Baclofen for hiccups: a large mixed methods multisite study.

OBJECTIVE: Hiccups can be bothersome and spawn morbidity. Although oral baclofen is perhaps the most prescribed agent for hiccups, a paucity of data supports its use. METHODS: This multisite, single institution study examined the medical records of patients who had hiccups and had been prescribed baclofenas noted in a clinical encounter. Mixed methods were used to assess baclofen's palliative efficacy. In view of the sometimes transient nature of hiccups and other such factors, cessation or palliation of hiccups in 75% of patients was sought to indicate true palliation. RESULTS: A total of 301 patients with a median age of 61 years (range 20-87 years) and a male predominance are the focus of this report. Baclofen was most often prescribed at 10 mg orally three times a day. Only 105 patients (35%) (95% CI: 30% to 41%) acquired hiccup palliation. Corroborative medical record quotations included, 'Still has hiccups.'Quotations such as, 'Responding to baclofen this AM', were also recorded. Baclofen appeared more likely to benefit patients with hiccups of >48 hours (chronic) duration in univariable analyses (OR for benefit: 0.51 (95% CI: 0.29 to 0.91; p=0.02) with similar conclusions drawn from multivariable analyses. Adverse events occurred in 15 patients with drowsiness the most common. CONCLUSIONS: Baclofen did not meet this study's a priori threshold for successful hiccup palliation, but further study is indicated to learn whether baclofen might help patients with chronic hiccups.

Gastrointestinal perforation after bevacizumab: a multi-site, single-institution study with a focus on survival.

BACKGROUND: Bevacizumab-induced gastrointestinal perforation is a rare but potentially devastating adverse event that has generated limited data on overall survival. Yet, such survival data are critical in guiding management. METHODS: This multi-site, single-institution retrospective study focused on all cancer patients who had received bevacizumab and who had suffered a well-documented gastrointestinal perforation from January 1, 2004 through January 20, 2022.The main goal was to report survival outcomes; Kaplan Meier curves and Cox survival models were used for this purpose. RESULTS: Eighty-nine patients are included in this report with a median age of 62 years (range 26-85). Colorectal cancer was the most common malignancy (n = 42). Thirty-nine patients underwent surgery for the perforation. Seventy-eight were deceased at the time of reporting with an overall median survival of all patients of 2.7 months (range 0-45 months), and 32 (36%) died within 30 days of perforation. In univariable survival analyses, no statistically significant associations were observed for age, gender, corticosteroid use, and time since last bevacizumab dose. However, surgically treated patients manifested a better survival (hazard ratio (HR) 0.49 (95% CI 0.31-0.78); p = 0.003). In multivariable analyses, surgery continued to be associated with improved survival (HR 0.47 (95% CI 0.29-0.74); p = 0.002), and corticosteroid use was associated with worse survival (HR 1.75 (95% CI 1.02-2.99); p = 0.04). CONCLUSION: Although gastrointestinal perforation after bevacizumab should be managed on a case-by-case basis, these descriptive survival data can help inform patients, their families, and healthcare providers as challenging management decisions arise.

What percentage of patients with cancer develop hiccups with oxaliplatin- or cisplatin-based chemotherapy? a compilation of patient-reported outcomes.

BACKGROUND: Chemotherapy-induced hiccups are understudied but can cause sleep deprivation, fatigue, pain in the chest and abdomen, poor oral intake, aspiration, and even death. As a critical next step toward investigating better palliative methods, this study reported patient-reported incidence of hiccups after oxaliplatin- or cisplatin-based chemotherapy. METHODS: The current study relied on 2 previous studies that sought to acquire consecutive direct patient report of hiccups among patients who had recently received chemotherapy with cisplatin or oxaliplatin. These patient-reported data in conjunction with information from the medical record are the focus of this report. RESULTS: Of 541 patients, 337 were successful contacted by phone; and 95 (28%; 95% CI: 23%, 33%) of these contacted patients reported hiccups. In univariable analyses, male gender (odds ratio (OR): 2.17 (95% confidence ratio (95% CI): 1.30, 3.62); p = 0.002), increased height (OR: 1.03 (95% CI: 1.00, 1.06); p = 0.02), and concomitant aprepitant/fosaprepitant (OR: 2.23 (95% CI: 1.31, 3.78); p = 0.002) were associated with hiccups. In multivariable analyses, these statistically significant associations persisted except for height. CONCLUSIONS: These patient-reported data demonstrate that oxaliplatin- or cisplatin-induced hiccups occur in a notable proportion of patients with cancer. Male gender and concomitant aprepitant/fosaprepitant appear to increase risk.

