Teaching perspectives on the communication of difficult news of genetic conditions to medical students.

Informing parents that their child has a diagnosis of Down syndrome (DS) is a common example of the delivery of unexpected or difficult news. Expectations and life planning will change, and if detected prenatally, discussions might include the option of pregnancy termination. Medical school curricula currently include training in breaking unexpected news; however, it is difficult to teach and assess. We use the perspectives of clinicians, educators, and a medical student who is the parent of a child with DS to frame a discussion on teaching, practicing, and assessing communication of difficult news in human genetics during medical school.

A longitudinal study of predictors of serious psychological distress during COVID-19 pandemic.

BACKGROUND: The prevalence of serious psychological distress (SPD) was elevated during the COVID-19 pandemic in the USA, but the relationships of SPD during the pandemic with pre-pandemic SPD, pre-pandemic socioeconomic status, and pandemic-related social stressors remain unexamined. METHODS: A probability-based sample (N = 1751) of the US population age 20 and over was followed prospectively from February 2019 (T1), with subsequent interviews in May 2020 (T2) and August 2020 (T3). Multinomial logistic regression was used to assess prospective relationships between T1 SPD with experiences of disruption of employment, health care, and childcare at T2. Binary logistic regression was then used to assess relationships of T1 SPD, and socioeconomic status and T2 pandemic-related stressors with T3 SPD. RESULTS: At T1, SPD was associated with age, race/ethnicity, and household income. SPD at T1 predicted disruption of employment (OR 4.5, 95% CI 1.4-3.8) and health care (OR 3.2, 95% CI 1.4-7.1) at T2. SPD at T1 (OR 10.2, 95% CI 4.5-23.3), low household income at T1 (OR 2.6, 95% CI 1.1-6.4), disruption of employment at T2 (OR 3.2, 95% CI 1.4-7.6), and disruption of healthcare at T2 (OR 3.3, 95% CI 1.5-7.2) were all significantly associated with elevated risk for SPD at T3. CONCLUSIONS: Elevated risk for SPD during the COVID-19 pandemic is related to multiple psychological and social pathways that are likely to interact over the life course. Policies and interventions that target individuals with pre-existing mental health conditions as well as those experiencing persistent unemployment should be high priorities in the mental health response to the pandemic.

Nationally Representative Sample Shows an Increase in Domestic Conflict Early in the COVID-19 Pandemic.

OBJECTIVE: The coronavirus disease (COVID-19) pandemic and associated social distancing increased stressors related to risk for domestic conflict, but increases in domestic conflict early in the pandemic have yet to be studied in community samples. METHODS: Increase in domestic conflict (verbal or physical fights) since the beginning of the pandemic was assessed in 1196 partnered and cohabitating respondents, drawn from a nationally representative sample, in May 2020. Chi-square tests and logistic regression analyses were used to estimate associations of demographic characteristics and financial worry with domestic conflict. RESULTS: An increase in domestic conflict was reported by 10.6% (95% CI: 7.7-13.4) of the sample. Domestic conflict increase was significantly associated with younger age, lower education, and financial worry. CONCLUSION: Increases in domestic conflict were seen in certain vulnerable groups and in those who report financial worry. Policies ensuring financial stability, particularly early in the disaster conditions, could reduce domestic conflict during continued COVID-19 conditions or other disasters.

A longitudinal study of psychological distress in the United States before and during the COVID-19 pandemic.

The COVID-19 pandemic has caused financial stress and disrupted daily life more quickly than any prior economic downturn and on a scale beyond any prior natural disaster. This study aimed to assess the impact of the pandemic on psychological distress and identify vulnerable groups using longitudinal data to account for pre-pandemic mental health status. Clinically significant psychological distress was assessed with the Kessler-6 in a national probability sample of adults in the United States at two time points, February 2019 (T1) and May 2020 (T2). To identify increases in distress, psychological distress during the worst month of the past year at T1 was compared with psychological distress over the past 30-days at T2. Survey adjusted logistic regression was used to estimate associations of demographic characteristics at T1 (gender, age, race, and income) and census region at T2 with within-person increases in psychological distress. The past-month prevalence of serious psychological distress at T2 was as high as the past-year prevalence at T1 (10.9% vs. 10.2%). Psychological distress was strongly associated across assessments (X2(4) = 174.6, p < .0001). Increase in psychological distress above T1 was associated with gender, age, household income, and census region. Equal numbers of people experienced serious psychological distress in 30-days during the pandemic as did over an entire year prior to the pandemic. Mental health services and research efforts should be targeted to those with a history of mental health conditions and groups identified as at high risk for increases in distress above pre-pandemic levels.

