Intra- and interpersonal effects of coping style and self-efficacy on anxiety, depression and life satisfaction in patient-partner couples after stroke.

Many stroke patients and partners suffer from anxiety, depression, and low life satisfaction. Psychological factors such as coping style and self-efficacy can be protective factors within individuals. The close relationship between stroke patients and partners suggests that there may be interdependence in psychological functioning. The aim of this study was to examine intra- and interpersonal effects of coping style and self-efficacy on anxiety, depression, and life satisfaction in patient-partners couples. In this prospective cohort study, pro-active coping (UPCC), general self-efficacy (GSES), anxiety (HADS-A), depression (HADS-D), and life satisfaction (1-6 scale) were assessed in 215 couples at 2 and 12 months post-stroke. Effects within couples were assessed using structural equation modelling. Several intra- and interpersonal effects of coping style and self-efficacy at 2 months post-stroke were related to emotional health at 12 months post-stroke. Most effects were intrapersonal effects. The interpersonal effects were small but showed that pro-active coping by the patient was associated with lower anxiety of the partner. Higher self-efficacy of the partner was associated with lower depression scores and higher life satisfaction of the patient. This study underscores the importance of a dyadic approach to post-stroke functioning. It supports a family-based approach for treating post-stroke emotional problems.

Estimating the global burden of scabies: what else do we need?

Scabies is one of the most common disorders identified in any estimate of global skin disease prevalence. Furthermore, quantifying its impact on individuals and societies has been problematic. There has been a lack of clear case definitions and laboratory tests. There have been few epidemiological studies, particularly those focusing on low-income countries, variation in prevalence within high-income countries, or estimates of the effect of scabies on health beyond the skin, such as renal disease or mental wellbeing. Economic studies are also lacking. However, the new strategy of integrating surveillance for skin Neglected Tropical Diseases may well produce advancements on these issues, in addition to providing an overarching structure for health improvement and disease control.

Evaluation of a case management service to reduce sickness absence.

BACKGROUND: It is unclear whether and to what extent intensive case management is more effective than standard occupational health services in reducing sickness absence in the health care sector. AIMS: To evaluate a new return to work service at an English hospital trust. METHODS: The new service entailed intensive case management for staff who had been absent sick for longer than 4 weeks, aiming to restore function through a goal-directed and enabling approach based on a bio-psycho-social model. Assessment of the intervention was by controlled before and after comparison with a neighbouring hospital trust at which there were no major changes in the management of sickness absence. Data on outcome measures were abstracted from electronic databases held by the two trusts. RESULTS: At the intervention trust, the proportion of 4-week absences that continued beyond 8 weeks fell from 51.7% in 2008 to 49.1% in 2009 and 45.9% in 2010. The reduction from 2008 to 2010 contrasted with an increase at the control trust from 51.2% to 56.1%-a difference in change of 10.7% (95% CI 1.5-20.0%). There was also a differential improvement in mean days of absence beyond 4 weeks, but this was not statistically significant (1.6 days per absence; 95% CI -7.2 to 10.3 days). CONCLUSIONS: Our findings suggest that the intervention was effective, and calculations based on an annual running cost of £57 000 suggest that it was also cost-effective. A similar intervention should now be evaluated at a larger number of hospital trusts.

Standards for clinical trials for treating TB.

BACKGROUND: The value, speed of completion and robustness of the evidence generated by TB treatment trials could be improved by implementing standards for best practice.METHODS: A global panel of experts participated in a Delphi process, using a 7-point Likert scale to score and revise draft standards until consensus was reached.RESULTS: Eleven standards were defined: Standard 1, high quality data on TB regimens are essential to inform clinical and programmatic management; Standard 2, the research questions addressed by TB trials should be relevant to affected communities, who should be included in all trial stages; Standard 3, trials should make every effort to be as inclusive as possible; Standard 4, the most efficient trial designs should be considered to improve the evidence base as quickly and cost effectively as possible, without compromising quality; Standard 5, trial governance should be in line with accepted good clinical practice; Standard 6, trials should investigate and report strategies that promote optimal engagement in care; Standard 7, where possible, TB trials should include pharmacokinetic and pharmacodynamic components; Standard 8, outcomes should include frequency of disease recurrence and post-treatment sequelae; Standard 9, TB trials should aim to harmonise key outcomes and data structures across studies; Standard 10, TB trials should include biobanking; Standard 11, treatment trials should invest in capacity strengthening of local trial and TB programme staff.CONCLUSION: These standards should improve the efficiency and effectiveness of evidence generation, as well as the translation of research into policy and practice.

