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1.  Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain 
Use of chronic opioid therapy for chronic noncancer pain has increased substantially. The American Pain Society and the American Academy of Pain Medicine commissioned a systematic review of the evidence on chronic opioid therapy for chronic noncancer pain and convened a multidisciplinary expert panel to review the evidence and formulate recommendations. Although evidence is limited, the expert panel concluded that chronic opioid therapy can be an effective therapy for carefully selected and monitored patients with chronic noncancer pain. However, opioids are also associated with potentially serious harms, including opioid-related adverse effects and outcomes related to the abuse potential of opioids. The recommendations presented in this document provide guidance on patient selection and risk stratification; informed consent and opioid management plans; initiation and titration of chronic opioid therapy; use of methadone; monitoring of patients on chronic opioid therapy; dose escalations, high-dose opioid therapy, opioid rotation, and indications for discontinuation of therapy; prevention and management of opioid-related adverse effects; driving and work safety; identifying a medical home and when to obtain consultation; management of breakthrough pain; chronic opioid therapy in pregnancy; and opioid-related polices. Perspective: Safe and effective chronic opioid therapy for chronic noncancer pain requires clinical skills and knowledge in both the principles of opioid prescribing and on the assessment and management of risks associated with opioid abuse, addiction, and diversion. Although evidence is limited in many areas related to use of opioids for chronic noncancer pain, this guideline provides recommendations developed by a multidisciplinary expert panel following a systematic review of the evidence.
PMCID: PMC4043401  PMID: 19187889
clinical practice guideline; opioids; opioid analgesics; risk assessment; monitoring; chronic pain
2.  Beyond the Levant: First Evidence of a Pre-Pottery Neolithic Incursion into the Nefud Desert, Saudi Arabia 
PLoS ONE  2013;8(7):e68061.
Pre-Pottery Neolithic assemblages are best known from the fertile areas of the Mediterranean Levant. The archaeological site of Jebel Qattar 101 (JQ-101), at Jubbah in the southern part of the Nefud Desert of northern Saudi Arabia, contains a large collection of stone tools, adjacent to an Early Holocene palaeolake. The stone tool assemblage contains lithic types, including El-Khiam and Helwan projectile points, which are similar to those recorded in Pre-Pottery Neolithic A and Pre-Pottery Neolithic B assemblages in the Fertile Crescent. Jebel Qattar lies ∼500 kilometres outside the previously identified geographic range of Pre-Pottery Neolithic cultures. Technological analysis of the typologically diagnostic Jebel Qattar 101 projectile points indicates a unique strategy to manufacture the final forms, thereby raising the possibility of either direct migration of Levantine groups or the acculturation of mobile communities in Arabia. The discovery of the Early Holocene site of Jebel Qattar suggests that our view of the geographic distribution and character of Pre-Pottery Neolithic cultures may be in need of revision.
PMCID: PMC3716651  PMID: 23894294
3.  Hominin Dispersal into the Nefud Desert and Middle Palaeolithic Settlement along the Jubbah Palaeolake, Northern Arabia 
PLoS ONE  2012;7(11):e49840.
The Arabian Peninsula is a key region for understanding hominin dispersals and the effect of climate change on prehistoric demography, although little information on these topics is presently available owing to the poor preservation of archaeological sites in this desert environment. Here, we describe the discovery of three stratified and buried archaeological sites in the Nefud Desert, which includes the oldest dated occupation for the region. The stone tool assemblages are identified as a Middle Palaeolithic industry that includes Levallois manufacturing methods and the production of tools on flakes. Hominin occupations correspond with humid periods, particularly Marine Isotope Stages 7 and 5 of the Late Pleistocene. The Middle Palaeolithic occupations were situated along the Jubbah palaeolake-shores, in a grassland setting with some trees. Populations procured different raw materials across the lake region to manufacture stone tools, using the implements to process plants and animals. To reach the Jubbah palaeolake, Middle Palaeolithic populations travelled into the ameliorated Nefud Desert interior, possibly gaining access from multiple directions, either using routes from the north and west (the Levant and the Sinai), the north (the Mesopotamian plains and the Euphrates basin), or the east (the Persian Gulf). The Jubbah stone tool assemblages have their own suite of technological characters, but have types reminiscent of both African Middle Stone Age and Levantine Middle Palaeolithic industries. Comparative inter-regional analysis of core technology indicates morphological similarities with the Levantine Tabun C assemblage, associated with human fossils controversially identified as either Neanderthals or Homo sapiens.