Differential Association of Stigma with Perceived Need and Mental Health Service Use.

This study examined the role of stigma at two stages of the treatment-seeking process by assessing associations between various types of stigma and perceived need for mental health treatment as well as actual treatment use. We analyzed cross-sectional data from the 2014 and 2016 California Well-Being Survey, a telephone survey with a representative sample of 1954 California residents with probable mental illness. Multivariable logistic regression indicated that perceived need was associated with less negative beliefs about mental illness (odds ratio [OR] = 0.72; 95% confidence interval [CI] = 0.54, 0.95) and greater intentions to conceal a mental illness (OR = 1.47; 95% CI = 1.12-1.92). Among respondents with perceived need, treatment use was associated with greater mental health knowledge/advocacy (OR = 1.63; 95% CI = 1.03-2.56) and less negative treatment attitudes (OR = 0.66; 95% CI = 0.43-1.00). Understanding which aspects of stigma are related to different stages of the help-seeking process is essential to guiding policy and program initiatives aimed at ensuring individuals with mental illness obtain needed mental health services.

Islands containing slowly hydrolyzable GTP analogs promote microtubule rescues.

Microtubules are dynamic polymers of GTP- and GDP-tubulin that undergo stochastic transitions between growing and shrinking phases. Rescues, the conversion from shrinking to growing, have recently been proposed to be to the result of regrowth at GTP-tubulin islands within the lattice of growing microtubules. By introducing mixed GTP/GDP/GMPCPP (GXP) regions within the lattice of dynamic microtubules, we reconstituted GXP islands in vitro (GMPCPP is the slowly hydrolyzable GTP analog guanosine-5'-[(α,ß)-methyleno]triphosphate). We found that such islands could reproducibly induce rescues and that the probability of rescue correlated with both the size of the island and the percentage of GMPCPP-tubulin within the island. The islands slowed the depolymerization rate of shortening microtubules and promoted regrowth more readily than GMPCPP seeds. Together, these findings provide new mechanistic insights supporting the possibility that rescues could be triggered by enriched GTP-tubulin regions and present a new tool for studying such rescue events in vitro.

Smoking-cessation interventions by type of provider: a meta-analysis.

OBJECTIVE: To synthesize the evidence on the effectiveness of smoking-cessation interventions by type of provider. METHODS: A random effects meta-regression was estimated to examine the effect of provider and whether the intervention contained nicotine replacement therapy (NRT), on the intervention's relative risk of quitting as compared to placebo or usual care from studies published in databases from inception to 2000. Thirty additional studies not included in the previous 1996 and 2000 U.S. Public Health Service clinical practice guidelines were used to provide the most comprehensive analysis to date of the comparative effectiveness of different types of providers in interventions for smoking cessation that have been published. RESULTS: The effectiveness without NRT follows: psychologist (1.94, 95% confidence interval [CI]: 1.04-3.62); physician (1.87, CI=1.42-2.45); counselor (1.82, CI=0.84-3.96); nurse (1.76, CI=1.21-2.57); unknown (1.27, CI=0.57-2.82); other (1.18, CI=0.67-2.10); and self-help (1.28, CI=0.89-1.82). Effectiveness of most providers increased by almost twofold with the use of NRT. CONCLUSIONS: Smoking-cessation interventions without NRT delivered by psychologists, physicians, or nurses are all effective. NRT increases the effectiveness of most providers.

Interventions for the prevention of falls in older adults: systematic review and meta-analysis of randomised clinical trials.

