Effect of Perioperative Palliative Care on Health-Related Quality of Life Among Patients Undergoing Surgery for Cancer: A Randomized Clinical Trial.

Importance: Involvement of palliative care specialists in the care of medical oncology patients has been repeatedly observed to improve patient-reported outcomes, but there is no analogous research in surgical oncology populations. Objective: To determine whether surgeon-palliative care team comanagement, compared with surgeon team alone management, improves patient-reported perioperative outcomes among patients pursuing curative-intent surgery for high morbidity and mortality upper gastrointestinal (GI) cancers. Design, Setting, and Participants: From October 20, 2018, to March 31, 2022, a patient-randomized clinical trial was conducted with patients and clinicians nonblinded but the analysis team blinded to allocation. The trial was conducted in 5 geographically diverse academic medical centers in the US. Individuals pursuing curative-intent surgery for an upper GI cancer who had received no previous specialist palliative care were eligible. Surgeons were encouraged to offer participation to all eligible patients. Intervention: Surgeon-palliative care comanagement patients met with palliative care either in person or via telephone before surgery, 1 week after surgery, and 1, 2, and 3 months after surgery. For patients in the surgeon-alone group, surgeons were encouraged to follow National Comprehensive Cancer Network-recommended triggers for palliative care consultation. Main Outcomes and Measures: The primary outcome of the trial was patient-reported health-related quality of life at 3 months following the operation. Secondary outcomes were patient-reported mental and physical distress. Intention-to-treat analysis was performed. Results: In total, 359 patients (175 [48.7%] men; mean [SD] age, 64.6 [10.7] years) were randomized to surgeon-alone (n = 177) or surgeon-palliative care comanagement (n = 182), with most patients (206 [57.4%]) undergoing pancreatic cancer surgery. No adverse events were associated with the intervention, and 11% of patients in the surgeon-alone and 90% in the surgeon-palliative care comanagement groups received palliative care consultation. There was no significant difference between study arms in outcomes at 3 months following the operation in patient-reported health-related quality of life (mean [SD], 138.54 [28.28] vs 136.90 [28.96]; P = .62), mental health (mean [SD], -0.07 [0.87] vs -0.07 [0.84]; P = .98), or overall number of deaths (6 [3.7%] vs 7 [4.1%]; P > .99). Conclusions and Relevance: To date, this is the first multisite randomized clinical trial to evaluate perioperative palliative care and the earliest integration of palliative care into cancer care. Unlike in medical oncology practice, the data from this trial do not suggest palliative care-associated improvements in patient-reported outcomes among patients pursuing curative-intent surgeries for upper GI cancers. Trial Registration: ClinicalTrials.gov Identifier: NCT03611309.

Advance Care Planning in Cancer: Patient Preferences for Personnel and Timing.

PURPOSE: Opportunities for advance care planning (ACP) discussions continue to be missed despite the demonstrated benefit of such conversations. This is in part because of a poor understanding of patient preferences. We aimed to determine oncology patients' preferences surrounding ACP with a focus on the choice of which health care providers to have the conversation with and the timing of conversations. METHODS: A cross-sectional 19-question survey of surgical and medical oncology patients in a tertiary care hospital was conducted that assessed knowledge, experience, and preferences surrounding ACP. Quantitative variables were reported with descriptive statistics, and a coding structure was developed to analyze qualitative data. RESULTS: Two hundred patients were surveyed. Only 24% of patients reported previously having ACP discussions with their physicians despite 82.5% reporting a wish to do so. Patients felt that these discussions were a priority for them (to alleviate familial guilt, maintain control, and prevent others' values from guiding end-of-life care), but they reported that previous experiences with ACP had been neither comprehensive nor effective. Most patients (43.5%) preferred to have ACP discussions with their primary care providers (PCPs) compared with 7% preferring their surgeon and 5.5% preferring their oncologist. Trust and familiarity with PCPs arose as the dominant theme underlying this selection. Most patients (94%) preferred to have ACP discussions early, with 45% wishing such a discussion had been initiated before their cancer diagnosis. CONCLUSION: Patients with cancer prefer to have ACP discussions with their PCPs and prefer to do so early in their disease course.

