Risk communication and informed consent in the medical tourism industry: A thematic content analysis of canadian broker websites

<p>Abstract</p> <p>Background</p> <p>Medical tourism, thought of as patients seeking non-emergency medical care outside of their home countries, is a growing industry worldwide. Canadians are amongst those engaging in medical tourism, and many are helped in the process of accessing care abroad by medical tourism brokers - agents who specialize in making international medical care arrangements for patients. As a key source of information for these patients, brokers are likely to play an important role in communicating the risks and benefits of undergoing surgery or other procedures abroad to their clientele. This raises important ethical concerns regarding processes such as informed consent and the liability of brokers in the event that complications arise from procedures. The purpose of this article is to examine the language, information, and online marketing of Canadian medical tourism brokers' websites in light of such ethical concerns.</p> <p>Methods</p> <p>An exhaustive online search using multiple search engines and keywords was performed to compile a comprehensive directory of English-language Canadian medical tourism brokerage websites. These websites were examined using thematic content analysis, which included identifying informational themes, generating frequency counts of these themes, and comparing trends in these counts to the established literature.</p> <p>Results</p> <p>Seventeen websites were identified for inclusion in this study. It was found that Canadian medical tourism broker websites varied widely in scope, content, professionalism and depth of information. Three themes emerged from the thematic content analysis: training and accreditation, risk communication, and business dimensions. Third party accreditation bodies of debatable regulatory value were regularly mentioned on the reviewed websites, and discussion of surgical risk was absent on 47% of the websites reviewed, with limited discussion of risk on the remaining ones. Terminology describing brokers' roles was somewhat inconsistent across the websites. Finally, brokers' roles in follow up care, their prices, and the speed of surgery were the most commonly included business dimensions on the reviewed websites.</p> <p>Conclusion</p> <p>Canadian medical tourism brokers currently lack a common standard of care and accreditation, and are widely lacking in providing adequate risk communication for potential medical tourists. This has implications for the informed consent and consequent safety of Canadian medical tourists.</p

Genotypic and functional impact of HIV-1 adaptation to its host population during the North American epidemic.

HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979-1989) and 382 modern (2000-2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver). Inferred HIV phylogenies were star-like, with approximately two-fold greater mean pairwise distances in modern versus historic sequences. The reconstructed epidemic ancestral (founder) HIV sequence was essentially identical to the North American subtype B consensus. Consistent with gradual diversification of a "consensus-like" founder virus, the median "background" frequencies of individual HLA-associated polymorphisms in HIV (in individuals lacking the restricting HLA[s]) were ∼ 2-fold higher in modern versus historic HIV sequences, though these remained notably low overall (e.g. in Gag, medians were 3.7% in the 2000s versus 2.0% in the 1980s). HIV polymorphisms exhibiting the greatest relative spread were those restricted by protective HLAs. Despite these increases, when HIV sequences were analyzed as a whole, their total average burden of polymorphisms that were "pre-adapted" to the average host HLA profile was only ∼ 2% greater in modern versus historic eras. Furthermore, HLA-associated polymorphisms identified in historic HIV sequences were consistent with those detectable today, with none identified that could explain the few HIV codons where the inferred epidemic ancestor differed from the modern consensus. Results are therefore consistent with slow HIV adaptation to HLA, but at a rate unlikely to yield imminent negative implications for cellular immunity, at least in North America. Intriguingly, temporal changes in protein activity of patient-derived Nef (though not Gag) sequences were observed, suggesting functional implications of population-level HIV evolution on certain viral proteins

Genotypic and Functional Impact of HIV-1 Adaptation to Its Host Population during the North American Epidemic