A randomized, double-blinded feasibility trial of educational materials for hiccups in chemotherapy-treated patients with cancer.

PURPOSE: Chemotherapy can cause hiccups but few randomized controlled trials have focused on hiccups. This trial examined the feasibility of such research. METHODS: This single-institution, multi-site trial used phone recruitment for patients: (1) 18 years or older, (2) able to speak/read English, (3) with a working e-mail address, (4) with hiccups 4 weeks prior to contact, and (5) with ongoing oxaliplatin or cisplatin chemotherapy. The primary outcome was feasibility. Patients were randomly assigned to one of two sets of educational materials, each of which discussed hiccups and palliative options. The experimental materials were almost identical to the standard materials but provided updated content based on the published medical literature. At 2 weeks, patients responded by phone to a 5-item verbally administered questionnaire. RESULTS: This trial achieved its primary endpoint of recruiting 20 eligible patients within 5 months; 50 patients were recruited in 3 months. Among the 40 patients who completed the follow-up questionnaire, no statistically significant differences between arms were observed in hiccup incidence since initial contact, time spent reviewing the educational materials, and the troubling nature of hiccups. Twenty-five patients tried palliative interventions (13 in the experimental arm and 12 in the standard arm), most commonly drinking water or holding one's breath. Eleven and 10 patients, respectively, described hiccup relief after such an intervention. CONCLUSIONS: Clinical trials for chemotherapy-induced hiccups are feasible and could address an unmet need.

Hiccups in patients with cancer: a multi-site, single-institution study of etiology, severity, complications, interventions, and outcomes.

BACKGROUND: To our knowledge, previous studies have not investigated hiccups in patients with cancer with detailed patient-level data with the goal of capturing a broad spectrum of hiccup symptomatology. METHODS: This multi-site, single institution study examined consecutive medical records to better understand hiccups in patients with cancer. RESULTS: A total of 320 patients are the focus of this report. The median age of patients when hiccups were first reported in the medical record was 63 years (range: 21, 97 years) with 284 (89%) men and 36 (11%) women. The most common diagnose was gastrointestinal cancer. Hiccups most frequently occurred daily, as seen in 194 patients (62%), and the most common duration was less than 1 week, as seen in 146 patients (47%). However, nine patients had had daily hiccups for greater than 6 weeks, and 5 had symptoms for years. Cited etiology was non-chemotherapy medications in 36 (11%) and cancer chemotherapy in 19 (6%). Complications occurred in approximately a third and included insomnia in 51 patients (16%); hospitalization or emergency department visit in 34 (11%); and musculoskeletal pain in 23 (7%). Baclofen was the single most prescribed agent for hiccup palliation, but 100 patients received more than one medication. Medical procedures, which included acupuncture, paracentesis, or phrenic nerve block, were performed in 5 patients. In 234 patients (73%), the medical record documented hiccup cessation. CONCLUSIONS: Hiccups appear to be highly problematic in a small subset of patients with cancer with no well-defined palliative approaches.

Olanzapine for cisplatin-induced hiccups: observations from a 338-patient study.