A Multicenter, Randomized Controlled Trial of Perioperative Palliative Care Surrounding Cancer Surgery for Patients and Their Family Members (PERIOP-PC).

Background: Despite positive outcomes associated with specialist palliative care (PC) in diverse medical populations, little research has investigated specialist PC in surgical ones. Although cancer surgery is predominantly safe, operations can be extensive and unpredictable perioperative morbidity and mortality persist, particularly for patients with upper gastrointestinal (GI) cancers. Objectives and Hypotheses: Our objective is to complete a multicenter, randomized controlled trial comparing surgeon-PC co-management with surgeon-alone management among patients pursuing curative-intent surgery for upper GI cancers. We hypothesize that perioperative PC will improve patient postsurgical quality of life. This study and design are based on >8 years of engagement and research with patients, family members, and clinicians surrounding major cancer surgery and advance care planning/PC for surgical patients. Methods: Randomized controlled superiority trial with two study arms (surgeon-PC team co-management and surgeon-alone management) and five data collection points over six months. The principal investigator and analysts are blinded to randomization. Setting: Four, geographically diverse, academic tertiary care hospitals. Data collection began December 20, 2018 and continues to December 2020. Participants: Patients recruited from surgical oncology clinics who are undergoing curative-intent surgery for an upper GI cancer. Interventions: In the intervention arm, patients receive care from both their surgical team and a specialist PC team; the PC is provided before surgery, immediately after surgery, and at least monthly until three months postsurgery. Patients randomized to the usual care arm receive care from only the surgical team. Main Outcomes and Measures: Primary outcome: patient quality of life. Secondary outcomes: patient: symptom experience, spiritual distress, prognostic awareness, health care utilization, and mortality. Caregiver: quality of life, caregiver burden, spiritual distress, and prognostic awareness. Intent-to-treat analysis will be used. Ethics and Dissemination: This study has been approved by the institutional review boards of all study sites and is registered on clinicaltrials.gov (NCT03611309, First received: August 2, 2018).

Integrating Advance Care Planning Videos into Surgical Oncologic Care: A Randomized Clinical Trial.

Background: Preoperative advance care planning (ACP) may benefit patients undergoing major surgery. Objective: To evaluate feasibility, safety, and early effectiveness of video-based ACP in a surgical population. Design: Randomized controlled trial with two study arms. Setting: Single, academic, inner-city tertiary care hospital. Subjects: Patients undergoing major cancer surgery were recruited from nine surgical clinics. Of 106 consecutive potential participants, 103 were eligible and 92 enrolled. Interventions: In the intervention arm, patients viewed an ACP video developed by patients, surgeons, palliative care clinicians, and other stakeholders. In the control arm, patients viewed an informational video about the hospital's surgical program. Measurements: Primary Outcomes-ACP content and patient-centeredness in patient-surgeon preoperative conversation. Secondary outcomes-patient Hospital Anxiety and Depression Scale (HADS) score; patient goals of care; patient and surgeon satisfaction; video helpfulness; and medical decision maker designation. Results: Ninety-two patients (target enrollment: 90) were enrolled. The ACP video was successfully integrated with no harm noted. Patient-centeredness was unchanged (incidence rate ratio [IRR] = 1.06, confidence interval [0.87-1.3], p = 0.545), although there were more ACP discussions in the intervention arm (23% intervention vs. 10% control, p = 0.18). While slightly underpowered, study results did not signal that further enrollment would have yielded statistical significance. There were no differences in secondary outcomes other than the intervention video was more helpful (p = 0.007). Conclusions: The ACP video was successfully integrated into surgical care without harm and was thought to be helpful, although video content did not significantly change the ACP content or patient-surgeon communication. Future studies could increase the ACP dose through modifying video content and/or who presents ACP. Trial Registration: clinicaltrials.gov Identifier NCT02489799.