OBJECTIVE: To assess the relative effectiveness of interventions to prevent falls in older adults to either a usual care group or control group. DESIGN: Systematic review and meta-analyses. DATA SOURCES: Medline, HealthSTAR, Embase, the Cochrane Library, other health related databases, and the reference lists from review articles and systematic reviews. DATA EXTRACTION: Components of falls intervention: multifactorial falls risk assessment with management programme, exercise, environmental modifications, or education. RESULTS: 40 trials were identified. A random effects analysis combining trials with risk ratio data showed a reduction in the risk of falling (risk ratio 0.88, 95% confidence interval 0.82 to 0.95), whereas combining trials with incidence rate data showed a reduction in the monthly rate of falling (incidence rate ratio 0.80, 0.72 to 0.88). The effect of individual components was assessed by meta-regression. A multifactorial falls risk assessment and management programme was the most effective component on risk of falling (0.82, 0.72 to 0.94, number needed to treat 11) and monthly fall rate (0.63, 0.49 to 0.83; 11.8 fewer falls in treatment group per 100 patients per month). Exercise interventions also had a beneficial effect on the risk of falling (0.86, 0.75 to 0.99, number needed to treat 16) and monthly fall rate (0.86, 0.73 to 1.01; 2.7). CONCLUSIONS: Interventions to prevent falls in older adults are effective in reducing both the risk of falling and the monthly rate of falling. The most effective intervention was a multifactorial falls risk assessment and management programme. Exercise programmes were also effective in reducing the risk of falling.

Construction of high-density bacterial colony arrays and patterns by the ink-jet method.

We have developed a method for fabricating bacterial colony arrays and complex patterns using commercially available ink-jet printers. Bacterial colony arrays with a density of 100 colonies/cm(2) were obtained by directly ejecting Escherichia coli (E. coli) onto agar-coated substrates at a rapid arraying speed of 880 spots per second. Adjusting the concentration of bacterial suspensions allowed single colonies of viable bacteria to be obtained. In addition, complex patterns of viable bacteria as well as bacteria density gradients were constructed using desktop printers controlled by a simple software program.

Meta-analysis of dyspepsia and nonsteroidal antiinflammatory drugs.

OBJECTIVE: Nonsteroidal antiinflammatory drug (NSAID) use is a known risk factor for gastrointestinal (GI) perforations, ulcers, and bleeds, but there are limited data on its association with the very common symptom of dyspepsia. Using published and unpublished data sources, we sought to determine estimates of the risks of dyspepsia associated with NSAIDs. METHODS: We searched computerized databases (1966-1998) for primary studies of NSAIDs reporting on GI complications. We also obtained Food and Drug Administration (FDA) new drug application reviews for the 5 most common NSAIDs. We included studies reporting defined upper GI outcomes among subjects (>17 years old) who used oral NSAIDs for more than 4 days. Two reviewers evaluated 4,881 published titles, identifying 55 NSAID versus placebo randomized controlled trials (RCTs), 37 unpublished (FDA data) placebo-controlled RCTs; 86 NSAID versus NSAID RCTs (sample size >or=50); and 103 observational studies. RESULTS: The majority of clinical trials were of good quality. Meta-regression identified an increased risk of dyspepsia for users of specific NSAIDs (adjusted odds ratio [OR] of indomethacin, meclofenamate, piroxicam = 2.8), and for high dosages of other NSAIDs (OR = 3.1), but not for other NSAIDs regardless of dosage (OR = 1.1). Dyspepsia was not reported as an outcome in the case control or cohort studies. CONCLUSIONS: Clinical trial data indicate that high dosages of any NSAID along with any dosage of indomethacin, meclofenamate, or piroxicam increase the risk of dyspepsia by about 3-fold. Other NSAIDs at lower dosages were not associated with an increased risk of dyspepsia.

How useful are unpublished data from the Food and Drug Administration in meta-analysis?