BACKGROUND: Several case reports suggest that olanzapine palliates hiccups. To our knowledge, however, no larger scale studies have confirmed that olanzapine prevents or palliatives hiccups. Hence, the current study sought to substantiate the conclusions from these earlier case reports. METHODS: This multi-site single institution study focused on cisplatin-treated cancer patients because this chemotherapy agent is associated with hiccups and because olanzapine is often used as an antiemetic with this agent. Relevant data were extracted from medical records. Hiccup incidence shortly after chemotherapy was compared between olanzapine exposed and non-exposed patients. Other relevant variables were also assessed descriptively in an exploratory manner. RESULTS: A total of 338 patients were studied. One hundred forty-one had received olanzapine and 197 had not. Twenty-one (6%) developed hiccups. Eleven (8%) of these patients with hiccups had received olanzapine, and 10 (5%) had not [odds ratio (OR): 1.58; 95% confidence interval (CI): 0.65-3.83; P=0.31]. Of note, hiccups were more often observed in men 17 of 188 (9%) than in women 4 of 150 (3%) (OR: 3.64; 95% CI: 1.20-11.02; P=0.01). CONCLUSIONS: Despite previous case reports and despite the relatively low incidence of hiccups in this study, it does not appear olanzapine prevents or palliates hiccups. The study of other promising agents is warranted. Furthermore, this study invites caution in relying on single case reports in making clinical decisions.

Olaparib for ovarian cancer: a single-institution, multi-site qualitative study.

PURPOSE: This qualitative study sought to learn patients' perspectives on olaparib - including maintenance olaparib - in their own words. METHODS: Olaparib-treated patients were interviewed by phone. A semi-structured interview guide that focused on symptoms and quality of life was formulated in alignment with the study objective. Interviews were transcribed and analyzed with content analysis. RESULTS: Twenty olaparib-treated patients were interviewed. Four themes emerged: (1) The Long Cancer Journey. Patients prescribed olaparib appear to have had a long cancer journey, sometimes with prior cancer ("I had breast cancer in 1996") and sometimes with a long interval from an ovarian cancer diagnosis; (2) Adherence. Despite this journey, patients were adherent to olaparib ("I set it for an alarm 15 min before I have to take [olaparib] and then exactly when I'm supposed to take it"); (3) Adherence Despite Challenges. Adherence continued despite side effects (although olaparib was "pretty tolerable"). This adherence also continued despite cost ("…for a month's supply, mine was $15,837… and my insurance covered some of it but not near enough"), and (4) Modifications in Perceptions of BRCA Status. Olaparib as cancer therapy influenced perceptions of BRCA mutations ("But I… I have to tell you, I'm grateful that I qualified to be on Lynparza®"). CONCLUSION: Although oral maintenance therapy for ovarian cancer is relatively new, patients appear willing to take olaparib long term; and they seem to take great lengths to remain adherent, despite having sometimes had a long cancer journey.

Establishing the Groundwork for Clinical Trials With Hiccupops® for Hiccup Palliation.

OBJECTIVE: Because hiccup palliation remains an unmet clinical need, we report here on an early experience with Hiccupops, ® a patented product designed for the express purpose of providing a mechanism-based intervention for hiccup palliation. METHODS: Meter Health, the developer and manufacturer of this patented product, used a purposive sampling approach to allow individuals with hiccups and a desire for hiccup palliation to purchase their agent and then to report on its efficacy or lack thereof. The authors of this report were provided these outcome data and allowed to analyze, report, and publish with no input from Meter Health with the exception of comments on accuracy. RESULTS: This report focused on 43 surveys that were completed. In response to the question, "Did the Hiccupops work for the person they were purchased for?" 29 (67%) responded, "yes." Seven individuals (16%) responded, "no;" and 7 (16%) were "not sure." Write-in comments appeared to substantiate the effective palliative nature of the intervention: "A friend with 10 days of hiccups following… brain tumor surgery, after 2 days, they stopped!!!#." Another noted the following: "I like that if my hiccups get painful they're there as a quick relief." Less favorable comments were also noted: "She couldn't get past the…. taste." Another read as follows: "They were not effective in stopping my father's intractable hiccups…. I like that there is someone out there who cares about trying to stop people's hiccups." CONCLUSIONS: This patented product appears to palliate hiccups in some individuals and merits further study.