HLA-restricted immune escape mutations that persist following HIV transmission could gradually spread through the viral population, thereby compromising host antiviral immunity as the epidemic progresses. To assess the extent and phenotypic impact of this phenomenon in an immunogenetically diverse population, we genotypically and functionally compared linked HLA and HIV (Gag/Nef) sequences from 358 historic (1979–1989) and 382 modern (2000–2011) specimens from four key cities in the North American epidemic (New York, Boston, San Francisco, Vancouver). Inferred HIV phylogenies were star-like, with approximately two-fold greater mean pairwise distances in modern versus historic sequences. The reconstructed epidemic ancestral (founder) HIV sequence was essentially identical to the North American subtype B consensus. Consistent with gradual diversification of a “consensus-like” founder virus, the median “background” frequencies of individual HLA-associated polymorphisms in HIV (in individuals lacking the restricting HLA[s]) were ~2-fold higher in modern versus historic HIV sequences, though these remained notably low overall (e.g. in Gag, medians were 3.7% in the 2000s versus 2.0% in the 1980s). HIV polymorphisms exhibiting the greatest relative spread were those restricted by protective HLAs. Despite these increases, when HIV sequences were analyzed as a whole, their total average burden of polymorphisms that were “pre-adapted” to the average host HLA profile was only ~2% greater in modern versus historic eras. Furthermore, HLA-associated polymorphisms identified in historic HIV sequences were consistent with those detectable today, with none identified that could explain the few HIV codons where the inferred epidemic ancestor differed from the modern consensus. Results are therefore consistent with slow HIV adaptation to HLA, but at a rate unlikely to yield imminent negative implications for cellular immunity, at least in North America. Intriguingly, temporal changes in protein activity of patient-derived Nef (though not Gag) sequences were observed, suggesting functional implications of population-level HIV evolution on certain viral proteins

Diversity of North American Gag and Nef sequences from historic (1979–1989) and modern (2000+) eras.

<p>Unrooted Maximum likelihood phylogenetic trees, drawn on the same distance scale, are shown for historic Gag (upper left), historic Nef (lower left), modern Gag (upper right) and modern Nef (lower right). Phylogenies are star-like, with Nef exhibiting greater diversity than Gag, and modern trees exhibiting greater diversity than historic ones. Cohort sequences are colored by sampling era: red (1979–1982), green (1983–1985), blue (1986–1989) and purple (2000+); North American sequences retrieved from the Los Alamos (LANL) database are in grey. Included in each tree is the HIV subtype B reference strain HXB2, shown in black and indicated with an arrow.</p

HLA-associated polymorphisms, identified via statistical association, in historic HIV sequences.

<p><b>Panel A:</b> Gag immune escape map, indicating the locations, specific amino acid residues and HLA restrictions of HLA-associated polymorphisms identified at q≤0.05 in our historic cohort. The HIV consensus B amino acid sequence is used as a reference. Shaded vertical bars separate blocks of 10 amino acids. “Adapted” amino acids (those over-represented in the presence of the HLA allele) are red. “Nonadapted” amino acids (those under-represented in the presence of the HLA allele) are blue. UPPERCASE letters distinguish polymorphisms that survive correction for HIV codon covariation (“direct” associations), while lowercase letters distinguish polymorphisms that do not survive correction for codon covariation (“indirect” associations). The notation “_ST” following an HLA (<i>e.g.</i> B58_ST) identifies associations identified at the supertype level. The locations of optimally-defined, HLA-restricted CTL epitopes straddling or adjacent to HLA-associated polymorphisms are indicated. The well-known A*02-SL9 epitope (SLYNTVATL) epitope is also shown; no historic HLA-associated polymorphisms were identified therein at q<0.05. The single “novel” historic HLA-associated polymorphism (B*49:01-62G) is indicated with a purple asterisk. A green filled circle denotes the single Gag residue (codon 67) where the ancestral founder sequence was reconstructed with <80% confidence. Orange filled circles denote the four Gag residues (67, 76, 91 and 102) where the inferred ancestral founder sequence differs from the published North American subtype B consensus sequence. None of these sites harbor HLA associations. <b>Panel B:</b> Nef historic immune escape map. Green filled circles denote the six Nef residues where the ancestral founder sequence was reconstructed with <80% confidence (15, 21, 51, 152, 178, 205); none harbor HLA associations.</p

Reconstructed ancestral sequences at the root of the inferred Gag and Nef phylogenies, representing the estimated most recent common ancestor (MRCA) of the North American epidemic.

<p>A minimum of ≥50,000 reconstructions of the ancestral sequence at the root of the Gag and Nef phylogenies were performed, and the inferred MRCA was computed as the “grand consensus” of these replicate reconstructions. For each codon, reconstruction confidence (computed as the frequency of each amino acid observed across all reconstructions) is indicated on the y-axis on a scale from 0 (0%) to 1 (100%). Blue letters represent the highest-confidence residue at each position; green letters represent lower-confidence residues. All amino acids observed at >0.01 (>1%) reconstruction frequency are shown. Yellow boxes highlight positions where the highest-confidence (blue) inferred ancestral residue differs from the North American consensus B sequence (displayed in <b><a href="http://www.plosgenetics.org/article/info:doi/10.1371/journal.pgen.1004295#pgen.1004295.s003" target="_blank">Figure S3</a></b>).</p