The goals of this systematic review and meta-analysis were to ascertain whether studies of nonsteroidal anti-inflammatory drugs (NSAIDs) summarized in the FDA reviews are ultimately published, to compare the methodologic and population characteristics of studies summarized in the FDA reviews with those reported in peer reviewed literature, and to compare the pooled relative risk of dyspepsia from NSAIDs in each data source. Summary measures of risk difference were calculated with a random effects model; meta-regression was used to assess the effect of study covariates. Among 37 studies described in the FDA reviews, one was published. Sample size, gender distribution, indication for drug use, and methodologic quality did not vary significantly between the published and FDA data. The pooled risk ratio for dyspepsia obtained using published data (1.21) or FDA data (1.07) did not differ significantly or practically. Data from FDA reviews may be a viable data source for systematic reviews and meta-analyses but only after being subjected to the same methodologic scrutiny as published data.

Do NSAIDs cause dyspepsia? A meta-analysis evaluating alternative dyspepsia definitions.

OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with dyspepsia, but the relationship is obscured by variations in the terminology used to report GI symptoms. Using alternative definitions, we assessed the relationship between NSAID use and dyspepsia. METHODS: We searched MEDLINE, EMBASE, HEALTHSTAR, and BIOSIS databases (1966-1997) and New Drug Application reviews, identifying randomized, placebo-controlled trials (5 days or more duration) of any NSAID, reporting original data on GI complications. Based upon reported terms describing upper GI symptoms, we derived three definitions: strict, using terms synonymous with epigastric pain/discomfort; loose, (containing the strict definition plus terms for heartburn, nausea, bloating, anorexia, and vomiting); and a loose definition without heartburn terms (the loose-less-heartburn definition). Using each definition, we performed a random-effects model meta-analysis of the relationship between NSAID exposure and dyspepsia. RESULTS: Fifty-five published and 37 unpublished controlled NSAID trials met our inclusion criteria. The mean duration of the trials was 33.2 days (SD 40 days). Application of the strict definition resulted in a pooled risk ratio of dyspepsia for NSAIDs compared with placebo of 1.36 (95% CI = 1.11-1.67). For the loose definition, the pooled risk ratio was 1.13 (95% CI = 0.98-1.32). The loose-less-heartburn definition yielded a pooled risk ratio of 1.19 (95% CI = 1.03-1.39). In the placebo-treated control groups, the percent of patients reporting dyspepsia ranged from 2.3% (strict definition) to 4.2% (loose and loose-less-heartburn definitions). CONCLUSIONS: Using the strict definition, based solely on epigastric pain-related symptoms, NSAIDs increased the risk of dyspepsia by 36% (p < 0.05). These findings may be useful in creating a standardized definition of NSAID-related dyspepsia.

Interventions that increase use of adult immunization and cancer screening services: a meta-analysis.

PURPOSE: The relative effectiveness of the diverse approaches used to promote preventive care activities, such as cancer screening and adult immunization, is unknown. Despite many high-quality published studies, practices and policymakers attempting to improve preventive care have little definitive information on which to base decisions. Thus, we quantitatively assessed the relative effectiveness of previously studied approaches for improving adherence to adult immunization and cancer screening guidelines. DATA SOURCES: MEDLINE, the Cochrane Effective Practice and Organization of Care Review Group register, previous systematic reviews, and the Medicare Health Care Quality Improvement Project database. STUDY SELECTION: Controlled clinical trials that assessed interventions to increase use of immunizations for influenza and pneumococcal pneumonia and screening for colon, breast, and cervical cancer in adults. DATA EXTRACTION: Two reviewers independently extracted data on characteristics and outcomes from unmasked articles. Intervention components to increase use of services were classified as reminder, feedback, education, financial incentive, legislative action, organizational change, or mass media campaign. DATA SYNTHESIS: Of 552 abstracts and articles, 108 met the inclusion criteria. To assess the effect of intervention components, meta-regression models were developed for immunizations and each cancer screening service by using 81 studies with a usual care or control group. The most potent intervention types involved organizational change (the adjusted odds ratios for increased use of services from organizational change ranged from 2.47 to 17.6). Organizational change interventions included the use of separate clinics devoted to prevention, use of a planned care visit for prevention, or designation of nonphysician staff to do specific prevention activities. The next most effective intervention components were patient financial incentives (adjusted odds ratios, 1.82 to 3.42) and patient reminders (adjusted odds ratios, 1.74 to 2.75); the adjusted odds ratios ranged from 1.29 to 1.53 for patient education and from 1.10 to 1.76 for feedback. CONCLUSIONS: Rates of adult immunization and cancer screening are most likely to improve when a health care organization supports performance of these activities through organizational changes in staffing and clinical procedures. Involving patients in self-management through patient financial incentives and reminders is also likely to positively affect performance.