PMCID: PMC3501467  PMID: 23185454
4.  Battling Prostate Cancer with 5-Alpha-Reductase Inhibitors: a Pyrrhic Victory? 
Given the relatively small impact of prostate cancer screening on cancer mortality, experts are now suggesting that chemoprevention with 5-alpha-reductase inhibitors (5-ARI) may be a more effective strategy for cancer control. Two large placebo-controlled randomized trials found that men receiving 5-ARI were about 25% less likely than controls to be detected with cancer. However, most cancers were detected on routine biopsies required by study protocols. The benefit from receiving 5-ARI was minimal among men who underwent biopsy for clinical indications. Additionally, men receiving 5-ARI were more likely than controls to be diagnosed with high-grade cancers, though post-hoc analyses adjusting for biases accounted for the excess risk in one of the studies. A recent guideline recommended that men considering prostate cancer screening also consider chemoprevention. The rationale is that reducing cancer incidence, given the known risks for overdiagnosis and subsequent overtreatment, is sufficient justification for chemoprevention. However, a large randomized controlled trial found that screening was associated with a 70% increase in prostate cancer diagnosis—which chemoprevention would then reduce by 25%. This does not seem an acceptable trade-off especially because the potential increased risk for high-grade cancers could lead to higher cancer mortality.
PMCID: PMC3138595  PMID: 21222171
prostatic neoplasms; chemoprevention; finasteride; dutasteride; evidence-based practice
5.  The Nubian Complex of Dhofar, Oman: An African Middle Stone Age Industry in Southern Arabia 
PLoS ONE  2011;6(11):e28239.
Despite the numerous studies proposing early human population expansions from Africa into Arabia during the Late Pleistocene, no archaeological sites have yet been discovered in Arabia that resemble a specific African industry, which would indicate demographic exchange across the Red Sea. Here we report the discovery of a buried site and more than 100 new surface scatters in the Dhofar region of Oman belonging to a regionally-specific African lithic industry - the late Nubian Complex - known previously only from the northeast and Horn of Africa during Marine Isotope Stage 5, ∼128,000 to 74,000 years ago. Two optically stimulated luminescence age estimates from the open-air site of Aybut Al Auwal in Oman place the Arabian Nubian Complex at ∼106,000 years ago, providing archaeological evidence for the presence of a distinct northeast African Middle Stone Age technocomplex in southern Arabia sometime in the first half of Marine Isotope Stage 5.
PMCID: PMC3227647  PMID: 22140561
6.  Systems medicine and integrated care to combat chronic noncommunicable diseases 
Genome Medicine  2011;3(7):43.
We propose an innovative, integrated, cost-effective health system to combat major non-communicable diseases (NCDs), including cardiovascular, chronic respiratory, metabolic, rheumatologic and neurologic disorders and cancers, which together are the predominant health problem of the 21st century. This proposed holistic strategy involves comprehensive patient-centered integrated care and multi-scale, multi-modal and multi-level systems approaches to tackle NCDs as a common group of diseases. Rather than studying each disease individually, it will take into account their intertwined gene-environment, socio-economic interactions and co-morbidities that lead to individual-specific complex phenotypes. It will implement a road map for predictive, preventive, personalized and participatory (P4) medicine based on a robust and extensive knowledge management infrastructure that contains individual patient information. It will be supported by strategic partnerships involving all stakeholders, including general practitioners associated with patient-centered care. This systems medicine strategy, which will take a holistic approach to disease, is designed to allow the results to be used globally, taking into account the needs and specificities of local economies and health systems.