Delineating the impact of obesity and its relationship on recovery after total joint arthroplasties.

OBJECTIVE: The primary aim of this study was to determine the impact of obesity in predicting short and long-term pain relief and functional recovery in total joint arthroplasty (TJA) either as an independent risk factor or a factor mediated by two chronic conditions associated with obesity-cardiac disease and diabetes mellitus. METHOD: A prospective observational study of 520 patients with primary joint arthroplasties. Pain and functional outcomes were evaluated with the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index within a month of surgery and then 6 months and 3 years post-operatively. Obesity, cardiac disease and diabetes mellitus were examined as potential risk factors for poor recovery. Patients were classified into four groups based on body mass index (BMI): (normal<25.0 kg/m(2); overweight 25.0-29.9 kg/m(2); obese Class 1 30.0-34.9 kg/m(2); severe obese Class 2&3 35.0 ≥ kg/m(2)). Linear mixed models for each joint type (hip and knee arthroplasty) were developed to examine the pattern of recovery and the effect of obesity. RESULTS: Ninety-nine (19%) patients were severely obese, 127 (24%) had cardiac disease and 58 (11%) had diabetes mellitus. Baseline pain and functional scores were similar regardless of BMI classification. Severe obesity was a significant risk factor for worse pain and functional recovery at 6 months but no longer at 3 years following total hip and knee arthroplasty. Cardiac disease predicted a slower recovery after hip arthroplasty. No significant interactions existed between obesity and cardiac disease or diabetes mellitus. DISCUSSION: Severe obesity is an independent risk factor for slow recovery over 3 years for both hip and knee arthroplasties.

Early mortality during rifampicin-resistant TB treatment.

BACKGROUND: Data suggest that treatment with newer TB drugs (linezolid [LZD], bedaquiline [BDQ] and delamanid [DLM]), used in Khayelitsha, South Africa, since 2012, reduces mortality due to rifampicin-resistant TB (RR-TB).METHODS: This was a retrospective cohort study to assess 6-month mortality among RR-TB patients diagnosed between 2008 and 2019.RESULTS: By 6 months, 236/2,008 (12%) patients died; 12% (78/651) among those diagnosed in 2008-2011, and respectively 8% (49/619) and 15% (109/738) with and without LZD/BDQ/DLM in 2012-2019. Multivariable analysis showed a small, non-significant mortality reduction with LZD/BDQ/DLM use compared to the 2008-2011 period (aOR 0.79, 95% CI 0.5-1.2). Inpatient treatment initiation (aOR 3.2, 95% CI 2.4-4.4), fluoroquinolone (FQ) resistance (aOR 2.7, 95% CI 1.8-4.2) and female sex (aOR 1.5, 95% CI 1.1-2.0) were also associated with mortality. When restricted to 2012-2019, use of LZD/BDQ/DLM was associated with lower mortality (aOR 0.58, 95% CI 0.39-0.87).CONCLUSIONS: While LZD/BDQ/DLM reduced 6-month mortality between 2012 and 2019, there was no significant effect overall. These findings may be due to initially restricted LZD/BDQ/DLM use for those with high-level resistance or treatment failure. Additional contributors include increased treatment initiation among individuals who would have otherwise died before treatment due to universal drug susceptibility testing from 2012, an effect that also likely contributed to higher mortality among females (survival through to care-seeking).

Development and operation of the defence COVID-19 lab as a SARS-CoV-2 diagnostic screening capability for UK military personnel.

