-adjusted rate was 0.91 hospitalisations per 100,000 population. Hospitalisation rates increased during the study period for both males and females, with the highest rate of 3.0 hospitalisations per 100,000 population among elderly men, but the most pronounced average increase of 6.4%/year among females, particularly those of young and middle age, and hospitalisations associated with cystic fibrosis. Overall, chronic obstructive pulmonary disease (COPD) was the most frequent PNTM infection-associated condition in 28.9% of hospitalisations and also showed a significant average annual increase of 4.8%. CONCLUSIONS: The prevalence of PNTM infection-associated hospitalisations is steadily increasing in Germany. COPD is currently the most important associated condition. Our population-based study provides evidence of a changing epidemiology of PNTM infections and highlights emerging clinical implications.

Direct healthcare costs of selected diseases primarily or partially transmitted by water.

Despite US sanitation advancements, millions of waterborne disease cases occur annually, although the precise burden of disease is not well quantified. Estimating the direct healthcare cost of specific infections would be useful in prioritizing waterborne disease prevention activities. Hospitalization and outpatient visit costs per case and total US hospitalization costs for ten waterborne diseases were calculated using large healthcare claims and hospital discharge databases. The five primarily waterborne diseases in this analysis (giardiasis, cryptosporidiosis, Legionnaires' disease, otitis externa, and non-tuberculous mycobacterial infection) were responsible for over 40 000 hospitalizations at a cost of $970 million per year, including at least $430 million in hospitalization costs for Medicaid and Medicare patients. An additional 50 000 hospitalizations for campylobacteriosis, salmonellosis, shigellosis, haemolytic uraemic syndrome, and toxoplasmosis cost $860 million annually ($390 million in payments for Medicaid and Medicare patients), a portion of which can be assumed to be due to waterborne transmission.

Arthroplasty tourism.

The practice of "medical tourism" is gaining popularity. Lower costs and shorter waiting times are compelling motivating factors. There are also increasing commercial interests promoting medical tourism. There are very limited clinical data to support or refute this practice. However, medical tourism breaks important elements in the traditional health care model, including patient selection, continuity of care, and practice auditing. When complications arise, challenges specific to medical tourism patients may be encountered.

Mycobacterium ulcerans treatment costs, Australia.

Mycobacterium ulcerans gives rise to severe skin ulceration that can be associated with considerable illness. The cost of diagnosis, treatment, and lost income has never been assessed in Australia. A survey of 26 confirmed cases of the disease in Victoria was undertaken. Data were collected on demographic details, diagnostic tests, treatment, time off work, and travel to obtain treatment. All costs are reported in Australian dollars in 1997-98 prices. The cost varies considerably with disease severity. For mild cases, the average direct cost is 6,803 Australian dollars, and for severe cases 27,681 Australian dollars. Hospitalization accounts for 61% to 90% of costs, and indirect costs amount to 24% of the total per case. M. ulcerans can be an expensive disease to diagnose and treat. Costs can be reduced by early diagnosis and definitive treatment. Research is needed to find cost-effective therapies for this disease.

An outreach education and treatment project in Ghana for the early stage of Mycobacterium ulcerans disease.

Mycobacterium ulcerans disease starts as a painless, subcutaneous nodule, excision of which prevents the development of large Buruli ulcers. An outreach programme was set up in Ghana to promote nodule recognition and excision. The programme was cost-effective and shifted the pattern of disease presentation. This could from a model for other countries.

Socioeconomic implications of Buruli ulcer in Ghana: a three-year review.

This study examines some of the socioeconomic cost of treating 102 cases of Buruli ulcer between 1994 and 1996 at the St. Martin's Catholic Hospital in Agroyesum in the Amansie West district of the Ashanti region of Ghana. Seventy percent of the cases were children (up to 15 years of age). There was no sex difference in the distribution of cases. Hospitalization was prolonged (average = 186 days in 1994, 103 days in 1995, and 102 days in 1996) with no significant age and sex differences. There were 10 limb amputations, 12 patients were left with contracture deformities, one patient lost sight in one eye, and two died of sepsis and tetanus. The average total treatment cost per patient was $966.85 (62% indirect) in 1994, $706.08 (75% indirect) in 1995, and $658.74 (79% indirect) in 1996. With increasing number of cases, high treatment costs, and serious complications, urgent attention should be given to the disease in terms of control and research efforts aimed at early detection and treatment.