Search

Aim: To systematically review the literature on the efficacy and harm of prostaglandin analogues (PGAs) compared to brimonidine and dorzolamide in treating elevated intraocular pressure (lOP). Methods: Keywords were searched in major literature databases to identify relevant randomised clinical trials (ACTs) of PGAs for ophthalmic use. The study quality of ACTs was assessed using the Jadad scale. Outcomes assessed included reduction in lOP in individual patients, adverse events (AEs) and withdrawals due to AEs. Results: Eight unique ACTs evaluating a total of 1,722 individuals were included in this systematic review. Analysis did not show a significant reduction in the mean lOP from patients receiving latanoprost compared with those receiving brimonidine (WMD = -1.04; p = 0.30). On the other hand, the latanoprost group showed a significant reduction in mean lOP compared to the dorzolamide group (WMD = -2.64; p<0.00001). The number of ocular AEs (excluding hyperaemia) was significantly higher in the brimonidine group compared with the latanoprost group (AR = 0.66; p = 0.0005). Conclusion: Latanoprost was found to be significantly superior to dorzolamide but not brimonidine. However, ocular adverse events were significantly fewer in latanoprost users than in brimonide users. Neither travoprost nor bimatoprost was compared to dorzolamide or brimonidine in the present literature. [ABSTRACT FROM AUTHOR]

The transition from a humid green Sahara to today's hyperarid conditions in northern Africa ~5.5 thousand years ago shows the dramatic environmental change to which human societies were exposed and had to adapt to. In this work, we show that in the 620,000-year environmental record from the Chew Bahir basin in the southern Ethiopian Rift, with its decadal resolution, this one thousand year long transition is particularly well documented, along with 20-80 year long droughts, recurring every ~160 years, as possible early warnings. Together with events of extreme wetness at the end of the transition, these droughts form a pronounced climate "flickering", which can be simulated in climate models and is also present in earlier climate transitions in the Chew Bahir environmental record, indicating that transitions with flickering are characteristic of this region., (© 2024. The Author(s).)

Understanding eastern African paleoclimate is critical for contextualizing early human evolution, adaptation, and dispersal, yet Pleistocene climate of this region and its governing mechanisms remain poorly understood due to the lack of long, orbitally-resolved, terrestrial paleoclimate records. Here we present leaf wax hydrogen isotope records of rainfall from paleolake sediment cores from key time windows that resolve long-term trends, variations, and high-latitude effects on tropical African precipitation. Eastern African rainfall was dominantly controlled by variations in low-latitude summer insolation during most of the early and middle Pleistocene, with little evidence that glacial-interglacial cycles impacted rainfall until the late Pleistocene. We observe the influence of high-latitude-driven climate processes emerging from the last interglacial (Marine Isotope Stage 5) to the present, an interval when glacial-interglacial cycles were strong and insolation forcing was weak. Our results demonstrate a variable response of eastern African rainfall to low-latitude insolation forcing and high-latitude-driven climate change, likely related to the relative strengths of these forcings through time and a threshold in monsoon sensitivity. We observe little difference in mean rainfall between the early, middle, and late Pleistocene, which suggests that orbitally-driven climate variations likely played a more significant role than gradual change in the relationship between early humans and their environment., (© 2022. The Author(s).)

Despite more than half a century of hominin fossil discoveries in eastern Africa, the regional environmental context of hominin evolution and dispersal is not well established due to the lack of continuous palaeoenvironmental records from one of the proven habitats of early human populations, particularly for the Pleistocene epoch. Here we present a 620,000-year environmental record from Chew Bahir, southern Ethiopia, which is proximal to key fossil sites. Our record documents the potential influence of different episodes of climatic variability on hominin biological and cultural transformation. The appearance of high anatomical diversity in hominin groups coincides with long-lasting and relatively stable humid conditions from ~620,000 to 275,000 years bp (episodes 1-6), interrupted by several abrupt and extreme hydroclimate perturbations. A pattern of pronounced climatic cyclicity transformed habitats during episodes 7-9 (~275,000-60,000 years bp), a crucial phase encompassing the gradual transition from Acheulean to Middle Stone Age technologies, the emergence of Homo sapiens in eastern Africa and key human social and cultural innovations. Those accumulative innovations plus the alignment of humid pulses between northeastern Africa and the eastern Mediterranean during high-frequency climate oscillations of episodes 10-12 (~60,000-10,000 years bp) could have facilitated the global dispersal of H. sapiens ., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2022.)