Trends in Outcomes After Cytoreductive Surgery With Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) have been shown to improve clinical outcomes among select patients presenting with peritoneal carcinomatosis. The aim of the present study was to describe temporal trends in clinical outcomes among patients undergoing CRS/HIPEC. MATERIALS AND METHODS: Patients who underwent CRS/HIPEC were identified using the American College of Surgeons National Surgical Quality Improvement Program databases from 2005 to 2013. A multivariable logistic regression analysis was performed to identify risk factors associated with postoperative morbidity and mortality. RESULTS: A total of 889 patients were identified who met the inclusion criteria. The most common primary tumor sites were the peritoneum (59.8%), followed by the appendix (13.7%) and colon (6.4%). The median operative time for all patients was 438 min (interquartile range: 328-550); postoperative morbidity was 41.3%, and 2.0% of patients died within 30 d of surgery. Over the time evaluated, a statistically significant decrease was observed in the median operative time (2005 versus 2013, 600 versus 403 min), postoperative morbidity (50.0% versus 36.1%), and length of stay (13.5 versus 8 d; all P < 0.05). On multivariable analysis, age > 65 y (odds ratio [OR] = 1.51; 95% confidence interval [CI]: 1.02-2.24; P = 0.037), a low preoperative hematocrit (OR = 1.66; 95% CI: 1.19-2.33; P = 0.003), and preoperative serum albumin < 3 g/dL (OR = 2.10; 95% CI: 1.13-3.90; P = 0.019) were independently associated with greater odds for developing a postoperative complication and/or postoperative death. CONCLUSIONS: Operative time, postoperative morbidity, and length of stay after CRS/HIPEC were observed to improve over the study period. Careful patient selection may result in favorable outcomes for select patients undergoing CRS/HIPEC.

Stakeholder Perspectives on the Use of Community Health Workers To Improve Palliative Care Use by African Americans with Cancer.

BACKGROUND: African Americans in the United States have worse end-of-life care and cancer outcomes than whites. Palliative care may improve this disparity. Community Health Workers may provide a means to improve palliative care disparities. METHODS: Semistructured in-depth interviews (five) and stakeholder focus groups (four) were conducted with cancer patients, caregivers, health care administrators, oncologists, and community health workers (CHWs). Patients were recruited through snowball sampling. Three raters coded interviews independently. Data were analyzed using interpretative phenomenological analysis. RESULTS: Seventy-one individuals were contacted to participate with 24 stakeholders (34%) participating in individual interviews or across 4 stakeholder engagements. Eleven constructs were identified and grouped in three broader themes: "hub of the wheel," understanding palliative care, and patient-provider relationships. Participants felt that the role of a CHW should be central, bridging patients with their providers, information, and resources, including psychosocial support and advance care planning documents. They also placed an emphasis on the background of CHWs, saying individuals selected should be familiar with the history, culture, and norms of the communities from which they operate. Stakeholders reported that a CHW could activate a patient to contact their primary care physician or oncologist who may refer to or provide palliative care. Stakeholders reported that given the barriers to palliative care, a CHW could contribute to patient-centered multidisciplinary care while addressing palliative care domains with patients and families in a culturally sensitive manner. CONCLUSION: Based on feedback from patients, caregivers, and providers, a culturally adapted CHW intervention may improve palliative care use for African American patients with advanced malignancies.