BACKGROUND: In the face of the COVID-19 pandemic, the Defence Science and Technology Laboratory (Dstl) and Defence Pathology combined to form the Defence Clinical Lab (DCL), an accredited (ISO/IEC 17025:2017) high-throughput SARS-CoV-2 PCR screening capability for military personnel. LABORATORY STRUCTURE AND RESOURCE: The DCL was modular in organisation, with laboratory modules and supporting functions combining to provide the accredited SARS-CoV-2 (envelope (E)-gene) PCR assay. The DCL was resourced by Dstl scientists and military clinicians and biomedical scientists. LABORATORY RESULTS: Over 12 months of operation, the DCL was open on 289 days and tested over 72 000 samples. Six hundred military SARS-CoV-2-positive results were reported with a median E-gene quantitation cycle (Cq) value of 30.44. The lowest Cq value for a positive result observed was 11.20. Only 64 samples (0.09%) were voided due to assay inhibition after processing started. CONCLUSIONS: Through a sustained effort and despite various operational issues, the collaboration between Dstl scientific expertise and Defence Pathology clinical expertise provided the UK military with an accredited high-throughput SARS-CoV-2 PCR test capability at the height of the COVID-19 pandemic. The DCL helped facilitate military training and operational deployments contributing to the maintenance of UK military capability. In offering a bespoke capability, including features such as testing samples in unit batches and oversight by military consultant microbiologists, the DCL provided additional benefits to the UK Ministry of Defence that were potentially not available from other SARS-CoV-2 PCR laboratories. The links between Dstl and Defence Pathology have also been strengthened, benefitting future research activities and operational responses.

Evaluating newly approved drugs for multidrug-resistant tuberculosis (endTB): study protocol for an adaptive, multi-country randomized controlled trial.

BACKGROUND: Treatment of multidrug- and rifampin-resistant tuberculosis (MDR/RR-TB) is expensive, labour-intensive, and associated with substantial adverse events and poor outcomes. While most MDR/RR-TB patients do not receive treatment, many who do are treated for 18 months or more. A shorter all-oral regimen is currently recommended for only a sub-set of MDR/RR-TB. Its use is only conditionally recommended because of very low-quality evidence underpinning the recommendation. Novel combinations of newer and repurposed drugs bring hope in the fight against MDR/RR-TB, but their use has not been optimized in all-oral, shorter regimens. This has greatly limited their impact on the burden of disease. There is, therefore, dire need for high-quality evidence on the performance of new, shortened, injectable-sparing regimens for MDR-TB which can be adapted to individual patients and different settings. METHODS: endTB is a phase III, pragmatic, multi-country, adaptive, randomized, controlled, parallel, open-label clinical trial evaluating the efficacy and safety of shorter treatment regimens containing new drugs for patients with fluoroquinolone-susceptible, rifampin-resistant tuberculosis. Study participants are randomized to either the control arm, based on the current standard of care for MDR/RR-TB, or to one of five 39-week multi-drug regimens containing newly approved and repurposed drugs. Study participation in all arms lasts at least 73 and up to 104 weeks post-randomization. Randomization is response-adapted using interim Bayesian analysis of efficacy endpoints. The primary objective is to assess whether the efficacy of experimental regimens at 73 weeks is non-inferior to that of the control. A sample size of 750 patients across 6 arms affords at least 80% power to detect the non-inferiority of at least 1 (and up to 3) experimental regimens, with a one-sided alpha of 0.025 and a non-inferiority margin of 12%, against the control in both modified intention-to-treat and per protocol populations. DISCUSSION: The lack of a safe and effective regimen that can be used in all patients is a major obstacle to delivering appropriate treatment to all patients with active MDR/RR-TB. Identifying multiple shorter, safe, and effective regimens has the potential to greatly reduce the burden of this deadly disease worldwide. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02754765. Registered on 28 April 2016; the record was last updated for study protocol version 3.3, on 27 August 2019.

Overcoming barriers to the access and uptake of newer drugs for multidrug-resistant TB.