Dose-dependent effects of aerobic exercise on clinically relevant biomarkers among healthy women at high genetic risk for breast cancer: A secondary analysis of a randomized controlled study.

BACKGROUND: Excess adiposity and dysregulated metabolism are associated with increased cancer risk. Triglycerides, cholesterol, glucose, insulin, HOMA-IR, and VO2 max are robust clinical-metabolic biomarkers of overall health. AIMS: Aerobic exercise may improve clinical-metabolic biomarkers and decrease cancer risk. This secondary analysis of the WISER Sister randomized controlled trial investigated dose-dependent effects of aerobic exercise on clinical biomarker levels in women at high genetic risk for breast cancer. METHODS AND RESULTS: One hundred thirty-nine participants were randomized to: control (<75 min/week), low-dose (150 min/week), and high-dose (300 min/week) aerobic exercise intervention groups. Intervention adherence was assessed via heart monitor. Fasting blood draws, cardio-pulmonary tests, and demographical surveys were taken at baseline and 5 months. Triglyceride, cholesterol, glucose, insulin, and VO2 max changes were assessed for 80 of the 122 study completers. Ninety-six percent of assayed-completers adhered to >80% of their exercise dose. A significant dose-dependent increase in VO2 max was observed for the low-dose and high-dose groups compared to control. No intervention effects were observed for plasma biomarkers. Overweight women (BMI > 25) showed a significant decrease in insulin levels and a trend for decreased triglycerides following exercise intervention. Significant increases in VO2 max were independent of BMI stratification. CONCLUSION: Women at high genetic risk for breast cancer should maintain healthy weights and aerobic capacities through aerobic exercise to achieve measurable benefits on overall health. For overweight women, exercise appears to improve subclinical metabolic dysregulation. However, normal weight women were unaffected by aerobic exercise as their biomarker levels may be below the threshold for improvement. VO2 max increases solely quantified the benefits of exercise in already healthy women at high-risk for breast cancer.

Frequency and Symptomatology of Hiccups in Patients With Cancer: Using an On-Line Medical Community to Better Understand the Patient Experience.

BACKGROUND: Cancer patients are at risk for hiccups, but the incidence and impact on quality of life are unclear. METHODS: A survey (modified from the Functional Living Index with the inclusion of qualitative elements) was developed and launched on an 80,000-member medical social media platform, Mayo Clinic Connect https://connect.mayoclinic.org/. RESULTS: Among 213 respondents, 34 (16%; 95% CI: 11, 22%) reported "yes" that they had experienced hiccups with cancer therapy. Of those patients who reported hiccups, only 12 (35%) were men, and most were older than 50 years of age. Over 25% noted that hiccups occurred frequently around the time of cancer therapy; 30% described that hiccups interfered with their leisure or recreational activities; and over 15% described hiccups interfered with their ability to enjoy a meal. A few patients seemed to express frustration with hiccups with comments such as, "Totally uncontrollable," "It's extremely pain[ful] with throat cancer," and "Once I had them bad. Almost choked." CONCLUSION: Hiccups occur in16% of patients who are receiving cancer therapy and, by our estimates and extrapolation, appear highly problematic in approximately 5%.

Dexamethasone and hiccups: a 2000-patient, telephone-based study.