The importance of early life touch for psychosocial and moral development

One of the primary means of communicating with a baby is through touch. Nurturing physical touch promotes healthy physiological development in social mammals, including humans. Physiology influences wellbeing and psychosocial functioning. The purpose of this paper is to explore the connections among early life positive and negative touch and wellbeing and sociomoral development. In study 1, mothers of preschoolers (n = 156) reported their attitudes toward positive/negative touch and on their children's wellbeing and sociomoral outcomes, illustrating moderate to strong positive correlations between positive touch attitudes and children's sociomoral capacities and orientations and negative correlations with psychopathology. In study 2, we used an existing longitudinal dataset, with at-risk mothers (n = 682) and their children to test touch effects on moral capacities and social behaviors in early life. Results demonstrated moderate to strong relationships between positive/negative touch and concurrent child behavioral regulation and positive correlations between low corporal punishment and child sociomoral outcomes. In a third study with adults (n = 607), we found significant mediation processes connecting retrospective reports of childhood touch to adult moral orientation through attachment security, mental health, and moral capacities. In general across studies, more affectionate touch and less punishing touch were positively associated with wellbeing and development of moral capacities and engaged moral orientation. (AU)

An advance care plan decision support video before major surgery: a patient- and family-centred approach.

OBJECTIVE: Video-based advanc care planning (ACP) tools have been studied in varied medical contexts; however, none have been developed for patients undergoing major surgery. Using a patient- and family-centredness approach, our objective was to implement human-centred design (HCD) to develop an ACP decision support video for patients and their family members when preparing for major surgery. DESIGN AND METHODS: The study investigators partnered with surgical patients and their family members, surgeons and other health professionals to design an ACP decision support video using key HCD principles. Adapting Maguire's HCD stages from computer science to the surgical context, while also incorporating Elwyn et al's specifications for patient-oriented decision support tool development, we used a six-stage HCD process to develop the video: (1) plan HCD process; (2) specify where video will be used; (3) specify user and organisational requirements; (4) produce and test prototypes; (5) carry out user-based assessment; (6) field test with end users. RESULTS: Over 450 stakeholders were engaged in the development process contributing to setting objectives, applying for funding, providing feedback on the storyboard and iterations of the decision tool video. Throughout the HCD process, stakeholders' opinions were compiled and conflicting approaches negotiated resulting in a tool that addressed stakeholders' concerns. CONCLUSIONS: Our patient- and family-centred approach using HCD facilitated discussion and the ability to elicit and balance sometimes competing viewpoints. The early engagement of users and stakeholders throughout the development process may help to ensure tools address the stated needs of these individuals. TRIAL REGISTRATION NUMBER: NCT02489799.

Shared Decision-Making in Acute Surgical Illness: The Surgeon's Perspective.

BACKGROUND: Surgical patients increasingly have more comorbidities and are of an older age, complicating surgical decision-making in emergent situations. Little is known about surgeons' perceptions of shared decision-making in these settings. STUDY DESIGN: Twenty semi-structured interviews were conducted with practicing surgeons at 2 large academic medical centers. Thirteen questions and 2 case vignettes were used to assess perceptions of decision-making, considerations when deciding whether to offer to operate, and communication patterns with patients and families. RESULTS: Thematic analysis revealed 6 major themes: responsibility for the decision to operate, perceived futility, surgeon judgment, surgeon introspection, pressure to operate, and costs of the operation. Perceived futility was universally considered a contraindication to surgical intervention. However, the challenge of defining futility led participants to emphasize the importance of patients' self-determined risk-to-benefit analysis when considering surgical intervention. More experienced surgeons reported greater comfort with communicating to patients that a condition was not amenable to an operation and reserved the right to refuse to operate. CONCLUSIONS: Due to external pressures and uncertainty, some providers err on the side of operative intervention, despite suspected futility. Greater experience allows surgeons to withstand external pressures, be confident in their assessments of perceived futility, and guide patients and their families away from additional interventions.

Developing the Storyline for an Advance Care Planning Video for Surgery Patients: Patient-Centered Outcomes Research Engagement from Stakeholder Summit to State Fair.