Biofeedback interventions for gastrointestinal conditions: a systematic review.

OBJECTIVE: To review evidence for the efficacy of biofeedback in the treatment of gastrointestinal problems. DATA SOURCES: Studies were identified through a search of MEDLINE, HealthSTAR, EMBASE, Allied and Complementary Medicine, MANTIS, PsycINFO, Social Science Citation Index, Science Citation Index, and CINAHL. STUDY SELECTION: Studies were selected if they used biofeedback as the intervention, addressed the treatment of a gastrointestinal condition, and included a control group. DATA EXTRACTION: All titles (4397), articles, and/or abstracts (1362) were evaluated by 2 independent reviewers who extracted data on study design and quality, sample size, type of intervention, and outcomes. DATA SYNTHESIS: We found 16 controlled trials of biofeedback for gastrointestinal problems. Ten studies had a comparison group that did not receive biofeedback (5 studies on constipation and/or encopresis, 3 on fecal incontinence, 1 on constipation, and 1 on abdominal pain). Of the 10 studies that had a "no biofeedback" control arm, 7 provided sufficient data to calculate an effect size. Of these 7 studies, 2 favored biofeedback: 1 study revealed a reduction in fecal incontinence among adults, and the other study showed an improvement in constipation with fecal incontinence (encopresis) among children. The other 5 had nonsignificant results. Three studies had a "no biofeedback" comparison arm but insufficient data to calculate an effect size. One of these studies in adult fecal incontinence reported statistically significant improvement. CONCLUSIONS: The evidence is insufficient to support the efficacy of biofeedback for these gastrointestinal conditions.

A metaanalysis of severe upper gastrointestinal complications of nonsteroidal antiinflammatory drugs.

OBJECTIVE: Prior metaanalyses of the risk of upper gastrointestinal (GI) complications associated with nonsteroidal antiinflammatory drugs (NSAID) have focused on the published English language epidemiologic literature and/or only a portion of the relevant evidence, restrictions that are now known to be associated with bias in metaanalysis. We synthesized the published and unpublished evidence to determine the least biased estimates of the risks of perforations, ulcers, and bleeds (PUB) associated with NSAID use from all study designs and all languages. DATA SOURCES: Using MEDLINE, EMBASE, HEALTHSTAR, and BIOSIS, we searched for English and non-English language studies of NSAID from 1966-1998 reporting primary data on GI complications. We obtained unpublished data from the US Food and Drug Administration (FDA) new drug application (NDA) reviews. NDA were hand searched to identify unpublished studies with inclusion criteria identical to those used for published reports. STUDY SELECTION: Studies had to assess the use of oral NSAID for more than 4 days duration in subjects > 18 years of age and report on the clinically relevant upper GI outcomes of PUB. RESULTS: Two reviewers evaluated 4881 published titles and identified 13 NSAID versus placebo randomized clinical trials and 3 previously unpublished FDA placebo controlled randomized controlled trials, 9 cohort studies, and 23 case control studies sufficiently clinically homogeneous to pool. Two reviewers extracted data about study characteristics and study quality. DATA SYNTHESIS: The majority of clinical trials were of good quality, but observational studies had methodologic limitations. The pooled odds ratio (OR) from 16 NSAID versus placebo clinical trials, comprising 4431 patients, was 5.36 (95% CI: 1.79, 16.1). The pooled relative risk of PUB from 9 cohort studies comprising over 750,000 person-years of exposure was 2.7 (95% CI: 2.1, 3.5). The pooled OR of PUB from 23 case control studies using age and sex matching, representing 25,732 patients, was 3.0 (95% CI: 2.5, 3.7). Data were insufficient to justify subgroup analyses stratified by age, comorbid conditions, drug, or dose. CONCLUSION: These data support an association between the use of NSAID and serious upper GI complications, including estimates from different study designs. Prior pooled estimates about the effect of patient and drug variables on increased risk must be viewed with caution.