In this study, we synthesize terrestrial and marine proxy records, spanning the past 620 ky, to decipher pan-African climate variability and its drivers and potential linkages to hominin evolution. We find a tight correlation between moisture availability across Africa to El Niño Southern Ocean oscillation (ENSO) variability, a manifestation of the Walker Circulation, that was most likely driven by changes in Earth's eccentricity. Our results demonstrate that low-latitude insolation was a prominent driver of pan-African climate change during the Middle to Late Pleistocene. We argue that these low-latitude climate processes governed the dispersion and evolution of vegetation as well as mammals in eastern and western Africa by increasing resource-rich and stable ecotonal settings thought to have been important to early modern humans., Competing Interests: The authors declare no competing interest.

Objective: To develop an evidence-based guideline for Peer Review of Electronic Search Strategies (PRESS) for systematic reviews (SRs), health technology assessments, and other evidence syntheses., Study Design and Setting: An SR, Web-based survey of experts, and consensus development forum were undertaken to identify checklists that evaluated or validated electronic literature search strategies and to determine which of their elements related to search quality or errors., Results: Systematic review: No new search elements were identified for addition to the existing (2008-2010) PRESS 2015 Evidence-Based Checklist, and there was no evidence refuting any of its elements. Results suggested that structured PRESS could identify search errors and improve the selection of search terms. Web-based survey of experts: Most respondents felt that peer review should be undertaken after the MEDLINE search had been prepared but before it had been translated to other databases. Consensus development forum: Of the seven original PRESS elements, six were retained: translation of the research question; Boolean and proximity operators; subject headings; text word search; spelling, syntax and line numbers; and limits and filters. The seventh (skilled translation of the search strategy to additional databases) was removed, as there was consensus that this should be left to the discretion of searchers. An updated PRESS 2015 Guideline Statement was developed, which includes the following four documents: PRESS 2015 Evidence-Based Checklist, PRESS 2015 Recommendations for Librarian Practice, PRESS 2015 Implementation Strategies, and PRESS 2015 Guideline Assessment Form., Conclusion: The PRESS 2015 Guideline Statement should help to guide and improve the peer review of electronic literature search strategies., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Episodes of environmental stability and instability may be equally important for African hominin speciation, dispersal, and cultural innovation. Three examples of a change from stable to unstable environmental conditions are presented on three different time scales: (1) the Mid Holocene (MH) wet-dry transition in the Chew Bahir basin (Southern Ethiopian Rift; between 11 ka and 4 ka), (2) the MIS 5-4 transition in the Naivasha basin (Central Kenya Rift; between 160 ka and 50 ka), and (3) the Early Mid Pleistocene Transition (EMPT) in the Olorgesailie basin (Southern Kenya Rift; between 1.25 Ma and 0.4 Ma). A probabilistic age modeling technique is used to determine the timing of these transitions, taking into account possible abrupt changes in the sedimentation rate including episodes of no deposition (hiatuses). Interestingly, the stable-unstable conditions identified in the three records are always associated with an orbitally-induced decrease of insolation: the descending portion of the 800 kyr cycle during the EMPT, declining eccentricity after the 115 ka maximum at the MIS 5-4 transition, and after ∼ 10 ka. This observation contributes to an evidence-based discussion of the possible mechanisms causing the switching between environmental stability and instability in Eastern Africa at three different orbital time scales (10,000 to 1,000,000 years) during the Cenozoic. This in turn may lead to great insights into the environmental changes occurring at the same time as hominin speciation, brain expansion, dispersal out of Africa, and cultural innovations and may provide key evidence to build new hypotheses regarding the causes of early human evolution., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to assist in the development of a health technology assessment (HTA) program for the Ministry of Health (MOH) of the Republic of Kazakhstan, Methods: Mentoring of an initial HTA program in Kazakhstan was provided by the Canadian Society for International Health (CSIH) by means of a partnership with the Kazakhstan MOH. HTA materials, courses, and one-on-one support for the preparation of a series of initial HTA reports by MOH HTA staff were provided by a seven-member CSIH team over a 2.5-year project., Results: Guidance documents on HTA and institutional strengthening were prepared in response to an extensive set of deliverables developed by the MOH and the World Bank. Introductory and train-the-trainer workshops in HTA and economic evaluation were provided for MOH staff members, experts from Kazakhstan research institutes and physicians. Five short HTA reports were successfully developed by staff in the Ministry's HTA Unit with assistance from the CSIH team. Challenges that may be relevant to other emerging HTA programs included lack of familiarity with some essential underlying concepts, organization culture, and limited time for MOH staff to do HTA work., Conclusions: The project helped to define the need for HTA and mentored MOH staff in taking the first steps to establish a program to support health policy decision making in Kazakhstan. This experience offers practical lessons for other emerging HTA programs, although these should be tailored to the specific context.