BACKGROUND: Patient-centered outcomes research (PCOR) methods and social learning theory (SLT) require intensive interaction between researchers and stakeholders. Advance care planning (ACP) is valuable before major surgery, but a systematic review found no extant perioperative ACP tools. Consequently, PCOR methods and SLT can inform the development of an ACP educational video for patients and families preparing for major surgery. OBJECTIVE: The objective is to develop and test acceptability of an ACP video storyline. DESIGN: The design is a stakeholder-guided development of the ACP video storyline. Design-thinking methods explored and prioritized stakeholder perspectives. Patients and family members evaluated storyboards containing the proposed storyline. SETTING/SUBJECTS: The study was conducted at hospital outpatient surgical clinics, in-person stakeholder summit, and the 2014 Maryland State Fair. MEASUREMENTS: Measurements are done through stakeholder engagement and deidentified survey. RESULTS: Stakeholders evaluated and prioritized evidence from an environmental scan. A surgeon, family member, and palliative care physician team iteratively developed a script featuring 12 core themes and worked with a medical graphic designer to translate the script into storyboards. For 10 days, 359 attendees of the 2014 Maryland State Fair evaluated the storyboards and 87% noted that they would be "very comfortable" or "comfortable" seeing the storyboard before major surgery, 89% considered the storyboards "very helpful" or "helpful," and 89% would "definitely recommend" or "recommend" this story to others preparing for major surgery. CONCLUSIONS: Through an iterative process utilizing diverse PCOR engagement methods and informed by SLT, storyboards were developed for an ACP video. Field testing revealed the storyline to be highly meaningful for surgery patients and family members.

Palliative Care Utilization among Patients Admitted for Gastrointestinal and Thoracic Cancers.

BACKGROUND: Although a growing body of literature recommends the early initiation of palliative care (PC), the use of PC remains variable. OBJECTIVE: The current study sought to describe the use of PC and to identify factors associated with the use of inpatient PC. DESIGN: Retrospective, cross-sectional analysis of data from the National Inpatient Sample. SETTING AND SUBJECTS: Patients admitted with a primary diagnosis of gastrointestinal and/or thoracic cancer from 2012 to 2013. MEASUREMENTS: In-hospital length of stay (LOS), morbidity, mortality, and total charges. RESULTS: A total of 282,899 patients were identified who met inclusion criteria of whom, 24,100 (8.5%) patients received a PC consultation during their inpatient admission. Patients who received PC were more likely to have a longer LOS (LOS >14 days: 5.4% vs. 9.4%) and were more likely to develop a postoperative complication (28.3% vs. 45.9%, both p < 0.001). Inpatient mortality was significantly higher among patients who had received PC than those who did not (5.4% vs. 44.1%, p < 0.001). On multivariable analysis, patient age (age ≥75 years: Odds Ratio [OR] = 2.54, 95% CI: 2.33-2.78), comorbidity (CCI >6: OR = 2.60, 95% CI: 2.48-2.74), and admission to larger hospitals (reference small: OR = 1.20, 95% CI: 1.14-1.25) were associated with greater odds of receiving PC (all p < 0.05). Patients who underwent a major operation during their inpatient admission demonstrated 79% lower odds of receiving PC (OR = 0.21, 95% CI: 0.20-0.22, p < 0.001). CONCLUSIONS: Among patients admitted for cancer, PC services were used in 8.5% of patients during their inpatient admission with surgical patients being 79% less likely to receive a PC consultation. Further research is required to delineate the barriers to the use of PC so as to promote the use of PC among high-risk patients.

Defining payments associated with the treatment of colorectal cancer.