OBJECTIVES: Dexamethasone causes hiccups in an undefined percentage of patients, and these hiccups are often ignored ('My doctors just shook their heads like I was joking …'). This study sought to learn the percentage of dexamethasone-treated patients who develop hiccups and to explore patients' responses to the availability of educational materials on hiccups. METHODS: English-speaking, adult outpatients treated with oral, intravenous or epidural dexamethasone 2 weeks prior were contacted by phone and asked about hiccups. Educational materials were offered, and patients were queried on their opinion of the availability of such materials. RESULTS: One hundred and twenty-seven patients or 11% (95% CI 9% to 13%) reported hiccups. This percentage was derived from 1186 reachable patients from 2000 total patients. Fifty-four (43%) of those with hiccups desired to learn about educational materials. Of these, 49 completed a single-item, 5-point scale item: 21 (43%) viewed the availability of educational materials 'extremely helpful,' providing a 5 rating; 8 (16%) provided a 4; 4 (8%) provided a 3; and 1 (4%) provided a 2. CONCLUSIONS: Dexamethasone-induced hiccups occur in a small percentage of patients. The fact that most patients responded favourably to learning about the availability of educational materials suggests some have unmet needs.

Should Loss of Appetite Be Palliated in Patients with Advanced Cancer?

OPINION STATEMENT: Loss of appetite is common among patients with advanced cancer. However, it remains controversial how, when, and if to palliate this symptom. Here, we provide an update on recent as well as past literature to address the question of whether loss of appetite should be palliated in patients with advanced cancer. In our opinion-and as discussed here-we believe that this symptom should be palliated, although perhaps not always with pharmacologic interventions.

Outpatient Sistrunk procedure: A retrospective analysis.

OBJECTIVE: The risk of expansile hematoma and airway compromise following neck surgery have been used to validate overnight observation. We investigated the outcomes of pediatric patients undergoing a Sistrunk procedure via either same day surgery or overnight observation. METHODS: A retrospective review of patients undergoing Sistrunk procedures between January 1, 2008 to January 1, 2019 was performed. 76 cases were identified for review. Bivariate and multivariable analyses were performed to determine predictive factors for overnight admission as well as associations between overnight observation and adverse outcomes (hematoma, seroma, airway compromise, infection). Factors evaluated for analysis included ASA class, surgeon type, history of pre-operative infection, recurrent case, operation >90 min, pharyngeal violation, intraoperative cyst rupture, cyst size, and drain placement. RESULTS: No patients had life-threatening adverse events. There was no difference in complication rates between same day discharge (17%) and overnight observation (23%, p = 0.47). Otolaryngologists were more likely to admit patients overnight (88% vs. 14%, p = 0.042) as well as place a drain (97% vs. 24%, p < 0.001) when compared to pediatric surgeons. Drain placement was associated with overnight observation (73% vs. 3%, p < 0.001). Multivariable logistic regression demonstrated drain placement (OR 21.9, 95%CI (2.5-189.7), p = 0.005) and otolaryngologist as operative surgeon (OR 11.7, 95%CI (2.8-48.2), p < 0.001) as strong predictive variables for overnight observation. There was no association between other investigated variables and adverse events or overnight stay. CONCLUSION: Same day Sistrunk operations are safe in select healthy patients. Overnight observation appears to be driven by drain placement and surgeon practice patterns.

Feasibility of same day surgery for pediatric second branchial cleft anomalies.

OBJECTIVE: The risk of expansile hematoma and airway compromise following neck surgery have been used to validate overnight observation. We investigated the outcomes of pediatric patients undergoing a removal of second branchial cleft anomalies (BCA) via either same day surgery or overnight observation. METHODS: A retrospective review of patients undergoing second BCA removal between January 1, 2008 to January 1, 2019 was performed. 40 cases were identified for review. Bivariate analyses were performed to determine predictive factors for overnight admission as well as associations between overnight observation and adverse outcomes (hematoma, seroma, airway compromise, infection). Factors evaluated for analysis included ASA class, surgeon type, history of pre-operative infection, recurrent case, operation >90 min, pharyngeal violation, intraoperative cyst rupture, cyst size, and drain placement. RESULTS: There were no life-threatening adverse events. Same day discharge was not associated with adverse events (p = 0.24). Overnight observation was associated with a history of preoperative infection (p = 0.003), cyst > 3.0 cm (p = 0.046), operative time > 90 min (p < 0.001), and drain placement (p = 0.001). There was no association between other investigated variables and adverse events or overnight stay. CONCLUSION: Same day discharge following second branchial cleft anomalies appears safe and feasible. Further study is needed to determine the safety profile of same day discharge and etiologies of practice patterns of overnight observation.