To improve the unsatisfactory treatment outcomes of multidrug-resistant TB (MDR-TB), it is essential we use new regimens based on newer drugs. To address challenges in the introduction of BDQ and the shorter treatment regimen (STR), the USAID has committed to support countries receiving BDQ (through the USAID/Janssen Bedaquiline Donation Program), with targeted short-term technical assistance (TA). Six MDR-TB clinical consultants were recruited and provided TA to 17 countries between 2017 and 2019. Building on other in-country support, this short-term TA proved instrumental in overcoming barriers, such as misconceptions about BDQ safety, inadequate clinical skills to manage patients and limited expansion plans to increase access to BDQ and the STR.

Clinical perspectives on treatment of rifampicin-resistant/multidrug-resistant TB.

Rapid diagnostics, newer drugs, repurposed medications, and shorter regimens have radically altered the landscape for treating rifampicin-resistant TB (RR-TB) and multidrug-resistant TB (MDR-TB). There are multiple ongoing clinical trials aiming to build a robust evidence base to guide RR/MDR-TB treatment, and both observational studies and programmatic data have contributed to advancing the treatment field. In December 2019, the WHO issued their second 'Rapid Communication´ related to RR-TB management. This reiterated their prior recommendation that a majority of people with RR/MDR-TB receive all-oral treatment regimens, and now allow for specific shorter duration regimens to be used programmatically as well. Many TB programs need clinical advice as they seek to roll out such regimens in their specific setting. In this Perspective, we highlight our early experiences and lessons learned from working with National TB Programs, adult and pediatric clinicians and civil society, in optimizing treatment of RR/MDR-TB, using shorter, highly-effective, oral regimens for the majority of people with RR/MDR-TB.

Sex differences in taste preference for glucose and saccharin solutions.

Taste preferences of mature male and female rats for caloric and noncaloric sweet solutions have been found to differ. Although females do not drink more water than males, they consume significantly greater quantities of a slightly sweet 3 percent glucose and a very sweet 0.25 percent saccharin solution. When given a choice, males switch their initial preference for a saccharin solution to a preference for a glucose solution after several days, while females maintain a preference for the saccharin solution. Females also prefer significantly higher concentrations of saccharin than males do.

Modification of motivated behavior elicited by electrical stimulation of the hypothalamus.

Previous reports demonstrated that hypothalamic stimulation may elicit either eating, drinking, or gnawing and emphasized both the specificity of the neural circuits mediating these behaviors and the similarity to behavior during natural-drive states such as hunger and thirst. We find that, after a period of very consistent elicitation of one of these behaviors, the animal may exhibit an equally consistent alternate behavior. A learning component is implicated in the association of hypothalamic stimulation with a particular behavior pattern.

Polydipsia elicited by the synergistic action of a saccharin and glucose solution.

Rats consume significantly more of a solution combining saccharin and glucose than equivalent solutions of these substances presented in separate bottles. Fluid consumption may exceed body weight. Experiments helping to delineate the basis of this synergistic action are presented.

Short-latency antidiuresis following the initation of food ingestion.

A factor associated with the ingestion of food is shown to produce a short-latency antidiuresis. Animals consuming large quantities of a highly palatable solution during a period of food deprivation exhibit an antidiuresis immediately following the initiation of eating. The rapidity of the response raises the possibility of a signaling factor separate from postingestional influences.

Object-carrying by rats: an approach to the behavior produced by brain stimulation.

Rats were provided with opportunity to turn reinforcing hypothalamic stimulation on and off by traversing back and forth across a chamber. When provided with edible and inedible objects, all animals that self-stimulated carried them from the stimulation to the nonstimulation side. Neither food deprivation nor a history of stimulus-bound eating produced a preference for the edible objects. Equivalent stimulation provided without regard to the animals' location in the chamber did not elicit object-carrying. Results are interpreted in terms of the natural conditions which normally elicit this species-specific unit of behavior. Implications for understanding other behavior patterns elicited by hypothalamic stimulation are suggested.

Health care gaps in the global burden of drug-resistant tuberculosis.