BACKGROUND: While bundled payments aim to reduce variations in health care spending across the continuum of care, data reporting on variations in payments for privately insured patients undergoing treatment for colon cancer (CC) are lacking. The current study sought to characterize variations in payments received for the treatment of CC using a cohort of commercially insured patients. METHODS: Patients who underwent a colectomy for CC were identified using the MarketScan Database for 2010-2014. Multivariable regression analysis was used to calculate and compare risk-adjusted payments between patients. RESULTS: A total of 18,337 patients were identified who met inclusion criteria. The median risk-adjusted payment for surgery was $26,408 (IQR: $19,193-$38,037) ranging from $19,762 (IQR: $15,595-$25,636) among patients in the lowest quartile of payments to $33,809 (IQR: $24,783-$48,254) for patients in the highest (+△71.1%). The median risk-adjusted payment for chemotherapy was $70,090 (IQR: $57,813-$83,216); compared with patients in the lowest quartile of payments, payments associated with chemotherapy were 40.4% higher among patients in the highest quartile of payments (Q1 versus Q4: $56,827 [IQR: 49,173-65,353] versus $79,801 [IQR: 67,270-90,999]). When stratified by treatment type, patients in the highest two quartiles of risk-adjusted payments accounted for a total of 58.5% of all payments, whereas patients in the lower two quartiles of risk-adjusted payments accounted for only 41.5% of all payments. A younger patient age, increasing patient comorbidity and undergoing an open operation were associated with higher overall payments. CONCLUSIONS: Wide variations in payments exist for the treatment for colon cancer. Episode-based bundle payments for surgery and chemotherapy may differentially impact reimbursement for CC.

Effect of surgeon "experience" with laparoscopy on postoperative outcomes after colorectal surgery.

BACKGROUND: Although the relationship between laparoscopic surgery and improved clinical outcomes has been well established across a variety of procedures, the effect of operative experience with laparoscopic surgery remains less defined. The present study sought to assess the comparative benefit of laparoscopic colorectal surgery relative to surgeon volume. METHODS: Commercially insured patients aged 18 to 64 years undergoing a colorectal resection were identified using the MarketScan Database from 2010-2014. Multivariable logistic regression analysis was used to calculate and compare postoperative mortality/morbidity by operative approach relative to surgeon volume. RESULTS: A total of 21,827 patients were identified who met inclusion criteria. The median age among patients was 53 years (interquartile range: 46-59) with a slight majority of patients being female (n = 11,248, 51.5%). Laparoscopic operations were performed in 49.2% of patients (n = 10,756), whereas 50.7% (n = 11,071) underwent an open colorectal resection. On multivariable analysis, laparoscopic surgery was associated with 64% decreased odds of developing a postoperative complication or mortality (odds ratio = 0.36, 95% confidence interval, 0.32-0.41, P < .001). Patients who underwent colectomy performed by a higher operative volume surgeon (high versus low: odds ratio = 0.68, 95% confidence interval, 0.61-0.77, P < .001) demonstrated decreased odds of developing a postoperative complication/mortality. Interestingly the potential decrease in risk-adjusted morbidity/mortality between laparoscopic and open surgery was somewhat greater among high-operative-volume surgeons (odds ratio = 0.29, 95% confidence interval, 0.25-0.34, P < .001) and intermediate-operative-volume surgeons (odds ratio = 0.30, 95% confidence interval, 0.25-0.36, P < .001) compared with low-operative-volume surgeons (odds ratio = 0.36, 95% confidence interval, 0.32-0.41, P < .001). CONCLUSION: Although laparoscopic surgery was associated with improved postoperative clinical outcomes, the effect of laparoscopic surgery varied somewhat according to surgeon volume.

Utilising advance care planning videos to empower perioperative cancer patients and families: a study protocol of a randomised controlled trial.