Bayesian phylogenetic analysis of Semitic languages identifies an Early Bronze Age origin of Semitic in the Near East.

The evolution of languages provides a unique opportunity to study human population history. The origin of Semitic and the nature of dispersals by Semitic-speaking populations are of great importance to our understanding of the ancient history of the Middle East and Horn of Africa. Semitic populations are associated with the oldest written languages and urban civilizations in the region, which gave rise to some of the world's first major religious and literary traditions. In this study, we employ Bayesian computational phylogenetic techniques recently developed in evolutionary biology to analyse Semitic lexical data by modelling language evolution and explicitly testing alternative hypotheses of Semitic history. We implement a relaxed linguistic clock to date language divergences and use epigraphic evidence for the sampling dates of extinct Semitic languages to calibrate the rate of language evolution. Our statistical tests of alternative Semitic histories support an initial divergence of Akkadian from ancestral Semitic over competing hypotheses (e.g. an African origin of Semitic). We estimate an Early Bronze Age origin for Semitic approximately 5750 years ago in the Levant, and further propose that contemporary Ethiosemitic languages of Africa reflect a single introduction of early Ethiosemitic from southern Arabia approximately 2800 years ago.

The genetic structure and history of Africans and African Americans.

Africa is the source of all modern humans, but characterization of genetic variation and of relationships among populations across the continent has been enigmatic. We studied 121 African populations, four African American populations, and 60 non-African populations for patterns of variation at 1327 nuclear microsatellite and insertion/deletion markers. We identified 14 ancestral population clusters in Africa that correlate with self-described ethnicity and shared cultural and/or linguistic properties. We observed high levels of mixed ancestry in most populations, reflecting historical migration events across the continent. Our data also provide evidence for shared ancestry among geographically diverse hunter-gatherer populations (Khoesan speakers and Pygmies). The ancestry of African Americans is predominantly from Niger-Kordofanian (approximately 71%), European (approximately 13%), and other African (approximately 8%) populations, although admixture levels varied considerably among individuals. This study helps tease apart the complex evolutionary history of Africans and African Americans, aiding both anthropological and genetic epidemiologic studies.

Contrasting patterns of Y chromosome and mtDNA variation in Africa: evidence for sex-biased demographic processes.

To investigate associations between genetic, linguistic, and geographic variation in Africa, we type 50 Y chromosome SNPs in 1122 individuals from 40 populations representing African geographic and linguistic diversity. We compare these patterns of variation with those that emerge from a similar analysis of published mtDNA HVS1 sequences from 1918 individuals from 39 African populations. For the Y chromosome, Mantel tests reveal a strong partial correlation between genetic and linguistic distances (r=0.33, P=0.001) and no correlation between genetic and geographic distances (r=-0.08, P>0.10). In contrast, mtDNA variation is weakly correlated with both language (r=0.16, P=0.046) and geography (r=0.17, P=0.035). AMOVA indicates that the amount of paternal among-group variation is much higher when populations are grouped by linguistics (Phi(CT)=0.21) than by geography (Phi(CT)=0.06). Levels of maternal genetic among-group variation are low for both linguistics and geography (Phi(CT)=0.03 and 0.04, respectively). When Bantu speakers are removed from these analyses, the correlation with linguistic variation disappears for the Y chromosome and strengthens for mtDNA. These data suggest that patterns of differentiation and gene flow in Africa have differed for men and women in the recent evolutionary past. We infer that sex-biased rates of admixture and/or language borrowing between expanding Bantu farmers and local hunter-gatherers played an important role in influencing patterns of genetic variation during the spread of African agriculture in the last 4000 years.