PMCID: PMC3221551  PMID: 21745417
7.  Catalysts for Stone Age innovations 
Fossil and genetic evidence suggests the emergence of anatomically modern humans (Homo sapiens) in sub-Saharan Africa some time between 200 and 100 thousand years (ka) ago. But the first traces of symbolic behavior—a trait unique to our species—are not found until many tens of millennia later, and include items such as engraved ochres and eggshells, tools made from bone, and personal ornaments made of shell beads. These behavioral indicators appear in concert with two innovative phases of Middle Stone Age technology, known as the Still Bay (SB) and Howieson's Poort (HP) industries, across a range of climatic and ecological zones in southern Africa. The SB and HP have recently been dated to about 72-71 ka and 65-60 ka, respectively, at sufficiently high resolution to investigate the possible causes and effects. A remarkable feature of these two industries is the spatial synchroneity of their start and end dates at archaeological sites spread across a region of two million square kilometers. What were the catalysts for the SB and HP, and what were the consequences? Both industries flourished at a time when tropical Africa had just entered a period of wetter and more stable conditions, and populations of hunter-gatherers were expanding rapidly throughout sub-Saharan Africa before contracting into geographically and genetically isolated communities. The SB and HP also immediately preceded the likely exit time of modern humans from Africa into southern Asia and across to Australia, which marked the beginning of the worldwide dispersal of our species. In this paper, we argue that environmental factors alone are insufficient to explain these two bursts of technological and behavioral innovation. Instead, we propose that the formation of social networks across southern Africa during periods of population expansion, and the disintegration of these networks during periods of population contraction, can explain the abrupt appearance and disappearance of the SB and HP, as well as the hiatus between them. But it will take improved chronologies for the key demographic events to determine if the emergence of innovative technology and symbolic behavior provided the stimulus for the expansion of hunter-gatherer populations (and their subsequent global dispersal), or if these Middle Stone Age innovations came into existence only after populations had expanded and geographically extensive social networks had developed.
PMCID: PMC2686379  PMID: 19513276
Middle Stone Age; southern Africa; Still Bay; Howieson's poort; technological innovation; symbolic behavior; human dispersal; demographic history; social networks
8.  Diagnosis and Treatment of Benign Prostatic Hyperplasia 
To define primary care physicians’ (PCPs) practices in managing patients with benign prostatic hyperplasia (BPH), and to compare these practices to portions of the Agency for Health Care Policy and Research BPH guideline and urologists’ practices.
Mail survey.
Nationwide random sample of PCPs and urologists, selected from the American Medical Association Registry.
Initial mailing, postcard reminder, second mailing, telephone reminder, final mailing.
Primary care physicians (n = 444, response = 51%) reported seeing a median of 35 patients with BPH over the preceding year, in contrast to 240 for urologists (n = 394, response = 68%). Regarding tests recommended by the guideline, two thirds of PCPs reported rarely or never using the American Urological Association (AUA) symptom index, nearly all reported routinely performing digital rectal examinations, and many (66%) reported routinely ordering tests to determine the serum creatinine level. Although considered “optional” by the guideline, more than 90% of PCPs reported routinely ordering a prostate-specific antigen test, while infrequently using other optional tests. Regarding “not recommended” studies, a substantial minority reported selectively or routinely ordering intravenous pyelography (34%) and renal ultrasound (33%), while two thirds reported rarely or never ordering these tests. Eighty-six percent of PCPs reported prescribing medications for BPH over the preceding year; α blockers to a median of 12 patients, and finasteride to a median of 2. Variation in urology referral thresholds was suggested in responses to two patient scenarios.
Primary care physicians are actively managing patients with BPH. Some of their diagnostic evaluations vary from the recommendations of a national guideline and urologists’ practices. Referral thresholds appear to vary considerably.
PMCID: PMC1497095  PMID: 9127226
prostatic hyperplasia; primary care physicians; practice patterns; practice guideline

Results 1-8 (8)