The drug-resistant tuberculosis (DR-TB) cascade-from estimated or incident cases to numbers successfully treated or disease-free survival-has long been characterised by sharp declines at each step in the cascade. The losses along the cascade vary across different settings, and the reasons why some countries have a higher burden of DR-TB are complex and multifactorial; broadly, weak health systems, inadequate financing and poverty all impact differential access to DR-TB care. Within a human rights framework that mandates the right to health and the right to benefit from scientific progress, the aim of this review is to focus on describing inequities in access to DR-TB care at critical points in the cascade.

Ischiorectal fossa: benign and malignant neoplasms of this "ignored" radiological anatomical space.

PURPOSE: To review the pertinent anatomy and the imaging features of common and uncommon benign and malignant neoplasms and masses of the ischiorectal fossa. RESULTS: The ischiorectal or ischioanal fossa is the largest space in the anorectal region. The benign neoplasms that develop in the ischiorectal originate from the different components that forms the fossa including vascular tumors such as aggressive angiomyxoma or hemangioma; neural tumors as plexiform neurofibroma or schwannoma; fat tumors as lipoma; skin/skin appendages tumors as hidradenoma papilliferum; smooth or skeletal muscle tumors as solitary fibrous tumor. The malignant neoplasms that develop in the ischiorectal fossa also originate from different components that forms the fossa including vascular tumors such as angiosarcoma, neural tumors as malignant granular cell tumor and malignant peripheral nerve sheath tumor; fat tumors as liposarcoma; smooth or skeletal muscle tumors as leiomyosarcoma, rhabdomyosarcoma, malignant PEComa, or undifferentiated pleomorphic sarcoma. Additionally, the ischiorectal fossa can also harbor secondary hematogenous metastases and be affected by direct invasion from neoplasms of adjacent pelvic organs and structures. Furthermore, other miscellaneous masses can occur in the ischiorectal fossa including congenital and developmental lesions, and inflammatory and infectious processes. CONCLUSION: Knowledge of the anatomy, and the spectrum of imaging findings of common and uncommon benign and malignant neoplasms of the ischiorectal fossa is crucial for the radiologists during interpretation of images allowing them to make contributions to the diagnosis and better patient management.

Tumor markers: myths and facts unfolded.

OBJECTIVE: The purpose of this article is to review the most commonly used tumor markers in abdominal and pelvic tumors, describe their limitations and explain how to use them in the context of known cancer in order to optimize multidisciplinary care of oncologic patients. CONCLUSION: Tumor markers are important for the diagnosis, staging, monitoring of treatment and detection of recurrence in many cancers. This knowledge is crucial in the daily interpretation of images of oncologic and non-oncologic patients. However, radiologists should also be aware of the limitations of the most commonly used tumor markers and they should not be used solely, but interpreted in conjunction with diagnostic imaging, clinical history and physical examination that will help optimize the multidisciplinary care and management of oncologic patients.

Global programmatic use of bedaquiline and delamanid for the treatment of multidrug-resistant tuberculosis.

SETTING: The World Health Organization recommended two new drugs, bedaquiline (BDQ) and delamanid (DLM), for the treatment of multidrug-resistant tuberculosis (MDR-TB) in 2013 and 2014, respectively. An estimated one third of patients with MDR-TB would benefit from the inclusion of these drugs in their treatment regimens. DESIGN: A convenience sample of 36 countries voluntarily reported monthly data on cumulative programmatic use of new drugs to the Drug-Resistant TB Scale-Up Treatment Action Team between 1 July 2015 and 31 June 2017. Programmatic use was defined as treatment for MDR-TB with newer drugs outside of clinical trials or compassionate use. RESULTS: A total of 10 164 persons were started on BDQ and 688 started on DLM during the reporting period. Only 15.7% of the 69 213 persons estimated to need newer drugs over the study period were reported to have received them. CONCLUSION: While there has been significant progress in some countries, uptake of the newer drugs has not kept pace with a conservative estimate of need; fewer than 20% of persons likely to benefit from either BDQ or DLM have received them. Concerted efforts are needed to ensure that the newer drugs are made available more widely for persons with MDR-TB in need of these therapeutic options.