INTRODUCTION: Despite positive health outcomes associated with advance care planning (ACP), little research has investigated the impact of ACP in surgical populations. Our goal is to evaluate how an ACP intervention video impacts the patient centredness and ACP of the patient-surgeon conversation during the presurgical consent visit. We hypothesise that patients who view the intervention will engage in a more patient-centred communication with their surgeons compared with patients who view a control video. METHODS AND ANALYSIS: Randomised controlled superiority trial of an ACP video with two study arms (intervention ACP video and control video) and four visits (baseline, presurgical consent, postoperative 1 week and postoperative 1 month). Surgeons, patients, principal investigator and analysts are blinded to the randomisation assignment. SETTING: Single, academic, inner city and tertiary care hospital. Data collection began July 16, 2015 and continues to March 2017. PARTICIPANTS: Patients recruited from nine surgical oncology clinics who are undergoing major cancer surgery. INTERVENTIONS: In the intervention arm, patients view a patient preparedness video developed through extensive engagement with patients, surgeons and other stakeholders. Patients randomised to the control arm viewed an informational video about the hospital surgical programme. MAIN OUTCOMES AND MEASURES: Primary Outcome: Patient centredness and ACP of patient-surgeon conversations during the presurgical consent visit as measured through the Roter Interaction Analysis System. SECONDARY OUTCOMES: patient Hospital Anxiety and Depression Scale score; patient goals of care; patient, companion and surgeon satisfaction; video helpfulness; medical decision maker designation; and the frequency patients watch the video. Intent-to-treat analysis will be used to assess the impact of video assignment on outcomes. Sensitivity analyses will assess whether there are differential effects contingent on patient or surgeon characteristics. ETHICS AND DISSEMINATION: This study has been approved by the Johns Hopkins School of Medicine institutional review board and is registered on clinicaltrials.gov (NCT02489799, First received: July 1, 2015). TRIAL REGISTRATION NUMBER: clinicaltrials.gov, NCT02489799.

"What took you so long?" The impact of PEPFAR on the expansion of HIV testing and counseling services in Africa.

HIV testing and counseling services in Africa began in the early 1990s, with limited availability and coverage. Fears of stigma and discrimination, complex laboratory systems, and lack of available care and treatment services hampered expansion. Use of rapid point-of-care tests, introduction of services to prevent mother-to-child transmission, and increasing provision of antiretroviral drugs were key events in the late 1990s and early 2000s that facilitated the expansion of HIV testing and counseling services. Innovations in service delivery included providing HIV testing in both clinical and community sites, including mobile and home testing. Promotional campaigns were conducted in many countries, and evolutions in policies and guidance facilitated expansion and uptake. Support from President's Emergency Plan for AIDS Relief and national governments, other donors, and the Global Fund for AIDS, Tuberculosis, and Malaria contributed to significant increases in the numbers of persons tested in many countries. Quality of both testing and counseling, limited number of health care workers, uptake by couples, and effectiveness of linkages and referral systems remain challenges. Expansion of antiretroviral treatment, especially in light of the evidence that treatment contributes to prevention of transmission, will require greater yet strategic coverage of testing services, especially in clinical settings and in combination with other high-impact HIV prevention strategies. Continued support from President's Emergency Plan for AIDS Relief, governments, and other donors is required for the expansion of testing needed to achieve international targets for the scale-up of treatment and universal access to knowledge of HIV status.

DNA replication checkpoint prevents precocious chromosome segregation by regulating spindle behavior.

The DNA replication checkpoint maintains replication fork integrity and prevents chromosome segregation during replication stresses. Mec1 and Rad53 (human ATM/ATR- and Chk2-like kinases, respectively) are critical effectors of this pathway in yeast. When treated with replication inhibitors, checkpoint-deficient mec1 or rad53 mutant fails to maintain replication fork integrity and proceeds to partition unreplicated chromosomes. We show that this unnatural chromosome segregation requires neither the onset of mitosis nor APC activation, cohesin cleavage, or biorientation of kinetochores. Instead, the checkpoint deficiency leads to deregulation of microtubule-associated proteins Cin8 and Stu2, which, in the absence of both chromosome cohesion and bipolar attachment of kinetochores to microtubules, induce untimely spindle elongation, causing premature chromosome separation. The checkpoint's ability to prevent nuclear division is abolished by combined deficiency of microtubule-destabilizing motor Kip3 and Mad2 functions. Thus, the DNA replication checkpoint prevents precocious chromosome segregation, not by inhibiting entry into mitosis as widely believed, but by directly regulating spindle dynamics.