Background: The objective of this study was to perform an economic analysis of the cost-effectiveness of prostaglandin analogues for the treatment of increased intraocular pressure (IOP). Prostaglandin analogues for ophthalmic use are more costly than alternative agents for the lowering of IOP. An important policy decision is whether to support continued open listing of these agents or to restrict them to limited use status., Methods: The cost-effectiveness of prostaglandin analogues was assessed using a decision analytic model. Latanoprost was compared with timolol, dorzolamide, and brimonidine, and travoprost was compared with timolol separately. The effectiveness data used for this economic analysis were the number of millilitres of mercury of IOP reduction compared with baseline and the incidence of adverse events resulting in a withdrawal of the patient from the study. Sensitivity analyses were conducted to assess the robustness of the study results., Results: Compared with latanoprost, dorzolamide was not a cost-effective strategy. Compared with brimonidine, latanoprost provided a higher IOP reduction with an incremental cost-effectiveness ratio of $16.17 (base case), but the additional IOP reduction with latanoprost was obtained at a cost higher than the average cost per millimetre of mercury reduction obtained with brimonidine. Compared with timolol, latanoprost and travoprost had a positive incremental cost-effectiveness ratio of $34.48 and $39.06, respectively., Interpretation: For the first-line treatment of glaucoma and elevated IOP, latanoprost is a more cost-effective strategy than dorzolamide and brimonidine. Latanoprost and travoprost are more effective than timolol but also more expensive. For those for whom timolol is not contraindicated, it would be preferable, from a cost-effectiveness standpoint, to initiate treatment with timolol and reserve the prostaglandin analogues as an alternative treatment or as add-on therapy for patients not achieving a clinical response with timolol. Better treatment compliance associated with these analogues improves their cost-effectiveness.

A common sexually transmitted infection, human papillomavirus (HPV) has been linked to the development of cervical, anogenital, and head and neck cancers and genital warts. (2) Several randomized controlled trials have explored the efficacy and safety of two vaccines for primary prevention of infection by HPV types 16 and 18, those most commonly implicated in the development of cervical cancer. (3) An HPV vaccine, Gardasil, was approved in Canada in 2006, and a second vaccine, Cervarix, is undergoing Health Canada review. (4) Some unresolved questions about HPV vaccinations relate to the ideal age for immunization, duration of effect, immunization of women already infected, vaccination of males, implications for Papanicolaou (Pap) smear programs, barriers to uptake, need for monitoring and registries, cost effectiveness, and programs to ensure access for special populations.

(1) Cigarette smoking is the leading cause of preventable disease and death in the world. (2) Nicotine vaccines produce antibodies that bind nicotine, the chief addictive agent in cigarettes, and prevent it from entering the brain. (3) Early trials suggest nicotine vaccines are safe and well tolerated, but the duration of effect is unclear, and immunological response varies across recipients. (4) Nicotine vaccines have not yet been studied in phase 3 trials and the relative performance of different vaccines, alone or in combination with existing therapeutic options, is unknown.

(1) In photoselective vaporization of the prostate (PVP) for benign prostatic hyperplasia (BPH), laser energy is used to vaporize prostatic tissue rapidly and bloodlessly. (2) Studies suggest that PVP performs well in the short term. (3) Randomized controlled trials (RCTs) and longterm follow-up are required to determine PVP's place in the management of BPH.

(1) Liver fibrosis is associated with significant morbidity and mortality. The major cause is hepatitis C, which affects 240,000 Canadians. (2) Assessing the degree of liver fibrosis is critical to its management. Liver biopsy, an invasive procedure, is considered to be the diagnostic gold standard. (3) FibroScan is a rapid, non-invasive technology that uses low frequency vibration and ultrasound to assess the stiffness of liver tissue. (4) The diagnostic performance of FibroScan is good for identifying severe fibrosis or cirrhosis, but it is less accurate for milder presentations. (5) FibroScan is a promising technology, but large multi-centre trials comparing a range of emerging non-invasive fibrosis staging technologies are required.

(1) Chronic lumbar (lower back) pain, which affects many Canadians, imposes a large economic burden. (2) Symptoms may occur in the vertebral facet joints of 15% to 40% of patients with lower back pain. (3) Medial branch radiofrequency neurotomy is a minimally invasive outpatient procedure that reduces pain by interrupting the nerve supply to painful facet joints. (4) Four systematic reviews of this procedure offer disparate conclusions. (5) One small well designed observational study has shown positive results, but no equally rigorous randomized controlled trial has been conducted.

(1) High risk types of human papillomavirus (HPV) are the causal agents of cervical cancer. The prevention of HPV infection can reduce the incidence of this cancer. (2) Five phase II clinical trials have been published, and several large phase III trials are underway. (3) Trials have shown marked reductions in HPV infection. Most studies did not evaluate the effect of the vaccines on cancer because of lengthy time spans between HPV infection and the development of cancer. (4) Injection site pain, headache, and fatigue are the most common adverse events reported. (5) Important considerations include vaccine efficacy; acceptability; integration into existing vaccine schedules; cost; role of cervical screening programs; and access, particularly for people in the developing world.

Several focal skeletal muscle diseases, including tumours and trauma lead to a limited loss of functional muscle tissue. There is still no suitable clinical approach for treating such defects. A promising approach could be the tissue engineering of skeletal muscle. However, a clinically reliable differentiation stimulus for three-dimensional (3-D) cultures is necessary for this process, and this condition has not yet been established. In order to quantify and analyze the differentiation potential of electrical cell stimulation, primary myoblasts were stimulated within a 3-D fibrin- matrix. Gene expression of MyoD, myogenin and AChR-epsilon were measured by real-time RT-PCR over a time period of eight days, showing immediate down-regulation of all marker genes. For tissue engineering approaches, cell multiplication is crucial for acquisition of sufficient tissue volumes for reconstruction. Therefore, all experiments were performed with high and low passaged myoblasts, demonstrating higher transcript rates of marker genes in lowpassage cells. Our findings strongly suggest a reconsideration of electrical stimulation in muscle tissue engineering.

Diabetes mellitus is a chronic condition with several late complications that can be delayed or avoided through proper preventive health care. Although practice guidelines have been established to improve the preventive care in diabetics, dissemination of these guidelines among physicians and educational programs have been only moderately successful in changing physicians' practice patterns. Previous efforts, however, did not utilize computer-generated reminders. We developed a system of computer-generated reminders for diabetic preventive care. We completed an implementation of the system in the outpatient clinics of internal medicine residents at our institution. This paper describes the development and implementation of this system. Our results showed that the system flagged an average of 13 items that deviated from diabetes guideline compliance, out of a possible 21 items per patient. The residents completed encounter forms used by the system for 37% of patients seen during a six month period. Physician users exhibited positive attitudes toward the use of guidelines which they judged improved quality at no additional cost of care. However, the complexity and length of the guideline encounter forms and the additional time demands proved to be significant obstacles to current routine use. Our experience will help to improve the system so that it is more usable and acceptable to physicians, especially in the future as health care increasingly makes use of electronic medical record systems.